This review aims to comprehensively summarize the application of electrophysiological methods, specifically repetitive nerve stimulation (RNS) and single fiber electromyography (SFEMG), in the diagnosis of neuromuscular junction (NMJ) disorders, including myasthenia gravis, Lambert-Eaton syndrome, and sarcopenia in the elderly. Both RNS and SFEMG have demonstrated high sensitivity and specificity in detecting NMJ abnormalities. RNS aids in distinguishing presynaptic from postsynaptic lesions, while SFEMG provides direct evidence of NMJ function by assessing single motor unit action potentials. Key parameters in SFEMG, such as fiber density, jitter, and pulse blocking, are crucial for evaluating NMJ function. Increased fiber density and jitter value, along with pulse blocking, are often observed in patients with NMJ disorders. However, despite the extensive application of these techniques in various NMJ-related diseases, their role in aging, particularly in sarcopenic patients, remains underexplored, highlighting the need for future research.

UNASSIGNED: It is generally believed that the decremental response in repetitive nerve stimulation (RNS) stabilizes at the fourth or fifth response. We have a preliminary impression that the decremental response approaches a plateau earlier in proximal muscles than in distal muscles. We investigated the speed of the completion of the decremental response in different muscles.
UNASSIGNED: The \"decrement completion ratio (DCR)\" in the second or third response (DCR2 or DCR3) was defined as the ratio of the decremental percentage of the second or third response to that of the fourth response. Patients showing more than 10% decremental response both in the abductor pollicis (APB) and deltoid muscles were retrospectively extracted from our EMG database. The DCR2 and DCR3 were compared between two muscles in patients with myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS).
UNASSIGNED: Identified subjects consisted of 11patients with MG and 11 patients with ALS. Multiple regression analysis revealed that only the difference of muscle influenced on DCR2 and DCR3, with no contribution from the different disorder (MG or ALS) or the initial amplitude of the compound muscle action potential (CMAP). Both DCR2 and DCR3 were significantly higher in deltoid than in APB. In ALS, the normalized CMAP amplitude was not different between APB and deltoid whereas the decremental percentage was significantly higher in deltoid, suggesting a lower safety factor of the neuromuscular transmission in proximal muscles.
UNASSIGNED: The decremental response completed more rapidly in deltoid than in APB which may be related to the lower safety factor also documented by this study.
UNASSIGNED: Unexpected early completion of the decrement such as at the second response in RNS is not a technical error but may be an extreme of the rapid completion in deltoid, a proximal muscle.

OBJECTIVE: Previous studies have suggested that treatments targeting the neuromuscular junction (NMJ) may play a role in the treatment of amyotrophic lateral sclerosis (ALS). However, factors impacting repetitive nerve stimulation (RNS), a technique to evaluate NMJ function, have yet to be fully elucidated. We aimed to identify independent factors contributing to the decremental response of the accessory nerve and evaluated its value in ALS clinical practice.
METHODS: A total of 626 patients who were diagnosed with ALS and underwent 3 Hz RNS tests on the accessory nerve were enrolled. Data on their clinical and electrophysiological indicators were divided into a training set (collected from June 2016 to December 2022) and a test set (collected from January to August 2023). Stepwise regression was used in independent variable selection and model building.
RESULTS: Forty-two percent of patients had a decrement larger than 10% and 24% had a decrement larger than 15%. Onset age, sex, onset site, forced vital capacity (FVC) and motor unit potential (MUP) duration were independent factors contributing to the results of the RNS test. MUP duration had the greatest impact on decremental response, followed by FVC and onset age. The decremental response in females was larger than in males. Upper limb onset was found to contribute more to the decrement than lower limb or bulbar onset.
CONCLUSIONS: In patients with ALS, NMJ safety factor is reduced during re-innervation. Decremental response is affected by multiple factors, which needs to be considered in clinical trials targeting the NMJ in these patients.

UNASSIGNED: Intermediate syndrome is an important cause of respiratory failure following acute organophosphorus pesticide poisoning. The objective of this study was to examine the pathophysiology of this syndrome by analysis of sequential repetitive nerve stimulation studies in patients with acute organophosphorus pesticide poisoning.
UNASSIGNED: Thirty-four consenting symptomatic patients with acute organophosphorus pesticide poisoning with intermediate syndrome (n = 10) or a milder forme fruste intermediate syndrome (n = 24) were assessed prospectively with daily physical examination and repetitive nerve stimulation done on the right and left median and ulnar nerves. The compound muscle action potential at 1, 3, 10, 15, 20 and 30 Hertz was measured with a train of ten stimuli. The amplitudes of the resulting stimuli were normalized to the first stimulus (100 per cent) and plotted against time. The decrease in the area under the curve of all the second stimulus compound muscle action potentials in the first 0.3 seconds was measured as a means of quantifying the refractory block. The decrease in the area under the curve under the 10, 15, 20 and 30 Hertz compound muscle action potentials relative to this pooled second stimulus compound muscle action potentials-area under the curve indicated the extent of additional rate-dependent block (decreasing compound muscle action potential-area under the curve over the first 0.3 seconds after the first stimulus with increasing Hertz).
UNASSIGNED: These new measurements strongly correlated with the severity of weakness. Refractory block was seen in most patients but was more severe in those with intermediate syndrome than those with forme fruste (partial) intermediate syndrome (median 55 per cent versus 16 per cent, P = 0.0001). Similar large differences were found for rate-dependent block (30 per cent versus 7 per cent, P = 0.001), which was uncommon in forme fruste intermediate syndrome but found in nine out of 10 patients with intermediate syndrome. Rate dependent block was generally only observed after 24 hours. The simplest strong predictor was total block at 30 Hertz repetitive nerve stimulation (89 per cent [interquartile range 73 to 94 per cent] versus 21 per cent [4 to 55 per cent]; P < 0.0001), which was very similar to total block calculated by summing other calculations.
UNASSIGNED: These findings likely represent depolarization and desensitization block from prolonged excessive cholinergic stimulation but it is not clear if these are from pre- or post-synaptic pathology. An animal model of intermediate syndrome with repetitive nerve stimulation studies might enable a better pathophysiological understanding of the two types of block.
UNASSIGNED: The limited number of repetitive nerve stimulation studies performed were sufficient to demonstrate proof-of-concept, but further studies with more patients are needed to better define the correlates, clinical relevance and possible diagnostic/prognostic roles for the use of this technique.
UNASSIGNED: There are two easily distinguishable pathophysiological abnormalities in the neuromuscular block in intermediate syndrome. While they often coincide, both may be observed in isolation. The total and rate-dependent block at 30 Hertz are strongly associated with more severe weakness.

Everyday physical activities, such as walking, are enabled by repeated skeletal muscle contractions and require a well-functioning neuromuscular transmission. In myasthenic disorders, activities of daily living are debilitated by a compromised neuromuscular transmission leading to muscle weakness and fatiguability in patients. To enable physical activity, acetylcholine (ACh) is released repeatedly from the motor nerve, however, the role of the nerve terminals\' capacity to sustain ACh release to support repetitive contractions under compromised neuromuscular transmission remains unclear. To explore this, we studied synaptic and contractile function during repeated contractions in healthy rat skeletal muscles under conditions of pharmacological induced compromised neuromuscular transmission. Using recordings of endplate potentials, compound muscle action potential (CMAP) and force production in isolated skeletal muscles and living, anesthetized animals, we found that force and CMAP were markedly reduced by even very light activity performed up to 5 s prior to contraction showing that recovery of ACh release was insufficient to maintain synaptic transmission strength. Our results suggest that the timing of depletion and restoration of ACh release may impact clinical signs of weakness and fatigability in patients with impaired neuromuscular transmission and affect the sensitivity of electromyographic recordings in the clinic.

UNASSIGNED: No previous studies investigated the association between decrement of low-frequency repetitive nerve stimulation (LF-RNS) and amyotrophic lateral sclerosis (ALS) survival. We aim to study the relationship between decrement and survival in ALS.
UNASSIGNED: Sporadic ALS patients diagnosed at the Department of Neurology, the First Medical Center, Chinese PLA General Hospital from January 2018 to December 2019 were enrolled in this study. Experienced neurologists followed up the participants regularly every 6 months until January 2022. A decremental response of 10% or greater at least in one muscle was considered positive. According to the decrement, the participants were divided into LF-RNS (+) and LF-RNS (-) groups.
UNASSIGNED: One hundred and eighty-one sporadic ALS patients were recruited in our study, including 100 males and 81 females. Among them, 10 cases (5.5%) were lost to follow-up, 99 cases (54.7%) died, and 72 patients (39.8%) were still alive at the last follow-up. The median survival time of all ALS patients in this study was 42.0 months. There was no significant difference of median survival in LF-RNS(+) group and LF-RNS(-) group (p = 0.159, Kaplan-Meier method). In multivariate Cox regression analysis, age of onset, diagnostic delay, and ALS Functional Rating Scale-Revised (ALSFRS-R) score were associated with ALS survival, but the decrement was not correlated with ALS survival (p = 0.238).
UNASSIGNED: The decrement in accessory and ulnar nerves was not associated with the survival of ALS. The decrement of LF-RNS could not be an electrophysiological marker to predict ALS survival.

OBJECTIVE: Electrodiagnostic testing is an important screening test for myotonic dystrophy type 1 (DM1). Although myotonic discharges are observed on electromyography in cases of DM1, it is difficult to distinguish DM1 from other myotonic disorders clinically. In the present study, afterdischarges, another type of pathological potential revealed by electrodiagnostic testing, were analyzed, and their role in distinguishing DM1 from other myotonic disorders was explored.
METHODS: Data from 33 patients with myotonic discharges on electromyography were analyzed retrospectively. According to gene testing, the patients were divided into DM1 (n = 20) and non-DM1 myotonia (n = 13) groups. Afterdischarges were investigated by retrospectively evaluating the electrodiagnostic findings of motor nerve conduction studies, F-waves, and repetitive nerve stimulations.
RESULTS: Afterdischarges were observed in 17 of the 20 patients with DM1, with an occurrence rate of approximately 85%. However, afterdischarges were absent in all patients with non-DM1 myotonia. There were significant differences in the occurrence rate between the two groups (P < 0.01).
CONCLUSIONS: Afterdischarges may serve as a suggestive role in clinical diagnosis of DM1. The discovery that DM1 can present with afterdischarges may pave a new way to study the pathogenesis of DM1.

The patient, a 58-year-old man, experienced weakness of the proximal muscles in both lower extremities, and Lambert-Eaton myasthenic syndrome and small cell carcinoma of unknown primary origin were diagnosed. He received symptomatic treatment for myasthenia and radiochemotherapy for small cell carcinoma; once this regimen, the myasthenic symptoms improved. However, acute myocardial infarction occurred, after which type II respiratory failure developed, and the patient required ventilator management with tracheal intubation. Acute-phase treatment, such as plasma exchange, intravenous immune globulin therapy, and methylprednisolone pulse therapy, and intensification of symptomatic treatment allowed for extubation, and eventually the patient was able to walk independently. According to electrophysiological examination, compound muscle action potentials were larger at discharge than at the time of exacerbation.

Although therapeutic electrical stimulation (TES) of injured peripheral nerve promotes axon regeneration and functional recovery, clinical applications of this therapy are limited to the intraoperative timeframe. Implantable, thin-film wireless nerve stimulators offer a potential solution to this problem by enabling delivery of electrical stimuli to an injured nerve over a period of several days post-surgery. The aim of this study was to determine the optimal time course of stimulation for maximizing functional recovery in a rat sciatic nerve isograft repair model.
Adult male Lewis rats underwent thin-film wireless nerve stimulator implantation following sciatic nerve transection and 40 mm nerve isograft repair. Immediately after surgery, animals began a daily regimen of TES for up to 12 consecutive days. Functional recovery was assessed by compound muscle action potential (CMAP), evoked muscle force, wet muscle mass, and axon counting.
Serial CMAP measurements increased in amplitude over the course of the study, yet no significant difference between cohorts for serial or terminal CMAPs was observed. Axon counts and wet muscle mass measurements were greatest in the 6-day stimulation group, which correlated with a significant increase in evoked muscle force for the 6-day stimulation group at the terminal time point.
Six daily sessions of TES were found to be most effective for augmenting functional recovery compared to other time courses of stimulation. Future studies should incorporate additional subjects and track axonal sprouting or measure neurotrophin levels during the therapeutic window to further elucidate the mechanisms behind, and ideal amount of, TES.

BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive hereditary neuromuscular disorder caused by the expanded trinucleotide repeat in the androgen receptors gene. The major clinical manifestations of SBMA consist of weakness in the bulbar and limb muscles, fasciculations, tremors, cramps, sensory impairment, and gynecomastia. However, atypical SBMA cases may lead to misdiagnosis. Muscular fatigue and decremental responses to repetitive nerve stimulation (RNS), despite being observed in some SBMA patients, are usually occurred in MG patients, and patient with the symptom of mastication fatigue was rarely reported. In addition, cardiological investigations have been performed in SBMA patients and several ECG alterations were identified. Here we report an SBMA patient presenting with a rare onset symptom of mastication fatigue, who has been detected with a positive titin antibody in the serum and showed a WPW pattern electrocardiogram.
METHODS: The patient showed mildly progressive fatigue in the muscles of mastication over 3 years. Neurological examination showed facial muscle weakness and a wasting tongue with fasciculations, but the weakness, wasting, or fasciculations were not obvious in the limbs. 3-Hz RNS showed a decremental response in bilateral orbicularis oculi. The test of titin antibody was positive in the serum, and the electrocardiogram showed a WPW pattern ECG. Genetic analysis revealed an increased number (39 repeats) of tandem CAG repeats in the AR gene, which confirmed the diagnosis of SBMA. The fatigue symptom was significantly improved after oral pyridostigmine bromide treatment.
CONCLUSIONS: This case calls for more attention to muscular fatigue as the onset symptoms of Kennedy\'s disease. ECG screening is of importance in SBMA patients and further studies are needed to investigate the titin antibody in SBMA patients as well as other neurogenic disorders.