Muscle & Nerve最新文献

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.

Introduction/aims: Nerve regeneration after injury must occur in a timely fashion to restore function. Current methods of assessment provide limited information following trauma, resulting in delayed management and suboptimal outcomes. In this study, we evaluated the ability of diffusion magnetic resonance imaging (MRI) and a mathematical model based on the Gompertz function to monitor nerve regeneration after injury and repair.

Methods: Sprague Dawley rats were assigned to two treatment groups (sham = 2, cut, immediate repair = 7), and in vivo diffusion tensor imaging (DTI) was performed every 2 weeks until 12 weeks post-surgery. Functional recovery was evaluated weekly over the same time period via the sciatic functional index (SFI).

Results: After injury, SFI and DTI-derived fractional anisotropy (FA) values exhibited similar longitudinal trends and distinctions in both sham and cut/repair (C/R) cohorts. FA values at the distal section displayed the highest correlation with behavioral indices at the region nearest to the injury (r = 0.84, p < 0.001), followed by FA values at the central section (r = 0.82, p < 0.001) and the section farthest from the injury (r = 0.70, p < 0.001).

Discussion: Findings suggest that automated analyses of FA profiles along the nerve may provide insights for distinguishing successful/unsuccessful nerve recovery. This tool, once proven in a larger-scale study, can provide clinicians with the needed tool to early diagnose nerve recovery and identify cases requiring a second repair surgery.

Introduction/aims: There is a lack of information about startle reflex (SR) in primary lateral sclerosis (PLS). This study examined the presence and prevalence of SR in PLS and compared findings with amyotrophic lateral sclerosis (ALS).

Methods: 46 PLS and 54 ALS participants were assessed through structured interviews in this cross-sectional study. Fisher's exact test was used to compare reported SR prevalence. Multivariable linear regression was utilized to study associations between disease group and SR frequency in response to sudden stimuli.

Results: SR differed markedly between the two groups, with a higher prevalence in PLS (93.5%) than ALS (20.4%; p < 0.001). Among ALS patients, SR was present in all upper motor neuron (UMN)-predominant cases, which accounted for 54.5% of the SR-positive ALS group, but only 10.4% of probable/definite ALS cases. In SR-positive patients, response frequency to sudden stimuli exceeded 60% in both ALS and PLS, most often triggered by auditory stimuli. Younger age, shorter disease duration, and PLS diagnosis were associated with more frequent SR.

Discussion: SR is significantly more common in PLS than in ALS. Notably, UMN-predominant ALS, although limited in number, showed a higher prevalence of SR (6 out of 6, 100%), indicating that predominant UMN involvement may be a key determinant of SR across both conditions. These hypothesis-generating findings suggest that SR may serve as a novel clinical marker in PLS and UMN-predominant ALS, warranting further validation through prospective studies.

Introduction/aims: Pneumothorax is a complication of mechanical ventilation (MV) in patients with amyotrophic lateral sclerosis (ALS); however, its clinical features and risk factors are not well defined. This study aimed to characterize the incidence, risk factors, and prognostic impact of pneumothorax in patients with ALS undergoing MV.

Methods: We retrospectively analyzed clinical data from patients with ALS admitted to our center between 2014 and 2024. Patient demographics and baseline characteristics, pneumothorax occurrence, MV details, chest computed tomography (CT) findings, and survival outcomes were reviewed. We analyzed independent risk factors for pneumothorax and evaluated cumulative incidence and survival.

Results: Among the 131 patients with ALS, 95 underwent MV, 19 of whom developed pneumothorax. Only low body mass index (BMI) (< 18.5 kg/m²; p = 0.015) was identified as an independent risk factor. The cumulative incidence rates of pneumothorax at 1, 3, 5, and 10 years after MV initiation were 4.5%, 13.4%, 24.3%, and 32.0%, respectively. The median post-pneumothorax survival was 16 months (95% confidence interval [CI]: 6-67), with no significant difference in overall survival from the time of initiation of MV between patients with and without pneumothorax (p = 0.88).

Discussion: This study identified low BMI as a potential risk factor for pneumothorax in ALS patients receiving MV. However, given the limited sample size, these findings should be interpreted with caution. Larger, multicenter studies are warranted to validate this association and to further elucidate long-term pulmonary effects and preventive strategies.

The electrodiagnostic instrument is foundational to the acquisition of electrophysiologic data and its subsequent interpretation and diagnostic implications. The initiation of data acquisition occurs at the three recording electrodes which consist of: E-1 (the noninverting amplifier port), E-2 (the inverting amplifier port), and E-0 (the so-called ground electrode). All three electrodes are essential in forming the recording montage. They must have similar, high-quality impedance and be properly connected to the amplifier. Their recording surfaces and the tissues from which they record must have low impedance and be properly prepared and applied at the recording site to ensure an accurate representation of the electrophysiologic signal. Both surface and needle electrodes can be used, contingent on the technique and data required (i.e., nerve conduction studies or needle electromyography, respectively). These biologic signals are small, ranging from millivolts to microvolts, depending on the generator source (e.g., muscle and nerve). Therefore, they must be amplified and subsequently filtered. Artifacts, distorted signal amplification, or inappropriate filtration will result in waveform distortion leading to erroneous interpretation (i.e., false positives or negatives). The electrodiagnostic medicine consultant (EMC) has other tools to deal with this, such as averaging. The signal is then digitized and displayed visually and acoustically through an analog-to-digital converter/loudspeaker requiring appropriate amplification and time scale to avoid any signal distortion. The EMC can then visually as well as auditorily analyze the signal of interest and store or print out the data for further interpretation. Current technology in instrumentation permits greater precision and accuracy in data analysis. Failure at any one of the above sequential processing steps can lead to data misinterpretation. It is incumbent upon the EMC to be thoroughly familiar with all of the steps in this process, including potential shortcomings.