Muscle & Nerve最新文献

Introduction/aims: Sex-specific differences in myasthenia gravis (MG) are widely acknowledged, yet data on sex-based outcomes of MG treatment are scarce. In accordance with Sex and Gender Equity in Research guidelines, this post hoc analysis assessed potential sex-specific differences in treatment outcomes in acetylcholine receptor antibody-positive (AChR-Ab+) generalized (g)MG participants in the Phase 3 ADAPT trial (NCT03669588).

Methods: Participants received four once-weekly efgartigimod infusions (10 mg/kg) or placebo per cycle. Endpoints (primary: proportion of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders (Cycle 1); secondary: proportion of Quantitative Myasthenia Gravis (QMG) and early (Cycle 1) MG-ADL responders, and time with clinically meaningful improvements in MG-ADL score; additional: quality of life outcomes, pharmacodynamics) were assessed according to sex.

Results: Females were younger (mean age: 42.9 vs. 54.8 years), more likely to have undergone thymectomy (65.1% [56/86] vs. 44.2% [19/43]), and had higher baseline QMG scores (16.3 vs. 14.3) compared with males. Efgartigimod demonstrated homogeneous effects between sexes, with no significant difference in proportions of MG-ADL (p = 0.7014), early (Cycle 1) MG-ADL (p = 1.00), or QMG responders (p = 0.1595). Improvements in quality-of-life assessments, rates of minimal symptom expression, and mean total immunoglobulin G reductions (Cycle 1) were greater with efgartigimod verso placebo in females and males. Efgartigimod was well tolerated, with similar safety profiles across sexes.

Discussion: In ADAPT, efgartigimod-treated female and male AChR-Ab+ gMG patients had similar efficacy and safety outcomes. These data provide valuable insight for clinicians, given the established sex differences in MG disease course and treatment responses.

Trial registration: The ADAPT trial is registered on ClinicalTrials.gov (NCT03669588).

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: For recording the compound muscle action potential (CMAP) of the deltoid muscle, the reference electrode over the acromion (Ac) has been used to avoid contamination of responses from other arm muscles to the distal tendon (DT). A recent article recommended the sternum (St) as the reference electrode. In this study, we aimed to find the appropriate reference site for the deltoid CMAP.

Methods: Subjects were 12 healthy volunteers. The deltoid CMAP was recorded using Ac, St and DT references. CMAPs of the biceps brachii (BB) and triceps brachii (TB) were also recorded. In addition to stimulation at Erb's point, selective stimulations of the axillary, musculocutaneous, or radial nerve were attempted at the axilla.

Results: The deltoid CMAPs with Ac reference had similar shapes following Erb's point (proximal) stimulation and axillary plus radial (distal) stimulation at the axilla. In contrast, CMAP using St reference was considerably smaller following proximal than distal stimulation. This difference was derived from the Ac-St lead, to which proximal muscles such as pectoralis major are supposed to contribute only following the proximal stimulation. Such a contribution can be explained by the far-field potential (FFP) theory, which suggests that the Ac-St lead can record FFPs from muscles situated between the Ac and St electrodes.

Discussion: Consistency between proximal and distal stimulations is preferred for motor nerve conduction studies. We propose that Ac reference that enables selective recording from the deltoid muscle is the most appropriate way to record deltoid CMAP to date.

Introduction/aims: Digital nerve lacerations are common. Current methods employed to differentiate intact and transected digital nerves lack diagnostic accuracy. This may result in patients with intact nerves undergoing unnecessary surgery. The objective of the study was to determine the best diagnostic method for detecting true sensory nerve transections and to delineate the sensitivities and specificities of common sensory tests.

Methods: Patients aged 18-65 years with suspected complete digital nerve lacerations were recruited. Sensory testing including static two-point discrimination (s2PD), Semmes-Weinstein Monofilaments, and Quantitative Sensory Testing were used prior to surgical exposure to evaluate different categories of sensory nerve fibers. Likelihood ratios, sensitivity, and specificity of each test were compared to direct visualization intraoperatively. Receiver operating characteristic (ROC) curves were used to determine the area under the curve (AUC) for each test.

Results: Of the 60 patients recruited, 41 (68%) had complete digital nerve transections while 19 (32%) had intact nerves. Heat pain threshold testing showed the greatest AUC at 0.812 ± 0.067 with a sensitivity of 90% and specificity of 65% at a cutoff of 22.1 just noticeable difference (JND). However, combining s2PD (7 mm, 100% sensitivity, 32% specificity) and warm detection threshold (WDT) (25 JND, 100% sensitivity, 37% specificity) in a two-step algorithm achieved 100% sensitivity and increased the specificity to 58%.

Discussion: Implementing a two-step diagnostic algorithm combining s2PD and WDT can effectively diagnose complete digital nerve laceration with high sensitivity and improved specificity. These findings underscore the utility of both tests in accurately identifying complete digital nerve lacerations.

Introduction/aims: Although nervous system maturation is a key factor underlying the difference in muscle strength between children and adults, specific neural strategies for modulating motor unit (MU) firing during graded force production remain largely unexplored. This study aimed to clarify the differences in MU firing behavior between children and young adults during submaximal isometric ramp contractions.

Methods: Eighteen healthy children (aged 6-12 years) and 18 healthy young adults performed maximal voluntary contractions (MVCs) and submaximal ramp contractions to 50% of MVC for isometric knee extension. High-density surface electromyography data were collected from the vastus lateralis muscle and were decomposed to identify individual MU firing. MUs were analyzed according to their recruitment thresholds (RTs) to compare their firing rates (FRs) and the change in FR (ΔMU FR) at various force intervals.

Results: Children consistently exhibited significantly higher MU FRs than adults across almost all RT groups and force levels. ΔMU FR was higher in children only during the initial 10%-20% MVC interval for the lowest-threshold MUs but was significantly lower for higher threshold MUs at higher force levels.

Discussion: Higher MU FRs in children likely represent a functional adaptation to compensate for immature muscle contractile properties, thereby ensuring effective force generation. This distinct neural control strategy, which combines high initial rates with subsequent firing saturation, may reflect the ongoing maturation of spinal motor control. These findings provide a valuable reference for assessing pediatric neuromuscular disorders and can inform the design of more effective exercise and rehabilitation programs.

Introduction/aims: Patients with non-length-dependent neuropathy (NLDN) exhibit reduced sensory nerve action potential (SNAP) amplitudes in both lower and upper limbs. This study aimed to determine a threshold for the sural/radial amplitude ratio (SRAR) suggestive of NLDN.

Methods: This retrospective case-control study involved 60 patients with definite NLDN (sensory neuronopathy [SNN] or chronic inflammatory demyelinating polyradiculoneuropathy [CIDP]) and 30 patients with length-dependent neuropathy (LDN). The diagnostic performance of SRAR was evaluated using the area under the curve (AUC) of the modeled receiver operating characteristic (ROC) curve. The presence of a length-dependent electrodiagnostic (EDX) pattern, defined as a sural SNAP amplitude lower than the radial one, was evaluated in each group.

Results: SRAR could be calculated in 90/164 (54.9%) of patients screened. Among patients with NLDN, the median SRAR was 0.74 (IQR 0.50-1.00) compared to 0.17 (IQR 0.12-0.23) in patients with LDN. The ROC curve analysis for NLDN versus LDN yielded an AUC of 0.94 (95% CI, 0.883-0.979). The SRAR threshold of 0.33 provided a sensitivity of 84.4% (95% CI, 77.8%-90.9%), specificity of 86.9% (95% CI, 79.7%-94%). The length-dependent EDX pattern was observed in 100% (30/30) of LDN patients and 63% (38/60) of NLDN patients. Among these 38 patients with NLDN, SRAR exceeded 0.33 in 78.9% (30/38).

Discussion: SRAR appears to be useful in the electrophysiological evaluation of neuropathies. In addition to usual diagnostic criteria, an SRAR > 0.33 may strongly suggest NLDN such as SNN or CIDP.

Introduction/aims: In global amyotrophic lateral sclerosis (ALS) trials, women and men appear to be proportionately enrolled, but quantification of enrollment by sex and race in U.S.-based ALS trials is limited. The objective of this study was to evaluate the sex and race of participants enrolled in U.S.-based ALS clinical trials.

Methods: Participant demographics were extracted from recent U.S.-based Phase 2 and 3 ALS trials identified in literature and on ClinicalTrials.gov. The Centers for Disease Control and Prevention (CDC) National ALS Registry and a 2014 State Surveillance Project were used as proxies for prevalence. Participation-to-prevalence (PPR) ratios were calculated for sex and race. A modified time-trend analysis was performed for race for participants enrolled before and after 2020.

Results: A total of 11 trials met criteria for inclusion with a total of 1153 patients enrolled. Compared to the CDC Registry, the PPR was 0.76 (95% CI: 0.63-0.90) for women, 1.26 (95% CI: 1.23-1.29) for White participants, 0.34 (95% CI: 0.17-0.51) for Black participants, and 0.35 (95% CI: 0.14-0.56) for all other races/multiracial. The modified time trend analysis showed no significant difference in the PPRs before and after 2020 (White: t = 1.44, p = 0.22; Black: t = -0.99, p = 0.37; Other races/multiracial: t = -1.50, p = 0.21). The comparison to the 2014 State Surveillance Project yielded similar findings.

Discussion: U.S.-based ALS trials significantly under-enroll non-White participants, and there are trends toward slight underrepresentation of women. Efforts to broaden trial enrollment amongst people with ALS will help with the generalizability of trial results and hasten trial completion.

Introduction/aims: The sensory nerve action potential (SNAP) of the superficial fibular nerve (SFN) is occasionally small and difficult to obtain using conventional surface recording (SR) or near-nerve needle recording. This study aimed to demonstrate a novel method of sensory conduction study of the SFN using ultrasound-guided near-nerve needle recording (US-NNNR) to obtain larger amplitude recordings.

Methods: Twenty healthy volunteers (40 legs) were analyzed. In the conventional sensory conduction study using SR, we stimulated the nerve on the lateral aspect of the mid lower leg. The SNAPs of the medial dorsal cutaneous nerve (MDCN) and intermediate dorsal cutaneous nerve (IDCN) of the SFN were recorded at the ankle. In the US-NNNR, the SFN was scanned on the lateral aspect of the mid lower leg and a needle electrode was inserted with an out-of-plane approach < 1 mm from the SFN. Through the needle electrode, we recorded the SNAPs evoked by the stimulation of the MDCN or IDCN at the ankle. The SNAP amplitudes were compared between the SR and US-NNNR using the Wilcoxon signed-rank test.

Results: The SNAP amplitude was significantly larger with US-NNNR than with SR for both the MDCN (p < 0.001) and the IDCN (p < 0.001).

Discussion: US-NNNR in sensory conduction study of the SFN produced a larger SNAP amplitude than SR. The larger SNAP observed using US-NNNR may aid in the diagnosis of disorders involving the SFN.

Introduction/aim: Survival outcomes have been inadequately studied among people with myasthenia gravis (MG) in the United States (US). We examined the impact of MG and comorbid conditions on longevity.

Methods: We performed a longitudinal study using Medicare claims data (2006-2019). Incident MG cohort was identified based on the following criteria: age ≥ 65 years; ≥ 1 month of fee-for-service Parts A and B coverage; no health maintenance organization coverage; initial and subsequent MG claims within 2010-2011 separated by ≥ 28 days. A non-MG cohort of five times the number of the MG group was selected, matching for age, sex, region, and Medicare coverage duration. Overall and cause-specific mortality were compared between cohorts in the subsequent 8-10 Years using Kaplan-Meier plots and Cox proportional hazard models, adjusted for the Charlson Comorbidity Index (CCI).

Results: Cohorts of 6024 incident MG and 30,083 control beneficiaries were Included. The mortality rate was higher in the MG cohort compared to controls (66.8 vs. 57.1 per 1000-person-year, p < 0.0001). After adjusting for time-varying CCI, no significant difference in survival was observed between two cohorts (adjusted hazard ratio 1.09 [0.87-1.36], p = 0.47). Sixteen percent of deaths in the MG cohort were attributed to MG. Compared to the non-MG cohort, mortality rates (per 1000-person-year) specific to infections were higher among the MG cohort (2.0 vs. 1.2) while malignancies and dementia-specific mortality rates were lower (10.3 vs. 12.5 and 4.7 vs. 7.2), all p < 0.01.

Discussion: Long-term mortality is increased in elderly MG patients compared to non-MG counterparts, driven by their higher comorbidity burden.