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.

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.

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.

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.

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.

Effects of intravascular photobiomodulation on motor deficits and brain perfusion images in intractable myasthenia gravis: A case report

BACKGROUND Myasthenia gravis(MG)is an autoimmune disorder caused by neuromuscular junction failure characterized by muscle weakness and fatigability.We herein report a case of MG that received intravascular laser irradiation of blood(ILIB)interventions and regained muscle power and better quality of life.To our knowledge,no previous study has investigated the benefits of ILIB treatment on patients with MG.We also evaluated the changes in brain perfusion scan and the MG activities of daily living(MG-ADL)and quantitative MG(QMG)scales.CASE SUMMARY A 59-year-old man presented to our outpatient hospital experiencing ptosis,diplopia,fibromyalgia,muscle fatigue,and fluctuating weakness in his limbs for 1 year.Based on his history,physical examination,and laboratory investigations,the final diagnosis was a flare-up of MG with poor endurance and muscle fatigue.The patient agreed to receive ILIB.Brain single-photon emission computed tomography(SPECT)was performed both before and after ILIB therapy.After receiving three courses of ILIB,the brain SPECT images showed greatly increased perfusion of the frontal lobe and anterior cingulate gyri.The patient’s MG-ADL scale score decreased markedly from 17/24 to 3/24.The QMG scale score also decreased remarkably from 32/39 to 9/39.The symptoms of MG became barely detectable and the patient was able to perform his activities of daily living and regain muscle power.CONCLUSION ILIB might have beneficial effects on MG,and brain SPECT images provided direct evidence of a positive correlation between ILIB and clinical performance.

Myasthenia gravis and pregnancy

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular junctionthat has higher incidence in younger women than men, which could be related todifferences in sex hormones physiology and immune system functioning betweenmales and females. MG can first present during pregnancy and variably affectpregnancy, labor, and postpartum period. In this paper, we had an updatedoverview on our understanding about MG presentation and its effect onpregnancy and vice versa, therapeutic options for MG pregnant women,management of pregnancy or labor complications in MG patients, and finally fetaland neonatal considerations in MG pregnant women. A multidisciplinaryapproach, involving obstetricians/gynecologists, neurologists, and anesthesiologists,plays a pivotal role in improving the clinical outcomes in both MGmothers and their infants during pregnancy, delivery and postpartum.

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.

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.

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.

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.

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.

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.

“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.

Atrophy and Fibrosis of Extra-Ocular Muscles in Anti-Acetylcholine Receptor Antibody Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.

Oinical study on thymomas and thymomas with myasthenia gravis

Objective To present the clinical experience in treating thymomas and thymomas with myasthenia gravis (MG). Methods Between 1975 to 1997,285 patients with thymoma were surgically treated. 168 cases of thymus tumor (TT,Group Ⅰ ) were compared to 90 cases of thymus tumor with myasthenia gravis (TTMG, Group Ⅱ ). Results In group Ⅰ , the average age was 38. 4 years, the youngest was 4 years old. In 93. 4%, the diameter of tumors was 5 cm. 61. 2% were in stages Ⅲ and Ⅳ of clinical pathology. In group Ⅱ ,the average age was 46.2 with the youngest of 20 years old,the diameter of tumor under 3 cm and 5 cm was 34.6 % and 65.6 % . 55.2 % was in stage Ⅰ of clinical pathology. Conclusion Many cases of thymoma in early stage received early treatment. The diagnostic standard of thymoma in early stage is: (1) the diameter of tumor is below 3 cm. (2) In stage I of clinical pathology. The clinical characteristics of TTMG are: short history, the rapid progress, serious MG symptoms,and the high incidence of thymus-

Enzyme-linked Immunosorbent Assay for Detection of Anti-idiotype Antibodies to Antibodies to Ligand of Nicotinic Acetylcholine Receptor in Sera of Patients with Myasthenia Gravis

Anti-bungarotoxin anti-serum,which has the internal image of nicotinicacetylcholine receptor,was used as a tool to measure anti-idiotypic antibodies toantibodies to Iigand of nicotinic acctylcholine receptor in scra from 81 patients withmyasthenia gravis.Enzyme-linked immunosorbcnt assay was adopted.Thc positive ratewas 46.9%(38/81).The specific cross inhibitory test with nicotinic acetylcholinereceptor was positive.Anti-idiotype antibodies to antibodies to ligand of nicotinicacetylcholine receptor in sera of different types of myasthenia gravis patients classified ac-cording to modified Osserman’s standard and myasthenia gravis patients with or withoutthymoma were comparcd in this study and the role of anti-idiotype antibodies toantibodies to Iigand of nicotinic acctylcholinc receptor in the immunity of myasthcniagravis and the possibility of thcrapeutic use of anti-idiotype antibodies arc discussed.