Myasthenia Gravis: Comparative Evaluation of Medical and Surgical Treatment

Sixty-eight patients with myasthenia gravis were evaluated and compared to determine the results of medical and surgical treatment; eight patients with thymoma were evaluated separately. In the group of 30 non-thymoma patients treated medically 50% of patients derived moderate to good improvement over a mean follow-up period of 11 years. Ten per cent of patients in this group died from myasthenia.In the group of 30 non-thymoma patients treated by thymectomy, 83% achieved good to excellent improvement. There was no surgical or myasthenic mortality over a mean follow-up period of nine years.The results of treatment in the eight thymoma patients were decidedly inferior and there was no significant difference between the medically and surgically treated patients. Fifty per cent showed only moderate improvement during a mean follow-up of five years and 50%, after initial improvement, deteriorated later and died from myasthenia between three and four years after thymectomy.Two additional patients had thymoma without myasthenia. Neither of them had developed myasthenia, two years following thymectomy in one case and after 25 years in the other, despite recurrence of the tumour with extensive invasiveness in the very long-standing case.     

Using swallow sound and surface electromyography to determine the severity of dysphagia in patients with myasthenia gravis

One of the main symptoms of patients with myasthenia gravis is dysphagia, which will reduce the patients’ nutritional absorption and influences the quality of living. The activity of swallowing involves interaction and coordination between a variety of muscles and the nervous system. It is, therefore, difficult for clinicians to detect dysphagia. Furthermore, the symptoms of myasthenia gravis are unstable, making clinical judgment troublesome. How to accurately diagnose the severity of dysphagia in the clinic has become an important research topic. This paper proposes a dysphagia severity discrimination system for patients with myasthenia gravis. It uses a non-invasive Adam's apple microphone and surface electromyography to collect the swallow signal generated by sound and muscle activity when the patient swallows water. The system then extracts features to discriminate the severity of dysphagia during each swallow phase. The experimental results show that the system can provide concrete features for clinicians to diagnose dysphagia in myasthenia gravis patients.     

Myasthenia Gravis: Anesthetic and Surgical Management of the Patient Undergoing Thymectomy

Experience in the anesthetic and surgical management of 25 patients with myasthenia gravis is recorded. These are subdivided into two groups: those operated on during the period 1950-1958 and those operated on during the period 1959-1964. The purpose of this paper is to indicate improvement in mortality and morbidity due to three major advances: (1) use of the decamethonium diagnostic test in a myasthenia gravis clinic; (2) improvements in assessment and management of respiratory insufficiency; and (3) avoidance of anticholinesterase treatment in the immediate and early postoperative recovery period.Fourteen patients with myasthenia gravis, including five with thymoma and two who were refractory to medication, were in the second (1959-1964) group. There were no deaths and no myasthenic or cholinergic crises. Three prophylactic tracheostomies were performed. No emergency bronchoscopies or tracheostomies were required.     

Galectin-1 is expressed by thymic epithelial cells in myasthenia gravis

Galectin-1, a member of a family of carbohydrate binding proteins, is synthesized by thymic epithelial cells in normal juvenile thymus, and mediates adhesion of immature T cells to thymic epithelium. Because cell adhesion molecules are proposed to play a role in the thymic hyperplasia and neoplasia seen in the autoimmune disease myasthenia gravis, we examined the expression of galectin-1 in myasthenic thymi. We detected abundant galectin-1 expression in thymic epithelial cells in 27 hyperplastic and neoplastic thymi from patients with myasthenia gravis. Primary cultures of neoplastic epithelial cells from a thymoma continued to express galectin-1, and bound immature T cells; T cell binding was inhibited by the addition of the -galactosides lactose and thiodigalactoside, suggesting that galectin-1 on the thymoma cells and a saccharide ligand on the T cells participated in cell-cell adhesion. Expression of galectin-1 by thymic epithelial cells may play a role in the thymic pathology seen in myasthenia gravis.     

Combination percutaneous cryotherapy and iodine-125 seed implantation for unresectable malignant thymoma: Experience in 19 patients

Thymomas are the most common tumors of the mediastinum. These tumors often compress vital mediastinal organs and severely impact the quality of life of thymoma patients. To avoid the side effects of chemoradiotherapy, some patients with unresectable malignant thymomas have opted to undergo cryotherapy in our hospital. We reviewed the cryosurgery, nursing and follow-up records of our hospital for the past 8 years, and evaluated the safety and efficiency of cryotherapy in 19 patients with unresectable malignant thymomas. No severe complications involving the vital organs surrounding the tumor occurred during or after cryosurgery. The most common side effect was pleural effusion, which occurred in 11 patients and healed after drainage within 1 week. Cough, mediastinal and pericardial effusions, pneumothorax, mild fever and chest tightness also occurred and resolved 1 week after symptomatic treatment. Since our patients had high KPS scores and mild myasthenia gravis symptoms before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14–29 months (median, 18 months), and did not differ between patients with large tumors and those with small tumors (P = 0.6753). In conclusion, cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma.     

Early autoimmune complications after thymomectomy in a patient with interstitial lung disease. Case report

Thymoma has been associated with a variety of autoimmune disorders. We report a case of myasthenia gravis and pancytopenia in a 53-year-old man with lymphoepithelial thymoma and interstitial lung disease. Preoperative examination revealed neither hematologic abnormality nor myasthenia gravis. The patient had enteritis prior to thymomectomy, sternal infection in the first month of operation, and urinary infection at the third month. About three months after thymomectomy, he required mechanical ventilation support due to myasthenia gravis-related respiratory failure. One month later, a rapidly progressing pancytopenia developed. The patient died within two weeks of overwhelming septicemia unresponsive to treatment with antibiotics and steroids. The possible onset of myasthenia gravis or pancytopenia after thymomectomy should be kept in mind during follow-up. Recurrent infections in the early stages of thymomectomy may suggest a lethal onset of pancytopenia.     

The Role of Radiation Therapy in Myasthenia Gravis

Myasthenia gravis is a serious and debilitating disease associated with conduction defects occurring at the myoneural junction. About 15 per cent of the patients have associated tumors of the thymus and 80 per cent of the remaining patients show abnormalities of the thymus. Although a definite relationship between cause and effect has not been proved, thymectomy or radiotherapy of the thymus does seem to influence the disease.Seven cases of myasthenia gravis in which radiation therapy was used at the University of California Medical Center are reported and compared with those described in the literature. It is concluded that patients whose disease is progressing and not well managed medically, and who have no evidence of thymoma, should be treated by irradiation—whether pre-operatively or as definitive treatment, depending on the result of irradiation. Those patients with evidence of thymoma should be irradiated before surgical procedure. Small tumors, or patients in whom surgical risk is increased, may be managed by radiation therapy alone.     

重症肌无力患者抗乙酰胆碱受体抗体的测定及意义

用ELISA法对56例重症肌无力(MG)患者治疗前后的血清乙酰胆碱受体(AchR)抗体进行了检测。检测结果为MG患者治疗前后的血清AchR抗体阳性率46.4%。而且发病年龄越大,患者体内AchR抗体阳性率越高。患者患病时间越长体内AchR抗体含量降低。伴发胸腺瘤的患者AchR抗体阳性率明显高于胸腺正常者,全身型MG患者AchR抗体检测阳性率高于眼肌型患者。     

激素联合丙种球蛋白治疗小儿重症肌无力的疗效及对患儿免疫球蛋白和补体的影响

目的：探讨激素联合丙种球蛋白治疗小儿重症肌无力的临床疗效及对患儿免疫球蛋白和补体的影响。方法：回顾性分析在我院治疗的70例重症肌无力患儿的临床资料,采用随机序号的方式将其分为观察组和对照组各35例,观察组给予甲泼尼龙联合丙种球蛋白,对照组仅给予甲泼尼龙,观察两组的临床疗效及免疫球蛋白和补体变化情况。结果：观察组总有效率为94．3％明显优于对照组74．3％,两组比较有统计学意义（P〈0．05）;观察组症状明显缓解时间（6．55±1．35）d以及总住院天数（17．15±3．65）d较对照组明显缩短,两组比较差异均有统计学意义（P〈0．05）。结论：采用激素联合丙种球蛋白治疗小儿重症肌无力,可以明显改善患者肌无力症状,获得较为满意的临床疗效,值得进一步推广使用。     

Possible relationship between poly(ADP-ribose)synthetase and formation of antibody against acetylcholine receptors in patients with myasthenia gravis

We examined the relationship of the serum levels of antibody against acetylcholine receptors to the serum levels of 13 enzymes, including various hydrolytic enzymes, poly(ADP-ribose)synthetase (Poly(ADP-ribose)Syn), and sialyltransferase (NANA-trans), in patients with myasthenia gravis. The patients were divided into two groups, depending on the presence or absence of thymoma. In spite of the absence of significant difference in the absolute levels of individual enzymatic activities between the two groups, the network relationships of such enzymes were quite different between the two groups. Of the 13 enzymes examined, only Poly(ADP-ribose)Syn showed a weak but significant correlation with the level of the antibody in the patients without thymoma. A multivariate study more clearly suggested the relationship between the antibody formation and Poly(ADP-ribose)Syn in the patients without thymoma. Such observations were not found in the patients with thymoma.     

Thymoma,myasthenia gravis,erythroblastopenic anemia and systemic lupus erythematosus in one patient

A 50-year-old woman who initially had myasthenia gravis subsequently presented with thymoma, erythroblastopenic anemia and systemic lupus erythematosus during 17 years of follow-up. In a review of the literature no similar documented cases were found, although 14 patients were reported with three of the above diseases, two also having positive LE cell tests. An association of several autoimmune disorders in one patient may be more frequent than was previously believed.     

The role of acetylcholine receptor antibodies in myasthenia gravis.

Myasthenia gravis is an autoimmune disease of man characterized by remitting and relapsing muscle fatigability. Although the etiology and pathogenesis are incompletely understood, the presence of circulating antibodies directed against the nicotinic acetylcholine (ACh) receptor in 80--90% of patients with myasthenia gravis and the identification of immune complexes at their neuromuscular junction have helped explain the altered neuromuscular transmission. The ACh receptor antibodies do not block access of ACh to the receptor, but do decrease the number of receptors by accelerating their degradation both in rat myotube cultures and in vivo models. In vitro these antibodies play a major role in myasthenia gravis. However, correlations of antibody titers with the clinical state following thymectomy or in neonatal myasthenia suggest that host factors may be equally important in determining whether the ACh receptor antibodies will result in clinical myasthenia.     

Ocular myasthenia gravis in a patient with euthyroid Graves' disease

Graves' disease (GD) and ocular myasthenia gravis (OMG) are autoimmune disorders which may occur in the same patient. Myasthenia gravis is 50 times more common in patients with Graves' disease when compared to the normal population. Typically, a patient may be diagnosed with one disorder and have no signs or symptoms of the other, including negative laboratory studies. Therefore, when managing patients with known Graves' disease, it is important to be alert to the possibility of ocular myasthenia.     

MYASTHENIA GRAVIS—Problems in Diagnosis

The possibility of myasthenia gravis must be considered in patients persistently complaining of weakness and fatigue. There may be many difficulties and pitfalls in differentiating myasthenia gravis from other disorders in which muscular weakness is a common complaint.Observation of a group of 36 patients with myasthenia gravis, and another group of 30 cases involving the differential diagnosis of myasthenia gravis, led to a conclusion that a physician should apply criteria carefully before arriving at a diagnosis of myasthenia gravis and instituting drug therapy, since nonmyasthenics may frequently respond with subjective improvement temporarily following administration of cholinergic drugs.Myasthenia gravis may be a more common disorder than was suspected in the past.     

Myasthenial gravis; problems in diagnosis

The possibility of myasthenia gravis must be considered in patients persistently complaining of weakness and fatigue. There may be many difficulties and pitfalls in differentiating myasthenia gravis from other disorders in which muscular weakness is a common complaint. Observation of a group of 36 patients with myasthenia gravis, and another group of 30 cases involving the differential diagnosis of myasthenia gravis, led to a conclusion that a physician should apply criteria carefully before arriving at a diagnosis of myasthenia gravis and instituting drug therapy, since nonmyasthenics may frequently respond with subjective improvement temporarily following administration of cholinergic drugs.Myasthenia gravis may be a more common disorder than was suspected in the past.     

Myasthenia Gravis: Analysis of Serum Autoantibody Reactivities to 1827 Potential Human Autoantigens by Protein Macroarrays

Background

Myasthenia gravis is a disorder of neuromuscular transmission associated with autoantibodies against the nicotinic acetylcholine receptor. We have previously developed a customized protein macroarray comprising 1827 potential human autoantigens, which permitted to discriminate sera of patients with different cancers from sera of healthy controls, but has not yet been evaluated in antibody-mediated autoimmune diseases.

Objective

To determine whether autoantibody signatures obtained by protein macroarray separate sera of patients with myasthenia gravis from healthy controls.

Methods

Sera of patients with acetylcholine receptor antibody-positive myasthenia gravis (n = 25) and healthy controls (n = 32) were analyzed by protein macroarrays comprising 1827 peptide clones.

Results

Autoantibody signatures did not separate patients with myasthenia gravis from controls with sufficient sensitivity, specificity, and accuracy. Intensity values of one antigen (poly A binding protein cytoplasmic 1, p = 0.0045) were higher in patients with myasthenia gravis, but the relevance of this and two further antigens, 40S ribosomal protein S13 (20.8% vs. 0%, p = 0.011) and proteasome subunit alpha type 1 (25% vs. 3.1%, p = 0.035), which were detected more frequently by myasthenia gravis than by control sera, currently remains uncertain.

Conclusion

Seroreactivity profiles of patients with myasthenia gravis detected by a customized protein macroarray did not allow discrimination from healthy controls, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor.     

生物Fas和Bcl-2在胸腺瘤患者瘤组织表达中与并发重症肌无力的相关性研究

探讨胸腺瘤患者瘤组织中凋亡诱导基因Fas和凋亡抑制基因Bcl-2的表达情况及其与胸腺瘤患者并发重症肌无力（MG）的相关性。通过免疫组化S-P法,检测经手术治疗的胸腺瘤伴MG患者切除瘤组织中Fas、Bcl-2的表达水平,并以胸腺瘤不伴MG患者瘤组织中Fas、Bcl-2的表达水平作为对照。Fas在伴有MG的胸腺瘤中的表达高于对照组,差别有显著性意义（P〈0.01）;Bcl-2在伴有MG的胸腺瘤中的表达低于对照组,差别有显著性意义（P〈0.01）。胸腺瘤合并MG患者瘤组织中凋亡诱导基因Fas呈高表达和凋亡抑制基因Bcl-2呈低表达与胸腺瘤患者并发MG有相关性。     

Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study

The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.     

Myasthenia Gravis,Autoantibodies, and HL-A Antigens

The serum of 100 patients with myasthenia gravis and 441 of their first-degree relatives was studied for the presence of autoantibodies against several antigens. Antibodies to skeletal muscle were present in 22% of the patients and in 2% of the relatives. Both these frequencies were significantly higher than those in matched control subjects. Also, antinuclear antibodies were present more often both in the patients and in the relatives. Typing for HL-A antigens had shown a positive correlation between HL-A 8 and myasthenia gravis which was significantly higher in women than in men. Antibodies to skeletal muscle and thymomas were found to be much rarer in HL-A 8-positive patients than in HL-A 8-negative patients; HL-A 8-positive patients acquired the disease at an earlier age.HL-A 2-positive patients more often had thymomas and antibodies to skeletal muscle than HL-A 2-negative patients; HL-A 2-positive patients acquired myasthenia gravis at a later age.The fact that the clinical aspects of the HL-A 8-negative and HL-A 2-positive patients were different from those of the HL-A 8-positive and HL-A 2-negative patients justifies the hypothesis that there are two forms of myasthenia gravis.