Thymectomy in the treatment of myasthenia gravis: report of 247 patients

Summary We made a retrospective assessment of the long-term outcome in 247 consecutive patients with myasthenia gravis (MG) who underwent thymectomy in the period January 1971–December 1985. In 84 cases a thymoma was found at surgery, while 163 patients had a non-neoplastic thymus. The duration of symptoms before surgery, the age at onset of the disease and the presence of germinal centres in the thymus did not appear to influence the prognosis. Patients with a non-neoplastic thymus showed a better response to thymectomy. Thymoma was associated with more severe disease and with a higher mortality; moreover, more thymoma patients required corticosteroid treatment in order to achieve good therapeutic results. In our opinion, thymectomy is indicated in the treatment of generalized MG, while ocular myasthenia seems not to be improved by the removal of the thymus.     

类固醇与胸腺放疗联合疗法治疗22例胸腺切除后无效的重症肌无力

本文报告用类固醇和胸腺放射联合疗法治疗２２例胸腺切除后无效的重症肌无力患者的疗效。２个月内的近期有效率高达１００％。经１～１２年的长期随访，达完全缓解和显著改善者１９例，占８６．４％。停用一切药物长达２～１０年而无任何症状者７例，占３１．８％。     

重症肌无力患者胸腺切除术后合并视神经脊髓炎1例（附文献复习）

目的：分析重症肌无力（MG）患者胸腺切除后合并视神经脊髓炎的临床特点,探讨两者合并发生的机制。方法：结合文献对1例MG胸腺切除后合并视神经脊髓炎患者的临床特点和血清学改变进行分析。结果：现有的MG合并视神经脊髓炎的文献报道中,绝大多数（13/15例）在胸腺切除后发生。胸腺切除后抑制T细胞产生减少,B细胞过度增殖,自身免疫抗体增加,可能与视神经脊髓炎的发病有关。此外,HLAB8、DR2和DR3也可能与MG合并视神经脊髓炎的发生相关。结论：MG患者胸腺切除后引起的免疫系统改变（如血清中抑制T细胞数的改变和自身抗体的出现）,患者的HLA抗原类型（如HLA-B8、DR2和DR3）可能与合并视神经脊髓炎的发生相关。     

重症肌无力19例临床分析

目的方法对19例重症肌无力(MG)患者的临床特点和治疗效果进行回顾性分析、总结临床经验。结果男性患者8例,女性患者11例,男女比例1:1.375。发病年龄为2~77岁,平均年龄40.63岁。首发症状为眼睑下垂者10例,占52.6%;其中眼睑下垂合并锥体束征1例,合并甲状腺功能亢进者4例,合并右耳听力下降者1例。19例患者均在应用抗胆碱酶药物溴吡斯的明基础上加用激素或丙种球蛋白治疗,其中有效16例,无效3例,总有效率为84.2%。合并胸腺瘤者5例,均行胸腺切除,术后有效4例,无效1例,总有效率80%。结论 MG多青壮年发病,10%~15%合并胸腺瘤,临床表现复杂多样,首发症状以眼睑下垂最为多见,激素、丙种球蛋白及胸腺切除术均为治疗MG的有效手段。     

Myasthenia gravis appearing after thymectomy

We aimed to evaluate the clinical characteristics of patients with postoperative myasthenia gravis (MG). We retrospectively studied the data of 174 thymoma patients treated between 1990 and 2008 in Xiangya Hospital. Six of 125 patients without preoperative MG (4.8%) developed postoperative MG. The anti-acetylcholine-receptor binding antibody (ARAb) titers were elevated preoperatively in 22 of the 125 patients (17.6%) who did not have preoperative MG (range, 0.5-67.6 nmol/L). Four of six patients with postoperative MG had positive ARAb levels preoperatively. Serum titers were exacerbated in all six patients at the onset of postoperative MG. Postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. We concluded that a thymectomy did not prevent postoperative MG. Exacerbated ARAb levels after thymectomy suggested an extrathymic production of ARAb. We suggest that a rise in the ARAb titer might be a risk indictor for post-thymectomy MG.     

Myasthenia Gravis: Immunohistological heterogeneity in microenvironmental organization of hyperplastic and neoplastic thymuses suggesting different mechanisms of tolerance breakdown

Four samples of thymoma obtained from patients affected by myasthenia gravis have been immunohistologically analysed on cryostat sections using a panel of antisera and monoclonal antibodies specific for antigens which define different stages of intrathymic lymphocyte differentiation and antigens specific for different types of thymic epithelial cells (cortical, medullary). When the thymoma samples were compared to age-matched normal thymuses and hyperplastic thymuses obtained from patients with myasthenia gravis some evident microenvironmental differences could be demonstrated using these reagents. In all the thymoma samples in fact the neoplastic lobules appeared as grossly enlarged cortical-type areas, formed by accumulations of T lymphocytes exhibiting the cortical immature phenotype (TdT+, T6+, etc.) within a network of putatively neoplastic epithelial cells characterized by cortical phenotype as defined by reactivity with various monoclonal antibodies (RFD4-, MR3+). These 'cortical' epithelia showed some abnormal features such as lack or irregular distribution of HLA-DR and enhanced keratin expression. Small areas of 'medullary' differentiation could be observed in 3/4 thymoma samples. In thymic hyperplasia, on the other hand, the cortical areas appeared somewhat compressed (but comparable to those observed in normal age-matched samples) by enlarged medullary areas. The expansion of medullary areas was due to the infiltration of 'peripheral' lymphoid tissue intruding through the extraparenchymal zone and forming organized B and T areas. These observations are discussed in the light of the clinical heterogeneity observed in myasthenia gravis.     

重症肌无力胸腺切除术后远期生存多因素分析

目的　探讨重症肌无力患者胸腺切除术后影响远期生存的因素。方法　采用胸腺切除术治疗重症肌无力170例,对其中124例进行平均39.8个月的长期随访,运用统计软件对年龄、性别、病程、临床分型、病理类型等因素进行COX回归模型多因素分析。结果　影响远期生存的因素是胸腺的不同病理类型(胸腺增生、胸腺萎缩、良性胸腺瘤、恶性胸腺瘤)(P<0.05),临床分型与病理类型具有相关性(P<0.01)。结论　重症肌无力胸腺切除术后远期生存率依胸腺增生、良性胸腺瘤、胸腺萎缩、恶性胸腺瘤等不同病理类型依次下降,临床分型在一定程度上可反映预后,强调早期手术治疗和术后巩固治疗是提高远期生存率的关键。     

伴胸腺瘤的重症肌无力患者治疗和预后

目的：研究伴有胸腺瘤的重症肌无力（MG）患者的治疗方法和影响预后的因素。方法回顾性研究103例经手术证实的MG伴胸腺瘤患者,给予皮质类固醇,化学疗法,放射疗法等治疗,观察患者的远期疗效和生存率。结果：MG总有效率为78．6％,其中完全缓解23例（22．3％）,药物缓解26例（25．2％）,部分缓解32例（31．3％）,5年和10年生存率分别为77．8％和48．5％,其中淋巴细胞为主型分别为88．9％和72．7％,混合型为83．3％和58．3％,上皮细胞为主型为55．6％和10．0％;按Masaoka分期标准,I期和II期患者的5,10年生存率分别为89．8％和76．2％,Ⅲ期和Ⅳ期为35．7％和0％,皮质类固醇和放疗等综合治疗患者5年和10年生存率分别达到88．9％和57．1％,结论：MG伴胸腺瘤患者手术后应给予皮质类固醇,放疗和化疗等综合, 提高疗效和和者生存,上皮细胞胞型胸腺瘤和Masaoka分期Ⅲ期和Ⅳ期患者预后较差。     

Thymectomy in myasthenia gravis a review

The role of thymectomy in the management of myasthenia gravis is reviewed in the light of the published data and of a personal series. The patients in whom the operation is most successful are non thymomatous patients aged between 10 and 40 years with an MG history of less than 3 years. There is no sex prevalence. Lasting improvement may be expected. There are no proven correlations between biological indices like the germinal centers in the thymus and/or AChR antibody titers and the postoperative course of the disease. Complete removal of the thymus seems to be crucial and hence the transsternal approach is preferred. The operation, less effective in patients with thymona than in those with an active thymus, is nonetheless necessary to in these patients prevent putative damage to surrounding organs from thymona infiltration. Why thymectomy should be effective in patients with an active thymus and not in those with a thymona may be revealed by in vitro studies of the interactions between thymic cells and peripheral B cells, now in progress.

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Sommario Viene rivisto alla luce dei dati della letteratura e della casistica personale il ruolo della timectomia nella terapia della miastenia. Dei pazienti non portatori di timoma i migliori risultati si ottengono in quelli di età fra i 10 e i 40 anni con una durata della malattia minore di tre anni. Non vi è prevalenza di sesso. Ci si può attendere un miglioramento duraturo. Non vi sono prove di una correlazione tra gli indici biologici germinativi quali i centri germinali nel timo e o il titolo degli anticorpi contro i ricettori acetilcolinici e il decorso post-operatorio della malattia. É fondamentale la completa asportazione del timo e perciò è preferibile la scelta della tecnica di approccio transternale. Nei pazienti con timoma la timectomia è meno efficace ma l'intervento è necessario per evitare danni derivanti dall'infiltrazione del timoma sugli organi circostanti. Il perché della efficacia della timectomia nei pazienti con un timo attivo ma non in quelli con timoma potrà essere chiarito dagli studi in vitro sulle interazioni tra cellule timiche e quelle periferiche B, studi che sono ormai in stadio avanzato.

     

重症肌无力合并胸腺瘤患者手术疗效（附26例）

目的 :研究重症肌无力 (MG)合并胸腺瘤患者胸腺切除术的疗效。方法 :按Masaoka分期将 2 6例MG合并胸腺瘤者分为Ⅰ期 6例 ,Ⅱ期 13例 ,Ⅲ期 6例 ,Ⅳ期 1例。全部行胸腺切除术。结果 :术后 4例发生危象。随访 2年 ,19例 ( 73 1% )的患者术后病情明显改善 ;7例 ( 2 6 9% )没有变化或者疗效差。结论 :MG合并胸腺瘤的患者应早期适时进行胸腺切除手术。     

药物及胸腺切除手术治疗重症肌无力的疗效分析

目的探讨伴有不同胸腺情况的重症肌无力(MG)患者对药物及胸腺切除术(TX)的疗效。方法对我院确诊的71例MG患者进行回顾性分析,根据胸腺CT情况将患者分为胸腺CT正常组、合并胸腺增生组、合并胸腺瘤组及合并胸腺癌组,采用Fisher精确检验法比较各组对两种治疗方法的疗效。结果胸腺CT正常的MG患者多采取药物治疗,缓解率为52%,有效率为88.5%;合并胸腺增生、胸腺瘤、胸腺癌的MG患者多采取了TX治疗。合并胸腺增生组的术后缓解率(62.5%)明显高于合并胸腺瘤组(8.3%)(P<0.05);合并胸腺增生组的术后有效率(93.7%)与合并胸腺瘤组差异无显著性(83.3%)(P>0.05)。结论合并胸腺增生的MG患者TX的术后疗效优于合并胸腺瘤者。     

Myasthenia gravis with thymoma and autoimmune haemolytic anaemia. A case report

Myasthenia gravis is an autoimmune disorder that affects the neuromuscular junction and leads to weakness of the skeletal muscles. Associated autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and pernicious anaemia are present in approximately 5% of the myasthenic patients. This report presents a 64-year-old man with autoimmune haemolytic anemia associated with myasthenia gravis and thymoma. The patient developed a severe Coomb's positive autoimmune haemolytic anaemia, which was resistant to treatment with large doses of prednisone. Haemolytic anaemia entered remission one month following thymectomy, and the patient has maintained a normal haemoglobin and a negative Coomb's test without the need for steroid or immunosuppressive therapy. In conclusion, thymectomy may induce a striking improvement of therapyresistant autoimmune haemolytic anemia in patients with MG and thymoma, but in terms of remission, a long follow-up is needed as autoimmune diseases can show spontaneous fluctuations. Received: 19 December 2001 / Accepted in revised form: 27 December 2002 Correspondence to: N. Tuncer Elmaci     

A Case Report of Myasthenia Gravis Associated with Hashimoto's Thyroiditis

Abstract: An unusual case of myasthenia gravis is presented. The disease was clinically established in a 71-year-old Japanese woman by an electromyographic, pharmachologic test and anti-acetylcholine receptor (anti-AChR) antibodies demonstrated in the circulating blood. The coexistence of Hashimoto's thyroiditis was diagnosed by the presence of a diffuse thyroid enlargement, anti-thyroglobulin and anti-microsomal antibodies and a lowered thyroidal ¹³¹I uptake. A delusion of persecution developed during the treatment with pyridostigmine and ephedrine chloride, but the symptom disappeared after discontinuing the use of ephedrine chloride.     

Improvement in Neuromuscular transmission in Myasthenia Gravis by 3,4-Diaminopyridine

Summary 3,4-Diaminopyridine (3,4-DAP), a potent potentiator of action potential evoked release of acetylcholine from presynaptic terminals in the neuromuscular junction was given i.v. and p.o. to two patients with myasthenia gravis. Effects were monitored electrophysiologically by repetitive nerve stimulation and by standardized clinical testing.Administration of 8 mg and 9 mg 3,4-DAP i.v. produced a clear improvement in the neuromuscular transmission after approximately 20 min.When 3,4-DAP was given p.o. 24 mg was shown to be effective. At a dosage of 18–24 mg p.o. 3,4-DAP significantly potentiated the effect of the cholinesterase inhibitor pyridostigmine at an optimal dose. The maximal effect of 3,4-DAP p.o. was obtained after 2.5–3 h.No significant CNS side-effects were found which is in contrast to those reported for 4-aminopyridine.The results suggest that 3,4-DAP may be useful as an addition to the conventional treatment with cholinesterase inhibitors when immunosuppressive treatment is considered contraindicated or when it has not yet reached its full effect.Supported by the Swedish Medial Research Council, Stockholm (project no. B84-04X-00084-20C) to the Department of Clinical Neurophysiology     

Treatment of myasthenia gravis

Summary In the treatment of myasthenia gravis (MG) considerable progress has recently been achieved. Our experience is based on the observation of 139 patients with an average follow-up of 3 years and 4 months.A treatment plan and results are presented.Indications for thymectomy: all cases of MG in adult life, apart from ocular myasthenia without radiological thymoma and without electrophysiological and pharmacological signs of generalization; before puberty only cases with radiological thymoma and severely incapacitating or life-threatening signs.Median sternotomy is preferable for thymoma, the transcervical approach with a sternal split for non-neoplastic thymus. Mediastinal radiotherapy is indicated after removal of an invasive or adhesive thymoma.Indications for corticosteroids: 1) before thymectomy: respiratory weakness; 2) soon after thymectomy: life-threatening signs; 3) later after thymectomy: incapacitating or life-threatening signs; 4) as an alternative to thymectomy: when surgery cannot be performed or it is not indicated. Oral Prednisone was nearly always preferred: alternate-day high single dose (75 to 115 mg) has given good results in most cases even if in some cases a small dose was required in the off day; inversely a lower alternate-day or daily dose was often sufficient.Long-term results: following this schedule for adult patients good results were scored in 67% of thymomas, in 94% of hyperplasias, and in 62% of unthymectomized patients: in prepuberal life the few cases of severe MG have all shown a favorable evolution.

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Zusammenfassung Bei der Behandlung der Myasthenie wurden in letzter Zeit beachtliche Fortschritte erzielt. Wir teilen hier unsere Erfahrungen anhand von 139 Patienten mit einer durchschnittlichen Katamnese von 3 Jahren und 4 Monaten mit.Wir betrachten als Indikationen für eine Thymektomie: alle Fälle von Myasthenie beim Erwachsenen mit Ausnahme der rein okulären Formen ohne radiologisch nachweisbares Thymom und ohne elektrophysiologische oder pharmakologische Zeichen einer Generalisierung; bei Kindern vor der Pubertät empfehlen wir die Thymektomie nur in Fällen mit radiologisch nachweisbarem Thymom und mit schwerer Beeinträchtigung oder gar Lebensgefährdung durch die Symptome.Die mediane Sternotomie ist beim Thymom vorzuziehen, der transzervikale Zugang mit Spaltung des Sternums für die nicht neoplastischen Thymusvergrößerungen. Mediastinale Strahlentherapie ist nach Exstirpation eines invasiven Thymoms oder eines Thymoms mit Adhäsionen angezeigt.Als Indikation für die Corticosteroidtherapie betrachten wir: 1. wenn vor der Thymektomie Atemstörungen bestehen; 2. wenn bald nach der Thymektomie lebensbedrohliche Symptome auftreten; 3. wenn später nach Thymektomie nennenswert behindernde oder lebensbedrohliche Symptome in Erscheinung treten; 4. als Alternative zur Thymektomie, wenn diese nicht durchgeführt werden kann oder nicht indiziert ist. Die orale Prednisontherapie wurde fast immer vorgezogen: wir gaben an alternierenden Tagen jeweils hohe Einzeldosen (75–115 mg) mit gutem Erfolg in den meisten Fällen. In gewissen Fällen war eine kleine Dosis an den Tagen zwischen der Hauptdose aber genügend, ebenso in Einzelfällen eine allgemein niedrigere Dosierung. Die Langzeiterfolge mit diesem therapeutischen Vorgehen betrugen 67% gute Ergebnisse bei Thymomen und 94% bei Thymushyperplasie. Unter den nicht thymektomierten Patienten wiesen 62% ein gutes Ergebnis auf. Vor der Pubertät zeigten die allerdings wenigen Fälle schwerer Myasthenie alle ein gutes Ansprechen auf die Therapie.