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Objectives: Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are the most common causes of acute neuromuscular respiratory failure resulting in ICU admission. This synthetic narrative review summarizes the evidence for the prediction and management of acute neuromuscular respiratory failure due to GBS and MG., Data Sources: We searched PubMed for relevant literature and reviewed bibliographies of included articles for additional relevant studies., Study Selection: English-language publications were reviewed., Data Extraction: Data regarding study methodology, patient population, evaluation metrics, respiratory interventions, and clinical outcomes were qualitatively assessed., Data Synthesis: No single tool has sufficient sensitivity and specificity for the prediction of acute neuromuscular respiratory failure requiring mechanical ventilation. Multimodal assessment, integrating history, examination maneuvers (single breath count, neck flexion strength, bulbar weakness, and paradoxical breathing) and pulmonary function testing are ideal for risk stratification. The Erasmus GBS Respiratory Insufficiency Score is a validated tool useful for GBS. Noninvasive ventilation can be effective in MG but may not be safe in early GBS. Airway management considerations are similar across both conditions, but dysautonomia in GBS requires specific attention. Extubation failure is common in MG, and early tracheostomy may be beneficial for MG. Prolonged ventilatory support is common, and good functional outcomes may occur even when prolonged ventilation is required., Conclusions: Multimodal assessments integrating several bedside indicators of bulbar and respiratory muscle function can aid in evidence-based risk stratification for respiratory failure among those with neuromuscular disease. Serial evaluations may help establish a patient's trajectory and to determine timing of respiratory intervention., Competing Interests: Dr. Mobach received funding from Biogen, Amylyx, Mitsubishi Tanabe, and Quralis. Dr. Rabinstein serves on the Clinical Events Classification committee for Boston Scientific and serves on advisory boards for Astra Zeneca, Shionogi, Brainomix, and Chiesi. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The complement system is a set of over 50 proteins that constitutes an essential part of the innate immune system. Complement system activation involves an organized proteolytic cascade. Overactivation of complement system activation is the main pathogenic mechanism of several diseases and contributes to the manifestations of many other conditions. This review describes the normal complement system and the role for complement dysregulation in critical illnesses, notably sepsis and acute respiratory distress syndrome. Complement activation is involved in the immune system response to pathogens but, when excessive, can contribute to tissue damage, runaway inflammation, and capillary leakage syndrome. Complement overactivation may play a key role in severe forms of coronavirus disease 2019 (COVID-19). Two diseases whose manifestations are mainly caused by complement overactivation, namely, atypical hemolytic and uremic syndrome (aHUS) and myasthenia gravis, are discussed. A diagnostic algorithm for aHUS is provided. Early complement-inhibiting therapy has been proven effective. When renal transplantation is required, complement-inhibiting drugs can be used prophylactically to prevent aHUS recurrence. Similarly, acetylcholine-receptor autoantibody-positive generalized myasthenia gravis involves complement system overactivation and responds to complement inhibition. The two main complement inhibitors used in to date routine are eculizumab and ravulizumab. The main adverse event is Neisseria infection, which is rare and preventable, but can be fatal. The complement system is crucial to health but, when overactivated, can cause or contribute to disease. Effective complement inhibitors are now available, although additional data are required to determine optimal regimens. Further research is also needed to better understand the complement system, develop advanced diagnostic tools, and identify markers that allow the personalization of treatment strategies., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction affecting children and adults. MG is a treatable condition with most patients requiring immunosuppression for disease control and/or remission. Juvenile myasthenia gravis (JMG) is rare in comparison with adult-onset MG but given the same underlying pathophysiology, treatment strategies are similar to those in adults. Until recently, there were only a few randomised controlled trials (RCTs) for MG treatments in adults and none in children, and management strategies were primarily based on expert consensus. In addition, treatment options for refractory MG cases have been severely limited, resulting in poor long-term quality of life in such patients due to the significant disease burden. Recently, there have been several RCTs focussing on novel therapeutic strategies with potentially promising outcomes, suggesting a change in MG management over the coming years and access to more effective and faster-acting drugs for MG patients. This paper will review current and new MG treatments including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, with a focus on juvenile myasthenia gravis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Based on HUANG Yuanyu 's theory of yiqi zhouliu (constant circulatory flowing of qi ) it is explored that the pathogenesis of myasthenia gravis refers to qi deficiency in the middle jiao and the disarrangement of zhouliu . It is summarized that the approach to acupuncture diagnosis and treatment should focus on replenishing qi of the middle jiao based on yangming and tonifying the functions of zang organs to eliminate pathogens, assisted with regulating shen (spirit) and opening the orifices so as to promote the recovery of motor and non-motor functions of the four limbs, eyelids, speech articulation, swallowing, vision, respiration and mental state in patients.

Background: Real-world data were employed to determine clinical characteristics of patients with myasthenia gravis (MG) with differing degrees of muscle weakness, as defined using the Myasthenia Gravis Foundation of America (MGFA) classification system., Methods: Data were drawn from the Adelphi MG Disease Specific Programme (DSP)™, a multinational (United States, France, Germany, Italy, Spain, United Kingdom) survey completed by physicians and their patients with MG in 2020. The association between MGFA class and impairment in activities of daily living (ADL) was tested using linear regression adjusting for sex and Charlson Comorbidity Index. Bivariate comparisons were performed for each individual item. A range of other clinical characteristics were also explored according to MGFA class., Results: Among 1232 patients, those in MGFA class I had significantly lower ADL impairment versus class II or III/IV (adjusted for sex and Charlson Comorbidity Index) (p < 0.01). However, heterogeneity occurred within each MGFA class. Bulbar symptoms (impaired speech, difficulty swallowing, and/or difficulty chewing/choking on food) were reported in some class I patients (mild in 1.1-1.9% and moderate in 0.3-1.1% of patients) and class II patients (mild in 8.5-16.4%, moderate in 4.7-7.4%, and severe in 0.3-0.9% of patients), and shortness of breath was reported in some class I (mild in 0.5% of patients) and class II patients (mild in 9.8%, moderate in 4.8%, and severe in 0.3% of patients). Conversely, in 11.2-19.2% of class III/IV patients, bulbar symptoms and shortness of breath reported were only mild in severity. In line with this finding, despite significant correlations between MGFA class and several clinical characteristics, patients across every class were at risk of experiencing myasthenic crisis or hospitalization, experiencing comorbidities including anxiety and depression, and not being in remission., Conclusions: Although MGFA class correlates with greater ADL impairment and presence of other clinical characteristics, there is variability between patients in each class in terms of symptoms experienced, overall disease burden, and the precise nature of ADL impairment., (© 2024. The Author(s).)

Introduction/aims: There is a lack of studies comparing the accuracy of neuromuscular jitter analysis during voluntary activation (v-jitter study) versus axonal stimulation (s-jitter study). The study aimed to compare these two techniques in the same population of patients with suspected ocular myasthenia gravis (OMG)., Methods: Fourteen control subjects (mean age: 55.5 ± 15.2 years) and 34 patients with suspected OMG (mean age: 59 ± 13.9 years) were prospectively evaluated. Twenty spike pairs and 30 individual spikes were analyzed during v-jitter and s-jitter study, respectively. Two different criteria for abnormal individual jitter values were evaluated: ≥ or > than 10% values exceeding the upper normal limit., Results: OMG was diagnosed in 19 patients based on clinical and laboratory findings, without considering jitter measurements. In most patients, v-jitter and s-jitter analyses provided comparable results. The maximum sensitivity (89%) was achieved with s-jitter study using the ≥10% criterion, while the maximum specificity (93%) was found with v-jitter study using the >10% criterion., Discussion: Both v-jitter and s-jitter studies showed good to very good accuracy for the diagnosis of OMG, in the absence of any statistically significant difference. Therefore, the patient's cooperation level and examiner's experience should guide the choice of performing v-jitter or s-jitter analysis in patients with suspected OMG., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient's age was 64 [42-76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3-10] days and the median total length of MV was 14 [10-23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials., (© 2024. The Author(s).)

Myasthenia gravis (MG) is one of the most well characterised autoimmune disorders affecting the neuromuscular junction with autoantibodies targeting the acetylcholine receptor (AChR) complex. The vast majority of patients present with ocular symptoms including double vision and ptosis, but may progress on to develop generalised fatiguable muscle weakness. Severe involvement of the bulbar muscles can lead to dysphagia, dysarthria and breathing difficulties which can progress to myasthenic crisis needing ventilatory support. Given the predominant ocular onset of the disease, it is important that ophthalmologists are aware of the differential diagnosis, investigations and management including evolving therapies. When the disease remains localised to the extraocular muscles (ocular MG) IgG1 and IgG3 antibodies against the AChR (including clustered AChR) are present in nearly 50% of patients. In generalised MG this is seen in nearly 90% patients. Other antibodies include those against muscle specific tyrosine kinase (MuSK) and lipoprotein receptor related protein 4 (LRP4). Even though decremental response on repetitive nerve stimulation is the most well recognised neurophysiological abnormality, single fibre electromyogram (SFEMG) in experienced hands is the most sensitive test which helps in the diagnosis. Initial treatment should be using cholinesterase inhibitors and then proceeding to immunosuppression using corticosteroids and steroid sparing drugs. Patients requiring bulbar muscle support may need rescue therapies including plasma exchange and intravenous immunoglobulin (IVIg). Newer therapeutic targets include those against the B lymphocytes, complement system, neonatal Fc receptors (FcRn) and various other elements of the immune system., (© 2024. The Author(s).)

Decreased cough strength in myasthenia gravis (MG) leads to aspiration and increases the risk of MG crisis. The aim of this study was to clarify the reliability and validity of cough peak flow (CPF) measurements in MG. A total of 26 patients with MG who underwent CPF measurements using the peak flow meter by themselves were included. MG symptoms were evaluated by pulmonary function tests and clinical MG assessment scales before and after immune-treatments. The relationship between CPF and pulmonary function tests and MG comprehensive were assessed. The cut-off value of CPF for aspiration risk was determined and the area under the curve (AUC) was calculated. The intraclass correlation coefficient was more than 0.95 for pre-and post-treatment. Positive correlations were found between CPF and almost all spirometric values as well as between the differences of pre-and post-treatment in CPF and quantitative myasthenia gravis score. The CPF for identifying the aspiration risk was used to calculate the CPF cut-off value of 205 L/min with a sensitivity of 0.77, specificity of 0.90, and AUC of 0.85. The CPF, a convenient measure by patients themselves, has a high reliability in patients with MG, and is a useful biomarker reflecting MG symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: The diagnostic challenge of myasthenia gravis (MG) is exacerbated by the variable efficacy of current testing methodologies, necessitating innovative approaches to accurately identify the condition. This study aimed to assess ocular muscle fatigue in patients with MG using video-oculography (VOG) by examining repetitive saccadic eye movements and comparing these metrics to those of healthy control participants., Methods: This prospective, cross-sectional study was conducted at a tertiary care center and involved 62 patients diagnosed with MG (48 with ocular MG and 14 with generalized MG) and a control group of 31 healthy individuals, matched for age and sex. The assessment involved recording saccadic eye movements within a ± 15° range, both horizontally and vertically, at a rate of 15 saccades per minute over a 5-min period, resulting in 75 cycles. Participants were afforded a 3-min rest interval between each set to mitigate cumulative fatigue. The primary outcome was the detection of oculomotor fatigue, assessed through changes in saccadic waveforms, range, peak velocity, latency, and the duration from onset to target, with a focus on comparing the second saccade against the average of the last five saccades., Results: In the evaluation of repetitive saccadic movements, patients with MG exhibited a reduced saccadic range and a prolonged duration to reach the target, compared to healthy subjects. Furthermore, a significant elevation in the frequency of multistep saccades was observed among MG patients, with a marked rise observed over consecutive trials. Receiver operating characteristic (ROC) analysis revealed the discriminative performance of multistep saccade frequency, in conjunction with variations in saccadic range and duration from onset to target achievement between the second saccade and the mean of the final five saccades, as effective in distinguishing MG patients from healthy subjects. Although alterations in peak saccadic velocity and latency were less pronounced, they were nevertheless detectable., Discussion: The utilization of VOG for repetitive saccadic testing in the diagnosis of MG has demonstrated considerable diagnostic precision. This methodology affords significant accuracy in evaluating ocular muscle fatigue in MG patients, providing class III evidence supportive of its clinical application., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Disturbed sleep and its impact on quality of life (QoL) are underrecognized in myasthenia gravis (MG)., Aims: To evaluate the quality of sleep in MG using standard sleep questionnaires and assess factors that determine sleep., Settings and Design: Prospective, cross-sectional, hospital-based study., Patients and Methods: Fifty patients on stable drug therapy for at least 1 month and age- and gender-matched controls were assessed using standard sleep questionnaires [Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and NIMHANS Comprehensive Sleep Disorders Questionnaire (NCSDQ)]., Results: Myasthenia Gravis Foundation of America (MGFA) grade was I, IIA, IIB, IIIA, IIIB, and IVA in 11, 19, 3, 10, 6, and 1 respectively. The mean PSQI and ESS scores were similar in patients and controls. Patients with abnormal ESS (>10) were older and had greater neck circumference (P = 0.018 and <0.001). Body mass index was greater in patients with PSQI > 5 (P < 0.05). Age, gender, and clinical severity did not affect PSQI. Compared with ESS and PSQI, NCSDQ showed higher frequency of disturbed sleep, snoring, early morning headache, difficulty in initiation, and maintenance of sleep in MG, although the differences between patients and controls were not significant. No correlation was found between QoL and ESS or PSQI., Conclusion: Patients of MG with stable clinical course with adequate treatment have sleep quality comparable with healthy controls. Longitudinal assessment of sleep quality at multiple time points throughout the disease course and correlating with cross-sectional disease severity may further delineate the impact of disease on sleep and QoL., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Patients with myasthenia gravis (MG) can present with respiratory dysfunction, ranging from exercise intolerance to overt respiratory failure, increased fatigue, or sleep-disordered breathing. To investigate the value of multiple respiratory tests in MG, we performed clinical and respiratory assessments in patients with mild to moderate generalized disease. One-hundred and thirty-six patients completed the myasthenia gravis quality-of-life score(MG-QOL-15), myasthenia gravis impairment index(MGII), Epworth sleepiness scale(ESS), University of California-San Diego Shortness of Breath Questionnaire(UCSD-SOB), Modified Medical Research Council Dyspnea Scales(MRC-DS), supine and upright forced vital capacity(FVC), maximal inspiratory pressures(MIPs) and sniff nasal inspiratory pressures(SNIP). Seventy-three (54 %) had respiratory and/or bulbar symptoms and 45 (33 %) had baseline abnormal FVC, with no significant postural changes (p = 0.89); 55 (40.4 %) had abnormal MIPs and 50 (37 %) had abnormal SNIPs. Overall, there were low scores on respiratory and disability scales. Females had increased odds of presenting with abnormal FVC (OR 2.89, p = 0.01) and MIPs (OR 2.48, p = 0.022). There were significant correlations between MIPs, FVC and SNIPs; between MGII/MG-QOL15 and UCSD-SOB/MRC-DS and between ESS and respiratory scales in the whole group. Our data suggests that office-based respiratory measurements are a useful screening method for stable MG patients, even when presenting with minimal respiratory symptoms and no significant disability., Competing Interests: Declaration of competing interest On behalf of all authors, I confirm that there are no conflict or competing interests related to this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Juvenile myasthenia gravis (JMG) is a rare autoimmune disease that causes fatigable muscle weakness in children aged <18 years. There is currently no curative treatment or internationally accepted standard of care for JMG. The objective is to investigate relationships between clinical presentation, antibody status, severity of disease onset, electrodiagnostic evaluation, and response to therapy in JMG., Methods: This study was a retrospective chart review. Congenital myasthenic syndromes were excluded. Data on demographics, treatments, and outcomes were collected. Disease severity was evaluated using Myasthenia Gravis Foundation of America (MGFA) clinical classifications., Results: We identified 84 patients with JMG at Children's Medical Center Dallas between January 2014 and February 2022. It was found that 52% of patients presented with ocular JMG (median onset age 4.5 years) and 48% with generalized JMG (median onset age 11.5 years); 81% tested positive for acetylcholine receptor antibodies. Patients were 17% non-Hispanic white, 29% Hispanic, 39% black, and 12% Asian. There was a significant difference in average MGFA scores between ethnicities (P = 0.047) and age groups (P = 0.004), with postpubertal patients having higher average MGFA scores than prepubertal patients. Seventy-one percent of patients who underwent thymectomy experienced a decrease in MGFA scores postprocedure., Conclusions: Our study showed that there were significant differences in disease severity between ethnicities and age groups and that most patients who underwent thymectomy showed clinical improvement. These outcomes highlight the need for additional therapies in the treatment of JMG and the importance of extending clinical trials to the pediatric population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Muscle-specific kinase myasthenia gravis (MuSK MG) is caused by autoantibodies against MuSK in the neuromuscular junction (NMJ). MuSK MG patients have fluctuating, fatigable skeletal muscle weakness, in particular of bulbar muscles. Severity differs greatly between patients, in spite of comparable autoantibody levels. One explanation for inter-patient and inter-muscle variability in sensitivity might be variations in compensatory muscle responses. Previously, we developed a passive transfer mouse model for MuSK MG. In preliminary ex vivo experiments, we observed that muscle contraction of some mice, in particular those with milder myasthenia, had become partially insensitive to inhibition by μ-Conotoxin-GIIIB, a blocker of skeletal muscle Na V 1.4 voltage-gated sodium channels. We hypothesised that changes in Na V channel expression profile, possibly co-expression of (μ-Conotoxin-GIIIB insensitive) Na V 1.5 type channels, might lower the muscle fibre's firing threshold and facilitate neuromuscular synaptic transmission. To test this hypothesis, we here performed passive transfer in immuno-compromised mice, using 'high', 'intermediate' and 'low' dosing regimens of purified MuSK MG patient IgG4. We compared myasthenia levels, μ-Conotoxin-GIIIB resistance and muscle fibre action potential characteristics and firing thresholds. High- and intermediate-dosed mice showed clear, progressive myasthenia, not seen in low-dosed animals. However, diaphragm NMJ electrophysiology demonstrated almost equal myasthenic severities amongst all regimens. Nonetheless, low-dosed mouse diaphragms showed a much higher degree of μ-Conotoxin-GIIIB resistance. This was not explained by upregulation of Scn5a (the Na V 1.5 gene), lowered muscle fibre firing thresholds or histologically detectable upregulated Na V 1.5 channels. It remains to be established which factors are responsible for the observed μ-Conotoxin-GIIIB insensitivity and whether the Na V repertoire change is compensatory beneficial or a bystander effect., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background and Objectives: We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia., Methods: In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm., Results: Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG., Discussion: The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG., Classification of Evidence: This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders., Trial Registration Information: ClinicalTrials.gov: NCT03049956.

Background: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disorder leading to muscle weakness, autonomic dysregulation and hyporeflexia. Psychosocial well-being is affected. Previously, we assessed burden of disease for Myasthenia gravis (MG). Here, we aim to elucidate burden of disease by comparing health-related quality of life (HRQoL) of patients with LEMS to the general population (genP) as well as MG patients., Methods: A questionnaire-based survey included sociodemographic and clinical data along with standardized questionnaires, e.g. the Short Form Health (SF-36). HRQoL was evaluated through matched-pairs analyses. Participants from a general health survey served as control group., Results: 46 LEMS patients matched by age and gender were compared to 92 controls from the genP and a matched cohort of 92 MG patients. LEMS participants showed lower levels of physical functioning (SF-36 mean 34.2 SD 28.6) compared to genP (mean 78.6 SD 21.1) and MG patients (mean 61.3 SD 31.8). LEMS patients showed lower mental health sub-scores compared to genP (SF-36 mean 62.7 SD 20.2, vs. 75.7 SD 15.1) and MG patients (SF-36 mean 62.7 SD 20.2, vs. 66.0 SD 18.). Depression, anxiety and fatigue were prevalent. Female gender, low income, lower activities of daily living, symptoms of depression, anxiety and fatigue were associated with a lower HRQoL in LEMS., Discussion: HRQoL is lower in patients with LEMS compared to genP and MG in a matched pair-analysis. The burden of LEMS includes economic and social aspects as well as emotional well-being. TRIAL REGISTRATION INFORMATION: drks.de: DRKS00024527, submitted: February 02, 2021, https://drks.de/search/en/trial/DRKS00024527 ., (© 2024. The Author(s).)

Myasthenia gravis is an autoimmune disease characterized by muscle weakness and pathological fatigue due to autoaggressive phenomena with the formation of antibodies directed against various structures of the neuromuscular synapse. In most patients, the disease begins with the involvement of extraocular muscles, presenting with symptoms such as intermittent ptosis of the upper eyelid and/or binocular diplopia. In 15% of cases, clinical manifestations are limited to impairment of the levator palpebrae superioris and extraocular muscles, characteristic of the ocular form of myasthenia gravis. Specialists often encounter challenges in diagnosing this form, as serological and electrophysiological studies may be uninformative, necessitating diagnosis based on patient history and clinical picture. This literature review outlines the key aspects of the pathogenesis, clinical manifestations, methods of diagnosis and treatment of ocular myasthenia gravis.

Objectives: To evaluate CT-derived radiomics for machine learning-based classification of thymic epithelial tumor (TET) stage (TNM classification), histology (WHO classification) and the presence of myasthenia gravis (MG)., Methods: Patients with histologically confirmed TET in the years 2000-2018 were retrospectively included, excluding patients with incompatible imaging or other tumors. CT scans were reformatted uniformly, gray values were normalized and discretized. Tumors were segmented manually; 15 scans were re-segmented after 2 weeks by two readers. 1316 radiomic features were calculated (pyRadiomics). Features with low intra-/inter-reader agreement (ICC<0.75) were excluded. Repeated nested cross-validation was used for feature selection (Boruta algorithm), model training, and evaluation (out-of-fold predictions). Shapley additive explanation (SHAP) values were calculated to assess feature importance., Results: 105 patients undergoing surgery for TET were identified. After applying exclusion criteria, 62 patients (28 female; mean age, 57±14 years; range, 22-82 years) with 34 low-risk TET (LRT; WHO types A/AB/B1), 28 high-risk TET (HRT; WHO B2/B3/C) in early stage (49, TNM stage I-II) or advanced stage (13, TNM III-IV) were included. 14(23%) of the patients had MG. 334(25%) features were excluded after intra-/inter-reader analysis. Discriminatory performance of the random forest classifiers was good for histology(AUC, 87.6%; 95% confidence interval, 76.3-94.3) and TNM stage(AUC, 83.8%; 95%CI, 66.9-93.4) but poor for the prediction of MG (AUC, 63.9%; 95%CI, 44.8-79.5)., Conclusions: CT-derived radiomic features may be a useful imaging biomarker for TET histology and TNM stage., Competing Interests: The authors have declared that no competing interests exist.

Objective: To prospectively compare oropharyngeal swallowing dysfunction in myasthenia gravis (MG) patients presenting with difficulty in swallowing between the neutral and chin-down positions, based on the results of high-resolution manometry (HRM) examination., Methods: We prospectively compared the HRM results of swallowing studies of seven MG patients showing difficulty in swallowing (neutral and chin-down positions) at the Department of Neurology of our institution during the period February-December 2018. The HRM assessment parameters were as follows: maximum swallowing pressure (SP) at the soft palate, meso‑hypopharynx, and upper esophageal sphincter (UES), and the duration of relaxation pressure at the UES. These parameters were compared between the two positions and their correlations with the results of neurological evaluations, such as the Quantitative Myasthenia Gravis (QMG) score (total and neck muscles alone), and grip strength, were also analyzed., Results: In comparison with the neutral position, in the chin-down position the maximum SP at the meso‑hypopharynx was significantly increased (p < 0.05), the maximum SP at the UES was significantly decreased (p < 0.05), and the duration of relaxing SP at the UES was significantly increased (p < 0.05). Interestingly, there were no correlations between the SP at any location and the results of the neurological evaluations., Conclusions: The chin-down position appears useful for improving pharyngeal clearance in MG patients, by promoting increased SP at the meso‑hypopharynx, relaxing SP at the UES, and increasing the duration of relaxation pressure at the UES., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2021. Published by Elsevier B.V.)

Introduction/aims: Ulnar nerve repetitive nerve stimulation (RNS) has been traditionally used in the electrophysiological evaluation of myasthenia gravis (MG). However, its low diagnostic sensitivity remains a limitation. Existing data may suggest that median nerve RNS outperforms that of the ulnar nerve, but a direct comparison is currently lacking. The aim of this study was to directly compare the diagnostic yields between median and ulnar nerve RNS in patients with generalized MG., Methods: We performed a retrospective analysis of patients with MG who underwent median and ulnar nerve RNS at a single tertiary center., Results: RNS studies of median nerve recording from the abductor pollicis brevis and ulnar nerve recording from the adductor digiti minimi were completed in 28 patients with generalized MG. Abnormal RNS was more frequently observed in the median compared with the ulnar nerve (60.7% vs 35.7%, P = .046). The average magnitude of decrement was higher in the median nerve compared with the ulnar nerve (17.3% vs 9.6%, P = .017). Differences between the median and ulnar nerve RNS studies were restricted to patients with mild manifestations (Myasthenia Gravis Foundation of America class II)., Discussion: Median nerve RNS has superior diagnostic sensitivity as compared with ulnar nerve RNS in the assessment of mild generalized MG., (© 2021 Wiley Periodicals LLC.)

Background and Objectives: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact., Methods: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19 + B220 high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated., Results: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19 + B220 high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy., Discussion: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction/aims: Videonystagmography (VNG) which directly records eye movements using infrared video goggles with mini-cameras, is used to measure nystagmus. Our aim is to explore whether VNG can be used to detect a decrement in the extraocular muscle (EOM) activity of patients with myasthenia gravis (MG)., Methods: Thirty-four patients with MG, including 13 with ocular-predominant and 21 with generalized MG, and 23 healthy controls participated. Using VNG we recorded the velocity of the eye movements of the patients as they followed a moving target. We then calculated the gain by dividing the eye movement velocity (degrees/second) by the target velocity (degrees/second)., Results: In MG subjects, the mean initial gain (maximum gain) was 1.23 ± 0.31 (range: 0.63-2.15) for the right eye and 1.22 ± 0.37 (range; 0.60-2.28) for the left eye. The mean minimum gain was 0.11 ± 0.12 (0.01-0.58) for the right and 0.14 ± 0.5 (0.02-0.55) for the left. Due to fatigue, the movement gain was reduced by 91.7% in the right eye and 88.2% in the left eye. After reaching minimum velocity, gain remained at a minimum for a mean of 1.08 ± 0.52 (0.3-2.4) s for the right and 1.49 ± 0.85 (0.4-3.6) s for the left, before the velocity increased again. There was no fatigue-induced decrement in healthy subjects., Discussion: Our study documents a decrement in EOM activity recorded by VNG in patients with MG which begins to improve within 1-2 s after reaching minimum velocity, analogous to traditional low-frequency repetitive nerve stimulation testing and its U-shaped pattern. Thus, VNG may be a promising diagnostic test for MG., (© 2021 Wiley Periodicals LLC.)

Objective: Patients with myasthenia gravis associated with muscle-specific tyrosine kinase antibodies (MuSK-MG) often manifest signs of cholinergic hyperactivity with standard doses of acetylcholinesterase inhibitors (AChE-Is). Aim of the study was to investigate whether repetitive compound muscle action potential (R-CMAP), the neurophysiological correlate of cholinergic hyperactivity, was present in MuSK-MG irrespective of AChE-I treatment., Methods: Patients with confirmed diagnosis of MuSK-MG were consecutively enrolled during follow-up visits, from January 2019 to April 2020. All these subjects underwent the same neurophysiological protocol, including motor nerve conduction studies and repetitive nerve stimulation. In patients taking pyridostigmine, neurophysiological testing was performed at least 12 hours after the last dose. For comparison, the presence of R-CMAP was investigated in 20 consecutive acetylcholine receptor antibody positive myasthenia gravis (AChR-MG) patients., Results: We enrolled 25 MuSK-MG patients (20 females), aged 16-79 years at the study time, with disease duration ranging 0.6-48.8 years (median: 17.7 years). R-CMAP was detected in 12/25 (48%) MuSK-MG cases and in none of the AChR-MG controls (p = 0.0003). In the MuSK-MG population, a history of muscle cramps and fasciculations, during low-dose pyridostigmine therapy, was significantly more frequent in R-CMAP positive than in R-CMAP negative patients (100% vs 31%, p = 0.001). At the time of the study, the proportion of patients still symptomatic for MG was higher among R-CMAP positive cases (92% vs 23%, p = 0.0005)., Conclusions: Cholinergic hyperactivity is a relatively common finding in MuSK-MG patients, independent of AChE-I treatment, and may constitute an intrinsic feature of the disease., Significance: R-CMAP detection can represent a useful diagnostic clue for MuSK-MG and predicts poor tolerance to AChE-Is., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Purpose: Myositis as a rare manifestation of COVID-19 is only recently being reported. This review examines the current literature on COVID-19-induced myositis focusing on etiopathogenesis, clinical presentations, diagnostic practices, and therapeutic challenges with immunosuppression, and the difficulties experienced by rheumatologists in established myositis in the COVID-19 era., Recent Findings: COVID-19 is associated with a viral myositis attributable to direct myocyte invasion or induction of autoimmunity. COVID-19-induced myositis may be varied in presentation, from typical dermatomyositis to rhabdomyolysis, and a paraspinal affliction with back pain. It may or may not present with acute exponential elevations of enzyme markers such as creatine kinase (CK). Virus-mediated muscle inflammation is attributed to ACE2 (angiotensin-converting enzyme) receptor-mediated direct entry and affliction of muscle fibers, leading on to innate and adaptive immune activation. A greater recognition of the stark similarity between anti-MDA5-positive myositis with COVID-19 has thrown researchers into the alley of exploration - finding common etiopathogenic basis as well as therapeutic strategies. For patients with established myositis, chronic care was disrupted during the pandemic with several logistic challenges and treatment dilemmas leading to high flare rates. Teleconsultation bridged the gap while ushering in an era of patient-led care with the digital transition to tools of remote disease assessment. COVID-19 has brought along greater insight into unique manifestations of COVID-19-related myositis, ranging from direct virus-induced muscle disease to triggered autoimmunity and other etiopathogenic links to explore. A remarkable shift in the means of delivering chronic care has led patients and caregivers worldwide to embrace a virtual shift with teleconsultation and opened doorways to a new era of patient-led care.

Introduction: In this study we aimed to investigate the dispersion of mean consecutive difference (MCD) of concentric needle jitter studies of patients with myasthenia gravis (MG) and its effect on diagnostic sensitivity for MG., Methods: One hundred fifty-three patients, including 76 patients with MG and 77 controls with possible MG who later received another diagnosis, underwent stimulated concentric needle jitter studies of the frontalis muscle. MCD mean, standard deviation (SD), and coefficient of variation (CV) were calculated. Diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) analyses., Results: MG patients showed a significantly greater MCD mean (MG: control, 26.3 μs; 13.5 μs [median]; P < .0001), MCD SD (MG: control, 12.8 μs; 5.1 μs [median]; P < .0001), and MCD CV (MG: control, 46.1; 37.5 [median]; P < .001) than those without MG. An ROC curve of SD showed a large area under the curve (0.88), and a cut-off value of 7.2 μs, which was calculated by maximum Youden index, exhibited high diagnostic sensitivity (86%) for MG. Combined MCD mean, outliers, and SD criteria showed higher sensitivity (88%) than conventional criteria alone (82%), at the expense of lower specificity. Five MG patients with normal MCD mean and abnormal MCD SD had only ocular symptoms., Discussion: The dispersion of MCD as measured by MCD SD greater than 7.2 μs is significantly increased in patients with MG and may be a useful measure of abnormal jitter in the diagnosis of MG, especially for identifying patients with mild disease., (© 2021 Wiley Periodicals LLC.)

Background: Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder caused by dysfunction at the neuromuscular junction spreads. The main clinical features of this disease are fluctuating fatigue, and weakness of the skeletal muscles of the eyes and limbs. At present, the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine has been widely used for MG. The present study was conducted to evaluate the efficacy and safety of the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine for MG., Methods: The following 10 databases were searched from inception to March 2021: PubMed, Cochrane Library, EMBASE, Web of Science, Springer, China National Knowledge Infrastructure (CNKI), Wan fang, VIP Chinese Science and Technique Journals Database, the Chinese Bio Medical Database (CBM), and Baidu Scholar. The language was limited to the Chinese and English language. Merely randomized controlled trials (RCTs) were included. The Cochrane Collaboration risk-of-bias tool was used for the methodological quality assessment and risk of bias. The meta-analysis was assessed using the Cochrane RevMan 5.3 software., Results: In the present study, a meta-analysis was conducted, and RCTs that met the eligibility criteria were included. Furthermore, the different outcome indicators of different methods were objectively compared. The main outcome indicators included the effective rate, quantitative myasthenia gravis (QMG) scores, adverse events, and quality of life (QOL). The secondary outcome indicators included AchRAb, serum-related immune cells (such as CD3+CD4+cells and CD4+/CD8+cells), the traditional Chinese medicine syndrome score scale (TCMSSS), the serum interleukin-6 level, the level of IFN-γ and its mRNA, and the clinical score that contains the clinical absolute score (CAS) and clinical relative score (CRS)., Conclusion: This study would provide credible evidence to determine whether the tonifying the spleen and replenishing the kidney method in traditional Chinese medicine is an effective treatment method for MG., Trial Registration Number: INPLASY202110097., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Myasthenia gravis (MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. IgG crystallizable fragment (Fc)-mediated effector functions, such as antibody-dependent complement deposition, contribute to disease development and progression. Despite progress in understanding Ab-mediated disease mechanisms, immunotherapy of MG remained rather unspecific with corticosteroids and maintenance with immunosuppressants as first choice drugs for most patients. More specific therapeutic IgG Fc-based platforms that reduce serum half-life or effector functions of pathogenic MG-related Abs are currently being developed, tested in clinical trials or have recently been successfully translated into the clinic. In this review, we illustrate mechanisms of action and clinical efficacies of emerging Fc-mediated therapeutics such as neonatal Fc receptor (FcRn)-targeting agents. Furthermore, we evaluate prospects of therapies targeting classical Fc receptors that have shown promising therapeutic efficacy in other antibody-mediated conditions. Increased availability of Fc- and Fc receptor-targeting biologics might foster the development of personalized immunotherapies with the potential to induce sustained disease remission in patients with MG.

Abstract: Patients with ocular myasthenia gravis (OMG) are frequently treated to prevent the development of generalized myasthenia gravis (GMG). This retrospective cohort study aimed to assess prognostic factors associated with conversion to GMG.We analyzed the time from the onset of OMG symptoms to GMG in relation to demographic variables, clinical findings, initial investigation results, and treatment regimens using Kaplan-Meier survival curves and multivariate Cox proportional regression analysis.Of 115 patients diagnosed with OMG (median follow-up time, 2.9 years), 28 (30.4%) developed GMG. The 2-year probability of GMG conversion was 23.7%. Patients with thymic abnormalities and a positive response to repetitive facial nerve stimulation had a significantly higher risk than those with negative results (hazard ratios [HR] 4.28, P < .001 and HR 3.84, P = .04, respectively). Treatment with immunosuppressants was found to be a preventive factor for secondary generalization (HR 0.36, P = .02).Patients with OMG had a low risk of developing GMG. Immunosuppressive treatments may mitigate disease progression. Chest imaging and repetitive nerve stimulation should be routinely performed to assess the risk of generalization., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ocular myasthenia gravis (OMG) and thyroid eye disease are two autoimmune conditions that have several overlapping clinical features, and these coexist with a small but not insignificant frequency. Segregating these diagnoses is typically straightforward, but, when the two diseases co-occur in the same individual, making a diagnosis of OMG can be very challenging. In this review we address what is known about the coexistence of OMG and thyroid eye disease and we highlight the clinical features that are suggestive of overlapping conditions. We also describe the major testing approaches used in the diagnosis of these two entities, with special emphasis on the potential shortcomings of individual tests in patients with overlapping disease. In patients with thyroid eye disease, securing a diagnosis of OMG may not be possible on the basis of a single positive test. A multimodal approach using clinical, serologic, imaging, and electrodiagnostic data, is typically required., (© 2020 Wiley Periodicals LLC.)

Introduction: Generalized myasthenia gravis (gMG) is an autoimmune disorder in which pathogenic autoantibodies damage the neuromuscular junction, causing disabling or life-threatening muscle weakness. Most treatments nonspecifically inhibit aspects of the immune system, do not directly address the causal mechanisms of tissue damage, and often have side-effect profiles that negatively impact patients. Understanding of the central pathogenic role of the complement cascade in gMG is advancing, and a new complement-targeting treatment is under investigation., Areas Covered: We provide an overview of gMG etiology, the complement cascade, current treatments, and the investigational gMG therapy zilucoplan. Zilucoplan is a small, subcutaneously administered, macrocyclic peptide that inhibits cleavage of complement component C5 and the subsequent formation of the membrane attack complex., Expert Opinion: In a randomized, double-blind, placebo-controlled, phase 2 clinical trial, zilucoplan demonstrated clinically meaningful complement inhibition in patients with acetylcholine receptor-positive gMG. Zilucoplan, a first-of-its-kind cyclic peptide targeting C5, appears to be a therapeutic option for the treatment of gMG based on available pharmacokinetic/pharmacodynamic data and phase 1 and 2 efficacy, safety, and tolerability data with limited long-term follow-up. Zilucoplan use earlier in the treatment paradigm would be suitable in this population should phase 3 efficacy and safety data be equally favorable.

Objective: To investigate the expression and clinical significance of miR-146a and tumor necrosis factor receptor-associated factor 6 (TRAF6) in myasthenia gravis (MG) patient serum., Methods: The serum of 52 patients with MG and 60 healthy individuals was collected in our hospital. The expression of miR-146a and TRAF6 in serum was measured by real-time PCR (RT-PCR). Comparison among serum miR-146a and TRAF6 mRNA group clinical characteristics and assorted expressions was done with the correlation among the two groups evaluated. Logistics regression was used to analyze the effect of miR-146a and TRAF6 mRNA on MG development with the ROC curve applied for an investigation into the diagnostic role of miR-146a and TRAF6 mRNA expression in MG development., Results: miR-146a and TRAF6 mRNA were significantly increased in the patients with MG compared with the healthy controls. Significant differences were identified in respiratory muscle endurance, muscle weakness level, vital capacity, and maximal voluntary ventilation between the two groups. Additionally, correlation analysis has discovered a positive correlation between miR-146a and TRAF mRNA expression in patients with MG. miR-146a and TRAF6 mRNA are independent MG occurrence factors exhibited by multivariate analysis while areas under ROC curve (AUCs) of miR-146a and TRAF6 mRNA in MG diagnosis were established by ROC curve analysis with results being 0.782 and 0.703, correspondingly., Conclusion: miR-146a and TRAF6 mRNA are highly expressed in MG patients and can affect MG occurrence. miR-146a is a suitable candidate marker for diagnosing MG., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mei Yan et al.)

Objective: Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in-hospital mortality. We aimed to identify immune signatures using in-depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally., Methods: We studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow-up visits occurred prospectively from crisis to 6 months off-mechanical ventilation. The frequencies of 20 CD4 + T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis., Results: Patients in crisis exhibited a proinflammatory CD4 + T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P < 0.001), Tnaive in Tfh cells (P < 0.001), ICOS - Tfh cells (P = 0.017), and T central memory in Tfh (P = 0.022) compared with controls, and increased frequencies of Tregs (P = 0.026) and Tfh17 (P = 0.045) compared with non-crisis MG. Cytokine cascade was identified in crisis including the ones associated with Th1 (IL-1β/2/12p70/18/27/IFN-γ/TNF-α), Th2 (IL-4/5/13), Th17 (IL-6/17A/21/22/23/GM-CSF), Th9 (IL-9), and Treg (IL-10). Longitudinally, seven immune biomarkers including Tregs, IL-2/4/17A/IFN-γ/TNF-α/GM-CSF had significant correlations with MG-activities of daily living score., Interpretation: Vigorous inflammatory CD4 + T signatures were identified in MC and are associated with clinical severity. Future research is needed to explore its potential candidacy for therapeutic intervention and predicting impending crisis., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: The majority of patients with myasthenia gravis (MG) initially present with ocular symptoms, but it is difficult to predict which cases will remain as ocular MG (OMG) or will progress to generalized MG. Herein we evaluated the serologic profile of Japanese OMG and its relationship with clinical features., Methods: Seventy-three patients with OMG from five Japanese myasthenia gravis (MG) centers were enrolled. Live cell-based assays (CBAs) were used to determine the presence of autoantibodies (Abs) to clustered adult (2α, β, δ, ε) and fetal (2α, β, δ, γ) acetylcholine receptor (AChR) isoforms, muscle-specific receptor tyrosine kinase (MuSK), and lipoprotein receptor-related protein-4 (LRP4)., Results: Thirty-four of 73 (46.5%) serum samples were positive for Abs against both the adult-type and fetal-type AChR, as expected, but 7 (9.6%) and 2 (2.7%) were positive only for fetal or adult AChR-Abs, respectively. Four (5.4%) samples were positive for MuSK-Abs, but two of these also contained antibodies to fetal AChR or LRP4. Twenty-six (35.6%) samples were seronegative., Discussion: Abs against fetal-specific AChR, MuSK, and LRP4 are found in some patients with OMG. Future studies attempting to predict conversion from ocular symptoms to generalized MG may benefit from measurement of these antibodies., (© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Background: Little is known about how different outlier estimation methods affect cutoff limits for outliers in single fiber electromyography., Methods: We compared in a prospective fashion the established 18th jitter value (18thjv) method to three, whole-distribution based, outlier detection methods: the interquartile range (IQR), the log-normal, and the Z-score method. The reference limits were probed in a normal cohort and in myasthenia gravis (MG) patients., Results: Differences in outlier cutoff values between the different methods were in the range of 2 μs. The number of abnormal muscles according to the computed criteria was similar for all four methods in the control group. Classification metrics (sensitivity, specificity, Youden's statistic, and predictive values) were also similar among the different methods. In the MG group, however, the Z-score method failed to identify the abnormal jitter values. Accordingly, Kappa agreement was substantial to perfect (0.658 to 1) between the three methods (18thjv, IQR, and log-normal), but was equivalent to chance between the three methods and the Z-score in the MG group., Conclusions: The established 18thjv method proved largely robust when compared to whole-distribution based methods, and its use in clinical practice is justified. Simple estimation of outlier limits by adding two SDs to the mean of the data, leads to unacceptable deviations from the true cutoff values. Moreover, in a clinical scenario in which the final electrodiagnosis depends only on the number of outliers, it is meaningful to accept a tolerance zone of about 2 μs, which is the approximate variation range among the different methods., (© 2020 Wiley Periodicals LLC.)

Introduction: The Duke Myasthenia Gravis (MG) Clinic Registry is a disease-specific database containing physician-derived data from patients seen in the Duke MG Clinic since 1980., Methods: Data from 1060 MG patients initially seen between 1980 and 2008 were reviewed., Results: Fifty-four percent were male. Symptoms began after age 50 in 66% of males and 42% of females. Peak onset age in males was in their 60's; females had no predominant onset age. Onset age for both sexes increased from 1980 to 2008. Thymoma was present in 8.5%. Weakness was limited to ocular muscles for at least 2 y in 22% and became generalized later in 8.3% of these. Acetylcholine receptor antibodies were present in 78% overall, 82% with generalized MG and 52% with ocular MG (OMG). The distribution of MG disease class was similar in males and females, except that a greater proportion of women experienced myasthenic crisis and men were more likely to have OMG., Discussion: Data in the Registry permit comprehensive and longitudinal analysis of a validated MG population. Analysis of Registry data shows that the frequency of AChR antibody negative MG, ocular MG, and thymoma are similar to other reports, but the onset age and proportion of males have progressively increased compared to studies published more than 20 y ago. These observations demonstrate the value of collecting comprehensive clinical information and comparing historic and contemporary populations. Other potential uses of Registry data include comparison of outcome measures in different disease subgroups and the response to specific treatments., (© 2020 Wiley Periodicals LLC.)

Fatigability is the hallmark of myasthenia gravis (MG). It is not clear, however, whether there is an analogous increase in jitter during the course of a single fiber electromyography (SFEMG) session. The individual jitter values of all potentials of 76 normal and 44 myasthenic orbicularis oculi muscles were assigned a rank number according to their temporal order in which they were collected and linear regression was performed to determine if the slope of the regression line was significantly different from zero. Control and MG subjects displayed rather flat linear regression lines with non-significant positive or negative slopes. Accordingly, ROC analysis yielded areas under the curve near 0.5. We conclude that there is no systematic jitter increase during the collection of 20 potential pairs in a typical SFEMG session.

Background: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals., Materials and Methods: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated., Results: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection., Conclusion: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis., (© 2021 S. Karger AG, Basel.)

Neuromuscular junction (NMJ) disorders include several dysfunctions that ultimately lead to muscle weakness. Myasthenia gravis (MG) is the most prevalent NMJ disorder with a highly polymorphic clinical presentation and many different faces. Being an autoimmune disease, MG correlates with the presence of detectable antibodies directed against the acetylcholine receptor, muscle-specific kinase, lipoprotein-related protein 4, agrin, titin, and ryanodine in the postsynaptic membrane at the NMJ. MG has become a prototype serving to understand both autoimmunity and the function of the NMJ better. The aim of this review is to synthesize some of the epidemiological data available. Epidemiological data regarding MG are important for postulating hypotheses regarding its etiology and facilitating the description of MG subtypes. Thus, adequate documentation through broad databases is essential. The incidence and prevalence of MG reported around the globe have been rising steadily and consistently over the past decades. Ethnic aspects, gender-related differences, and environmental risk factors have been described, implying that these might contribute to a specific phenotype, further suggesting that MG may be considered an umbrella term that covers several clinical entities., (©2020 JOURNAL of MEDICINE and LIFE.)

Background: Muscle weakness and fatigability, the prominent symptoms of autoimmune myasthenia gravis (MG), negatively impact daily function and quality of life (QoL). It is currently unclear as to what extent symptoms limit activity and whether physical activity (PA) behaviours are associated with reduced QoL., Objectives: This study aimed to describe habitual PA patterns and explore relationships between PA metrics, clinical MG characteristics, and health-related QoL (HRQoL)., Methods: PA data from a tri-axial trunk accelerometer worn for seven days, was collected from females with generalized, stable MG and compared to control subjects. MG-specific evaluations, the six-minute walk test and knee extension strength were assessed in individuals with MG (IwMG). Mann-Whitney tests were used to study between-group differences. Spearman rank correlation coefficient was performed to explore relationships between variables., Results: Thirty-three IwMG (mean (SD) age 45 (11) years) and 66 control subjects were included. IwMG perform less vigorous-intensity PA than control subjects (p = 0.001), spend more time sedentary (p = 0.02) and engage in less and shorter durations of moderate-vigorous-intensity PA (MVPA). For IwMG, habitual PA correlated positively with 6 min walking distance (rho = 0.387, p = 0.029) and negatively with body mass index (rho = -0.407, p = 0.019). We did not find any association between PA or sedentary behaviour and; HRQoL, symptom severity nor lower limb strength., Conclusions: Individuals with stable MG perform less PA, at lower intensities, and are more inactive than control individuals. Further research is warranted to understand factors influencing PA patterns in MG and whether interventions could be successful in increasing PA quantity and intensity in IwMG.

BackgroundIn myasthenia gravis, impaired postsynaptic sensitivity to acetylcholine results in failure of neuromuscular transmission and fatiguing muscle weakness.ObjectiveDevelop an ex vivo muscle contraction assay to test cannabinoids and other substances that might act on the myasthenic neuromuscular junction to restore control of the muscle.MethodsTubocurarine was added to an ex vivo, mouse phrenic nerve-hemidiaphragm muscle preparation to reduce acetylcholine sensitivity. This produced a myasthenia-like decrement in twitch force during a train of 10 nerve impulses (3 / sec). Endplate potential (EPP) recordings were used to confirm and extend the findings.ResultsSurprisingly, addition to the bath of dimethylsulphoxide (DMSO), at concentrations as low as 0.1%(v/v), partially reversed the decrement in nerve-evoked force. Intracellular electrophysiology, conducted in the presence of tubocurarine, showed that DMSO increased the amplitudes of both the spontaneous miniature EPP (MEPP) and the (nerve-evoked) EPP. In the absence of tubocurarine (synaptic potentials at physiological levels), an adaptive fall in quantal content negated the DMSO-induced rise in EPP amplitude. The effects of cannabinoid receptor agonists (solubilized with DMSO) in the contraction assay do not support their further exploration as useful therapeutic agents for myasthenia gravis. CP 55,940 (a dual agonist for cannabinoid receptor types 1 and 2) reversed the beneficial effects of DMSO.Conclusions:We demonstrate a powerful effect of DMSO upon quantal amplitude that might mislead pharmacological studies of synaptic function wherever DMSO is used as a drug vehicle. Our results also show that compounds targeting impaired neuromuscular transmission should be tested under myasthenic-like conditions, so as to avoid confounding effects of synaptic homeostasis.