Muscle & Nerve最新文献

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: Juvenile myasthenia gravis (JMG) patients report symptomatic improvement following thymectomy; however, there is a lack of published literature on biomarkers for interval improvement. This study aimed to investigate the utility of single-fiber electromyography to quantify changes post-thymectomy.

Methods: This was a retrospective medical record review of JMG patients who underwent thymectomy at Children's Healthcare of Atlanta between 2014 and 2024. Pre- and post-thymectomy orbicularis oculi jitter values and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores were recorded. A two-sided paired t-test was used to compare results pre- and post-thymectomy and Pearson's correlations were calculated.

Results: Twelve JMG patients (6 female) with a mean age at diagnosis of 12.9 ± 4.5 (range 1.6-17.1) years, positive acetylcholine receptor antibodies, and normal thymus imaging underwent thoracoscopic thymectomy at 15.2 ± 3.3 (range 7.4-18.2) years. Post-thymectomy, there was a statistically significant decrease in mean jitter (interval 7.3 ± 7.4 months, mean difference -33.2 ± 32.6 μs, p = 0.04, n = 7) and MG-ADL scores (interval 2.5 ± 2.1 years, mean difference -2.2 ± 2.5, p = 0.02, n = 11). There were no significant correlations between timing of thymectomy after diagnosis and the change in mean jitter (r = 0.11, p = 0.8, n = 7) and MG-ADL (r = -0.19, p = 0.58, n = 11). No major post-surgical complications were observed.

Discussion: Thymectomy is well-tolerated and leads to both objective and subjective improvement in JMG patients.

Introduction/aims: Natural history data for adult patients with spinal muscular atrophy (SMA) remain scarce, which is particularly relevant in the current therapeutic era. This study aimed to identify the most sensitive clinical, patient-reported, and neurophysiological measures to detect short-term disease progression in untreated adult SMA patients.

Methods: This prospective, one-year longitudinal study included 21 genetically confirmed adult patients with SMA types 2B and 3. Clinician-reported outcomes (CROs) included the Motor Function Measure (MFM), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module (RULM). Additionally, patient-reported outcomes (PROs) were assessed using the Modified Fatigue Impact Scale (MFIS). Neurophysiological evaluations included compound muscle action potential (CMAP) amplitude and motor unit number index (MUNIX) recorded from the ulnar nerve. Sensitivity to change was determined using standardized response means (SRMs), and associations between clinical and neurophysiological data were analyzed via Spearman correlation.

Results: The majority of participants were non-ambulatory (16/21). The MFM total score was the only outcome to show a statistically significant decline over 12 months (p = 0.02), with the highest SRM (-0.55), indicating superior sensitivity. MFM also demonstrated the strongest correlations with CMAP amplitude (ρ = 0.90) and MUNIX (ρ = 0.75), compared to other CROs. No significant longitudinal changes were observed in RULM, HFMSE, MFIS, CMAP, or MUNIX.

Discussion: Among evaluated outcome measures, the MFM was the most sensitive to short-term progression and most closely aligned with neurophysiological markers. These findings support the use of MFM as a primary outcome in clinical trials involving adult SMA patients.

CNTNAP1 encodes the Contactin-Associated Protein 1 (CNTNAP1), also known as Caspr1, which is a transmembrane protein critical for nervous system function. CNTNAP1 is localized to the paranodal regions of all myelinated axons, flanking either side of the node of Ranvier. It plays a vital role in axonal domain organization and is essential for the propagation of action potentials along nerve fibers. This specialized arrangement of axonal domains, which contain distinct molecular complexes, enables saltatory conduction and significantly increases the speed and efficiency of neuronal communication. To date, there are 47 children with biallelic CNTNAP1 variants who have been reported exhibiting a wide spectrum of phenotypes including congenital hypomyelinating neuropathy, hypotonia, and joint contractures among other clinical features. In this review, we compiled all previously published cases and detailed the specific genetic variants of every known individual, including clinical manifestations. Additionally, we present seven new cases of individuals identified through direct collaborations with clinicians and families, bringing the total to 54 individuals who harbor biallelic variants in CNTNAP1. This review and the additional case studies demonstrate that while children with CNTNAP1 mutations can present with a broad spectrum of symptoms, there is a recurrence of key clinical features across these cases. These key features commonly include respiratory distress, generalized hypotonia, hypomyelination, intellectual disabilities, and reduced life expectancy. These newly described cases provide valuable insights into the phenotypic diversity of CNTNAP1 variants, deepening our understanding of the clinical impact in patients with this rare genetic disorder.

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.

Amyotrophic lateral sclerosis (ALS) progresses relentlessly and is characterized by a median survival of 2-5 years from symptom onset with death from respiratory failure. ALS is a complex, multi-system neurodegenerative disorder with significant phenotypic heterogeneity and markedly variable disease progression. This variability presents challenges in determining the optimal timing for therapeutic interventions, complicates clinical trial design due to lack of effective stratification methods, and makes it difficult to reliably measure the longitudinal impact of specific interventions. Accurately capturing disease progression in ALS can be challenging. We propose that early respiratory phenotyping offers a promising approach to facilitate patient stratification, improve assessments of disease progression, and predict survival.

Introduction/aims: Corticosteroids improve muscle strength and motor function in Duchenne muscular dystrophy (DMD) and are essential to the standard of care. We aimed to quantify effects of earlier versus later corticosteroid initiation on modern measures of motor function among younger patients for whom timeliness of diagnosis, and thus opportunity for treatment, is variable.

Methods: We compared patients with DMD aged 4 to < 8 years initiating daily corticosteroids at trial baseline (n = 114; FOR-DMD [NCT01603407]) to those not initiating (n = 42; PolarisDMD [NCT03703882]). Changes in motor function, weight, and height were compared over 12 months between these groups. Baseline prognostic factors were balanced via propensity score weighting.

Results: Initiating daily corticosteroids was associated with significantly better 12-month motor function outcomes compared to not initiating, with mean (95% confidence interval) differences of 6.9 (5.5, 8.3) North Star Ambulatory Assessment (NSAA) points, 0.47 (0.36, 0.59) meters/s for 10 m walk/run, and 0.10 (0.08, 0.12) tasks/s for rise from supine, each exceeding minimal clinically important differences. Benefits were consistent across baseline age and motor function subgroups. Weight gain was similar and height gain was lower among corticosteroid-treated patients by 2.0 (1.3, 2.7) cm.

Discussion: Given persistent delays between symptom onset and diagnosis in DMD, which contribute to an average diagnosis age of 5 years, these findings underscore the importance of earlier diagnosis to allow time for informed discussions about corticosteroids and to optimize meaningful functional benefits during early developmental years.

Introduction/aims: Thymectomy is associated with positive effects on myasthenia gravis (MG), but there is conflicting evidence regarding potential deleterious long-term outcomes, such as increased cancer and autoimmune disease risk. We aimed to assess these outcomes in thymectomized versus non-thymectomized MG patients.

Methods: We retrospectively reviewed the medical records of patients with acquired, autoimmune MG followed at the Prosserman Neuromuscular Clinic, University Health Network (UHN), between January 2000 and July 2025. We excluded patients with malignancy or other autoimmune diseases before MG. We created matched datasets (thymectomy vs. no-thymectomy) and built Cox models to assess the rate of new malignancy or autoimmune disease. We also used inverse probability of treatment weights (IPTW) to balance relevant covariates (age at MG onset, sex, disease duration, medications) in the full sample, and tested Cox models in the weighted dataset for each outcome.

Results: Of 566 patients, 106 had a thymoma and were excluded. Of the 460 patients included, 161 had a thymectomy. There was no difference in the hazard ratio (HR) for a new malignancy in the matched cohort (HR: 0.94, CI 0.83-1.07) nor in the IPTW model. The incidence of autoimmune disease was slightly higher in the thymectomy group in the matched cohort (HR 1.33 [1.15-1.52]), but there was no difference in the IPTW analyses (HR 1.55, CI [0.40-5.9]).

Discussion: In this cohort of patients with non-thymomatous MG, thymectomy was not associated with an increased risk of malignancy. Different models for a second autoimmune disease had conflicting findings, requiring further research.

Introduction/aims: The diagnosis of neuromuscular diseases in adults can be challenging and novel ultrasound methods could facilitate the process. This study investigated the diagnostic value of automated thresholding in identifying hereditary neuromuscular disorders (HNMDs) in adults and in distinguishing between neurogenic and myopathic processes.

Methods: Thirty-one patients with neurogenic HNMD, 37 with myopathic HNMD, and 68 healthy controls underwent ultrasound examination based on a four-muscle scanning protocol, including biceps brachii, flexor carpi radialis, rectus femoris, and tibialis anterior. The hyperechoic fraction of Otsu (Otsu-HF) and Triangle (Triangle-HF) thresholding algorithms, grayscale value (GSV), and echovariation (EV) were measured. Global estimates were calculated by averaging individual muscle values. Diagnostic accuracy of echogenicity measures and correlations with muscle strength were investigated.

Results: Global and individual Otsu-HF, GSV and EV parameters showed high diagnostic accuracies in identifying HNMDs. All areas under receiver operating characteristic curve were > 0.9 for global parameters and > 0.8 for individual muscle estimates. Global cut-offs of the suggested protocol showed a specificity of 88.2%-98.5% and a sensitivity of 83.8%-89.7%. Furthermore, global Otsu-HF differentiated echogenicity between neurogenic and myopathic HNMDs, yielding a higher accuracy than grayscale analysis (71.6% vs. 63.1%, p = 0.0065). Significant relationships were shown between muscle strength, global and individual Otsu-HF, GSV, and EV.

Discussion: Our quantitative muscle ultrasound (QMUS) screening protocol was shown to be a useful tool for assessing adult subjects with suspected HNMDs. In the era of next-generation sequencing, QMUS could be a valuable neurophysiological biomarker in the initial diagnostic workflow, guiding targeted further testing.