Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy.

More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.

Current state of research on exercise for the treatment of myasthenia gravis: A scoping review.

OBJECTIVE: To provide a comprehensive overview of existing evidence, research gaps, and future research priorities concerning the treatment of myasthenia gravis (MG) using exercise therapies. METHOD: Clinical studies on exercise treatment for MG were searched in nine databases to conduct a scoping review. Two independent researchers screened the literature and comprehensively analyzed the characteristics and limitations of the included articles. RESULTS: A total of 5725 studies were retrieved, of which 24 were included. The included studies were conducted in 16 different countries/regions and 456 patients were enrolled. Study designs included both interventional and observational studies. Exercise interventions included aerobic exercise, resistance exercise, balance training, and stretch training, and are typically administered in conjunction with medication, usual care, or some other interventions. The intensity, frequency, and duration of exercise interventions varied hugely among studies. Six-minute walk test, adverse events, muscle strength, MG quality of life-15 scale, forced vital capacity, quantitative MG scale, and MG activities of daily living scale were the most frequently used outcomes. All studies reported results in favor of the efficacy and safety of exercise in MG, and exercise-related adverse events were reported in two studies. CONCLUSION: This scoping review provides an overview of the evidence concerning exercise treatment for MG. Key gaps in evidence include a limited number of participants, complex interventions, variability in outcome selection, and insufficient reporting in publications. The promotion of exercise treatment for MG still encounters several obstacles. A larger population, rigorous study design and conduction, standardized interventions and outcomes, and standardized reporting are essential.

Effects of acupuncture treatment for myasthenia gravis: A systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) of acupuncture for myasthenia gravis (MG) were searched and the efficacy of acupuncture in the treatment of MG was evaluated by meta-analysis. METHODS: We searched for RCTs in six main electronic databases, and collected RCTs of acupuncture treatment for MG from database creation to 28 February 2023. The main outcome was the effective rate and the secondary outcome was the Traditional Chinese Medicine (TCM) relative clinical score, absolute clinical score (ACS) of MG, Quantitive myasthenia gravis score (QMG), quality of life, and adverse events. Odds ratios (ORs) and weighted mean differences (WMD) and 95% confidence intervals (CI) were used to assess pooled effect estimates using Review Manager software. RESULTS: A total of 14 RCTs were included. Meta-analysis showed that the effective rate in the acupuncture group was significantly improved compared with conventional Western medicine alone [OR = 4.28, 95% CI (2.95, 6, 22), P<0.005]. The pooled WMDs revealed that TCM relative clinical score [WMD = -2.22, 95% CI = (-2.53, -1.90), P<0.005], ACS of MG [WMD = -3.14, 95% CI = (-3.67, -2.62), P<0.005], and QMG [WMD = -0.88, 95% CI = (-1.46, -0.29), P<0.005] in the acupuncture group was lower than the control group. Adverse reactions related to acupuncture and quality of life were less mentioned among included RCTs. CONCLUSION: This meta-analysis demonstrated that acupuncture as an auxiliary may play a positive role in treating MG. It can improve the effective rate of treatment, and reduce TCM relative clinical score, ACS of MG, and QMG. However, the quality of included studies was generally low and caution should be exercised when considering this treatment option. In the future, more rigorous study designs and high-quality RCTs are needed to verify the efficacy of acupuncture in the treatment of MG, because the results of high-quality RCTs are more reliable and accurate.

Effects of Qishen Dihuang Granules on Intestinal Microbiota in Experimental Autoimmune Myasthenia Gravis Model Rats.

Objective: Effects of Qishen Dihuang (QSDH) granules on intestinal flora of an experimental autoimmune myasthenia gravis (EAMG) model rat were investigated (CNBI:PRJNA910532). Methods: Thirty-six female Lewis rats were assigned to Control, EAMG, QSDH-low-dose, QSDH-medium-dose, QSDH-high-dose, and Prednisone groups using the random number table method (6 rats/group). A rat EAMG model was established by injecting Rα97-116 peptide antigen. Each day for 30 days, gavages were administered to rats in the Chinese medicine group (QSDH granules in different concentrations), Prednisone group (prednisone), and Control and Model groups (0.5% CMC). After 30-day gavages, rat fecal samples were collected and the microbial community composition and diversity differences between intestinal microbiota of EAMG and QSDH granule-treated groups were analyzed using 16S amplicon sequencing to explore the effect underlying QSDH granules alleviation of EAMG. Results: The clinical symptoms of rats in each treatment group improved significantly after the intervention treatment with QSDH granules. Comparison of the relative abundance of microorganisms in the gut flora of different groups with that of the EAMG group rats revealed: significantly lower phylum-level Bacteroidetes abundance and significantly greater Actinobacteria abundance in the QSDH-high-dose group and a significantly greater Firmicutes/Bacteroidetes ratio in the QSDH-medium-dose group; significantly increased family-level QSDH-high-dose group abundances of Lachnospiraceae and Trichospiraceae (Firmicutes), significantly increased QSDH-medium-dose group Lactobacillaceae abundance, and significantly increased QSDH-low-dose group Bacteroidaceae abundance; genus-level, QSDH-high-dose group Prevotella and Coprococcus abundances were significantly increased and Turicibacter and Lactobacillus abundances were significantly decreased, while QSDH-medium-dose group Akkermansia and Lactobacillus abundances were significantly increased. Greater overall community richness, diversity, and genetic diversity were observed in QSDH granules-treated groups, but differences were insignificant (P > .05). The most significant inter-group genus-level community marker differences involved Prevotella, Ruminococcus, Coprococcus, and Turicibacter. Conclusion: QSDH granules may regulate EAMG rat intestinal flora by decreasing relative abundances of Turicibacter and Clostridium and increasing relative abundances of Bifidobacterium, Lachnospiraceae, and Prevotella.

Preoperative respiratory muscle training combined with aerobic exercise improves respiratory vital capacity and daily life activity following surgical treatment for myasthenia gravis.

OBJECTIVE: The effects of preoperative respiratory muscle training (RMT) on postoperative complications in patients surgically treated for myasthenia gravis (MG) remain unclear. The present study therefore evaluated the effects of preoperative moderate-to-intense RMT and aerobic exercise, when added to respiratory physiotherapy, on respiratory vital capacity, exercise capacity, and duration of hospital stay in patients with MG. METHODS: Eighty patients with MG scheduled for extended thymectomy were randomly divided into two groups. The 40 subjects in the study group (SG) received preoperative moderate-to-intense RMT and aerobic exercise in addition to respiratory physiotherapy, whereas the 40 subjects in the control group (CG) received only chest physiotherapy. Respiratory vital capacity (as determined by VC, FVC, FEV1, FEV1/FVC, and PEF) and exercise capacity (as determined by the 6-min walk test [6 MWT]) were measured pre- and postoperatively and before discharge. The duration of hospital stay and activity of daily living (ADL) were also determined. RESULTS: Demographic and surgical characteristics, along with preoperative vital capacity and exercise capacity, were similar in the two groups. In the CG, VC (p = 0.001), FVC (p = 0.001), FEV1 (p = 0.002), PEF (p = 0.004), and 6MWT (p = 0.041) were significantly lower postoperatively than preoperatively, whereas the FEV1/FVC ratio did not differ significantly. Postoperative VC (p = 0.012), FVC (p = 0.030), FEV1 (p = 0.014), and PEF (p = 0.035) were significantly higher in the SG than in the CG, although 6MWT results did not differ. ADL on postoperative day 5 was significantly higher in the SG than in the CG (p = 0.001). CONCLUSION: RMT and aerobic exercise can have positive effects on postoperative respiratory vital capacity and daily life activity, and would enhance recovery after surgery in MG patients.

Biological therapies for myasthenia gravis.

INTRODUCTION: Recently, treatments for myasthenia gravis (MG) have progressed significantly. Symptoms of some patients with refractory MG are not relieved by conventional therapies, and such patients might benefit from novel biological treatments that are being developed. AREAS COVERED: We review several novel biological therapies for MG, such as complement inhibitors, neonatal Fc receptor inhibitors, anti-B cell drugs, and IL-6 receptor inhibitors. We also report the modes of action, efficacy, safety, and tolerability of these drugs. EXPERT OPINION: Several biological therapies have been developed for MG, and these biologics are promising agents for treating refractory MG. Establishing biomarkers and accumulating evidence of therapeutic response is required to provide the most appropriate biological treatment for each patient.

Percutaneous Electrical Nerve Stimulation (PENS) for Infrapatellar Saphenous Neuralgia Management in a Patient with Myasthenia gravis (MG).

Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness of the cranial and skeletal muscles, however, neuropathies are extremely rare. In this case report we present a case of a 61-year-old man diagnosed Myasthenia gravis who came to our attention due to a 1 week of acute deep pain [NPRS 8/10] in the anterior and medial right knee which occurred during walking [NPRS 8/10] or stair climbing [NPRS 9/10]. A complete medical record and clinical examination based on physical exploration and ultrasound assessment confirmed a infrapatellar saphenous neuralgia. Therapeutic interventions included Percutaneous nerve electrical stimulation combined with pain neuroscience education, neural mobilization of the saphenous nerve and quadriceps resistance exercises. After 4 weeks, pain intensity [NRPS = 1/10], knee functionality [OKS = 41/48] and lower limb functionality [LLFI = 80%] were notably improved, nevertheless, fatigue [RPE = 2/10] was similar than baseline. At 2 months of follow-up, the effect on intensity of pain NRPS [0/10] and functionality OKS [40/48] and LLFI [82%] was maintained, however, no significant clinical changes were detected on perceived fatigue RPE Scale [2/10]. Despite the important methodological limitations of this study, our case report highlights the efficacy of percutaneous electrical nerve stimulation combined with physical agents modalities for pain and functionality of infrapatellar saphenous neuralgia in the context of Myasthenia gravis.

Evidence for genetic causal relationships between gut microbiome, metabolites, and myasthenia gravis: a bidirectional Mendelian randomization study.

Background: Myasthenia gravis (MG) is an autoimmune disease observed to have connections with gut microbiome. We aimed to systematically assess the causal relationships between gut microbiome, gut microbiome-derived metabolites, and MG using Mendelian randomization (MR) approach. Methods: Summary-level genetic datasets from large-scale genome-wide association studies regarding 196 gut microbial taxa from the MiBioGen consortium (n=18,340), 72 derived metabolites from the TwinsUK and KORA studies (n=7,824), and antiacetylcholine receptor (AChR) antibody-positive MG (case=1,873, control=36,370) were employed for MR causal estimates. The inverse-variance weighted (IVW) method was utilized as the main analysis with MR-Egger, maximum likelihood, simple mode, and weighted median as complements. The tests of Cochran's Q, MR-Egger intercept, Steiger, MR-PRESSO and leave-one-out were implemented for sensitivity analyses. Results: The forward MR estimates of IVW revealed significant causal associations of the abundance of phylum Actinobacteria, class Gammaproteobacteria, family Defluviitaleac, family Family XIII, and family Peptococcaceae with a reduced risk of MG. Conversely, the abundance of phylum Lentisphaerae, order Mollicutes RF9, order Victivallales, and genus Faecalibacterium was causally associated with an increased risk of MG. The reversed MR analysis proved negative causal correlations between the MG and the abundance of family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum. Regarding the derived metabolites, the IVW estimates revealed that elevated levels of beta-hydroxyisovalerate and methionine were causally associated with a decreased risk of MG, while increased levels of choline and kynurenine were linked to an increased risk of MG. Furthermore, genetically predicted MG was associated with a decreased level of cholesterol. The results obtained from complementary MR methods were similar. These findings remained robust in all sensitivity analyses. Conclusion: Our MR findings support the causal effects of specific gut microbiome taxa and derived metabolites on AChR antibody-positive MG, and vice versa, yielding novel insights into prevention and therapy targets of MG. Future studies may be warranted for validation and pursuing the precise mechanisms.

Invigorating spleen, replenishing qi and tonifying kidney method treatment of traditional Chinese medicine for myasthenia gravis: A protocol for systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease related to the production of autoantibodies. It is mediated by antibodies against acetylcholine receptor (AChR), muscle specific kinase (MuSK) or other AChR related proteins in the postsynaptic muscle membrane, which interfere with the transmission of signals at the neuromuscular junction, resulting in clinical symptoms of skeletal muscle weakness and fatigue, leading to the occurrence and development of MG. At present, the incidence rate of Mg is increasing year by year. At present, the method of invigorating spleen, replenishing qi and tonifying kidney in traditional Chinese medicine has been widely used in the clinical treatment of MG, and the effect is good. The purpose of this study was to systematically evaluate the efficacy and safety of the method of invigorating the spleen, supplementing qi and tonifying the kidney in the treatment of MG. METHODS: We will search from the following eight databases: PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Sinomed, Wanfang, and Vip. All randomized controlled trial (RCT) literature has been searched and classified since the establishment of the database to date. In this study, two researchers independently screened and evaluated the quality of the retrieved literature. Cochrane risk bias assessment tool was used to evaluate the risk of bias. The meta-analysis uses RevMan 5.3 software provided by Cochrane Collaboration Network for meta analysis. RESULTS: This study compared the main outcome indicators: clinical response rate, recurrence rate, incidence of adverse reactions, quantitative myasthenia gravis score (QMG). Secondary outcomes were clinical absolute score, quality of life score (QOL), levels of inflammatory factors such as IL-6, IL-10, and serum acetylcholine receptor antibody (AChR-Ab) levels. CONCLUSION: The purpose of this study was to evaluate the efficacy and safety of the method of invigorating the spleen, supplementing qi and tonifying the kidney in treating MG, and to provide evidence based medicine.

Effect of treatment with Fufang Huangqi decoction on dose reductions and discontinuation of pyridostigmine bromide tablets, prednisone, and tacrolimus in patients with type I or II myasthenia gravis.

OBJECTIVE: To investigate the clinical efficacy of Fufang Huangqi decoction in combination with pyridostigmine bromide tablets, prednisone, and tacrolimus in the treatment of type I and II myasthenia gravis (MG) through changes in the clinical symptom scores of 100 patients with type I and II MG. This study also aimed to examine dose reductions and dis-continuation of these 3 Western medicines after administration of Fufang Huangqi decoction. METHODS: The clinical data on 100 patients with type I or II MG who were treated in the outpatient department of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China, between June 2017 and June 2020 were collected. The patients were divided into 4 groups based on whether they had taken pyridostigmine bromide tablets, prednisone, and/or tacrolimus at the time of their hospital visit: the Fufang Huangqi decoction group (group A), the pyridostigmine bromide tablets + Fufang Huangqi decoction group (group B), the pyridostigmine bromide tablets + prednisone + Fufang Huangqi decoction group (group C), and the pyridostigmine bromide tablets + tacrolimus + Fufang Huangqi decoction group (group D). The average treatment time was (15.6 ± 11.5) months (range: 0.5-55 months). Changes in the clinical symptom scores of the 4 groups of patients after medication administration and dose reductions and discontinuation of the 3 Western medicines were analyzed. RESULTS: An overall effectiveness rate of 86.00% was achieved in the 100 patients after treatment for (15.6 ± 11.5) months (range 0.5-55 months). The effectiveness rates were 85.71% in group A, 88.24% in group B, 76.92% in group C, and 80.00% in group D. The dosage of pyridostigmine bromide was reduced for 69.12% of the patients in group B for the first time after (4.2 ± 4.1) months, and 45.59% of the patients in group B discontinued pyridostigmine bromide after (8.8 ± 6.1) months. The dosage of pyridostigmine bromide was reduced for 46.15% of the patients in group C for the first time after (5.3 ± 3.4) months, and 23.08% of the patients in group C discontinued pyridostigmine bromide after (19.8 ± 11.0) months; 76.92% reduced hormone dosage after (2.8 ± 1.9) months, and 23.08% discontinued hormone treatment after (6.7 ± 2.9) months. The dosage of pyridostigmine bromide was reduced for 1 patient in group D after 1 month; this patient discontinued pyridostigmine bromide after 3 months and reduced tacrolimus dosage after 5 months. One patient in group D discontinued pyridostigmine bromide and tacrolimus on his own initiative at 0.5 months and took Fufang Huangqi decoction for 2 months without discontinuing Western medicine. CONCLUSION: Fufang Huangqi decoction is effective for the treatment of type I and II MG and improves the associated clinical symptoms. Moreover, this agent is conducive to dose reductions and discontinuation of basic Western medicines, thereby reducing the side effects experienced by patients.

[Acupuncture combined with western medication for ocular myasthenia gravis: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism. METHODS: A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 µs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method. RESULTS: After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 µs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05). CONCLUSION: Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.

Giant cell myositis associated with metastatic thymoma and granulomatous hypercalcaemia.

Giant cell myositis (GCM) is a rare inflammatory myopathy associated with myasthenia gravis and thymoma. Here, we report on a woman in her late 50s with a history of myasthenia gravis, systemic lupus erythematosus and stage IV thymoma with pleural metastases, who presented with proximal weakness, neuromuscular respiratory failure and hypercalcaemia. She was diagnosed with GCM via muscle biopsy and screened for myocarditis but showed no evidence of myocardial involvement. Her hypercalcaemia was consistent with a granulomatous process, likely driven by her GCM. Her strength gradually improved, and her hypercalcaemia did not recur after treatment with high dose steroids, intravenous immune globulin and plasma exchange. Her course was complicated by several opportunistic infections in the setting of her immunosuppression. Despite the high morbidity associated with GCM, she demonstrated clinical improvement after initiating immunosuppressive therapy and continues to be managed in the outpatient setting.

Effectiveness of modified Buzhong Yiqi decoction in treating myasthenia gravis: study protocol for a series of N-of-1 trials.

BACKGROUND: Myasthenia gravis (MG) is an acquired autoimmune disease with high heterogeneity. The disease is chronic, relapsing repeatedly and progressive with acute exacerbation occasionally. Although the treatment of MG has developed, it is still unsatisfactory and has some unexpected side effects. Traditional Chinese medicine (TCM) has shown great potential in MG treatment, including relief of muscle weakness syndrome, improvement of patient's quality of life, and reduction of side effects of western medicine. The purpose of this study is to evaluate the effectiveness of modified Buzhong Yiqi decoction (MBYD) as an add-on therapy for MG through a small series of N-of-1 trials. METHODS: Single-centre, randomized, double-blind, 3 crossover N-of-1 trials will be conducted to enroll patients with MG diagnosed as spleen-stomach deficiency syndrome or spleen-kidney deficiency syndrome in TCM. Each N-of-1 trial has 3 cycles of two 4-week periods containing the MBYD period and placebo period. The wash-out interval of 1 week is prior to switching each period. PRIMARY OUTCOME: quantitative myasthenia gravis (QMG). SECONDARY OUTCOMES: the following scales: myasthenia gravis composite (MGC), myasthenia gravis activities of daily living profile (MG-ADL), myasthenia gravis quality of life (MG-QOL); the level of CD4+FoxP3+Treg cells and cytokines (IL-4, IL-17A, INF-γ, TGF-ß) in the peripheral blood; the alterations of the composition of gut microbiota; reduction of the side effects of western medicine. DISCUSSION: Used by WinBUGS software, we will conduct a hierarchical Bayesian statistical method to analyze the efficacy of MBYD in treating MG in individuals and populations. Some confounding variables such as TCM syndrome type and potential carryover effect of TCM will be introduced into the hierarchical Bayesian statistical method to improve the sensitivity and applicability of the trials, and the use of prior available information within the analysis may improve the sensitivity of the results of a series of N-of-1 trials, from both the individual and population level to study the efficacy of TCM syndrome differentiation. We assumed that this study would reveal that MBYD is effective for MG and provide robust evidence of the efficacy of TCM to treat MG. TRIAL REGISTRATION: Chinese Clinical Trial Register, ID: ChiCTR2000040477 , registration on 29 November 2020.

Epidemiological profile of myasthenia gravis in South Korea using the national health insurance database.

OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue. Our objective was to investigate the incidence of MG using the National Health Insurance database of South Korea. MATERIALS AND METHODS: We conducted a retrospective cohort analysis of patients with the G70.0 code designated as MG and administered with MG medications for >3 months from 2007 to 2018 using nationwide data from South Korea. RESULTS: A total of 8,376 patients with MG during the period of 2010-2018 were identified. There were 3,862 (46.1%) male and 4,517 (53.9%) female patients. The standardized incidence rate was 1.18/100,000 in 2010, and increased to 1.81/100,000 in 2018. The standardized prevalence was 7.50/100,000 in 2010, and changed to 11.15/100,000 in 2018. Pyridostigmine was used to treat 82.3 ± 1.2% of patients with MG during 2010-2018. Among MG patients, 85.7 ± 0.9% used steroids, 31.6 ± 4.8% used azathioprine, 12.9 ± 9.5% used tacrolimus, 7.2 ± 2.1% used cyclosporine, 6.2 ± 1.8% used mycophenolate mofetil, and 0.4 ± 0.1% used methotrexate. Thymectomy was performed in 1,130 MG patients, and the time from MG diagnosis to thymectomy decreased from 2010 to 2018. CONCLUSION: Based on the national registry data from 2010 to 2018, the incidence and prevalence rate in South Korea has increased. Whereas the use of IVIG has remained stable, thymectomy is performed earlier than before, and the distribution of immunosuppressant therapies has changed over the years with an increase in tacrolimus and mycophenolate mofetil. We expect that this study will serve as a basis for future South Korean MG epidemiological studies.

Treatment of myasthenia gravis with the method of tonifying spleen and replenishing qi in traditional Chinese medicine: A protocol for systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease that is associated with the production of autoantibodies. The symptoms of MG are mainly mediated by pathogenic antibodies directed against nicotinic acetylcholine receptors, resulting in a decrease in the number of acetylcholine receptors molecules on the postsynaptic membrane of the neuromuscular junction endplate, leading to clinical symptoms of muscle fatigue and weakness. At present, traditional Chinese medicine (TCM) treatment of MG has a better effect by tonifying spleen and replenishing qi. The purpose of this study was to systematically evaluate the efficacy and safety of TCM therapy for tonifying spleen and replenishing qi in the treatment of myasthenia gravis. METHODS: We searched the following databases from their establishment until December 2021: PubMed, Cochrane Library, EMBASE, Web of Science, Springer, CNKI, Wanfang, China Biomedical Database, China Science and Technology Journal Database, Chinese Knowledge Infrastructure, China Clinical Trial Registry, and Baidu Scholars. The literature search language was limited to Chinese and English, and publication time and status were not limited. Randomized controlled trials (RCTs) were included. Two researchers independently searched and screened the articles, assessed their quality, and used the RevMan 5.4.1 software to perform a meta-analysis of the included literature. RESULTS: This study compared the main outcome indicators: efficacy rate, recurrence rate, quality of life, and quantitative myasthenia gravis (QMG). Secondary outcome indicators were the clinical absolute score, TCM syndrome score, serum acetylcholine receptor antibody level, and electromyogram low-frequency repetitive nerve stimulation. CONCLUSION: This study aimed to evaluate whether the TCM method of tonifying spleen and replenishing qi is effective in the treatment of MG and to provide evidence-based data. ETHICS AND DISSEMINATION: The protocol of the systematic review did not require ethical approval because it did not involve human subjects. This article will be published in peer-reviewed journals and will be presented at conferences.

Effects of Natural Products on Neuromuscular Junction.

Neuromuscular junction (NMJ) disorders result from damage, malfunction or absence of one or more key proteins involved in neuromuscular transmission, comprising a wide range of disorders. The most common pathology is antibody-mediated or downregulation of ion channels or receptors, resulting in Lambert-Eaton myasthenic syndrome, myasthenia gravis, and acquired neuromyotonia (Isaac's syndrome), and rarely congenital myasthenic syndromes caused by mutations in NMJ proteins. A wide range of symptomatic treatments, immunomodulating therapies, or immunosuppressive drugs have been used to treat NMJ diseases. Future research must be directed at a better understanding of the pathogenesis of these diseases, and developing novel disease-specific treatments. Numerous secondary metabolites, especially alkaloids isolated from plants, have been used to treat NMJ diseases in traditional and clinical practices. An ethnopharmacological approach has provided leads for identifying new treatments for NMJ diseases. In this review, we performed a literature survey in Pubmed, Science Direct, and Google Scholar to gather information on drug discovery from plant sources for NMJ disease treatments. To date, most research has focused on the effects of herbal remedies on cholinesterase inhibitory and antioxidant activities. This review provides leads for identifying potential new drugs from plant sources for the treatment of NMJ diseases.

Severe complications and management of a patient with myasthenia gravis undergoing anterior cervical spinal surgery: a case report.

Surgical management of patients with comorbid long-term myasthenia gravis (MG) is particularly challenging and MG thus represents an independent risk factor for perioperative complications. However, few studies have reported on the perioperative assessment, prevention measures, and risks in MG patients undergoing major surgery, especially for anterior cervical spine surgery. We herein report the rare case of a 62-year-old man with a 20-year history of MG, who was admitted to our hospital with diagnosis of degenerative cervical spondylosis. He safely underwent anterior cervical corpectomy of C4, discectomy of C5-6, and fusion of C3-6. Intraoperative motor evoked potential was recorded to detect significant improvement after decompression. However, the patient suffered from progressive dysphagia, bucking, and hyperpyrexia 20 days after the initial operation. Imaging revealed titanium cage sliding and graft dislodgement. Secondary surgery was performed for posterior internal fixation from C2-7 and anterior revision from C3-6 after Halo-Vest traction, antibiotic treatment, and immunoglobulin therapy. He underwent a series of postoperative treatments, including cervicothoracolumbosacral orthosis, atomization inhalation, chest physiotherapy, antibiotics, and nutritional support. His condition improved markedly and he had no recurrence of symptoms during the 6-month follow-up. It is the rare reported case of anterior cervical spinal surgery in a patient with MG. This rare case indicates a relative contraindication to anterior-only approaches especially with multiple levels for MG patients with cervical spondylosis. Posterior approach, intraoperative monitoring, osteoporosis, postoperative strong brace protection, and supportive management should be considered for patients who were on large doses of steroids for long duration of time, given the lack of sufficient bone mineral density.

High-dose vitamin C therapy for symptomatic deficiency in a patient with myasthenia gravis and Crohn's disease.

Vitamin C (ascorbic acid) is an essential water-soluble antioxidant, and deficiency (ie, plasma level <11 µmol/L) can result in scurvy. People at the highest risk for vitamin C deficiency (ie, scurvy) are those with inadequate intake, such as patients with alcohol abuse disorder, malnutrition, psychiatric disorders, restrictive eating habits, and food insecurity, as well as those with malabsorptive syndromes. We present a case of a 26-year-old woman with Crohn's colitis, myasthenia gravis, and juvenile rheumatoid arthritis who presented with frequent bruising, epistaxis, and excessive bleeding from small cuts and who was found to be deficient in vitamin C. Plasma levels initially normalized with oral vitamin C supplementation, but bleeding symptoms eventually returned despite high-dose oral supplementation with 2000 mg daily. She ultimately required routine intravenous supplementation in the home setting for the normalization of levels and the resolution of symptoms. Case reports of vitamin C deficiency typically involve patients with an inadequate intake of vitamin C-containing foods or inadequate absorption. In contrast, our patient reported a regular intake of vitamin C-containing foods, in addition to oral supplementation, but continued to have difficulty maintaining normal vitamin C levels. Scurvy should be considered for any patient with symptoms of bleeding, petechiae, or ecchymosis and, although it can typically be treated with oral vitamin C, intravenous repletion may be necessary in some cases.

Myasthenia gravis: The pharmacological basis of traditional Chinese medicine for its clinical application.

We aimed to investigate the target and signal pathway of Smilacis Glabrae Rhixoma (SGR) in the treatment of myasthenia gravis (MG) based on network pharmacology, and to explore its potential molecular mechanism. The main active components of SGR were searched in the pharmacology database of traditional Chinese medicine systems, and analysis platform. The related targets of SGR were obtained by Genecards, connective tissue disease, therapeutic target database, Drugbank, and Online Mendelian Inheritance in Man database. Moreover, the target information was corrected through UniProtKB and also, this data integrated to draw the "Ingredients-targets" network of SGR. Protein interaction analysis was performed in data platform, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways as well as enrichment analysis on disease-drug target was carried out through metascape online platform. A total of 15 active components were collected from SGR, which correspond to 159 targets; There were 1758 MG-related targets; there are 81 targets related to both drug components and diseases, including 12 key targets. In GO bioaccumulation analysis, 1933 GO items were gathered, which were mainly related to the metabolism of active oxygen species and the active factors of postsynaptic neurotransmitter receptor. According to KEGG analysis, SGR may play a role in the treatment of MG through phosphatidylinositol-3-kinase-protein kinase B signaling pathway, T-cell receptor, cAMP, tumor necrosis factor (TNF), and interleukin-17 (IL-17) signaling pathway, Th17 cell differentiation, endocrine resistance, hepatitis, and some cancer pathways. This study shows that SGR mainly treat myasthenia gravis through the regulation of TNF, MAPK1, JUN, TP53 and other targets, T-cell receptor, TNF, and IL-17 signaling pathway, Th17 cell differentiation and other pathways, which reflects the characteristics of multicomponent, multitarget, and multichannel of traditional Chinese medicine, and providing a certain pharmacological basis for the follow-up study.

Acupuncture combined with western medication for ocular myasthenia gravis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism.@*METHODS@#A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 μs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method.@*RESULTS@#After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 μs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05).@*CONCLUSION@#Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.