Steroid therapy without primary dose escalation for postthymectomy crisis in 2 thymomatous myasthenia gravis patients

We report 2 cases of thymomatous myasthenia gravis associated with postoperative crisis and medicated with steroid therapy using prednisolone without primary dose escalation. Two women, a 38 years old and the other 64 years old, underwent extended thymectomy under the diagnosis of myasthenia gravis associated with invasive thymoma. Bulbar symptoms in both were severe despite preoperative anticholinesterase medication. Myasthenic crises with an antiacetylcholine receptor antibody (anti-AchR Ab) elevation were encountered in the postoperative clinical course. Daily administrations of a large amount of prednisolone without primary dose escalation and the subsequent tapering therapy effectively improved myasthenic symptoms and decreased their anti-AchR Ab titer. We also discuss difficulties in treatment in these cases.     

重症肌无力血清抗乙酰胆碱受体抗体和抗突触前膜抗体监测的临床意义

用ＡＢＣ－ＥＬＩＳＡ法对５０例重症肌无力（ＭＧ）病人血清中抗乙酰胆碱受体抗体（ＡｃｈＲａｂ）和抗突触前膜抗体（ＰｒＭａｂ）进行检测。结果发现：①ＭＧ患者抗体总阳性３７例（阳性率７４％），其中ＡｃｈＲａｂ阳性３３例（６６％），ＰｒＭａｂ２９例（５８％），二者均显示重症患者阳性率高于轻症。②血清中两种抗体滴度重症患者均明显高于轻症，胸腺肿瘤ＡｃｈＲａｂ滴度明显高于胸腺增生病例，抗体滴度与胸腺病理关系呈肿瘤＞萎缩或正常＞增生。③ＡｃｈＲａｂ和ＰｒＭａｂ高度相关。结果表明ＡｃｈＲａｂ与ＭＧ病情轻重和胸腺病理有一定关系，可用于ＭＧ的病情监测，ＰｒＭａｂ同样可以作为ＭＧ的一项免疫学诊断指标，有重要的临床应用价值。     

A case of encapsulated noninvasive thymoma (stage I) with myasthenia gravis showing metastasis after a 2-year dormancy

We herein describe a case of thymoma in which metastasis to the left lower visceral and parietal pleura was noticed after a 2-year dormancy. A closer examination revealed no evidence that the metastatic tumors were of lymph node origin. The initial thymoma was well encapsulated, and thus it was thought that the development of metastasis might have reflected a sudden rapid growth of the thymoma cells after a 2-year period of inactivity.     

A comparative histological and immunohistochemical study of thymomas with and without myasthenia gravis

Because myasthenia gravis (MG) is frequently associated with thymoma, in this study the histological patterns of thymomas from 11 patients with MG (group A) were compared with those from 8 patients without MG (group B). An immunohistochemical examination was also conducted to determine whether the thymoma associated with MG is the site where autoantibodies are produced or secreted. Lymphoid follicles (LFs) and medullary differentiation (MD) were histologically evident only in group A in 4 and 5 patients, respectively, but were completely absent in group B. Moreover, an elevated serum antiacetylcholine receptor antibody titer was found in group A. Typical LFs were histologically and phenotypically similar to the lymph follicles seen in reactive lymph nodes. The number of cells expressing the B-cell antigen differed between groups A and B in terms of IgM- or IgD-bearing cells in the mantle zones and LNI-positive cells in the germinal centers of Us. Thus, it is thought that LFs consist of B cells under stimulatory conditions and that these B cells may have the potential to produce autoantibodies in MG; however, since the differentiation of these Ig-bearing cells to plasma cells was hardly evident, the thymoma itself is possibly not the site of autoantibody production or secretion in patients with MG.     

Sevoflurane as a sole anaesthetic for thymectomy in myasthenia gravis

Myasthenia gravis is a challenging situation for anaesthesiologists due to its neuromuscular involvement. The main concerns are respiratory muscle weakness and side effects due to a heavy dose of anticholinesterases. This limits the use of sedatives, hypnotics and muscle relaxants. Inhalational anaesthetics are best suited. We describe our experience with sevoflurane as a sole anaesthetic in a child having juvenile-type myasthenia gravis with thymoma, who underwent thymectomy by midsternal incision. Very smooth and short duration of induction (35 s) and easy intubation within 60 s without use of muscle relaxant were the remarkable features. Sevoflurane in oxygen and nitrous oxide (MAC=0.5-0.7) was used for maintenance of anaesthesia. Recovery was smooth and fast with no residual respiratory insufficiency. Hence we found sevoflurane to be a highly suitable agent for thymectomy in mysthenia gravis.     

The effect of thymectomy on myasthenia gravis,thrombocytopenia, and granulocytopenia associated with thymoma: Report of a case

We report the case of a 47-year-old woman with thymoma who developed myasthenia gravis, thrombocytopenia, and granulocytopenia, simultaneously, the concurrent association of these four disorders being extremely rare. Thymectomy was performed, and, during the post-thymectomy course, there were surprising findings concerning the recovery of not only the myasthenia gravis but also of the hematologic disorders. Immediately after thymectomy, the myasthenic symptoms completely disappeared, and the granulocyte and platelet counts recovered to within the normal range within a few days. The laboratory data revealed no difference between pre- and post-thymectomy in the release of cytokines (tumor necrosis factor; TNF, interleukin; IL-2, and IL-6), anti-acetylcholine receptor antibody, or platelet-associated IgG. On the other hand, the serum level of anti-neutrophil cytoplasmic antibody (p-ANCA), against the myeloperoxidase of the granulocytes was dramatically decreased, after thymectomy, showing a significant correlation with the granulocyte count. According to our survey of the literature, this is the first report to show that the removal of a thymoma led to the dramatic resolution not only of myasthenia gravis but also of other associated diseases. It is possible that p-ANCA may be regulated by thymoma, thus causing severe granulocytopenia.     

Myasthenia gravis with thymoma associated with occult thyroid carcinoma

We report herein a case of myasthenia gravis associated with thymoma and occult thyroid carcinoma with metastasis to a cervical lymph node, which was treated in two stages by a total thymectomy and radical dissection of the bilateral neck after a total thyroidectomy. A 48 year old woman was admitted with right blepharoptosis and hypodynamia of the proximal muscles. After various examinations, a diagnosis of myasthenia gravis was made. The association of thymoma was clarified upon CT scanning and a total thymectomy performed. However, after surgery, swelling of the cervical lymph nodes became apparent and a biopsy revealed metastasis of thyroid carcinoma in the lymph nodes. A diagnosis of occult thyroid carcinoma with metastasis to a cervical lymph node was subsequently made and a total thyroidectomy and radical dissection of the bilateral neck performed 37 days after the total thymectomy. The patient's postoperative course was uneventful and for the time being, no recurrence is expected. It is considered better to perform two-stage operations for easier and safer postoperative management when myasthenia gravis associated with occult thyroid carcinoma is treated, although it depends on the development of thyroid carcinoma being occult.     

Role of thymectomy in the surgical treatment of myasthenia gravis

Of the 26 patients with myasthenia gravis undergone thymectomy, 11 cases had either benign or malignant thymoma as judged not only by hitological examination but also by their clinical and operative findings. Age of initial onset ranged from 13 to 64 years old. Fifteen out of 26 (58 per cent) benefited from thymectomy. Duration of the symptom from the onset to the operation and the presence or absence of the thymoma are not related to their outcome. Benign or malignant nature of thymoma should not be determined by histological examination alone but by combined evaluation of clinical and operative findings. Serial studies of serum immunoglobulin levels before and after thymectomy suggested that this disorder could be associated with humoral antibody (IgG). HLA typing of the patients with myasthenia gravis did not indicate the presence of any specific antigens.     

Triad of thymoma, myasthenia gravis and pure red cell aplasia combined with Sj?gren’s syndrome

A 36-year-old woman complained of cough and high fever. Computed tomographic scans demonstrated a mediastinal mass. A couple of months later, she developed dryness in her eyes and mouth. Biopsy of the lip confirmed the diagnosis of Sj?gren’s syndrome. She underwent thymo-thymomectomy. Pathological findings of the mass revealed thymoma. At two months after surgery, she developed ptosis and dysphagia that were compatible with myasthenia gravis. The clinical symptoms were adequately controlled with prednisolone. At eleven months after surgery, she presented with severe anemia, which led to the diagnosis of pure red cell aplasia. The following treatment with cyclosporin caused hemoglobin concentration to rise. However, she continues to suffer from dryness of her eyes and mouth. The case is the first to be reported with Sj?gren’s syndrome and the triad of thymoma, myasthenia gravis and pure red cell aplasia, and is compared with previously reported cases of the three conditions.     

胸腺瘤合并重症肌无力与单纯重症肌无力的临床特征及手术疗效分析

目的　探讨胸腺瘤合并重症肌无力 (MG)与单纯MG的临床特征及手术疗效。方法回顾性分析 1978年至 2 0 0 3年 2 4 3例MG患者临床资料 ,比较胸腺瘤合并MG组 (6 8例 )与单纯MG组 (175例 )的临床特点 ,以及术后并发症、缓解率、生存情况。结果　胸腺瘤合并MG组较单纯MG组年龄大 [平均年龄分别为 (41± 14 )与 (2 8± 16 )岁 ,t=6 .138,P =0 0 0 0 ]、病程短 (平均分别为 10、2 4个月 ,t =3 783,P =0 0 0 0 ) ,术后肌无力危象发生率高 [分别为 5 0 0 % (34/ 6 8)与 5 7% (10 / 175 ) ,χ2=6 4 77,P =0 0 0 0〗 ,两组Osserman分型差异无显著意义 (χ2 =7 6 78,P =0 10 4 )。胸腺瘤合并MG组肌无力症状完全缓解率、部分缓解率 ,术后 1年分别为 10 2 % (6例 )、6 2 7% (37例 ) ,术后 3年分别为 2 1 6 % (8例 )、75 7% (2 8例 ) ,低于单纯MG组 [术后 1年分别为 2 2 1% (30例 )、94 1% (12 8例 ) ,术后 3年分别为 4 4 4 % (44例 )、94 9% (94例 ) ,P值分别为 0 0 4 9、0 0 0 0、0 0 15、0 0 10 ];术后 5年两组比较肌无力症状完全缓解率、部分缓解率差异无显著意义 (P =0 4 5 7,P =0 6 99)。胸腺瘤合并MG组 3、5年生存率分别为 96 3%、84 4 % ,显著低于单纯MG组的 98     

Suxamethonium in myasthenia gravis

The effects of suxamethonium 1.0 and 0.5 mg/kg were studied in myasthenic patients. Resistance was not encountered at the 1.0 mg/kg dose but was seen at the lower dose. A non-depolarising type of block developed in patients in both groups. However, recovery from the non-depolarising block was not prolonged beyond the requirements of surgery. The neurophysiological basis for, and clinical implications of these findings are discussed.     

胸腺瘤合并重症肌无力术后发生肌无力危象处理体会

目的探讨胸腺瘤切除术后发生重症肌无力危象的原因及治疗方法。方法回顾分析2000年1月至2007年6月我科收治的43例胸腺瘤合并重症肌无力患者中11例发生术后危象的病例资料。结果11例患者中除l例放弃治疗外,其余均治愈出院。术后危象发生率25.5%(11/43),重症肌无力危象主要发生于术后早期。术前准备不充分,手术的创伤,服用抗胆碱酯酶药物剂量不当,感染(尤其是肺部感染)是围术期发生危象的诱因。结论加强围术期管理,可以改善危象的预后,减少发病率和病死率。     

Undiagnosed myasthenia gravis unmasked by neuromuscular blockade

Myasthenia gravis is an uncommon autoimmune disease resultingin destruction of the post-synaptic nicotinic receptors at theneuromuscular junction. We describe a 43-yr-old, 95 kg patientwho presented for elective laparoscopic cholecystectomy. Shewas given vecuronium 10 mg to facilitate tracheal intubation.At the end of the procedure the patient could not maintain adequatespontaneous ventilation despite administration of two dosesof neostigmine 2.5 mg. Subsequent investigation led to a diagnosisof myasthenia gravis. We discuss the investigation, diagnosis,and subsequent management of such a patient and emphasize thattactile estimation of the train-of-four ratio is not a reliableindicator of adequate recovery of neuromuscular function. Br J Anaesth 2001; 86: 727–30     

滤泡辅助性T细胞在重症肌无力伴胸腺瘤患者胸腺中的表达

目的探讨滤泡辅助性T细胞（Tfh）在重症肌无力（MG）伴胸腺瘤患者胸腺组织中的表达变化。 方法采用免疫荧光染色技术、免疫组织化学法和蛋白质印迹法,检测30例MG伴胸腺瘤患者（MG组）、20例无MG的胸腺瘤患者（NMG组）的瘤旁组织及10例心脏手术患者（对照组）萎缩胸腺组织中的Tfh细胞比例及其蛋白分子CXCR-5、ICOS、PD-1和Bcl-6的表达水平。 结果与NMG组和对照组相比,MG组胸腺组织中Tfh细胞比例及其CXCR-5、ICOS、PD-1和Bcl-6的表达水平显著增高,差异有统计学意义（P<0.05）;NMG组胸腺组织中Tfh细胞比例及其CXCR-5、ICOS表达水平显著高于对照组,差异有统计学意义（P<0.05）;NMG组与对照组胸腺组织中Tfh细胞PD-1和Bcl-6的表达水平差异无统计学意义（P>0.05）。 结论MG伴胸腺瘤患者瘤旁胸腺组织中的Tfh可能通过提高自身免疫活性参与MG的发生和进展,抑制Tfh信号通路可能为MG的治疗提供新途径。     

Carcinoid syndrome with myasthenia gravis

The anaesthetic management of a patient suffering from carcinoid syndrome and myasthenia gravis is described including the successful treatment of a carcinoid attack with intravenous aprotonin. The differences between myasthenia gravis and the myasthenic (Eaton-Lambert) syndrome are considered and the rationale for the choice of vecuronium as the muscle relaxant is discussed.     

免疫吸附疗法治疗晚发型重症肌无力

目的 观察蛋白A免疫吸附（IA）治疗对晚发型重症肌无力（MG）相关抗体的清除效果及短期临床疗效。 方法 随机选取25例晚发型MG患者，其中10例MG患者接受IA治疗，15例接受丙种球蛋白（0.4 g·kg-1·d-1）冲击治疗5 d。观察两组治疗前后血清中特异性标志物连接素抗体（Titin-ab）、抗乙酰胆碱受体抗体（AchR-ab）、突触前膜抗体（PrsmR-ab）的变化，同时测定治疗前后定量重症肌无力（QMG）评分。比较两组患者治疗有效率、临床症状缓解时间、呼吸机使用人数和平均住院天数的差异，并分析3种抗体水平的下降和QMG评分改善的相关性。 结果 与治疗前比较，治疗后免疫吸附组和丙种球蛋白组的Titin-ab（P/N值）、AchR-ab（P/N值）、PrsmR-ab（P/N值）均显著下降（均P < 0.05）。其中免疫吸附组的Titin-ab下降幅度显著大于丙种球蛋白组（54.7%±3.5%比19.9%±3.1%，P < 0.05）。免疫吸附组的QMG评分下降幅度显著大于丙种球蛋白组（42.4%±4.2%比23.8%±3.7%，P < 0.05）。免疫吸附组的治疗有效率显著高于丙种球蛋白组（70%比40%，P < 0.05）；临床症状开始缓解的时间也明显缩短[（5.38±0.42） d 比 （8.40±1.54） d，P < 0.01]；呼吸机使用人数（1/10 比 6/15，P < 0.05）和平均住院天数[（13.50±0.50） d比(16.00±0.50) d，P < 0.05]均低于丙种球蛋白组。相关分析显示Titin-ab的下降幅度和QMG评分下降呈正相关（r = 0.6315，P < 0.01）。 结论 免疫吸附疗法能快速有效清除晚发型重症肌无力患者体内的致病抗体，短期疗效优于丙种球蛋白。