Muscle & Nerve最新文献

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.

Introduction/aims: As corneal dendritic cells (DCs) are immune cells that can reflect systemic inflammatory activity, this study aimed to investigate whether the density and maturity of corneal DCs are associated with diabetes, diabetic peripheral neuropathy (DPN), and neuropathic pain.

Methods: Participants included individuals with type 1 diabetes mellitus (T1DM) and painful DPN (n = 19), T1DM and painless DPN (n = 15), T1DM without DPN (n = 19), and healthy controls (n = 20). Corneal confocal microscopy was used to quantify and categorize DCs as either mature or immature and based on their proximity to corneal nerves.

Results: No significant differences between groups were observed in total DC density (p = 0.34). Subgroup analysis revealed distinct patterns in which participants with DPN (regardless of pain status) exhibited a higher density of immature DCs distant from corneal nerves compared to those without DPN (14.4 [6.64-37.5] vs. 3.75 [0-17.7] no./mm², p < 0.05). Healthy controls had a greater density of immature DCs near the nerves compared to the T1DM + DPN group (2.8 [0-8.44] vs. 8.3 [3.12-15.1] no./mm²), while the T1DM + DPN group had a higher density than the painful DPN (3.1 [1.25-5.62] no./mm²). For mature DCs near the nerves, individuals with painful DPN (2.5 [1.4-3.12] no./mm²) had a lower density compared to all other groups.

Discussion: This study demonstrates distinct patterns of corneal DC distribution in relation to painful and painless DPN. The findings suggest that immune-mediated mechanisms may play a role in the development of neuropathy and neuropathic pain in diabetes. The pathophysiological significance remains to be clarified.

Trial registration: ClinicalTrials.gov: NCT04078516.

Introduction/aims: Congenital myasthenic syndromes (CMS) are often underdiagnosed due to phenotypic overlap with other neuromuscular disorders. Limited epidemiological data and low awareness hinder early diagnosis, which is key for effective treatment. Early recognition of CMS is important as symptomatic treatments often specific for genetic subtypes exist and emerging therapies are in the pipeline. This study aims to estimate the prevalence of genetically confirmed CMS in the United Kingdom and explore geographical variations.

Methods: Prevalence was calculated as of 31 December 2023, including genetically confirmed CMS patients residing in the United Kingdom and known to be alive. Patients with missing geographic or living status data were excluded. Prevalence was estimated overall and compared between UK regions served by a highly specialized neuromuscular service (hsNMS) and those without such services (non-hsNMS).

Results: A cohort of 442 genetically confirmed CMS patients was identified. CHRNE deficiency, DOK7, RAPSN were the most common subtypes. The UK prevalence was 6.5 cases per million overall and 8.5 cases per million in the pediatric population. The overall prevalence was statistically higher in hsNMS (8.8 cases per million) compared to non-hsNMS regions (5.9 cases per million). Homozygous patients had a more clustered distribution particularly around urban area.

Discussion: Our results suggest there is likely underdiagnosis of CMS in many areas of the United Kingdom and hsNMS may play an important diagnostic role. Variations may also be related to other cultural clustering and founder effects. Further research should explore how healthcare access, ethnicity, and consanguinity contribute to regional variation and diagnostic rates.

Introductions/aims: The clinical utility of serum neurofilament light chain (sNfL) in the evaluation and management of peripheral neuropathy (PN) remains poorly defined. This study aimed to evaluate the utility of sNfL for diagnosing PN, assessing disease activity, and monitoring treatment response using a commercially available assay.

Methods: This was a retrospective cohort study at the University of Pennsylvania between June 2024 and March 2025. Patients with, or at risk for, PN who underwent sNfL testing were included. Demographics, PN etiology, clinical findings, and sNfL levels were analyzed.

Results: One hundred and twenty-eight patients were included: 41 with chronic inflammatory demyelinating polyneuropathy (CIDP), 36 with transthyretin amyloidosis (ATTR), 13 with vasculitic PN, 13 with Charcot-Marie-Tooth disease (CMT), 6 with multifocal motor neuropathy (MMN), 4 with anti-MAG neuropathy, 4 with Guillain-Barré syndrome (GBS), and 11 with other PN types. Of these, 113 had definite large fiber PN; 14 were asymptomatic TTRv carriers, and one had small fiber neuropathy. Elevated sNfL levels were observed in 31 patients (24%). The odds ratio of having elevated sNfL in treatable vs. non-treatable PN was 28.33 (95% CI: 5.04-159.18). Among CIDP and ATTRv-PN patients, sNfL was most often elevated in treatment-naïve or refractory cases and decreased with treatment.

Discussion: Routine sNfL testing is warranted in selected patients with PN, such as treatment-naïve or refractory CIDP, active vasculitic PN, and ATTRv-PN. Elevated sNfL in patients with PN should prompt evaluation for a potentially treatable cause and may offer useful adjunctive information to support clinical decision-making.