Thymectomy for myasthenia gravis: 12-year experience

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation is the complete removal of the thymus, but there is no consensus on the selection criteria of patients for surgery and the choice of surgical approach. We retrospectively reviewed 56 patients with myasthenia gravis who had been treated surgically by transsternal radical thymectomy between January 1990 and March 2002. The patients were symptomatically grouped according to the modified Osserman clinical classification. There was 1 hospital death, and 53 patients had been followed up for between 1 month and 12 years. Improvement after thymectomy was observed in 1 of 4 patients (25%) in Osserman group I, 25 of 34 patients (74%) in Osserman group IIA, and 16 of 18 patients (89%) in combined Osserman groups IIB and IIC. Transsternal radical thymectomy is an effective therapy for myasthenia gravis. Sustained improvement is achievable in female patients with moderate to severe symptoms and in patients with thymic hyperplasia.     

胸腺瘤伴重症肌无力患者瘤组织中Bcl-2和Fas的表达水平

目的 探讨凋亡相关基因bcl-2、Fas在胸腺瘤伴重症肌无力患者瘤组织中的表达状况及其临床意义。方法经手术治疗的25例胸腺瘤伴重症肌无力患者的肿瘤组织标本为病例组，25例先天性心脏病患者手术时切取的正常胸腺组织标本为对照组，通过免疫组化的方法检测两组标本中Bcl-2和Fas蛋白的表达水平。结果胸腺瘤中Bcl-2及Fas表达水平均显著高于对照组，经Ridit分析两者差异均有统计学意义（U值分别为2．645、3．200，P均〈0．05），但Bcl-2和Fas的表达水平与胸腺瘤患者的重症肌无力Ossermen分型、术前病程、年龄及性别等临床因素均无显著相关。结论 Bcl-2和Fas在胸腺瘤伴重症肌无力的发病中可能具有重要作用。     

Microscopic-sized "microthymoma" in patients with myasthenia gravis

BACKGROUND: In 2005, Cheuk et al reported two patients with microscopic-sized thymomas and proposed the term microthymoma to distinguish it from the nodular hyperplasia of thymic epithelium, so-called microscopic thymoma. Here, we present microthymomas that were found in 196 patients with myasthenia gravis (MG) who had undergone thymectomy. MATERIALS AND METHODS: Thymic tissues in 196 patients with MG who underwent thymectomy or thymothymomectomy were examined. Of these patients, 73 patients had thymoma indicated by CT before surgery, and the other 123 patients had no mediastinal tumors. From the resected thymic tissues, an average of 14 hematoxylin-eosin-stained sections (range, 4 to 55 sections) were prepared for microscopic examination. The histologic type of the thymoma was classified according to the World Health Organization (WHO) classification. RESULTS: From the 196 patients, we found three microthymomas in 3 patients (1.5%). While these three tumors could not be seen grossly in pathology section, they were found microscopically (range, 2 to 4 mm). The histologic subtype according to the WHO classification system was B1 in one patient and B2 in two patients. CONCLUSION: Microthymoma was found in 3 of 196 patients (1.5%) with MG. Microthymoma might exist in thymus of patients with MG, even in patients who have no thymoma indicated by CT.     

重症肌无力胸腺切除术后发生肌无力危象的危险因素分析

目的:回顾性分析研究重症肌无力患者胸腺切除术后发生肌无力危象的危险因素。 方法:对本医院1970年-2011年实施的胸腺切除术的306例MG患者进行回顾分析，利用Logistic回归从多种相关因素（例如年龄、分型、术前术后处理、手术方式、预后等）中筛选出危险因素。 结果:术后发生肌无力危象与患者发病年龄、手术时间、病程、术前分型、术前是否累及吞咽肌、术前是否发生危象、是否确定为胸腺瘤相关，并且关系着患者的预后。 结论:术前吞咽肌受累、术前发生危象、确诊胸腺瘤是预测胸腺切除术后肌无力危象发生的独立危险因素。     

血清Ryanodine受体抗体检测对胸腺瘤并重症肌无力的诊断价值

目的 探讨血清Ryanodine受体抗体（RyR-Ab）对胸腺瘤并重症肌无力（MG）的诊断价值。方法 选择经病理检查证实为胸腺病变并MG的患者35例,其中胸腺瘤并MG患者（MGT组）17例、胸腺增生并MG患者（MGH组）12例、胸腺萎缩并MG患者（MGA组）6例,同时选择胸腺正常的MG患者（NTMG组）27例,健康对照者（NC组）50例;采用ELISA法检测其血清RyR-Ab。结果 MGT组血清RyR-Ab阳性率为76．5％,MGH组为8．3％,MGA组为16．6％,NTMG组为0,NC组为0。结论MGT患者血清RyR-Ab阳性率较高,检测血清RyR-Ab有助于MGT的诊断。     

Retrospective analyses of clinical features and therapeutic outcomes in thymectomized patients with myasthenia gravis at Shinshu University

OBJECTIVES: Thymectomy has become recognized as an integral element in the treatment of patients with myasthenia gravis (MG). Although the incidence of elderly-onset MG has recently been increasing, there is little data demonstrating the efficacy and complications of thymectomy in this population. To clarify this point, we divided the thymectomized patients with MG into young and elderly groups, and retrospectively examined their clinical features and therapeutic outcomes. PATIENTS AND METHODS: We reviewed 57 MG patients who had been admitted to our hospital between 1988 and 2002. The patients were classified into young (younger than 60) and elderly (60 or older) groups according to the age of onset, and the therapeutic outcomes of thymectomy were evaluated using myasthenic severity scales and the duration from operation to discharge. RESULTS: Myasthenic severity scales significantly improved after thymectomy in the elderly group both with (p<0.005) and without thymoma (p<0.05) compared with before. With regard to the duration from thymectomy to discharge, no significant difference could be found between the young and elderly groups, irrespective of associated thymoma. There were no serious complications during and after thymectomy in either the young or the elderly group. CONCLUSIONS: Despite various possible complications due to aging, thymectomy should be actively considered also in the treatment of elderly MG patients because it can reliably and safely improve myasthenic symptoms in combination with immunosuppressive agents, including corticosteroid.     

Complications and efficacy of transsternal thymectomy in myasthenia gravis

Between January 1977 and September 1985, 75 patients in our department underwent elective surgery for myasthenia gravis through a median sternotomy. The main prerequisite was optimal stabilization by medical treatment with the best possible vital capacity. The Osseman types were as follows: type I (22), type IIa (19), type IIb (26), type III (7), and type IV (1). All patients, except for 3 who were mechanically ventilated for a few hours after surgery, were immediately extubated at the end of the operation. The most frequent histologic finding was thymic hyperplasia (36%); 21.3% of the patients had thymomas. No surgery-related deaths occurred. Wound healing was impaired in 6.7% of the patients, including one patient with complete sternal instability, while 5.3% developed pneumonia. The most serious complications were myasthenic (9.3%) and cholinergic (2.7%) crises. Paresis of the phrenic (2.7%) and recurrent laryngeal (1.3%) nerves occurred only in the thymoma patients, who also had a higher frequency of all other complications. The effect on the myasthenic symptoms 3 months after surgery was as follows: 7.5% of the patients were in complete remission, 61.2% had improved, 9% had deteriorated. In a logistic regression model, the parameters age, sex, duration of disease, Osserman type, histology, pre-operative antibody titer to acetylcholine receptors, and post-operative change in titer were examined with respect to their influence on the effect of surgery. Only thymic histology had an appreciable influence (p = 0.057). The effect of these parameters on the success of surgery as well as the type and frequency of complications in relation to perioperative procedure are discussed in detail.     

Clinical characteristics and prognosis of myasthenia gravis in older people

OBJECTIVES: To investigate the characteristics of myasthenia gravis (MG) in older people and to evaluate the benefits of immunosuppressive treatments at this age. BACKGROUND: Myasthenia gravis in older adults has not been extensively studied. In patients with disease onset after the age of 60, treatment mainly relies on medical therapy because thymectomy is generally not performed unless a thymoma is present. METHODS: Of 837 myasthenic patients followed since 1978, we identified 172 cases with onset after age 60. All patients were treated with anticholinesterases. In the decade from 1978 to 1988, immunosuppressive therapy was performed mainly with corticosteroids (prednisone); since 1989, azathioprine alone or, more often, associated with prednisone, has been increasingly used in MG patients. Long-term outcome was evaluated in 149 cases with follow-up longer than 1 year. Remission, pharmacological remission, and marked improvement with reduction in drug dosage were considered good results. RESULTS: Patients older than age 60 at onset of the disease were 20.5% of our series, male/female ratio was 1.9, age at onset ranged from 61 to 86 years, 87.2% patients had generalized disease, thymoma was detected in 37 patients (21.5%). Of 149 cases with sufficient follow-up data, 9 were in remission, 111 achieved good results, 3 died of MG, and 120 required immunosuppressive therapy at some time. Sixty-seven patients had been treated with prednisone for 0.5-16 years (mean, 5 years); good results were recorded in 51 patients (76.1%) and severe side effects in 12 (17.9%). Forty-six patients had received combined therapy with prednisone and azathioprine for 1 to 12 years (mean, 3.9 years); good results were recorded in 41 patients (89.1%) and severe side effects in six (19.5%). Seven patients had been treated with azathioprine alone for 1 to 4 years (mean, 2.3 years) with good results in five and with no side effects. CONCLUSIONS: The prognosis of MG in older people seems to be favorable, although full remission is rare and MG weakness, treatment side effects, and associated thymoma can contribute to mortality rate. In our experience, the combined therapy with prednisone and azathioprine was more effective than prednisone alone, and steroid-related side effects were more frequent than those related to azathioprine.     

A comparative study of ocular and generalized myasthenia gravis

We compared the relations and therapeutic outcomes of ocular and generalized types of myasthenia gravis (MG) and used retrospective analysis for 65 patients with myasthenia gravis during a mean follow-up time of 30.4 months. There were 35 ocular and 30 generalized MG patients. Items of comparison included sex, age, clinical presentations, serum antibody titer, the association with thymus status, and therapeutic outcome. Of the patients with generalized MG, males were significantly older than females. Ptosis and diplopia were the most common symptoms in patients with MG, but there were no significant differences between the two types of MG. The eyelid levator muscle and lateral rectus muscle were the most commonly involved extraocular muscles in patients with MG. The associations with thymoma or thymus hyperplasia were more common in generalized MG than in ocular MG, and more common in younger than in older patients. The result of positive neostigmine test was 93.8% in all patients, but there were no significant differences between the two types of MG. Acetylcholine receptor antibody (AchRAb) presented an 81.1% positive rate and was significantly higher in generalized MG than that in ocular MG (96.2% vs 66.7%). There were no significant differences between the two types of MG regarding successful treatment strategies in both initial therapy and maintenance therapy. Only two of 16 patients had complete remissions after thymectomy. From the viewpoint of clinical presentations or from the therapeutic strategy outcome, the boundary between both types of MG seems to be vague. Both types of MG probably share the same entity in nature and the difference is just a matter of degree of severity. The benefit of thymectomy in treatment of MG needs further investigation.     

MYASTHENIA GRAVIS : CLINICAL,SEROLOGICAL AND HISTOLOGICAL STUDIES IN RELATION TO THYMECTOMY

In 10 cases of myasthenia gravis correlative studies were made by means of autoimmune serological tests, electromyography, thymic X-ray examination (pneumomediastinography) and assessment of thymic morphology in relation to the effects of thymectomy (nine cases) and thymic irradiation (one case). The 10 patients were placed in three groups, namely (a) three young females with a non-involuted thymus showing “thymitis” and negative results to serological tests who derived benefit from thymectomy, (b) four older females with thymic atrophy and positive results to serological tests who for the most part gained no benefit from thymectomy, and (c) three males with thymomas and positive results to serological tests who obtained benefit from thymectomy in two instances. The presence of the characteristic autoantibody—the myoid antibody which reacted with thymic myoid cells and skeletal muscle—was helpful in diagnosis but did not appear to be related to neuromuscular block, neither was it of value in predicting the response to thymectomy. Electromyography with the decamethonium test showed, with one exception, the characteristic myasthenic responses irrespective of the patient's age, the presence or absence of myoid antibody, or the nature of the microscopic lesion in the thymus. The radiographic outline of the thymus as determined by pneumomediastinography correlated well with the size and shape of the resected thymus. The typical histological appearance in the thymus of abundant cortex and prominent medullary germinal centres and lymphocytosis was termed “thymitis” ; it was characteristic of the thymus of patients in group (a) and the residual thymus of patients with thymoma in group (c). Our clinical observations could be correlated with experimental studies, indicating that myasthenia gravis is associated with a destructive “autoimmune thymitis”. It is suggested that “thymitis” is associated with the release from the medulla of an uncharacterized humoral agent which causes neuro-muscular block.     

Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis

STUDY OBJECTIVES: Minimal-access thymectomy has become increasingly popular as surgical treatment for patients with nonthymomatous myasthenia gravis (NTMG) because of its comparable efficacy, safety, and lesser degree of tissue trauma compared with conventional open surgery. We reviewed and analyzed our data on video-assisted thoracic surgery (VATS) thymectomy and present the clinical outcomes according to the Myasthenia Gravis Foundation of America classification. DESIGN: A retrospective review of VATS thymectomy for NTMG in a university hospital over a 12-year period. Data were collected from the medical records and supplemented with telephone surveys. The impact of surgery and other variables potentially affecting complete stable remission (CSR) were calculated using Kaplan-Meier survival curves; comparisons between survival curves was performed using the log-rank test. RESULTS: A total of 38 consecutive patients underwent VATS thymectomy for NTMG. Median postoperative stay was 3 days. Pathologic examination revealed thymic hyperplasia in 61.1% of cases, normal thymus in 22.2%, and thymic atrophy in 16.6%. There was no perioperative mortality; complications occurred in four patients. After a median follow-up of 69 months, 91.6% of patients experienced improvement, with crude CSR achieved in 22.2%. Kaplan-Meier survival curve demonstrated a 75% CSR rate at 10-year follow-up. On univariate analysis, only disease duration < or = 12 months (p = 0.03) was associated with a statistically significant improvement in CSR. CONCLUSIONS: VATS thymectomy for NTMG results in symptomatic improvement in the vast majority of patients, with a high rate of CSR. The procedure is associated with low morbidity and no perioperative mortality. Future studies on thymectomy for myasthenia gravis should be reported in a standardized manner to allow accurate comparisons between results in the absence of randomized prospective trials.     

51例重症肌无力患者的临床与胸腺病理和电镜分析

目的分析胸腺增生与伴胸腺瘤的重症肌无力患者临床表现及其胸腺病理类型和超微结构特点。方法对51例MG患者的病例资料进行回顾性分析。按照胸腺瘤组和胸腺增生组,对临床症状、MG危象发生率、胸腺瘤WHO组织学分型、胸腺超微结构特点等各项指标进行对比。结果胸腺瘤组临床症状重、MG危象发生率高、术后MG症状改善程度差。结论胸腺瘤组MG患者病情重,WHO组织学分型对于区别良恶性肿瘤及预后有指导意义,胸腺超微结构特点的研究有助于澄清MG的发病机制。     

Myasthenia gravis with membranous nephropathy, successfully treated with extended total thymectomy

A 46-year-old woman showed proteinuria and hematuria after left blepharoptosis, and revealed a histopathology of membranous nephropathy (MN) at renal biopsy. She was diagnosed as having myasthenia gravis (MG) because of a positive edrophonium test and anti-acetylcholine receptor (AchR) antibodies in serum. We found a decrease in anti-AchR antibodies after extended total thymectomy, in parallel with an improvement in both urinary findings and myasthenic symptoms. In this case, MG preceded MN and the thymectomy was effective for both diseases, suggesting that the thymus might play an important role in the pathogenesis of MN.     

Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma

Background

To investigate the presence of T follicular helper (TFH) cells and their associated molecules in myasthenia gravis (MG) patients with thymoma.

Methods

TFH cells are detected in thymus around the thymoma region of 50 patients and atrophic thymus in 10 patients as control. The percentage of TFH cells among CD4⁺ T cells and the expression level of surface markers CXC chemokine receptor 5 (CXCR5), inducible co-stimulator (ICOS), programmed cell death 1 and the cytoplasmic marker B cell lymphoma 6 (Bcl-6) were analyzed by immunohistochemistry (IHC) staining, immunofluorescence (IF) and western blotting (WB).

Results

Higher percentage of thymic TFH cells was found in MG patients with thymoma compared with both thymoma patients without MG and control group. The expression levels of the four markers in thymoma of MG patients were significantly higher than thymoma patients without MG and control group. No significant difference was found in the levels of programmed cell death 1 (PD-1) and Bcl-6 between thymoma patients without MG and the control, while the levels of CXCR5 and ICOS in thymoma patients without MG were higher than control group.

Conclusions

These results suggested thymic TFH cells might involve in the pathogenesis of MG with thymoma. However, it needs further study to test if the inhibition of the function of TFH cells could effectively alleviate the severity of MG.     

Myasthenia in children: long-term course

Twenty three children with myasthenia were followed up in our Department for 10 years. There were no familial forms of the disease; there were no patients with the pure ophthalmic form but 61 p. 100 of patients had serious respiratory disease. Steroid therapy was possible in 10 cases: in 4 patients under 15 years of age, short courses of steroids were ineffective; in 6 patients over the age of 15, long term steroid therapy resulted in some improvement but cortico-dependence developed in 4 cases. One child responded to treatment with veinoglobulin (R). Sixteen children underwent thymectomy; the symptoms in the 7 non-thymectomized patients were equivalent. The myasthenic syndrome was stable or worsened in 75 p. 100 of cases after thymectomy; only 56 p. 100 of children improved 2 years after surgery. The incidence of complete remission was the same in the children undergoing thymectomy and in those not treated surgically at 7 years after thymectomy. Our attitude is therefore not to refer myasthenic children for routine thymectomy and to avoid steroid therapy whenever possible.     

La myasthénie du côté de l’interniste

Myasthenia gravis is an autoimmune disease due to specific antibodies inducing a neuromuscular transmission defect causing muscle fatigability. If onset of the disease may be at any age, myasthenia gravis concerns mostly young adults, in majority females. The disease characteristic features are the following: ocular symptoms (ptosis or diplopia) as main initial manifestation, extension to other muscles in 80 % of the cases, variability of the deficit, effort induced worsening, successive periods of exacerbation during the disease course, severity depending on respiratory and swallowing impairment (if rapid worsening, a myasthenic crisis is to be suspected), association with thymoma in 20 % of patients and with other various autoimmune diseases, most commonly hyperthyroidism and Hashimoto's disease. Diagnosis relies on the clinical features, improvement with cholinesterase inhibitors, detection of specific autoantibodies (anti-AChR or anti-MuSK), and significant decrement evidenced by electrophysiological tests. The points concerning specifically the internist have been highlighted in this article: diagnostic traps, associated autoimmune diseases, including inflammatory myopathies that may mimic myasthenia gravis, adverse effects of medications commonly used in internal medicine, some of them inducing myasthenic syndromes. The treatment is well codified: the treatment is well codified: (1) respect of adverse drugs contra-indications, systematically use of cholinesterase inhibitors, (2) thymectomy if thymoma completed with radiotherapy if malignant, (3) corticosteroids or immunosuppressive agent in severe or disabling form, (4) intensive care unit monitoring, plasmapheresis or intravenous immunoglobulins for patients with myasthenic crisis.     

Lambert-Eaton myasthenic syndrome and follicular thymic hyperplasia in systemic lupus erythematosus

Fatigue is a prominent feature of systemic lupus erythematosus (SLE), usually ascribed to various factors, such as muscle or joint involvement, anaemia or depression. The Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoantibody-mediated disorder of neuro-muscular transmission. We report on a well-defined LEMS associated with thymus hyperplasia in a SLE patient. An African 41 years-old SLE patient presented with persisting fatigue, myalgia and dyspnea, abolished reflexes and a bilateral ptosis. Neuromuscular electrodiagnostic study showed a clear-cut potentiation that was typical of a pre-synaptic neuromuscular junction disease. Anti-calcium gated channels antibodies were disclosed in serum and a diagnosis of LEMS was made. A total body CT-scan revealed an antero-superior mediastinal mass, compatible with thymoma. The tumour was surgically removed with a final diagnosis of follicular thymic hyperplasia. In conclusion, our observation provides a new example of entangled organ-specific and systemic autoimmunity in the context of thymus pathology. Potentiation study during electromyography should be performed systematically to rule out LEMS in patients with SLE and muscle weakness.     

Thymectomy versus tumor resection for early-stage thymic malignancies: a Chinese Alliance for Research in Thymomas retrospective database analysis

Background

To evaluate the surgical outcomes of tumor resection with or without total thymectomy for thymic epithelial tumors (TETs) using the Chinese Alliance for Research in Thymomas (ChART) retrospective database.

Methods

Patients without preoperative therapy, who underwent surgery for early-stage (Masaoka-Koga stage I and II) tumors, were enrolled for the study. They were divided into thymectomy and thymomectomy groups according to the resection extent of the thymus. Demographic and surgical outcomes were compared between the two patients groups.

Results

A total of 1,047 patients were enrolled, with 796 cases in the thymectomy group and 251 cases in the thymomectomy group. Improvement rate of myasthenia gravis (MG) was higher after thymectomy than after thymomectomy (91.6% vs. 50.0%, P<0.001). Ten-year overall survival was similar between the two groups (90.9% after thymectomy and 89.4% after thymomectomy, P=0.732). Overall, recurrence rate was 3.1% after thymectomy and 5.4% after thymomectomy, with no significant difference between the two groups (P=0.149). Stratified analysis revealed no significant difference in recurrence rates in Masaoka–Koga stage I tumors (3.2% vs. 1.4%, P=0.259). However in patients with Masaoka-Koga stage II tumors, recurrence was significantly less after thymectomy group than after thymomectomy (2.9% vs. 14.5%, P=0.001).

Conclusions

Thymectomy, instead of tumor resection alone, should still be recommended as the surgical standard for thymic malignancies, especially for stage II tumors and those with concomitant MG.     

Disorders of the thymus. A review

The thymus remains one of the least understood organs in the body. It has gone from the villain to the hero. For many years, it was blamed for what is now recognized as the sudden infant death syndrome; now, its role of immunosurveillance is being recognized. In spite of the fact that there are only two predominant cell types within the thymus, there are nearly 15 histologically different neoplasms of the thymus. These, in turn, are associated with more than 20 parathymic syndromes that affect approximately 40% of patients with thymoma. The three most common of these syndromes associated with thymic disorders are myasthenia gravis (MG), pure red cell aplasia (PRCA), and hypogammaglobulinemia. Thymomas are found in 15% of patients with MG, 50% of those with PRCA, and 10% of those with adult-onset hypogammaglobulinemia. Of all thymomas, 35% are malignant, that is, invasive or metastatic.     

Early and late results after thymectomy in myasthenia gravis: a retrospective study [correction of analysis]

BACKGROUND: This study aims to evaluate the early and late outcome of patients treated by surgery for myasthenia gravis and the diagnostic value of the Besinger Score, which is based on a correlation of severity of symptoms with specific antibodies to acetylcholine receptors, in the follow-up investigation after surgical therapy. METHODS: Between June 1984 and April 1992 thoracotomy was performed in 51 myasthenia gravis cases at our department. The retrospective analysis considered patients with (n = 13) or without thymoma (n = 38). The Besinger score was used to describe the severity of disease preoperatively and up to 5 years postoperatively. RESULTS: The Besinger score fell continually post surgery. Changes in relative serum concentrations of antibodies were similar to the Besinger score. Five years after thymectomy complete remission was diagnosed in 40% of the patients. The required dosage of pyridostigmine had fallen by two thirds after 5 years. Patients with follicular hyperplasia had significantly higher remission rates than those with thymoma. CONCLUSIONS: Surgery for myasthenia gravis is successful. The Besinger score well quantifies the severity of the disease.