Perioperative cardiac risks in myasthenia gravis

Myasthenia gravis(MG)is an autoimmune disorder that affects the neuromuscular junction.The primary pathology in MG involves the presence of autoantibodies to acetylcholine receptors(AChRs),which results in qualitative and quantitative reductions in the availability of functional AChRs.Cardiac muscles are also affected,resulting in various perioperative cardiac complications.Antistriational antibodies are commonly reported in MG cases with cardiac involvement.In the presence of thymoma,the prevalence of cardiac manifestations in patients with MG increases to approximately 10%-15%.Cardiac involvement in MG may range from asymptomatic electrocardiogram changes to ventricular tachycardia,myocarditis,conduction disorders,heart failure,and sudden death.Increased incidence of atrial fibrillation,ventricular and supraventricular extra systoles,and prolonged QTc have also been reported in patients with MG.Clinicians should consider the evaluation of autonomic dysfunction and risk of cardiovascular disease in patients with MG.

Cardiac implications in myasthenia gravis

This editorial aimed to consolidate the current evidence in literature on the association between myasthenia gravis(MG)and cardiac involvement,focusing on the impact of thymoma,antistriational antibodies,and late-onset MG.Additionally,the study aimed to explore the influence of genetic differences among populations on the association with cardiac disease.We conducted a review of existing literature in PubMed and Google Scholar to find relevant studies on cardiac involvement in MG.We created search criteria using a combination of free text words,including MG,antistriational antibodies,thymectomy,cardiomyopathy,myocarditis,arrhythmias,autonomic dysfunction.Relevant articles published in English language were analyzed and incorporated.The findings indicate a strong association between thymoma,myasthenic crisis,antistriational antibodies,and late-onset MG with cardiac involvement.The study also revealed that genetic differences among populations influence the risk of cardiac disease and electrocardiography(ECG)abnormalities in MG patients.Autonomic dysfunctions altered cardiac autonomic response and increased susceptibility to arrhythmias and sudden cardiac death in MG patients.The study supports the significance of thymoma,antistriational antibodies,and late-onset MG as key factors associated with cardiac involvement in MG patients.It emphasizes the importance of ECG as the initial test in managing MG patients,particularly in the perioperative period,to identify and genetic testing if needed to address their cardiac risk effectively.

FcRn inhibitors:a novel option for the treatment of myasthenia gravis

Myasthenia gravis is an acquired,humoral immunity-mediated autoimmune disease characterized by the production of autoantibodies that impair synaptic transmission at the neuromuscular junction.The intervention-mediated clearance of immunoglobulin G(IgG)was shown to be effective in controlling the progression of the disease.The neonatal Fc receptor(FcRn)plays a key role in prolonging the serum half-life of IgG.Antagonizing FcRn to prevent its binding to IgG can accelerate the catabolism of the latter,resulting in decreased levels of IgG,including pathogenic autoantibodies,thereby achieving a therapeutic effect.In this review,we detail the substantial research progress,both basic and clinical,relating to the use of FcRn inhibitors in the treatment of myasthenia gravis.

Intraoperative cardiogenic shock induced by refractory coronary artery spasm in a patient with myasthenia gravis: A case report

BACKGROUND Coronary artery spasm(CAS)is a rare but critical condition during surgery.Clinical manifestations can vary from only subtle electrocardiography change to sudden death.In this case report,we present the case of a patient with myasthenia gravis(MG)who developed refractory CAS-related cardiogenic shock during thymoma surgery.CASE SUMMARY A 61-year-old man had a history of cigarette smoking and coronary artery disease with a bare metal stent placed.Three months ago,he suffered from coronary spasms,with three vessels involved,after surgery for cervical spine injury.He started having progressive dysphagia 4 wk prior and was diagnosed with MG via serologic tests,and computed tomography declared a thymoma in the anterior mediastinum.After the symptoms of MG subsided,he was referred for thy-mectomy.The operation was uneventful until the closing of the sternal wound.Electrocardiography showed sudden onset ST elevation,followed by ventricular tachycardia and severe hypotension.Cardiopulmonary cerebral resuscitation was initiated immediately with electrical defibrillation,extracorporeal membrane oxygenation was performed due to refractory cardiogenic shock,and the patient was transferred to an angiography room.Angiography showed diffuse CAS with three vessels involved.Intracoronary isosorbide dinitrate and adenosine were administered,and then the patient was transferred to the intensive care unit.CONCLUSION Our case highlights the importance of being prepared for clinical situations such as the one described here and suggests the necessity of developing an appropriate anesthesia plan that includes proactive analgesia and preemptive coronary vaso-dilators.

New Progress in the Treatment of Myasthenia Gravis

In recent decades, the treatment of myasthenia gravis has been extensively developed, but a standardized standard still needs to be used. Its treatment strategy is associated with patient prognosis, economic costs, and complications. This article reviews the pathogenesis, treatment methods, and complications of myasthenia gravis, providing new ideas for diagnosing and treating myasthenia gravis and fully embodies the principle of safety and precision.

Surgical approaches for stage Ⅰ and Ⅱ thymoma-associated myasthenia gravis:feasibility of complete video-assisted thoracoscopic surgery (VATS) thymectomy in comparison with trans-sternal resection

Complete resection could be achieved in virtually all myasthenic patients with Masaoka stage I and II thymoma us- ing the trans-sternal technique. Whether this is appropriate for minimally invasive approach is not yet clear. We evalu- ated the feasibility of complete video-assisted thoracoscopic surgery （VATS） thymectomy for the treatment of Ma- saoka stage I and Ⅱ thymoma-associated myasthenia gravis, compared to conventional trans-sternal thymectomy. We summarized 33 patients with Masaoka stage I and II thymoma-associated myasthenia gravis between April 2006 and September 2011. Of these, 15 patients underwent right-sided complete VATS （the VATS group） by us- ing adjuvant pneuomomediastinum, comparing with 18 patients using the trans-sternal approach （the T3b group）. No intraoperative death was found and no VATS case required conversion to median sternotomy. Significant differences between the two groups regarding duration of surgery and volume of intraoperative blood loss （P = 0.001 and P 〈 0.001, respectively） were observed. Postoperative morbidities were 26.7% and 33.3% for the VATS and T3b groups, respectively. All 33 patients were followed up for 12 to 61 months in the study. The cumulative probabilities of reaching complete stable remission and effective rate were 26.7% （4/15） and 93.3% （14/15） in the VATS group, which had a significantly higher complete stable remission and effective rate than those in the T3b group （P = 0.026 and P = 0.000, respectively）. We conclude that VATS thymectomy utilizing adjuvant pneuomo- mediastinum for the treatment of stage I and II thymoma-associated myasthenia gravis is technically feasible but deserves further investigation in a large series with long-term follow-up.

Effectiveness of progressive resistance training in improving muscle strength in myasthenia gravis:a single subject study design

Background:To investigate the effectiveness of the progressive resistance training(PRT)using thera band in improving muscle strength in myasthenia gravis(MG).Methods:In this prospective study,12 MG patients with generalised stable disease performed progressive resistance training with thera band for four times per week for 24 weeks.The isometric muscle force of shoulder abductors,biceps brachii and knee extensors using handheld dynamometer,Myasthenia Gravis Composite(MGC)score,Quantitative myasthenia gravis score(QMG),were assessed before and after the training period.Results:Progressive resistance training was well tolerated,and the isometric muscle strength was significantly improved in shoulder abductors,biceps brachii and knee extensors(P<0.05).The disease course(QMG and MGC)was slowed down and improved(P<0.05).Conclusion:Progressive resistance training is effective in improving muscle strength specifically in most affected muscles in MG.

Histologic Classification of Thymoma and Its Relationship with Myasthenia Gravis and Clinical Stages of the Tumor

Objective： To investigate the relationship among the latest WHO classification of thymoma, myasthenia gravis （MG） and clinical stages. Methods： To review the pathological sections of 74 patients with thymoma from 1980-2004 using WHO classification （1999）, the statistical software was used to analyze the relationship among the WHO classification, MG and clinical stages. Results： （1） Two cases of type A, 23 cases of type AB, 4 cases of type B1, 27 cases of type B2, 16 cases of type B3 and 2 cases of type C were classified. Type B2 more likely accompanied MG （P〈0.05）, while none with MG occurred for type C. （2） One patient was in stage Ⅰ, 30 were in stage Ⅱ, 38 were in stage Ⅲ, and 5 were in stage Ⅳ. The latest histologic classification was significantly correlated with Masaoka stages （P〈0.01）. Conclusion： The latest WHO classification was correlated with occurrence of MG and finely reflected clinical stage. It can also evaluate the prognosis of patients.

Myasthenia gravis and thymic neoplasms: A brief review

Thymoma is the most common mediastinal tumor. They have varied presentation ranging from asymptomatic incidental mediastinal masses to locally extensive tumor with compressive symptoms and distant metastases. They have frequent association with various paraneoplastic syndromes(PNS). The most common PNS associated with thymoma is myasthenia gravis(MG). Patients of thymoma with MG have a favourable outcome due to early disclosure of the disease. Histologically they are classified into five subtypes and MasaokaKoga staging system is used for staging. Surgery, chemotherapy and radiotherapy play an important role along with anti-myasthenia drugs. This review would like to highlight the association of thymoma with MG and associated clinical and therapeutic issues.

TUMOR NECROSIS FACTOR-ALPHA POLYMORPHISM AND SECRETION IN MYASTHENIA GRAVIS

Objective To analyze the relationship between tumor necrosis factor-alpha (TNFα) gene promoter -308 polymorphism and myasthenia gravis (MG) in Chinese and analyze secretion of TNFα in peripheral blood mononuclear cells (PBMC) in MG patients. Methods A biallelic polymorphism at position -308 in the promoter of TNFα gene was screened by PCR amplification and NcoI recognition site. One hundred and twenty-three MG cases and 115 healthy controls were included in this study. MG patients were classified to different groups according to clinical type, age at onset, and sex respectively. PBMC were isolated from 20 patients and 20 healthy controls, and then cultured in the presence or absence of phytohemag- glutinin (PHA) and acetycholine receptors (AchR). The supernatants were harvested after incubation and stored until TNFα was assayed by enzyme-linked immunosorbent assay. Results The frequency of TNFα-308 allele 2 (A) was found significantly increase in MG patients and showed a trend especially in late onset (≥ 40 years) and male patients (P < 0.05). The allele A had no relationship with thymic pathogenesis in MG patients. But frequency of allele A was significantly higher in general type than in ocular type (P < 0.05). MG patients had a higher inducible level of TNFα by PHA and AchR, and could be down regulated after treatment. Conclusion Polymorphism in TNFα gene promoter -308 is associated with onset of MG. The microsatellite allele TNFα2 confer risk for the development of MG in Chinese patients. MG patients have a higher inducible level of TNFα.

Effectiveness of Thymectomy in Non-thymomatous Myasthenia Gravis: a Systematic Review

There is continuous debate regarding the effectiveness of thymectomy in the treatment of non-thymomatous myasthenia gravis （MG）. This systematic review was undertaken to determine whether thymectomy was effective in non-thymomatous MG. We retrieved articles published between January 1980 and September 2013. Sixteen cohort studies were included. Given the considerable het- erogeneity, we used a descriptive method instead of statistical synthesis. The median relative rates （RRs） and their interquartile ranges were used to estimate the magnitude of benefit. Compared to conserva- tively treated MG patients, thymectomized patients had higher survival, clinical remission, pharma- cologic remission and improvement rates, and RRs were 1.07 （1.01-1.17）, 1.83 （0.82-2.99）, 1.55 （1.22-1.95） and 1 （1.00-1.09）, respectively. Subgroup analyses showed that patients with moderate to severe generalized MG benefited more from thymeetomy, with RRs of survival and pharmacologic re- mission increasing to 1.35 （1.24-1.49） and 2.68 （1.73-4.17）, respectively. These results suggested that thymectomy might be an effective procedure in non-thymomatous MG patients. The patients with mod- erate to severe generalized MG might benefit more. Taking into account the poor methodological qual- ity of present studies, more well-designed prospective randomized controlled trials （RCTs） are still re- quired to reach uneouivocal conclusion.

Investigation on the Mechanism of Exacerbation of Myasthenia Gravis by Aminoglycoside Antibiotics in Mouse Model

To investigate the underlying mechanism of the exacerbation of myasthenia gravis by aminoglycoside antibiotics. C57/BL6 mice were immunized with acetylcholine receptor (AChR), extracted from electric organ of Narcine timilei according to Xu Haopeng's methods, in complete Fruend's adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG). EAMG mice were divided randomly into 5 groups: MG group, NS group and three antibiotics groups. The clinical symptom scores of mice were evaluated on d7 after the last immunization and d14 of antibiotics treatment. Repetitive nerve stimulation (RNS) was performed and the levels of anti-AChR antibody (AChR-Ab) were tested at the same time. The mean clinical symptom grades of gentamycin group (1.312, 2.067), amikacin group (1.111, 1.889) and etimicin group (1.263, 1.632) were significantly higher than those of MG group (1.000, 1.200) (P<0.05). The positive rates of RNS of three antibiotics groups were 69.23 %, 58.82 % and 63.16 % respectively, which were significantly higher than those of MG group and NS group (40.00 %, 40.00 %, P<0.05). The AChR-Ab level in serum and the expression of AChR on neuromuscular junction (NMJ) of mice in three antibiotics groups were also higher than those of MG group. Our results indicated that aminoglycoside antibiotics could aggravate the symptom of myasthenia gravis. The exacerbation of myasthenia gravis by these antibiotics probably involves competitively restraining the release of acetylcholine from presynaptic membrane, impairing the depolarization of postsynaptic membrane, depressing the irritability of myocyte membrane around the end-plate membrane and consequently leading to the blockade of neuromuscular junction.

Myasthenia gravis exacerbation and diarrhea associated with erythromycin treatment

An important problem in management of the case with myasthenia gravis (MG) is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.

Possible implications of dysregulated nicotinic acetylcholine receptor diffusion and nanocluster formation in myasthenia gravis

Myasthenia gravis is a rare and invalidating disease affecting the neuromuscular junction of voluntary muscles.The classical form of this autoimmune disease is characterized by the presence of antibodies against the most abundant protein in the neuromuscular junction,the nicotinic acetylcholine receptor.Other variants of the disease involve autoimmune attack of non-receptor scaffolding proteins or enzymes essential for building or maintaining the integrity of this peripheral synapse.This review summarizes the participation of the above proteins in building the neuromuscular junction and the destruction of this cholinergic synapse by autoimmune aggression in myasthenia gravis.The review also covers the application of a powerful biophysical technique,superresolution optical microscopy,to image the nicotinic receptor in live cells and follow its motional dynamics.The hypothesis is entertained that anomalous nanocluster formation by antibody crosslinking may lead to accelerated endocytic internalization and elevated turnover of the receptor,as observed in myasthenia gravis.

“Warming yang and invigorating qi” acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis

Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction.＂Warming yang and invigorating qi＂ acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis.However,few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction.Here,we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following ＂warming yang and invigorating qi＂ acupuncture therapy.Needles were inserted at acupressure points Shousanli（LI10）,Zusanli（ST36）,Pishu（BL20）,and Shenshu（BL23） once daily for 7 consecutive days.The treatment was repeated after 1 day of rest.We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment.This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide.These findings suggest that ＂warming yang and invigorating qi＂ acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.

Reduction of natural regulatory T cells in thymomas accompanying myasthenia gravis and its possible association with Foxp3 and thymic stromal lymphopoietin

Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistochemistry and real-time reverse trancription polymerase chain reaction (real-time RT-PCR) techniques to determine Foxp3+ Treg counts and the expression levels of Foxp3 mRNA and TSLP mRNA in thymomas of 23 MG patients and thymuses of 4 healthy controls. Results: The CD4+ Foxp3+ nTreg (natural regulatory T cells) counts in thymomas were significantly lower than those in normal thymuses (P<0.01), and the expression levels of Foxp3 mRNA and TSLP mRNA were also lower in thymomas(P<0.01). Among the thymoma types, type B1 thymoma had the highest Foxp3+ nTreg count and standard values of Foxp3 mRNA and TSLP mRNA. There was a strong positive correlation between the mRNA transcriptional levels of Foxp3 and TSLP. Conclusion: The insufficient expression of Foxp3 in thymoma, which may be caused by decreased transcription of TSLP, may result in the reduction of Tregs and cause autoimmune disorders.

Non-coronary myocardial infarction in myasthenia gravis: Case report and review of the literature

Cardiovascular adverse events in patients with myasthenia gravis (MG) are rare, but the early recognition of such events is crucial. We describe a case of a noncoronary myocardial infarction (MI) during the initial treatment period with pyridostigmine bromide in a female patient with MG. Clinicians should be cautious about the appearance of potential MI in patients with MG. A baseline electrocardiogram is advocated, when the early recognition of the MI clinical signs and the laboratory findings (myocardial markers) are vital to the immediate and appropriate management of this medical emergency, as well as to prevent future cardio-vascular events. In this case report possible causes of myocardial adverse events in the context of MG, which may occur during the ongoing treatment and the clinical course of the disease, are discussed.

Computer Aided Study of Mechanism of Immunoadsorbent for Myasthenia Gravis

Myasthenia Gravis (MG) is an organ specific autoimmune disease mediated by autoantibodies (AChR Ab) against the acetylcholine receptor (AChR). Literature reported that the AChR Ab can be removed by absorbent linked with tryptophan. It was studied in detail in our lab. With the aid of computer, we docked some ligands into AChR Ab, and the results from scores of docking under different generations showed that there was no specific binding between tryptophan and scFv fragment just as the binding between antigen-antibody. The interaction between Trp and immunoglobulin was a broad-spectrum binding.

The Clinical Study and HLA Genotyping of 112 Familial Myasthenia Gravis Patients

Summary: One hundred and twelve cases of familial myasthenia gravis (MG) from 44 families selected from 2100 patients with MG diagnosed since 1983 in the Department of Neurology were studied. The clinical pictures and immunological features of the patients showed a great resemblance to those of sporadic cases. The pedigree analysis disclosed that the hereditary patterns of familial patients were basically Mendellian autosomal inheritance. Many predisposing factors such as fever, infection, use of aminoglycoside or vaccines, played an important role in presenting the phenotype of subclinical cases. The HLA genotyping suggested that the complement polymorphism C4A*4, the complotype S42, and the genes 0901 and 1301 of DRB1 allele, were related to the pathogenesis of MG. It was concluded that the phenotype of MG may be the result of interaction between hereditary defects and environmental factors.

Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a gluten-free diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 (or, about 4.3%) was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.