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.

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.

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.

EXPRESSION AND SUBCELLULAR LOCALIZATION OF P9-ZFD PROTEIN IN PATIENTS WITH MYASTHENIA GRAVIS

To express and purify the protein coded by the TRAF-type zinc finger domain of myasthenia gravis (MG)-re-lated gene P9 ( P9-ZFD ) and to prepare P9-ZFD antiserum for detecting expression and subcellular distribution of P9-ZFD protein in the skeletal muscles of patient with MG. Methods The cDNA encoding P9-ZFD was amplified by RT-PCR. The cloned P9-ZFD cDNA was ligated into pET-24a, and the P9-ZFD recombinant protein was induced via E.coli. BL21 (DE3) and purified by histidine affinity chromato-graphy. P9-ZFD antiserum was prepared and its titer and specificity were determined by ELISA and Western blot. Expres-sion and subcellular distribution of P9-ZFD protein in the skeletal muscles of MG and control were studied. Results The molecular weight of purified P9-ZFD protein was about 30 kD. Its purity was more than 95%. Antiserum specific for P9-ZFD was excellent. P9-ZFD protein is fully confined to the cytoplasm membrane of skeletal muscle cell of MG, obvious immunostaining was absent in the A, I, and Z bands of cytoplasm and no immunoreactivity was observed in the skeletal muscle cell of control. Conclusion P9-ZFD protein is expressed as a cytoplasm membrane-bound protein and has obvious distribution difference in the skeletal muscle cells of patient with MG and normal control.

Clinical Measurement of Antibodies against Acetylcholine Receptor (AchR),SOD and LPO in Patients with Myasthenia Gravis (MG)before and after Thymectomy

The antibodies against acetylcholine receptor AchR and levels of SOD and LPO were measured in 11 patients with myasthenia gravis (MG),and the results were compared with normal controls and patients with diseases other than MG.The results showed that the antibodies against AchR were higher as compared with other groups before and after operation. The post-operative level of antibodies was obviously lower than the pre-operative value. An slight increase in SOD and significant decrease in mean value of LPO after surgery were noted. The possible mechanism was discussed.

Rare Case of a Patient with Newly Diagnosed Thymoma Presenting with Paraneoplastic Systemic Lupus Erythematosus, Myasthenia Gravis, and Hypogammaglobulinemia

A Pleural mass biopsy was performed showing an invasive thymoma. Computed tomography (CT) scan of the chest performed on admission revealed a left sided pleural mass, anterior mediastinal mass, lymphadenopathy and pericardial effusion. Pleural mass biopsy showed an invasive thymoma. Due to her clinical presentation, a complete work-up was performed revealing paraneoplastic systemic lupus erythematous (SLE), myasthenia gravis (MG) and hypogammaglobulinemia. We reviewed the literature regarding thymoma and its relationship with paraneoplastic SLE, MG and hypogammaglobulinemia.

Successful Anaesthetic Management of Caesarean Section: An Experience on a Patient with Myasthenia Gravis and Difficult Airway

The anaesthetic management of the pregnant woman with myasthenia gravis (MG) is very challenging to the anaesthesiologist. This situation becomes exaggerated in emergency settings in a low resource area, especially when attending anesthesiologists for the first time took care of her. Here, we present a case that illustrates this situation. A G3 P2 pregnant woman presented for an emergency caesarean section (CS) due to premature rupture of the membranes. The patient had been misinformed by her neurophysician not to undergo general anaesthesia at CS. She had no motor weakness and no bulbar symtoms. The only abnormal finding was a stiff neck and a Mallampati #2 score, which predicted a difficult airway. Spinal anaesthesia was not successful after several attempts. General anaesthesia was considered but again intubation was not successful. We performed anesthesia with a second generation laryngeal mask airway with successful CS. Pregnant women with MG require personalised care from a multidisciplinary team. While regional anaesthesia is reported to be the better choice in CS for women with MG, regional anesthesia is not always possible. Anesthesia should be chosen in a patient-by-patient manner. The present case illustrates such conditions, of which description may be useful for anesthesiologists and obstetricians.

Successful Combination Therapy of Nivolumab and Radiation for Massive Mucosal Melanoma in Patient with Autoimmune-Myasthenia Gravis, Systemic Lupus Erythematosus and Rheumatoid Arthritis

A 58-year-old woman complicated with autoimmune diseases of myasthenia gravis (MG), rheumatoid arthritis, and systemic lupus erythematosus noticed an irregular black macule on her bilateral major labia, which was diagnosed as malignant melanoma. The melanoma lesion involving the vagina, uterus, and ventral side of rectum was not operable and was treated with nivolumab and concurrent radiotherapy with good control of the MG. This resulted in remarkable tumor shrinkage, possibly due to synergistic effects of both treatments. To our knowledge, few reports have described the effectiveness of combination therapy with nivolumab and radiation for malignant melanoma. The present case showed an enhanced anti-tumor effect with combination therapy.

Clinical study of surgery for patients with myasthenia gravis and hyperthyroidism

目的 :探讨重症肌无力 (MG)并发甲状腺机能亢进 (甲亢 )病人的临床治疗特点和外科治疗的效果。方法 :对 1 1例患 MG并发甲亢病人分别行甲状腺次全切除、胸腺切除和甲状腺次全切除同时胸腺切除 ,并对这些病例进行术后随访。结果 :本组 7例 b 型病人中 2例由于气管切开所致颈部切口感染 ,经外科治疗后痊愈。3例 ( a 型 1例 , b 型 2例 )在单纯甲状腺次全切除术后 3～ 6个月 MG复发。2例 ( a型和 b 型各 1例 )在单纯胸腺切除术后 8个月和 1 2个月 MG复发。6例 ( 型 1例、 a 型 1例、 b 型 4例 )同时实施了甲状腺次全切除和胸腺切除术 ,术后 3个月 1例MG复发 ;3例 ( a 型 1例和 b 型 2例 )的 MG缓解 ,2例 ( b 型 )的 MG改善。结论 :MG并发甲亢病例同时实施胸腺切除和甲状腺次全切除疗效好 ,但由于气管切开增加了颈部切口感染的机会。MG并发甲亢时甲状腺次全切除或胸腺切除远期效果不理想。

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.

抗GQ1b、GT1a、Sulfatide抗体阳性的类重症肌无力Miller-Fisher综合征1例报告

Miller-Fisher综合征(Miller-Fisher syndrome,MFS)是吉兰-巴雷综合征(Guillain-Barre syndrome,GBS)的一种临床变异型,以共济失调、眼肌麻痹及腱反射消失为主要临床特征,极少出现瞳孔改变和瞳孔对光反射异常,一般无症状波动,部分患者可检测到抗GQ1b IgG抗体阳性。本文报告了1例抗GQ1b、GT1a、Sulfatide抗体阳性的MFS,以波动性眼外肌麻痹起病,伴双侧瞳孔散大、对光反射迟钝及四肢麻木无力,症状少见不典型,临床极易误诊。

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.