Muscle & Nerve最新文献

Introduction/aims: Direct involvement of the neuromuscular junction (NMJ) in the inflammatory process of Guillain-Barré syndrome (GBS) has been described. Despite this, the NMJ very rarely serves as a target for direct medical intervention in GBS. Here, we report the use of an acetylcholinesterase inhibitor, pyridostigmine, in four pediatric patients with axonal GBS.

Methods: All patients received standard immune therapy. Pyridostigmine treatment was started 7 weeks to 5 months after disease onset, and 5-11 weeks from reaching the plateau phase. Treatment efficacy was monitored by the 6-min walk, quadriceps femoris and hamstring strength (manual muscle testing), the pediatric evaluation of disability inventory-functional skills, and the GBS disability score. All tests were performed before and during drug intervention.

Results: All treated patients showed marked improvement in their motor and functional abilities. After 1 month of treatment, quadriceps femoris and hamstring strength increased by at least two points, and walking distance increased by 10-272 m. The pediatric evaluation of disability inventory functional skills mobility test increased by 22.3-34.7 points. No serious side effects were documented.

Discussion: Pyridostigmine may be a safe and effective add-on treatment in pediatric patients with axonal GBS who show insufficient response to immune therapy, and may be effectively used even at a late stage. Additional, larger studies are needed.

Introduction/aims: Voluntary muscle contractions result in a temporary increase in twitch force, a phenomenon termed post activation potentiation (PAP). In rodents and other species, PAP is observed predominantly or exclusively in fast twitch muscles. However, it has been suggested that in humans, PAP occurs more or less independently of muscle fiber type.

Methods: Eighteen healthy men and women (27 ± 8 years) underwent an electrical stimulation protocol during which two sets of four twitches were elicited both pre and post 6 s maximal voluntary contractions of the triceps surae (60%-70% slow twitch) and triceps brachii (60%-70% fast twitch) muscles.

Results: Unpotentiated peak twitch torque (PTT) was higher in the larger triceps surae versus the smaller triceps brachii (i.e., 13.4 ± 5.3 vs. 3.4 ± 2.1 nm; p < 0.001), but time to peak torque was shorter (i.e., 84 ± 7 vs. 132 ± 14 ms; p < 0.001) and relative rate of torque development (RTD) was greater in the triceps brachii (2294 ± 257 vs. 1425% ± 102%/s; p < 0.001). PAP increased PTT by 172% ± 124% in the triceps brachii versus 20% ± 20% in the triceps surae (p < 0.001). Absolute RTD also increased more in the triceps brachii (i.e., 240% ± 170% vs. 31% ± 24%; p < 0.001). However, PAP-induced changes in half-relaxation time and relative rate of relaxation did not differ between muscle groups.

Discussion: We conclude that PAP influences contraction but not relaxation of human muscle in a fiber type dependent manner. This should be kept in mind when interpreting individual differences in the results of neuromuscular testing, response to varying warm-up protocols, etc.

Introduction/aims: Diagnosing neuromuscular disorders in children is challenging. Concentric needle electromyography (CNEMG) is the standard for electrophysiological assessments but has limitations in pediatric populations. High-density surface electromyography (HDsEMG) provides a noninvasive technique with superior spatial resolution, enabling the identification and analysis of motor unit (MU) firing dynamics throughout the entire period of MU activity. This study assessed the feasibility of HDsEMG MU decomposition in children and explored parameters that differentiate neuropathy, myopathy, and normal findings.

Methods: One hundred children (mean age 9.1 years, standard deviation [SD] 5.1) underwent CNEMG followed by HDsEMG. EMG signals were decomposed into individual MU spike trains, and MU yield, as well as firing properties (mean discharge rate [MDR], discharge rate variability [DRV]) were analyzed across diagnostic groups. Furthermore, correlations were assessed between MU action potential parameters obtained from CNEMG (MU amplitude and duration) and those obtained from HDsEMG.

Results: MUs were reliably identified in 86.0% of children, with an average of 7 (4.2) MUs per participant. Among MU firing parameters, DRV was significantly higher in children with myopathy (p = 0.005). Additionally, MU duration from HDsEMG correlated weakly with CNEMG values (r = 0.31) and successfully discriminated myopathy from normal and neuropathic groups (p = 0.02).

Discussion: HDsEMG MU decomposition is feasible in children with neuromuscular disorders, providing valuable insights into MU firing and MU action potential properties. This technique has the potential to improve diagnosis and monitoring of pediatric neuromuscular conditions. Nevertheless, further signal processing refinements are warranted to enhance its discriminative capacity for detecting neuromuscular disorders in children.

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: Some patients diagnosed with juvenile myasthenia gravis (JMG) have corticosteroid-refractory myasthenia gravis (CRMG). The aim of this study was to evaluate the biomarkers of corticosteroid (CS) responsiveness and refractoriness in children, and the overall prognosis of patients after receiving nonsteroidal immunosuppressants (ISs).

Methods: This cross-sectional study was conducted at the Department of Pediatrics, Xiangya Hospital, Central South University. Data of the patients diagnosed with JMG from 2010 to 2023 were collected and analyzed.

Results: Two hundred and seventy-five patients were included in this study; 215 utilized CS, of whom 44.2% had CRMG. Ptosis only was an independent predictor of CS responsiveness (OR = 2.13, SE = 0.36, OR 95% CI = 1.05-4.32, p value = 0.003). The presence of acetylcholine receptor antibodies (AChR-Abs) was an independent predictor of CS refractoriness (OR = 2.78, SE = 0.48, OR 95% CI = 1.09-7.05, p value = 0.033). At last follow-up, 65.8% of the CRMG patients responded to ISs including tacrolimus, azathioprine, intravenous immunoglobulin, mycophenolate mofetil, and rituximab. About 71.0% of the patients that received ≤ 2 ISs were responders; however, only 14.3% of the patients that received subsequent ISs responded.

Discussion: This study provides an approximate prevalence of CRMG in children, as well as predictors of CS responsiveness and refractoriness, which can guide clinicians in prescribing alternative ISs in a timely manner. It can also help researchers understand the burden of CRMG in children when developing promising new therapies.

Neuromuscular junction (NMJ) disorders such as myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism are characterized by impaired synaptic transmission leading to weakness. This review examines the electrodiagnostic evaluation of these conditions, emphasizing the importance of techniques such as repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG) for confirming the diagnosis and distinguishing presynaptic from postsynaptic defects. The reduced safety factor of neuromuscular transmission (NMT) in postsynaptic disorders produces a decrement in compound muscle action potential (CMAP) amplitude and area with low-frequency stimulation, whereas presynaptic disorders show small baseline CMAPs that increase markedly in amplitude and area (postactivation facilitation) after brief exercise or during high-frequency stimulation. SFEMG, the most sensitive test of abnormal NMT, measures neuromuscular jitter-temporal variability in action potential generation-and also reflects a compromised safety factor. Fiber density remains normal in primary NMJ disorders, distinguishing them from conditions with neuropathic reinnervation, such as motor neuron disease. Proper performance and interpretation of these electrodiagnostic studies are essential for accurate diagnosis, assessment of disease severity, and guiding management of NMJ disorders.

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.

Introduction/aims: Studies on pregnancy in myasthenia gravis (MG) are limited by small sample sizes or examine a limited number of outcomes. The objective of this study was to estimate the prevalence of perinatal and infant outcomes and characterize perinatal treatment patterns in MG.

Methods: We conducted a retrospective cohort study in Merative MarketScan Commercial Claims and Encounters (CCAE) and two other United States health insurance claims databases. Pregnancies in females aged 18-49 years were identified and maternal and infant records were linked. MG was defined by ≥ 1 inpatient or ≥ 2 outpatient diagnoses within a 365-day period. The prevalence of six perinatal outcomes was calculated in the MG and total populations. Treatments were summarized by class.

Results: In pregnancies from CCAE between 2000-2023, preeclampsia (10.7% vs. 7.1%), Cesarean section (42.9% vs. 36.7%), preterm birth (18.0% vs. 9.9%), and small for gestational age (4.3% vs. 1.7%) were more frequent among MG (n = 900) than the age-adjusted total population (n = 5,185,726). Lack of treatment for MG was common across the perinatal period: 54.3% were untreated in the 6 months preconception, 61.2% in pregnancy, and 57.8% in the 6 months postpartum. Of those taking acetylcholinesterase inhibitors or corticosteroids in pregnancy, 21.8% and 33.1% had not been taking them before pregnancy, respectively.

Discussion: MG was associated with a greater prevalence of certain perinatal outcomes, occurring in both mother and infant. In parallel, though most patients did not receive treatment in pregnancy those who did showed variation over time, suggesting a potential need for this population.

Myasthenia gravis (MG), a fluctuating autoimmune neuromuscular disease, presents unique challenges for remote assessment due to its reliance on detailed physical examination. To address this, we developed a quantitative telemedicine platform that augments traditional neurological assessments using computer vision, signal processing, and augmented intelligence. In response to the COVID-19 pandemic that motivated a shift to telemedicine evaluations, the Myasthenia Gravis Core Exam (MGCE) was developed by the rare disease consortium MGNet, to provide guidance in the performance of telemedicine clinical encounters. The MGCE includes eight sentinel tasks such as ptosis assessment, sit-to-stand, and speech-based respiratory measures, all amenable to digital capture. To assess the reproducibility and reliability of the MGCE, videos of 52 MG patients across six centers were performed with each having examinations performed twice. We utilized this unique resource to apply machine learning algorithms to extract clinically relevant features from video and audio data, enabling quantitation of continuous variation, in contrast to the categorical measures (mild, moderate, and severe) used in standard clinical assessments. Inter-rater variability prompted the development of a reproducibility of score metric and revealed that variations in examiner instructions and video quality significantly affect reliability. Our findings suggest that a digital examination framework can enhance MG assessment precision, reduce variability in physical examination evaluation, and support the telemedicine examination. This scalable approach has the potential to integrate digital biomarkers into neuromuscular disease care and clinical trials.

Introduction/aims: The functional diversity of the PLEC gene is largely attributed to its multiple tissue-specific transcript isoforms. This study investigated the tissue-specific differential expression of plectin transcript isoforms in a patient with plectin 1f deficiency who presented solely with muscular dystrophy (LGMDR17) and lacked epidermolysis bullosa simplex (EBS) symptoms. We aimed to characterize the isoform-specific expression patterns that may underlie this tissue-restricted pathology.

Methods: RNA was isolated from skeletal muscle tissue and primary fibroblast cells of both the patient and a healthy control. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression levels of total PLEC and its isoforms. Semi-quantitative PCR was also performed in fibroblasts to evaluate the total PLEC expression.

Results: In the patient's muscle tissue, PLEC 1b and 1d isoforms were downregulated compared to the control. In contrast, a semi-quantitative analysis revealed an increase in total PLEC expression level within primary fibroblasts. Furthermore, RT-qPCR analyses validated the upregulation of mRNA expressions for total PLEC (5.6-fold) and its isoforms PLEC 1, 1a, 1b, and 1d (2.8; 5; 1.4; 4.2-fold, respectively) in these cells. PLEC 1c, 1e, and 1g exhibited either unchanged or undetectable expression in both fibroblast and muscle samples from the patient compared to control.

Discussion: These findings suggest that tissue-specific regulation of PLEC isoforms may explain the absence of skin involvement in plectin 1f deficiency. Understanding the molecular mechanisms behind isoform-specific expression in a tissue-selective manner could inform novel therapeutic strategies for LGMDR17 and other PLEC-related disorders.