Muscle & Nerve最新文献

Randomized controlled trials (RCTs) remain the gold standard for establishing the efficacy and safety of new treatments. However, clinical evidence derived from the systematic analysis of real-world data generated through routine clinical practice can complement RCT data by offering insights into treatment performance in broader, more heterogeneous patient populations and clinical care settings. The integration of high-quality clinical evidence into health economics and outcomes research (HEOR) is increasingly important, as it supports healthcare decision-making across multiple stakeholders, including regulatory agencies, payers, clinicians, and patients. Multiple study designs, such as pragmatic trials, hybrid RCTs, external control arms, and observational studies, can provide valuable clinical evidence beyond the controlled trial setting. These data can enhance understanding of comparative effectiveness, patient-reported outcomes, treatment safety, and healthcare utilization and costs. The field of amyotrophic lateral sclerosis offers a compelling example of how clinical evidence derived from global registries and clinical studies has advanced understanding of disease epidemiology, treatment patterns, and the effectiveness of therapies, including riluzole and edaravone. Consequently, this review and the associated supplementary articles are meant to serve as a primer to inform clinicians of the potential contribution of clinical evidence to HEOR studies.

While randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of therapies in amyotrophic lateral sclerosis (ALS), post hoc analyses can provide critical insights into clinical effectiveness, treatment durability, and subpopulation responses. Several post hoc analyses of Study MCI186-19 (Study 19), the pivotal phase 3 RCT that supported the United States Food and Drug Administration approval of intravenous edaravone, have been performed to explore the broader clinical impact of this therapy. These analyses assessed the long-term treatment efficacy, changes in individual ALS Functional Rating Scale-Revised item scores, survival and additional milestone events, and the impact of edaravone in patient subgroups defined by disease progression trajectories using latent class analysis. Collectively, these findings reinforce the long-term clinical benefit of edaravone and demonstrate that edaravone may offer benefits across a spectrum of ALS disease trajectories, beyond those defined in the original study criteria. These studies help address questions not captured in the original RCT and may inform future trial design and treatment decisions.

Randomized controlled trials remain the cornerstone of evidence generation in amyotrophic lateral sclerosis (ALS), yet their inherent challenges, including disease rarity, heterogeneity, and limited validated biomarkers, highlight the need for complementary clinical evidence. This exploratory, retrospective study assessed overall survival in patients with ALS treated with intravenous (IV) edaravone using data from a large United States administrative claims database of patients enrolled from August 2017 to March 2020. Patients receiving IV edaravone (n = 318) were propensity score matched 1:1 with controls not treated with IV edaravone (n = 318), adjusting for 11 covariates. Median overall survival was 29.5 versus 23.5 months for the edaravone-treated group compared to controls, with a 27% reduced risk of death observed in the treated cohort (p = 0.005). These findings, together with existing data from the pivotal phase 3 Study MCI186-19 of IV edaravone, contribute to the growing body of literature suggesting a dual benefit of edaravone on both function and survival in ALS, offering critical insights for clinicians, patients, and payers navigating ALS treatment decisions.

This article summarizes the post-marketing pharmacovigilance safety data of intravenous (IV) edaravone during the 1- and 3-year periods following its launch for amyotrophic lateral sclerosis (ALS) in the United States. The most frequently reported adverse events (AEs) and serious AEs (SAEs) included those consistent with ALS disease progression, such as fatigue and muscular weakness, and were not qualitatively different from those reported in previous ALS trials. There were AEs and SAEs associated with IV administration, such as administration site reactions, and five non-fatal anaphylaxis SAEs were reported. No new safety signals were identified, and IV edaravone continues to demonstrate a favorable safety profile. These insights are especially useful as treatment transitions to edaravone oral suspension, which avoids IV-related complications. These findings underscore the importance of ongoing clinical safety assessments in informing ALS treatment decisions.

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.