Muscle & Nerve最新文献

Introduction/aim: Variants in the EMD gene cause Emery-Dreifuss muscular dystrophy type 1 (EDMD1). While the pattern of fat replacement in the legs of patients with EDMD1 is known, the involvement of the trunk and arms remains unclear. This study aimed to characterize the whole-body distribution of fatty replacement in EDMD1 and clarify its relationship with clinical symptoms.

Methods: Imaging data from eight Japanese EDMD1 patients was analyzed. Fatty replacement in 47 skeletal muscles was scored using the modified Mercuri score (mMS). Hierarchical clustering classified patients according to mMS, and intercluster differences were assessed.

Results: Fatty replacement was observed in the soleus and paraspinal muscles in all patients, as well as in the medial gastrocnemius, semimembranosus (Sm), biceps femoris long head (BFL), serratus anterior (SA), and biceps brachii (BB) in seven patients. A significant difference in mMS was observed between the low- and high-score groups in the SA (p = 0.0042), BB (p = 0.0031), semitendinosus (p = 0.0015), Sm (p < 0.0005), and BFL (p = 0.0031). Elbow flexion strength on manual muscle testing strongly correlated with BB mMS (p = 0.03, r = -0.75). The patient with a missense variant had a lower mMS than those with truncating variants.

Discussion: Elbow flexion strength is a potential marker of disease severity. The finding that the patient with a missense variant had a lower mMS supports previous reports that missense variants are associated with milder phenotypes. Genetic variant type should be considered in biomarker development for EDMD1.

Introduction/aims: With implementation of newborn screening (NBS) for Duchenne muscular dystrophy (DMD), creatine kinase-muscle (CK) values will be reported on newborns. Maternal, labor, delivery, and newborn factors may elevate CK levels, raising concern for DMD. Predictive modeling could aid hyperCKemia interpretation while awaiting diagnostic confirmation.

Methods: In this single-center, prospective cohort study, parents of 8365 newborns were offered DMD-NBS. Electronic health records provided data on candidate predictors of hyperCKemia defined by values > 97th or 99th percentiles, or 2000 ng/mL in babies with normal DMD sequences. Exposures included maternal, newborn and perinatal factors. Associations between predictors and hyperCKemia were evaluated using univariate logistic regression. A multivariable prediction model for the 97th percentile was derived using backward stepwise logistic regression and externally validated in a cohort of 2672 newborns.

Results: HyperCKemia > 97th percentile was the main outcome. Univariate analyses revealed associations between hyperCKemia and maternal ethnicity, primiparity, labor and delivery complications, oxytocin induction or augmentation, duration of ruptured membranes, forceps or vacuum-assisted delivery, neonatal resuscitation, sex, gestational age, birth weight, and Apgar scores. Lower odds of hyperCKemia were associated with later hour-of-life at sample collection and birth by cesarean section. The final model included parity, shoulder dystocia, forceps or vacuum-assisted delivery, gestational age, neonatal resuscitation, Apgar score (1 min), and time of sample collection.

Discussion: Elevated CK levels may be used for DMD-NBS. Multiple perinatal factors are associated with transient non-DMD hyperCKemia. Our model considers the potential combined impact of such factors and generates a non-disease likelihood for preliminary hyperCKemia interpretation.

Introduction/aims: Pain-related evoked potentials with concentric electrodes (PrEP-CE) provide a method for screening for small fiber neuropathy, which is usually the first manifestation of hereditary transthyretin amyloid polyneuropathy (ATTR v-PN). Despite that, this technique has not yet been fully explored in this condition. The current study aimed to compare PrEP-CE responses among patients with ATTRv-PN, presymptomatic carriers of TTR mutations, and healthy controls.

Methods: We recruited 17 patients with ATTRv-PN, 12 presymptomatic TTR mutation carriers (pre-ATTRv-PN), and 13 healthy controls. PrEP-CE were obtained by separately stimulating the hands and feet. We analyzed the latencies of negative (N1) and positive (P1) peaks and peak-to-peak amplitudes between groups using nonparametric tests.

Results: Median ages were 45 years for both ATTRv-PN and pre-ATTRv-PN groups, and 32 years for controls. In the arms, N1 and P1 latencies were significantly longer in the ATTRv-PN group compared to controls (p < 0.05). In the legs, P1 latency was significantly longer in the ATTRv-PN (p = 0.005) and the pre-ATTRv-PN (p = 0.001) groups vs. controls. PrEP-CE amplitudes were reduced in both the ATTRv-PN (p = 0.015) and the pre-ATTRv-PN (p = 0.021) compared to the control group.

Discussion: PrEP-CE facilitates recognition of ATTRv-PN, with lower limb P1 latency and amplitude indicating small fiber involvement. It is a rapid, well-tolerated technique that may support the assessment of small-fiber impairment in ATTRv-PN.

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.