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.

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.

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.

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.

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.

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.

Effect of Buzhong Yiqi decoction on anti-acetylcholine receptor antibody and clinical status in juvenile ocular myasthenia gravis.

ABSTRACT: Ocular myasthenia gravis (MG) is the mainly widespread type of MG among juveniles. Buzhong Yiqi decoction (BZ) is a well-known traditional Chinese medicine prescription for treating MG. It has rarely been discussed whether the concentration of anti-acetylcholine receptor (AChR) antibodies is related to the clinical status of juvenile ocular myasthenia gravis (JOMG) treated with BZ.The patients with JOMG who had more than once AChR-antibody (ab) test and treated with BZ were retrospectively identified from June 2013 to January 2020 in the first hospital in Shijiazhuang. The presence or absence of ocular symptoms was used to grade the effectiveness of treatment. Generalized estimating equations logistic regression analysis was used to evaluate the effect of AChR ab concentration on the clinical status of MG.A total of 549 AChR-ab tests were performed in 135 patients, and the corresponding clinical status was recorded. One hundred two patients received treatment with BZ only and 33 combined with immunosuppressive drugs. In the group receiving only BZ treatment, the anti-acetylcholine receptor ab concentration was positively correlated with the clinical score after treatment.The results suggest that BZ could affect the AChR-ab. Repeated AChR-ab assays can provide information about the clinical status. For JOMG patients who only receive Buzhong Yiqi Decoction treatment, this can support treatment decisions.

Efficacy and safety of Buzhong Yiqi decoction combined with western medicine in the treatment of myasthenia gravis: A protocol for systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis is a common autoimmune disease in clinic. Although there are various ways and drugs for the treatment of myasthenia gravis in Western medicine, there are still a variety of adverse reactions. Studies have shown that Buzhong Yiqi decoction combined with Western medicine has a certain efficacy in the treatment of myasthenia gravis, but there is a lack of evidence-based medicine. The research carried out in this scheme is to systematically evaluate the efficacy and safety of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis, and to provide reliable evidence for guiding clinical practice. METHODS: English databases (the Cochrane Library, PubMed, Web of Science, Embase) and Chinese databases (China Biomedical Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang) will be searched by computer. In addition, Baidu Academic and Chinese Clinical Trial Registration Center will be searched manually. A randomized controlled clinical trial of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis will be conducted from the establishment of the database to December 2020. The 2 researchers independently carry out data extraction and literature quality evaluation on the quality of the included study, and meta-analysis of the included literature will be carried out by using RevMan 5.3 software. RESULTS: This study will evaluate the efficacy and safety of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis by Quantitive MGscore, the number of Tregs cells and the content of anti-acetylcholine receptor antibody (AchR-Ab). CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of Buzhong Yiqi decoction combined with Western medicine in the treatment of myasthenia gravis. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/MXUPK.

The history of acetylcholinesterase inhibitors in the treatment of myasthenia gravis.

The beneficial effects of acetylcholinesterase inhibitors for the treatment of myasthenia gravis (MG) was a major discovery that came about through one young physician putting together a string of previous observations. To understand how this discovery came to light, we must first go back to earlier times when men hunted by bow-and-arrow to capture their prey. The substance used to poison the prey was eventually was identified as curare. Centuries later, a connection was made between the physiological effects of curare and a disease entity with no known pathological mechanism or treatment, myasthenia gravis. In 1935, house officer Dr. Mary Walker was the first physician to try physostigmine in the treatment of MG, which had previously been used to treat curare poisoning. What she saw was a dramatic improvement in the symptoms experienced in patients with MG, and thus became the first documented case of use of physostigmine, an acetylcholinesterase inhibitor, in the treatment of MG. This article is a summary of the history of the use of acetylcholinesterase inhibitors in the treatment of myasthenia gravis. This article is part of the special issue entitled 'Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield'.

Therapeutic efficacy and immunoregulatory effect of Qiangji Jianli Capsule for patients with myasthenia gravis: Study protocol for a series of randomized, controlled N-of-1 trials.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease in which antibodies directly target components of the neuromuscular junction, causing neuromuscular conduction damage that leads to muscle weakness. The current pharmaceutical treatment for MG is still not ideal to address the problems of disease progression, high recurrence rate, and drug side effects. Clinical observations suggest that traditional Chinese medicine (TCM) can strengthen immunity and improve symptoms of MG patients, delay the progression of the disease, reduce or even prevent the need for immunosuppressive therapy when used in combination with acetylcholinesterase inhibitors or low-dose prednisone, as well as improve the quality of life of patients. The Qiangji Jianli Capsule (QJC) is a combination of medicinal herbs which is used in traditional Chinese medicine. Since MG is a rare disorder, randomized controlled trials comparing large cohorts are difficult to conduct. Therefore, we proposed to aggregate data from a small series of N-of-1 trials to assess the effect of the Chinese medical prescription QJC, which strengthens the spleen and nourishes Qi, as an add-on treatment for MG with spleen and stomach Qi deficiency syndrome. METHODS AND ANALYSIS: Single-center, randomized, double-blind, multiple crossover N-of-1 studies will compare QJC versus placebo in 5 adult MG patients with spleen and stomach Qi deficiency syndrome. Patients will undergo 3 cycles of two 4-week intervention periods. According to the treatment schedule, patients will continue to be treated with pyridine bromide tablets, prednisone acetate, tablets and/or tacrolimus capsules throughout the entire trial. Each period consisting of 4-week oral add-on treatment with QJC will be compared with 4-week add-on treatment with a placebo. The primary endpoints are quantitative myasthenia gravis (QMG) test; measurement of the amount of Treg cells and cytokines such as interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), and transforming growth factor-ß (TGF-ß); and corticosteroid or immunosuppressive agent dosage. Secondary outcome measures: Clinical: Evaluation of the effect of TCM syndromes; MG-activities of daily living (MG-ADL) scales; adverse events. ETHICS AND DISSEMINATION: This study was approved by The First Affiliated Hospital of Guangzhou University of Chinese Medicine (GZUCM), No. ZYYECK[2019]038. The results will be published in a peer-reviewed publication. Regulatory stakeholders will comment on the suitability of the trial for market authorization and reimbursement purposes. Trial registration: Chinese Clinical Trial Register, ID: ChiCTR2000033516. Registered on 3 June 2020, http://www.chictr.org.cn/showprojen.aspx?proj=54618.

Traditional Chinese medicine for myasthenia gravis: Study protocol for a network meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is a disease that is difficult to cure, mainly manifested in the affected skeletal muscle weakness and morbid fatigue, which seriously affects the patients' daily life and work. A large number of randomized controlled trial have shown that Traditional Chinese medicine (TCM) has a good effect in treating MG. However, due to the variety of TCM treatment methods, its relative effectiveness and safety have not been verified. Therefore, this study will use a network meta-analysis method to verify the effectiveness and safety of different types of TCM in the treatment of MG. METHODS: We will search the following databases from inception to June 2020: the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, Pubmed, Embase, Web of Science, and the Cochrane library. Collect all randomized controlled trial of TCM for the treatment of MG, The 2 authors will independently select studies and extract data based on pre-designed inclusion and exclusion criteria. Methodological quality assessment and risk of bias will be assessed using Cochrane bias risk tool. All data analysis will be conducted using Revman5.3, WinBUGS 1.4.3, and Stata14.2 software. RESULTS: This study will directly and indirectly compare the different outcome indicators of various studies, and rank the effectiveness of different TCM methods. The main outcome indicators include effectiveness, remission rate (no drug symptoms), relapse rate, clinical absolute score, and relative score. Secondary outcome indicators: including any related adverse reactions, the concentration of acetylcholine receptor antibody in serum. CONCLUSION: The conclusion of this systematic review will provide credible Evidence-based for the relative advantages of different TCM treatment methods for MG.

Modified Buzhong Yiqi decoction for myasthenia gravis: A systematic review protocol.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by the transmission of dysfunction in the neuromuscular junction, manifesting partial or systemic skeletal muscle weakness and fatigue, which are exacerbated by activities and relieved after rest. Currently, the conventional therapy is applying cholinesterase inhibitors, steroids, immunosuppressant, and thymectomy. However, these drugs have obvious side effects. According to traditional Chinese medicine (TCM) theory, Buzhong Yiqi decoction (BYD) is a Qi-supplementing formula which is suitable for MG management as MG is generally diagnosed as "flaccidity syndrome" and considered caused by Qi-deficiency. An increasing number of clinical controlled studies also have found that BYD could improve the efficacy and reduced adverse effects in treating MG, but there is no systematic review of it. Therefore, we will use meta-analysis to evaluate the efficacy and safety of BYD for MG. METHODS: PubMed, MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Scientific Journals Database (VIP), and China biomedical literature database (CBM) will be searched to obtain the eligible studies published up to June 1, 2018. The primary outcome will be clinical absolute score before and after treatment, clinical relative score as well as effective rate. The secondary outcome will be the concentration of acetylcholine receptor antibody (AchRAb) in serum and adverse events incidence. Data analysis will be conducted using RevMan5.3 and Stata V.9.0 software. Trial sequential analysis (TSA) will be performed to assess the risk of random error and the validity of conclusion using TSA program version 0.9 beta. RESULTS: This systematic review will provide a high-quality synthesis of BYD and its modified forms for MG from various evaluation aspects including clinical absolute score before and after treatment, clinical relative score, effective rate, the concentration of AchRAb in serum and adverse events incidence. CONCLUSION: The systematic review will provide evidence to assess the efficacy and safety of BYD and its modified forms in the treatment of MG. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018095241.

Treatment of Myasthenia Gravis With High-Dose Cholinesterase Inhibitors and Calcineurin Inhibitors Caused Spontaneous Muscle Cramps in Patients.

OBJECTIVES: The objective of this study was to investigate the influence of treatment with cholinesterase inhibitors (ChEIs) and calcineurin inhibitors (CNIs) on the occurrence of cramps in myasthenia gravis (MG) patients. METHODS: The frequency and duration of cramp and serum electrolytes were evaluated in 81 patients with MG. The patients were classified using Myasthenia Gravis Foundation of America postintervention status scores based on the treatment and the responsiveness to the treatment. Quantitative MG score, MG activities of daily living score, MG composite score, or MG quality of life 15 score was used to assess the health-related quality of life (QOL). RESULTS: Muscle cramps developed in 44 (54.3%) of 81 MG patients. The scores of MG activities of daily living, MG composite, or MG-QOL 15-item questionnaire in patients with cramp were significantly higher than those in patients without cramps (P = 0.002, P = 0.01, or P = 0.0022, respectively). The serum magnesium concentrations were lower in patients treated with CNI (n = 16) than in those not treated with CNI (n = 65) (P = 0.002). The probability of cramps was significantly higher in patients treated with ChEIs (≥180 mg/d) in addition to CNI than in patients who were treated with a low dose of ChEIs (≤60 mg/d) without concomitant CNI treatment (P = 0.017). CONCLUSIONS: Our data suggested that treatment with a high dose of ChEI and CNI accelerated the probability of cramps and reduced the QOL in MG patients.

Effect of Qiangji Jianli decoction on mitochondrial respiratory chain activity and expression of mitochondrial fusion and fission proteins in myasthenia gravis rats.

Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by the production of antibodies against acetylcholine receptors (AChRs). Qiangji Jianli (QJJL) decoction is an effective traditional Chinese medicine (TCM) that is used to treat MG. Our study aimed to investigate the effect of QJJL decoction on MG and to clarify the mechanism by which QJJL regulates mitochondrial energy metabolism and mitochondrial fusion and fission (MFF). SPF female Lewis rats were administered Rat 97-116 peptides to induce experimental autoimmune myasthenia gravis (EAMG). The treatment groups received QJJL decoction (7.8 g/kg, 15.6 g/kg and 23.4 g/kg). Mitochondria were extracted from gastrocnemius tissue samples to detect respiratory chain complex enzymatic activity. Quantitative PCR and western blot analysis were performed to detect Mfn1/2, Opa1, Drp1 and Fis1 mRNA and protein expression, respectively, in the mitochondria. Transmission electron microscopy examination was performed to show the improvement of mitochondria and myofibrils after QJJL treatment. The results indicated that QJJL decoction may attenuate MG by promoting the enzymatic activity of respiratory chain complexes to improve energy metabolism. Moreover, QJJL decoction increased Mfn1/2, Opa1, Drp1 and Fis1 mRNA and protein expression to exert its curative effect on MFF. Thus, QJJL decoction may be a promising therapy for MG.

Manejo odontológico del paciente con Miastenia Gravis / Dental treatment in patients with myasthenia gravis

La miastenia gravis es el trastorno neuromuscular más frecuente caracterizado por una afectación en la transmisión del impulso nervioso que repercutirá directamente en el tratamiento odontológico del paciente. Tiene gran importancia en odontología por su clínica, ya que afecta a la musculatura facial y masticatoria por lo que se deberá seguir un protocolo de actuación. El odontólogo deberá tener conocimiento de las interacciones y efectos secundarios medicamentosos para poder evitarlos durante el procedimiento, ya que estos pueden dar lugar a una crisis miasténica que acabe con la vida del paciente (AU)

Myasthenia gravis is the most common neuromuscular disorder characterized by an affection in the transmission of the nerve impulse that will directly affect the dental treatment of the patient. It is of great importance in dentistry because of its clinical manifestations, as it affects the facial and masticatory musculature, so a protocol of action should be followed. The dentist must be aware of the interactions and side effects of the medication in order to avoid them during the procedure, as these can lead to a myasthenic crisis that could kill the patient (AU)

Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment.

BACKGROUND: Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission. CASE REPORT: This is a case report of a patient with severe and refractory myasthenia gravis (MG) who followed a "high-dose vitamin D treatment", a massive-dose treatment (80,000 to 120,000 IU/day) promoted by a medical center in Brazil (but still not proven), and she had her first complete remission after this type of treatment with increased vitamin D serum levels (400 to 700 ng/mL). CONCLUSIONS: This case report may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double-blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases.