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.     

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。     

Factors influencing improvement and remission rates after thymectomy for myasthenia gravis.

BACKGROUND: Thymectomy has become an accepted option in the treatment of myasthenia gravis (MG). However, the optimal selection of patients for surgery remains controversial. OBJECTIVE: The objective of the study is to define factors influencing improvement and remission rates after thymectomy for MG. METHODS: We retrospectively reviewed our experience in the surgical management of patients with MG over the last 20 years, and analyzed if patient's age, sex, preoperative Osserman Stage, thymic histology, duration of symptoms, or radiological findings influenced outcome. RESULTS: There were 25 women and 10 men. Most of them presented with Osserman stage IIA (n = 12) and stage IIB (n = 17). Hyperplasia of the thymus was observed in 15 patients (43%), thymoma in 12 (34%), and atrophic or normal thymus in 8 (23%). Computed tomography (CT) had a positive predictive value of 91% in detecting thymoma and of 80% in detecting thymic hyperplasia. Over a mean follow-up of 96 months, MG improved markedly in 26 patients. Postoperative improvement was significantly greater in patients with advanced MG (stage IIB, III and IV), whereas a higher rate of remission occurred in patients with mild MG (stage I and IIA), and in those with thymic hyperplasia. No relation was observed between outcome and age, sex, duration of symptoms and abnormal CT findings. CONCLUSIONS: The beneficial effects of thymectomy are characterized by postoperative clinical improvement in most patients with moderate to severe preoperative myasthenic involvement and by a higher remission rate in patients with thymic hyperplasia and/or mild myasthenic symptoms.     

Therapeutic Apheresis in Myasthenia Gravis

Abstract: Plasma exchange (PE) is an easily applicable technique for rapid and massive removal of antibodies, and its beneficial role is well established in the management of myasthenia gravis (MG), an antibody‐mediated disorder of the neuromuscular junction. PE is useful in myasthenic crisis, in most severe forms of MG before thymectomy, in the early postoperative period, and in cases of symptom worsening during tapering or initiation of immunosuppressive therapy. Clinical efficacy varies from 55% to 100%, and improvement rarely persists for more than 4–10 weeks; thus immunosuppressive therapy has to be associated. New apheretic techniques (double filtration plasmapheresis, immunoadsorption systems with staphylococcal protein A columns or thryptophan‐polyvinyl alcohol gel columns) that allow the selective removal of IgG and anti‐AChR antibody were recently used in the management of MG with positive effects. Whether their therapeutic effect and cost effect prove more favorable than those obtained by PE still must be demonstrated.     

Resolution of autoimmune oophoritis after thymectomy in a myasthenia gravis patient

Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies against acetylcholine receptors. MG is generally an isolated disorder but may occur concomitantly with other autoimmune diseases. We describe an eighteen-year-old girl with MG who was admitted to our clinic with secondary amenorrhea and diagnosed as autoimmune oophoritis. Since her myasthenic symptoms did not resolve with anticholinesterase therapy, thymectomy was performed. After thymectomy, her menses have been regular without any hormonal replacement therapy. To our knowledge, this is the first report on a patient with autoimmune ovarian insufficiency and MG in whom premature ovarian insufficiency resolved after thymectomy, without hormonal therapy.     

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.     

Robotic thymectomy for myasthenia gravis surgical techniques and outcomes

Myasthenia gravis (MG) is an autoimmune disorder in which antibodies are produced against post-synaptic acetylcholine receptors, thereby causing impairment of neuromuscular transmission. Diagnosis of MG is confirmed with the AChR antibody test and via an Electromyography. Although medical treatment with acetylcholinesterase inhibitors remains the main treatment of MG, in recent years thymectomy has become an integral part of the treatment algorithm. Numerous factors such as the Patient’s age, presence of AChR antibodies, or MuSK antibody, the severity of disease affect the decision of preforming the thymectomy. Historically thymectomy was preformed via sternotomy associated with significant morbidity. Advancement in the minimally invasive approaches to thymic resection has led to more acceptance of thymectomy in the management of MG. Among these approaches, robotic thymectomy is gaining popularity across the globe due to the unique advantages of the robotic platform like 3D visibility, enhanced dexterity, and wrist like articulating movements of instruments. This has led to less post-operative pain and morbidity; faster recovery and shorter hospital stay. Successful treatment of MG requires a multi-modality approach, which has led to the formation of MG teams in most academic centers, comprising of a specialist neurologist, intensivist, and thoracic surgeon. In this article, we describe the techniques and outcomes of the robotic thymectomy for 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.     

Plasma Exchange for Treatment of Myasthenia Gravis: Pathophysiologic Basis and Clinical Experience

Abstract: Myasthenia gravis is an autoimmune disease characterized by production of antibodies to acetylcholine receptors located at the motor end plate in skeletal muscles. The antibodies bind and subsequently induce degeneration of these receptors. Loss of acetylcholine receptors results in inadequate contraction of muscle fibers in response to acetylcholine released from nerve terminals and clinically apparent muscle weakness. Plasma exchange removes the circulating antibodies in myasthenic patients with short‐term clinical improvement. Plasma exchange may be indicated in patients with acute exacerbation of neuromuscular weakness with bulbar or respiratory compromise, preoperative optimization prior to thymectomy, and postoperative deterioration following thymectomy or other surgical procedures. Long‐term, intermittent plasma exchange for patients who do not adequately respond to standard treatment is another evolving indication.     

Sevoflurane for induction and intubation in children undergoing congenital cardiac surgery

The induction and intubation characteristics of sevoflurane were studied prospectively in 23 children, aged 3 months to 6 years (mean 24 +/- 20.25), undergoing repair of congenital cardiac defects. After premedication with syrup chloral hydrate (75mg/kg orally), anaesthesia was induced with 8% sevoflurane and 50% nitrous oxide in oxygen. Nasal endotracheal intubation was performed once the pupils were small and central, without the use of neuromuscular blocking agents or opioids. Characteristics of induction and intubating conditions were recorded. Induction time (from application of face mask to loss of eyelash reflex) was 43.7 +/- 4.57 secs (mean +/- SD). Mean intubation time was 149.1 +/- 15.6 secs. Intubating conditions were excellent in 21 patients (91.3%) and good in 2 patients (80.7%). Haemodynamic parameters (heart rate, rhythm, and systolic blood pressure) were recorded at loss of eyelash reflex, immediately before intubation and at 1, 3 and 5 min after intubation. All children remained haemodynamically stable throughout induction and there were no adverse airway events.     

Small thymomas and myasthenia gravis: a poorly understood association

Myasthenia gravis (MG) is associated with about 20% of all patients with thymomas, but the occurrence in patients with small thymomas is rare. The pathogenetic relevance of these small thymomas for MG is poorly understood until now. We report on the clinical course of a 39-year-old female patient suffering from MG and undergoing thymectomy for a small thymoma and discuss the pathogenetic importance of small thymomas for MG.     

Mycophenolate mofetil and myasthenia gravis

Myasthenia gravis (MG) represents the prototypic autoimmune disorder with well characterized immunopathology. Advances in the diagnosis and treatment of this neuromuscular transmission disorder have significantly improved the management of myasthenic patients. Unfortunately the currently available immunomodulating treatments have significant side effects and some patients do not tolerate them or adequately respond to them. Therefore the possibility of a new immunosuppressant agent that is safe, effective and has steroid-sparing effect is very appealing. Mycophenolate mofetil (MMF) has shown promising effects in MG patients in preliminary studies and is currently being studied in two prospective, randomized, double-blind, placebo controlled, multicenter trials to better establish its role in the treatment of MG.     

Recurrence of thymic hyperplasia after thymectomy in myasthenia gravis: Its importance as a cause of failure of surgical treatment

Persistence of symptoms in patients with myasthenia gravis who have undergone previous thymectomy has been attributed to thymus remnants. Patients with partial or no recovery were studied 40 ± 31 months (mean ± SD) after surgery, which had been carried out by the transcervical approach in 20 and trans-sternal approach in four. Lateral x-ray tomography of the mediastinum after injection of air showed images compatible with residual thymus gland in 18 patients (75 percent). Thirteen of these underwent reoperation by the trans-sternal approach, and thymic tissue was found in 11 (85 percent). After repeated thymectomy, 67 percent of the patients improved clinically. Therefore, it is quite reasonable to infer that incomplete removal of the thymus was responsible, at least partly, for failure of the first procedure.     

Recurrence of thymic hyperplasia after trans-sternal thymectomy in myasthenia gravis

A 23-year-old woman with myasthenia gravis underwent thymectomy in September, 1975 by a trans-sternal approach for the removal of an hyperplastic gland. Surgical intervention was followed by marked improvement of her symptoms. Five years later, symptoms recurred. In March, 1982 diagnostic pneumomediastinum disclosed an anterosuperior mediastinal mass which, on excision, proved to be an hyperplastic thymus. This report confirms previous findings of thymus regrowth after surgery. It also demonstrates that surgical techniques using the trans-sternal approach do not guarantee complete removal of the thymus.     

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.     

Prognosis of patients with myasthenia gravis

AIM: To study the correlation between therapy and outcome of patients with late adult onset and ocular type myasthenia gravis (MG). METHODS: The 58 MG patients admitted to our hospitals from 1991 to 2003 were classified into juvenile (younger than 20), early adult onset (20-64) and late adult onset (65 or older) groups, or also ocular and generalized types. We evaluated their therapeutic outcomes. RESULTS: The late adult onset group consisted of 11 patients, classified as 4 ocular and 7 generalized types. There were more women than men in both the late and early adult onset groups. Anti-acetylcholine receptor (anti-AchR) antibodies were positive in all patients. Four patients had thymus lesions. Ten patients received treatment as follows: steroid therapy in 6, thymectomy in 4 and only choline-esterase (ChE) inhibitor therapy in 4 patients. However 4 patients worsened after treatment because of inadequate steroid therapy, 2 of whom experienced myasthenic crisis. On the other hand 21 patients were ocular type, of whom anti-AchR antibodies were positive in 12. They received treatments of the 21, steroid therapy was given to 12, thymectomy was performed in 4 and only ChE inhibitor therapy was given to 8 patients. One ocular type patient progressed to the generalized type. Six of 16 improved patients showed distinct recovery. CONCLUSION: In the late adult onset group careful assessment concerning timings of administration and reduction of steroid are required to avoid side effects and complications. One ocular type patient progressed to the generalized type and most patients had a good outcome, which might be related to steroid therapy.     

七氟醚用于老年患者麻醉诱导的临床观察

目的 采用七氟醚吸入麻醉诱导,观察起效时间、心血管系统反应,探讨其在老年患者中应用的有效性和安全性. 方法 选择60例美国麻醉学会(ASA)Ⅰ～Ⅲ级择期手术,年龄65～78岁的患者,分为七氟醚吸入诱导(七氟醚组)和丙泊酚诱导(对照组)麻醉.七氟醚组药物浓度采用阶梯式下降法,即由7%每隔30 s下调1%,至4%时停止下调并维持其浓度.对照组静脉滴注给予丙泊酚1.5～2.5 mg/kg.在脑电双频指数(BIS)≤60时静脉注射舒芬太尼和罗库溴铵,行气管插管.记录两组睫毛反射消失(LOER)、BIS≤60时间,两组基础值、插管前及插管后1、3、5 min的平均动脉压、心率、氧饱和度(SpO2)和BIS,观察插管中有无呛咳、喉痉挛等不良反应,术后随访患者对插管操作有无知晓及满意度. 结果七氟醚组LOER、BIS≤60所用时间长于对照组(P＜0.01).对照组术后血压、心率插管前低于基础值,插管后1 min高于插管前,差异有统计学意义(P＜0.05).七氟醚组平均动脉压、心率、插管后1 min与插管前比较,差异无统计学意义.插管前平均动脉压与对照组比较,差异有统计学意义(P＜0.05).插管呛咳七氟醚组和对照组分别为5例和3例,均无喉痉挛发生.随访两组患者麻醉诱导时无知晓,均满意. 结论 七氟醚可用于老年患者的麻醉诱导,心血管系统未见异常,不增加诱导时的不良反应,是老年患者麻醉诱导的理想选择之一.     

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.     

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 Case Report of the Efficient Reduction of Calcium Channel Antibodies by Tryptophan Ligand Immunoadsorption in a Patient With Lambert–Eaton Syndrome

Lambert–Eaton myasthenic syndrome (LEMS) is a neuromuscular transmission disease caused by autoantibodies directed against voltage-gated calcium channels (VGCC). We report on a patient with LEMS and a cerebellar syndrome associated with lymphatic proliferation in the thymus. As thymectomy and immunosuppressive therapy failed to efficiently reduce clinical symptoms and VGCC antibody titer, we performed immunoadsorption using a tryptophan-ligand column for the first time. Repeated treatments resulted in a considerable decrease in antibody levels and a marked subjective and objective amelioration of LEMS as well as of the cerebellar symptoms.