Muscle & Nerve最新文献

Introduction/aims: A previous publication reported that the number of months of training and the number of patient studies independently influenced examination scores for the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) self assessment examination (AANEM-SAE). The purpose of this study was to explore additional questions regarding how electrodiagnostic (EDx) training impacts AANEM-SAE score.

Methods: This was a retrospective review of the 2024 and 2025 AANEM-SAE results. Participants were asked the number of: patient studies performed, months of training completed, hours of didactic training received, and hours they studied to prepare for the AANEM-SAE. There were also questions regarding neuromuscular ultrasound training.

Results: A total of 1530 participants completed the proctored examinations. Scores steadily improved with additional months of training but leveled off after 300-400 patient studies. Regression analysis indicated that higher numbers of patient studies and higher numbers of didactic training hours and study hours were correlated with higher examination scores even after accounting for the number of months of training. Of the 2025 participants, 56% received training in neuromuscular ultrasound, but most completed no more than 30 patient studies. No association was found between ultrasound training and performance on ultrasound questions, but the number of questions was small.

Discussion: EDx training program directors should continue to emphasize core elements of EDx training and design their curricula with attention to providing sufficient numbers of studies and hours of didactic instruction for trainees.

Introduction/aims: Although classically characterized as a motor neuron disease, spinal muscular atrophy (SMA) is increasingly recognized as a multisystem disorder. We previously showed hepatocyte-intrinsic steatosis in SMA, raising the question of whether SMA carriers, who are typically asymptomatic, may also exhibit subclinical hepatic abnormalities.

Methods: We generated induced hepatocyte-like cells (iHeps) from induced pluripotent stem cells (iPSCs) derived from an SMA Type 2 proband, his isogenic wild-type (Iso-WT) line, and both carrier parents, comprised of three carrier lines from the father and one from the mother. Steatosis was assessed by Oil Red O staining and image analysis. Survival motor neuron (SMN) expression was evaluated by immunoblotting. Proteotranscriptomic profiling and mitochondrial respiration assays were performed. Risdiplam, an SMN2 splicing modulator, was used to assess reversibility of observed phenotypes.

Results: SMA and carrier iHeps demonstrated increased lipid accumulation compared to Iso-WT. Risdiplam reduced steatosis by 65.9% in SMA patient-derived iHeps and by 43.6% and 56.9% in father- and mother carrier-derived iHeps, respectively. Carrier and SMA iHeps exhibited downregulation of genes involved in lipid metabolism and liver function, along with altered expression of lipid-related proteins. Mitochondrial dysfunction was present only in SMA iHeps. Carrier-derived induced motor neurons showed normal viability under oxidative stress, consistent with preserved neuromuscular function clinically.

Discussion: Our data reveal hepatocyte-intrinsic lipid metabolic defects in SMA carriers, partially reversible with risdiplam. These findings suggest subclinical hepatic involvement in carriers and support further investigation into the systemic impact of SMN deficiency.

Introduction/aims: Previous studies of children with spinal muscular atrophy (SMA) have focused on the ulnar and median nerves, while lower-limb and proximal motor nerves remain insufficiently characterized. This study aimed to evaluate compound muscle action potential (CMAP) amplitudes in upper- and lower-limb motor nerves in children with SMA and changes after nusinersen treatment.

Methods: In this single-center retrospective study, CMAP amplitudes were collected from children with SMA and age-matched controls without neuromuscular disease. CMAP amplitudes of the tibial, peroneal, femoral, median, and ulnar nerves were assessed in children with SMA types 1-3. A cross-sectional analysis was conducted to assess CMAP amplitudes prior to treatment. Longitudinal changes after SMA disease-modifying therapies (nusinersen monotherapy or nusinersen plus risdiplam treatment) were evaluated.

Results: A total of 47 children with SMA were included. The baseline CMAP amplitudes of the peroneal, tibial, median, and ulnar nerves were the highest in type 3, followed by type 2, and lowest in type 1. Femoral nerve CMAP amplitudes were low in all SMA subtypes. At preliminary diagnosis, children with SMA had significantly reduced CMAP amplitudes for the five nerves compared with age-matched controls (n = 63, p < 0.05). After 18 months of nusinersen treatment, CMAP amplitudes showed significant increases from baseline in the peroneal, femoral, median, and ulnar nerves (p < 0.05).

Discussion: CMAP amplitudes can differentiate SMA disease severity and may increase after nusinersen treatment. Large-scale longitudinal studies are required to investigate CMAP amplitude as a biomarker of treatment response in patients with SMA.

Introduction/aims: Effective management remains lacking for recurrent episodes of acute weakness in hypokalemic periodic paralysis (HypoPP). We assessed the efficacy of a second-generation potassium channel agonist, XEN1101, to prevent and abort the low-K⁺ induced loss of force in mouse models of HypoPP.

Methods: An ex vivo contractility assay was used to interrogate the efficacy of XEN1101 for preserving contractile force and for enhancing recovery of force in the setting of a low-K⁺ challenge for HypoPP mice carrying the sodium channel Na_V1.4-R669H or the calcium channel Ca_V1.1-R528H mutations.

Results: The acute loss of force for HypoPP muscle, triggered by a 2 mM K⁺ challenge, was prevented by low micromolar XEN1101, with an effective concentration of 0.30 μM for 50% protection. Application of 1 μM XEN1101, after the onset of 2 mM K⁺ induced weakness, restored the peak contractile force (70%-100% of baseline).

Discussion: The K_V7 potassium channel agonist XEN1101 is effective as both a prophylactic agent and as abortive therapy for management of low-K⁺ induced weakness in murine models of HypoPP. XEN1101 is more potent than the first-generation Kv7 agonist, retigabine, in our murine models of HypoPP and is also better tolerated in patients. These improvements provide a rationale for future clinical trials of XEN1101 in HypoPP patients.

Introduction/aim: As humans return to the Moon, safe efficient ambulation and fall prevention on the lunar surface are key concerns. The analysis of gait from archived Apollo mission video footage is now possible with pose estimation video analysis software. Thus, this study aims to retrospectively quantify parameters of Apollo astronauts' stance and gait on the Moon.

Methods: Publicly available National Aeronautics and Space Administration (NASA) footage of astronauts ambulating on the Lunar surface was examined using body pose analysis software. Goniometric lower limb joint/torso angles and width of base of stance and gait were derived. Gait cycle stance phase, swing phase, double support time, and estimated speed of gait were all computed.

Results: Lunar stance was characterized by 13.3 ± 3.6 SD to 14.3 ± 3.9 SD inch base of stance (based on a 6.5 or 7.0 in. shoe width, respectively), 39.3° ± 9.0° hip flexion, 42.2° ± 14.8° knee flexion, and 17.0° ± 7.5° ankle dorsiflexion. Upper torso anterior tilt was 16.4° ± 8.8°. Lunar gait demonstrated 14.0 ± 2.8 SD to 15.1 ± 2.9 SD base of gait, 0.42 ± 0.16 m/s speed of gait, and 15.4 ± 3.3 in. step length with 40% double support time. Stance phase was 69% and swing phase was 31% of the gait cycle.

Discussion: Decreased speed of gait with wide base, short steps, and increased double support time was seen in astronaut gait patterns. This pattern is adopted on Earth to increase stability and prevent falls.

Introduction/aims: Amyotrophic lateral sclerosis (ALS) affects military veterans at a higher rate than the general civilian population. The aim of the present study is to assess symptom burden and satisfaction with care among persons with ALS care enrolled in the US Veterans Health Administration (VA).

Methods: A custom online survey was created with questions about symptom prevalence and management as well as care satisfaction. A survey link was sent by email to all veterans with an ICD-10 diagnosis of ALS in the VA for whom an email address was available in the electronic health record.

Results: Responses were received from 413 individuals (16% response rate). Respondents reported high care satisfaction and higher prevalence of treatment of symptoms compared to prior surveys of persons with ALS in the United States. Self-reported outcomes, including treatment, education, and satisfaction, were better for Veterans receiving care exclusively within the VA compared to those receiving care at both VA and non-VA facilities or receiving care exclusively at non-VA facilities. Areas for further improvement identified in the survey include education on genetic testing and research and management of non-motor symptoms.

Discussion: This survey indicates that, overall, veterans with ALS receive comprehensive symptom-based care within the nationalized VA care system and report high levels of satisfaction. Furthermore, this study provides baseline data and findings that may be used for quality improvement efforts across a large healthcare system and may serve as a model for similar efforts in other health systems.

Introduction/aims: While neurofilament light chain is a promising biomarker in spinal muscular atrophy (SMA), its dynamics in presymptomatic patients have not yet been determined. This study aimed to analyze the plasma neurofilament light chain (pNfL) as a treatment response biomarker in patients with presymptomatic spinal muscular atrophy (SMA) undergoing nusinersen treatment.

Methods: Eight 5q-SMA patients with three SMN2 copies (four presymptomatic patients from newborn screening and four symptomatic patients) were prospectively enrolled from August 2022 to June 2023. All patients received nusinersen treatment and were followed up for 660 days. pNfL levels were measured at baseline and throughout the treatment, analyzing their temporal changes and correlation with motor function outcomes.

Results: At baseline, presymptomatic patients exhibited higher pNfL levels than symptomatic patients (388.74 ng/L vs. 113.60 ng/L). During the loading phase, pNfL levels decreased markedly in both groups, with greater reductions in presymptomatic patients (94.64% vs. 79.50%). All presymptomatic patients achieved age-appropriate motor milestones. Decreased pNfL levels correlated moderately with motor function improvements, as measured by CHOP INTEND (r = -0.548, p < 0.01) and HINE-2 scores (r = -0.635, p < 0.01).

Discussion: pNfL is a promising biomarker for monitoring treatment response in patients with presymptomatic SMA, highlighting the importance of early diagnosis and treatment through newborn screening.

Introduction/aims: Hypokalemic periodic paralysis (HypoKPP) is an ion channelopathy causing episodic skeletal muscle weakness triggered by hypokalemia. Reduced inward rectifier K⁺ (Kir) channel activity contributes to membrane depolarization and paralysis, suggesting that pharmacologic activation of muscle K⁺ channels may restore excitability. The Kv7 channel agonist retigabine previously mitigated low-K⁺ weakness in HypoKPP models. Here, we tested whether this effect persists under conditions producing sustained, severe weakness.

Methods: Extensor digitorum longus (EDL) muscles from mice homozygous for the SCN4A R669H mutation were studied by isometric twitch force recording at 34°C, with or without 20 U/L insulin. Weakness was induced by reducing extracellular K⁺ to 1.0 mM. Retigabine (10 μM) was applied to the bath, and twitch force was analyzed by paired or unpaired t tests (n = 4-7 per group).

Results: Baseline twitch force in 4.75 mM K⁺ was ~50% lower in HypoKPP than wild-type muscle (p = 0.01). Force declined further after 1 h in 4.75 mM K⁺ (p = 0.016) and was completely lost at 1.0 mM K⁺ with insulin. Retigabine significantly reduced loss of force at both 4.75 and 1.0 mM K⁺ (p = 0.047 and p = 0.007, respectively).

Discussion: Kv7 channel activation by retigabine preserved contractile force even during sustained depolarization from severe hypokalemia. These findings extend prior work and support development of K⁺ channel agonists as a therapeutic approach for HypoKPP.

Introduction/aims: Durable medical equipment (DME)-wheelchairs, non-invasive ventilation, gastrostomy tubes, and communication devices-provides vital support for individuals with amyotrophic lateral sclerosis (ALS). Here, we describe DME use in COURAGE-ALS evaluating reldesemtiv's efficacy and safety in ALS, to evaluate if DME use can be considered an endpoint of interest in ALS trials.

Methods: COURAGE-ALS, a multicentre, double-blind, randomized, placebo-controlled clinical trial was conducted at 83 sites in the United States, Canada, Europe, and Australia. Participants were randomized 2:1 to receive reldesemtiv or placebo for 24 weeks, followed by 24 weeks of active drug treatment. Exploratory outcomes included reasons for prescribing, extent of use, DME types, and regional differences.

Results: Among 482 participants, 166 (34.4%) were using at least one DME item at baseline. Among 276 participants completing study visits through Week 24, 130 (47.1%) initiated use of a total of 188 new DME items post-baseline through 24 weeks. Manual wheelchairs were most used at baseline (89 items) and initiated (47 items) during the trial. Both baseline DME use and initiating a new item were associated with lower ALS Functional Rating Scale-Revised scores and worse quality of life. The trial was terminated early due to futility. Treatment assignment did not impact DME use. Regional disparities were noted.

Discussion: This study shows that DME is commonly prescribed to ALS trial participants. Further understanding of geographic differences in DME access and their impact on clinical outcomes is warranted prior to including DME use as an endpoint in ALS trials.

Trial registration: ClinicalTrials.gov identifier: (NCT04944784).

Introduction/aims: Segmental zoster paresis (SZP) of the upper limb is a complication of herpes zoster (HZ), but the risk factors for onset and prognosis of SZP are still unknown. The aims of this study were to analyze the correlations between neural foraminal stenosis (NFS) and the incidence and prognosis of upper-limb SZP.

Methods: In this retrospective case-control study, 87 HZ inpatients with C5-T1 spinal nerves affected were reviewed and divided into a case group (n = 21) and a control group (n = 66) based on whether they had SZP. Logistic regression analysis was used to assess correlation between NFS and the incidence of upper-limb SZP. Within the case group, Cox regression analyses were used to evaluate the correlation between NFS and complete muscle strength recovery at 24 months.

Results: Univariate and multifactor logistic analysis revealed that the grade of NFS was an independent risk factor for the incidence of upper extremity SZP [mild NFS (aOR = 18, p < 0.05); moderate NFS (aOR = 30, p < 0.05); severe NFS (aOR = 90, p < 0.05)]. Univariate and multifactorial Cox regression analyses confirmed the grade of NFS (HR = 0.186, p < 0.05) and baseline muscle strength (HR = 23.015, p < 0.05) as independent prognostic factors affecting complete muscle strength recovery of upper-limb SZP.

Discussion: The grade of NFS is an independent risk factor for the occurrence and poor prognosis of SZP in patients with upper extremity HZ. The evaluation of NFS should be incorporated into the prognosis assessment and individualized treatment strategy development for patients with upper limb SZP. Prospective cohort studies with larger sample sizes are needed.