Thymectomy in the treatment of ocular myasthenia gravis

BACKGROUND: Thymectomy is an effective and accepted treatment for myasthenia gravis, but thymectomy for ocular myasthenia gravis (Osserman stage I) is controversial. OBJECTIVE: To assess the efficacy and propriety of thymectomy for the treatment of ocular myasthenia gravis. METHODS: We conducted a review and follow-up of all patients who had thymectomy for the treatment of ocular myasthenia gravis between 1970 and 1998 at the University of California, Davis, Medical Center, and the University of Rome, "La Sapienza," Rome, Italy. Patient response to thymectomy was categorized as follows: cured, patients who became symptom-free and required no further medication; improved, patients who required less medication and whose symptoms were less severe; unchanged, patients whose symptoms and medications were the same; worse, patients who had more severe symptoms, needed more medication, or died. RESULTS: Sixty-one patients (mean age 37 years; range 14-73 years) were followed up for a mean duration of 9 years (range 0.5-29 years). Ocular myasthenia gravis with mixed and cortical thymomas, stages I to IV, occurred in 12 patients, and ocular myasthenia without thymomas occurred in 49 patients. Transsternal thymectomy (n = 55) and transcervical thymectomy (n = 6) resulted in cure in 31 (51%) patients, improvement in 12 (20%) patients, no change in 16 (26%) patients, and worsening of symptoms (including 1 postoperative death) in 2 patients. Patient outcomes were statistically independent of the duration of preoperative symptoms (mean 9.5 months), patient age, or the presence or absence of thymoma. In patients with ocular myasthenia, 70% were cured or improved after thymectomy; in the subgroup of patients with ocular myasthenia and thymoma, 67% were cured or improved. CONCLUSION: Thymectomy is an effective and safe treatment for patients with ocular myasthenia gravis.     

Experience with programmed steroid treatment with thymectomy in nonthymomatous myasthenia gravis

BACKGROUND: The benefit of thymectomy in myasthenia gravis management is recognized but the perioperative course can fluctuate. The goal of this study was to assess the feasibility and clinical benefit of dose-escalated steroid therapy with thymectomy for nonthymomatous myasthenia gravis. METHODS: We reviewed the records of 69 myasthenia gravis patients who were followed up after undergoing transsternal thymectomy with extended anterior mediastinal dissection in our hospital between 1976-2000. Forty-eight patients in the programmed treatment group who had dose-escalated and de-escalated steroid therapy during the perioperative period comprised 17 patients with ocular myasthenia gravis and 31 patients with generalized myasthenia gravis. Clinical benefits and clinical remission, which was diagnosed when the patients were symptom-free without medications for at least 1 year, were compared with those of 21 patients in the occasional treatment group who received medications occasionally over the perioperative period. RESULTS: Postoperative respiratory failure and myasthenic crisis did not occur in the programmed treatment group but did occur in 6 patients in the occasional treatment group. Remission rates in the programmed treatment group (mean follow-up, 6.4 years) were 30% at 3 years, 38% at 5 years, and 46% at 10 years; rates in the occasional treatment group (mean follow-up, 9.6 years) were 25% at 3 years, 25% at 5 years, and 45% at 10 years. CONCLUSIONS: Programmed steroid therapy in patients with nonthymomatous myasthenia gravis is feasible and it provides clinical benefit when fluctuating symptoms occur during the perioperative period.     

Thymoma is associated with relapse of symptoms after transsternal thymectomy for myasthenia gravis

Thymectomy is considered a therapeutic option for patients with myasthenia gravis. A myasthenic patient who has not received any treatment for years and shows no signs or symptoms of the disease after operation is still susceptible to a recurrence of myasthenic symptoms. To investigate which factors are related to relapse of symptoms in patients having thymectomy, we conduct a retrospective review in the patients who had experienced complete remission after thymectomy. Complete remission was achieved in 92 of 154 patients who received extended transsternal thymectomy for myasthenia gravis. Among these 92 patients, 20 patients had relapse of symptoms and needed medication again after complete remission was achieved (21.7%). Ten of 22 patients in the thymomatous group had relapse of symptom after complete remission was achieved, while only 10 of 70 patients in the nonthymomatous group had relapse of symptom (P=0.006). Multivariate Cox regression analysis revealed that thymoma was an independent factor for the development of relapse of symptoms. In conclusion, thymoma is an adverse prognostic factor for the MG patients who have experienced complete remission after thymectomy. The patients with thymoma had a greater possibility to develop relapse of symptoms than the patients without thymoma.     

"Maximal" thymectomy for myasthenia gravis. Results

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation has been complete removal of the thymus, but there has been controversy about the surgical technique and its relation to results. Surgical-anatomic studies have shown gross and microscopic thymus widely distributed in the neck and mediastinum. We believe that an en bloc transcervical-transsternal "maximal" thymectomy is required to remove all thymic tissue predictably. Ninety-five patients with generalized myasthenia gravis underwent "maximal" thymectomy consecutively between 1977 and 1985 and were evaluated 6 months to 89 months after operation. In Group A (N = 72), myasthenia gravis without thymoma, the uncorrected data revealed that 96% (69) had benefited from operation: 79% (57) had no symptoms; 46% (33) were in remission; 33% (24) were symptom free when receiving minimal doses of pyridostigmine; and none were worse. Life table analysis yielded a remission rate of 81% at 89 months. In group B (N = 8), myasthenia gravis without thymoma for which patients underwent reexploration for incapacitating weakness after earlier transcervical or transsternal operations, residual thymus was found in all. One patient was in remission, two were symptom free when receiving medication, one was unchanged, and none were worse. In group C (N 15), myasthenia gravis and thymoma, two patients were in remission and nine were symptom free when receiving medication. Two patients in this group died 2 and 4 years postoperatively in crisis. Response to thymectomy in group A was greater in patients with mild myasthenia gravis and may have been better in patients who had symptoms for less than 60 months preoperatively, but the response did not depend on age, sex, presence or absence of thymic hyperplasia or involution, or titers of acetylcholine receptor antibodies. The response to thymectomy in group B was striking but slower than in group A, perhaps because symptoms were more severe and of longer duration. The response in group C was also less good than in group A and proportionately fewer benefited. These results support the recommendation for thymectomy in the treatment of patients with generalized myasthenia gravis and indicate the desirability of a maximal procedure. For persistent or recurrent severe symptoms after previous transcervical or submaximal transsternal resections, reoperation by this technique is also recommended.     

Aggressive surgical approach for drug-free remission from myasthenia gravis.

A series of 27 patients with generalized myasthenia gravis is presented. All patients were treated by a sternal split and extended thymectomy and radical mediastinal dissection. The overall drug-free remission rate was 63%, although three additional patients are likely to achieve drug-free remission in the near future, with the total drug-free remission rate then being 74%. Of the remaining patients, all but three improved and require decreased medication, for an improvement rate of approximately 90%. One patient who has not improved had an invasive malignant thymoma. Drug-free remission was achieved in 46% of the male patients and in 82% of the female patients despite that the mean duration of disease was greater than 3.5 years. There was one serious complication, that of sterile sternal dehiscence. There was no mortality. The results suggest that an aggressive, radical surgical approach to myasthenia gravis, even in a group of patients considered somewhat less favorable because of a relatively long duration of disease, can result in a high percentage of drug-free remissions. Radical surgery for myasthenia gravis appears to be the treatment of choice, with medical therapy being reserved for those patients who are not likely to survive operation.     

Effects of thymectomy in myasthenia gravis.

Factors influencing onset of remission in myasthenia gravis were evaluated in 2062 patients, of whom 962 had had thymectomy. Multivariate analysis showed that appearance of early remissions among all patients was significantly and independently influenced by thymectomy, by milder disease, and by absence of coexisting thymomas. Patients with mild generalized symptoms treated with thymectomy reached remission more frequently, even when compared with those with ocular myasthenia treated without surgery. Short duration of disease before thymectomy in mild cases was another factor associated with earlier remissions. Mortality for all patients was significantly and independently influenced by severity of symptoms, age, associated thymomas, and failure to remove the thymus. Patients without thymectomy and with thymomas had, in addition, earlier onset of extrathymic neoplasms. Morbidity after the transcervical approach was minimal. This study demonstrates that early thymectomy by the transcervical approach, when technically feasible, has significant clinical advantages over the transthoracic approach and should be advocated for all patients with myasthenia gravis, including those with ocular disease.     

Notice from the American Board of Thoracic Surgery

Sixty-five patients with thymomatous myasthenia gravis were investigated. Thymomas were present in 44% of the male patients and 19% of the female patients with myasthenia gravis. The incidence of thymomatous disease in male patients was higher than in female patients in all age groups. Eighty percent of men more than 50 years old and women more than 60 years old had myasthenia gravis with thymoma. Germinal center formation in the thymus of patients with thymomatous myasthenia gravis was positive in 91% and was high grade.The prognosis for patients undergoing extended thymectomy of thymomatous myasthenia gravis was significantly better than in those having transsternal simple thymectomy, but it was worse than the prognosis for patients with nonthymomatous myasthenia gravis. No increase in the rate of remission or palliation was seen one year after thymectomy. It is concluded that early thymectomy is effective in control of myasthenia gravis in thymomatous myasthenia gravis.     

Management of myasthenia gravis by extended thymectomy with anterior mediastinal dissection.

BACKGROUND. Thymectomy has continued to gain acceptance as definitive treatment for myasthenia gravis. Because of the nature of thymic embryology with scattered rests throughout the anterior mediastinum, we advocate a transsternal thymectomy with extended anterior mediastinal dissection. METHODS. A series of 48 patients with myasthenia gravis treated by thymectomy between 1979 and 1991 were reviewed. RESULTS. The mean length of duration of disease from onset to operation was 48.7 +/- 11.3 months, and the mean length of follow-up was 51.6 +/- 6.5 months. The operation was associated with a 21% morbidity rate (4% major morbidity) with no deaths. Forty-five patients (94%) have improved, requiring decreased medication. The overall drug-free remission rate was 42%. Of the 20 patients in remission, three had thymomas and four had hyperplastic glands. All of the patients who achieved drug-free remission were classified as Osserman's I or II. CONCLUSIONS. An aggressive surgical approach to myasthenia gravis can result in a high percentage of overall improvements and drug-free remissions. The best results are achieved in patients with lower-stage disease. Therefore transsternal extended thymectomy for myasthenia gravis appears to be the procedure of choice and should be advocated as soon as the diagnosis is made and the patient stabilized.     

Effects of preoperative duration of symptoms on patients with myasthenia gravis

In 80 patients with type II nonthymomatous myasthenia gravis who underwent extended thymectomy, we investigated preoperative duration of symptoms, prognosis after thymectomy, immunological findings, and germinal center formation in the thymus. Our findings included the following. First, the palliation rate after thymectomy ranged from 73 to 100% and was independent of the preoperative duration of symptoms. The remission rate was high in patients with a short preoperative duration. Second, the lymphocyte count of peripheral blood decreased as preoperative duration increased. Third, the percentage of positive reactions to purified protein derivative of tuberculin decreased as preoperative duration increased: 100% in the one-year group, 78% in the two-year group, 75% in the three-year group, and 56% in the four-year group. Fourth, the degree of germinal center formation in the thymus was higher in patients with a longer preoperative duration. The correlation between germinal center formation and preoperative duration was significant. Finally, the T-cell population in peripheral blood and immunoglobulin, and antibody to acetylcholine receptor in serum, had no significant relationship with the preoperative duration of myasthenia gravis.     

Thymectomy in myasthenia gravis. A series of 68 patients

Since January 1988 to December 1998, by the Department of Thoracic Surgery, Haut-Lévêque Hospital, University of Bordeaux, 68 consecutive patients were operated for myasthenia gravis. The aim of our study was to evaluate the results obtained in a group of patients who underwent a thymectomy for myasthenia gravis, in order to contribute for the determination of the prognostic factors which can influence the post-operative course. This series consists on 68 patients. Females were predominant, 41 patients (60.2%) versus 27 males (39.7%). The age extended between 15 and 80 years, average of 45.2 years. The follow-up concerned 52 patients (76.4%); out of there, 8 are in complete remission (15.3%), 31 (59.6%) are in a phase of clinical improvement, 11 patients did not benefit from thymectomy (21.1%), 1 patient died immediately after the surgical operation, I patient died some years after the surgical operation for another reason. In conclusion the thymectomy is a beneficial procedure for myasthenia gravis patients.     

Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy

BACKGROUND: It remains controversial whether transcervical thymectomy offers results equivalent to thymectomy by way of a median sternotomy in the treatment of myasthenia gravis. Furthermore, preoperative prognostic factors have not been clearly defined. METHODS: This study is a retrospective chart review and interview of 78 patients completing transcervical thymectomy for myasthenia gravis between 1992 and 1999. RESULTS: There were 24 men and 54 women. Mean age was 40 years (range, 13 to 78 years). Twelve patients were in Osserman class 1, 25 in class 2, 30 in class 3, and 11 in class 4 (mean, 2.5). There was no perioperative mortality and 6 (7.7%) morbidities. Mean length of stay was 1.5 days and mean follow-up, 54.6 months. The crude cumulative complete remission (asymptomatic off medications for 6 months) rate was 39.7% (n = 31). Only 8 patients (10.3%) failed to improve after transcervical thymectomy. Kaplan-Meier estimates of complete remission were 31% and 43% at 2 and 5 years, respectively. Eight patients with thymoma had a 5-year estimated complete remission rate of 75% in contrast to 43% in 38 patients with thymic hyperplasia and 36% in 32 patients with neither thymoma nor hyperplasia (p = 0.01). Twelve patients with ocular myasthenia had a 5-year estimated complete remission rate of 57%, whereas patients with mild-to-moderate (n = 55) or severe (n = 11) generalized symptoms had 5-year complete remission rates of 43% and 30%, respectively (p = 0.21). CONCLUSIONS: Overall, extended transcervical thymectomy offers results that are comparable to those published for the transsternal procedure. Patients with milder disease (including isolated ocular disease) and taking no preoperative immunosuppressive agents appear to experience higher remission rates. In contrast to previous studies, we also find that small thymomas predict better responses to thymectomy.     

Extended thymectomy for myasthenia gravis in an octogenarian. A case report

An 86-year-old woman with myasthenia gravis successfully underwent an extended thymectomy. The patient had a 2-year history of generalized myasthenia and had limited response to anticholinesterases and steroids. An extended thymectomy was successfully performed in the usual fashion. The postoperative course was uneventful except for an episode of psychosis probably due to postoperative steroid therapy. The steroid dosage was gradually reduced to 5 mg/day over seven months after the operation, during which she became fully asymptomatic. No symptoms due to myasthenia have surfaced for over 2 years after surgery. Although elderly patients are usually considered to be less responsive to an operation, thymectomy may sometimes be the treatment of choice for myasthenia gravis even in octogenarians.     

Experience in the treatment of acute fulminating myasthenia gravis]

During past 15 years, 188 myasthenia gravis (MG) patients underwent thymomectomy or thymectomy with extended resection of the adipose tissue around the thymus in our institution. Four of 188 patients (2%) had to be given respiratory support within 2 months after the onset of MG. We defined this MG as the acute fulminating type. There were 2 male and 2 female patients, ranging in age from 22 to 44 years (average, 32.5 years). Three of these patients had thymoma. One of these patients was post-thymomectomy myasthenia gravis and another patient was d-penicillamine induced myasthenia gravis. Two patients admitted on respirator for respiratory crisis. All patients underwent operation within 2 weeks after admission. The duration of respiratory support ranged from 10 to 120 days (mean 44) after operation. The period of the hospital stay ranged from 8 months to 2 years 1 month (mean 1 year 5 months). During acute stage after operation, the patients needed ACTH, steroid, immunosuppressants (azathioprine, Bredinin) and plasma pheresis depending on their severity of myasthenic symptoms. In 2 patients dose of steroid could be reduced without deterioration of the symptoms. They are doing well with small dose of steroid. In one patient plasma pheresis was performed 6 years after thymectomy. Various symptoms due to myasthenia gravis and rheumatoid arthritis has recurred 10 years after thymectomy. The titer of acetylcholine receptor antibody of this patient has been continuing in high level.     

Favorable results of thymectomy combined with prednisolone alternate-day administration in myasthenia gravis

Administration of anti-cholinesterase before operation and high doses of prednisolone after the operation are commonly prescribed in cases of thymectomy for the treatment of myasthenia gravis. Our policy is to carry out an extended thymectomy combined with pre- and post-operative administration of prednisolone on alternate days. Our method was used in the treatment of 50 patients with generalized myasthenia gravis, from January 1979 to December 1984. The results were examined in conjunction with the necessity for preoperative administration of an anti-cholinesterase preparation and also with factors influencing the follow-up result and postoperative process. This method made it feasible to perform surgery under conditions of stabilization of clinical symptoms and satisfactory postoperative management. A postoperative period of unstable symptoms could thus be avoided. The palliation rate at one year after the operation was 96 per cent, while the remission rate at 5 years after the operation was 70 per cent. The preoperative supplement of anti-cholinesterase and preoperative per cent forced vital capacity were considered to be predictive factors concerning the necessity of artificial respiration.     

Surgical treatment for myasthenia gravis.

A new surgical technique for thymectomy is presented. Three hundred and seventeen patients with myasthenia gravis and 20 with thymomas who had myasthenic symptoms were operated on. The new surgical approach--a small transverse sternotomy--was used in 257 cases (in 240 patients with myasthenia gravis and 17 with thymomas) and conventional median sternotomy in 80. In myasthenic patients small transverse sternotomy enabled radical thymectomy to be performed with an uneventful postoperative course and very good cosmetic results. There were no hospital deaths among patients with myasthenia gravis after thymectomy. The long term results, assessed after 18-24 months, were good: the total remission rate was 39.5%, and there was a great improvement in 48.5% and an improvement in 9%. After thymectomy about 30% of patients received supplementary treatment with prednisone. A correlation between the duration of symptoms and the result of thymectomy was established: the shorter the duration of myasthenia gravis the better the results. In the small group of 20 patients with thymomas two died in hospital. In 12 patients with encapsulated thymic tumours the long term results were similar to those in patients with myasthenia gravis, whereas in patients with infiltrating thymic tumours the results were unsatisfactory.     

Favorable results of thymectomy combined with prednisolone alternate-day administration in myasthenia gravis

Administration of anti-cholinesterase before operation and high doses of prednisolone after the operation are commonly prescribed in cases of thymectomy for the treatment of myasthenia gravis. Our policy is to carry out an extended thymectomy combined with pre- and post-operative administration of prednisolone on alternate days. Our method was used in the treatment of 50 patients with generalized myasthenia gravis, from January 1979 to December 1984. The results were examined in conjunction with the necessity for preoperative administration of an anti-cholinesterase preparation and also with factors influencing the follow-up result and postoperative process. This method made it feasible to perform surgery under conditions of stabilization of clinical symptoms and satisfactory postoperative management. A postoperative period of unstable symptoms could thus be avoided. The palliation rate at one year after the operation was 96 per cent, while the remission rate at 5 years after the operation was 70 per cent. The preoperative supplement of anti-cholinesterase and preoperative per cent forced vital capacity were considered to be predictive factors concerning the necessity of artificial respiration.     

Thymectomy for myasthenia gravis: 14-year experience.

Forty-eight consecutive patients with myasthenia gravis (MG) attended by generalized weakness were treated by complete thymectomy, performed transsternally in 46 patients and through a left thoracotomy in two with thymomas. There were no operative deaths. A 12-year-old child with fulminating MG died of acute pneumonia shortly after hospital discharge. Of the remaining 47 evaluable patients, thymectomy resulted in complete remission in six, marked improvement with a reduced need for medication in 20, and mild improvement on the same dosage of medication in 18. Neither the age of the patient, nor the histopathology of the excised thymus, nor the postoperative change in acetylcholine receptor antibody titer were found to have a significant influence on the response to thymectomy. If the ten patients who were 20 years of age or younger were excluded, the patients with a shorter duration of MG achieved a better response to operation. The authors conclude that thymectomy is effective treatment for MG, regardless of the age of the patient or the type of thymic pathology.     

胸腺切除治疗重症肌无力的远期疗效

目的 探讨胸腺切除治疗重症肌无力的远期疗效。方法 １９９０年４月地１９９４年８月胸腺切除治疗重症肌无力１２４例中,１０４例获得远期随访随访期平均为２３．６个月。患者平均年龄２９．２岁。术前病程平均为３４．２个月。按改良Ｏｓｓｅｎｎａｎ标准分为Ⅰ型２９例、Ⅱ型６４例、Ⅲ型１１例。随访疗效评价分优、良、无效和差。结果 总有效率为８２．７％,无效１３．５％,差１．９％,２例死亡,手术疗效与临床分型,术前     

Clinical and pathologic predictors of outcome in thymoma-associated myasthenia gravis

BACKGROUND: Myasthenia gravis is by far the most common paraneoplastic syndrome of thymomas. There is little information regarding the influence of clinical variables and thymoma-associated factors on biologic development of myasthenia gravis. The aim of the study was to determine independent predictors of clinical outcome in thymoma with myasthenia gravis. METHODS: We studied 108 patients with thymoma-associated myasthenia gravis undergoing removal of the mediastinal mass between 1967 and 2000. Clinical and pathologic variables associated with clinical outcome of myasthenia were assessed by multivariate Cox regression analysis. RESULTS: Patients were followed for a mean period of 10 years (9 months to 33 years). A total of 38 patients died (35.2%), in 14 cases (37%) because of myasthenia gravis and in 6 (16%) because of recurrence of thymoma. With respect to clinical outcome of myasthenia gravis, at the end of the follow-up period, the rate of remission was 16% (n = 17). Of the 91 patients in whom remission was not achieved, 55 had no symptoms with immunosuppressive medication and 36 had symptoms with medication. CONCLUSIONS: In patients with thymoma-associated myasthenia gravis, well-differentiated thymic carcinoma (Müller-Hermelink system), age more than 55 years, and interval from the onset of symptoms to thymectomy of less than 1 year were found to be independent predictors of nonremission of myasthenia gravis after thymectomy.     

Autoimmune myasthenia gravis: Recommendations for treatment and immunologic modulation

Opinion statement Treatment for myasthenia gravis should be individualized to each patient based on the clinical characteristics of myasthenia including the distribution, duration, and severity of weakness and resulting functional impairment; the risks for treatment complications related to age, gender, and medical comorbidities; and the presence of thymoma. Acetylcholinesterase inhibitors provide temporary, symptomatic treatment for all forms of myasthenia gravis. Immune modulators address the underlying autoimmune process in myasthenia gravis, but are associated with potential complications and side effects. Most patients with generalized myasthenia who have significant weakness beyond the ocular muscles and who remain symptomatic, despite treatment with cholinesterase inhibitors, are candidates for immune modulation. Although corticosteroids are effective for long-term immune modulation in myasthenia gravis, several more contemporary immunomodulators including azathioprine, cyclosporine, and mycophenolate mofetil have shown efficacy in myasthenia gravis and are used increasingly as first-line treatments and as steroid-sparing agents. Plasma exchange is used to achieve rapid improvement in patients with myasthenic crisis or exacerbation, to improve strength before a surgical procedure or thymectomy, and to minimize steroid-induced exacerbation in patients with oropharyngeal or respiratory muscle weakness. Intravenous immunoglobulin represents an alternative to plasma exchange in patients requiring relatively rapid short-term improvement in the setting of poor venous access. Because of a lack of controlled trials, the role of thymectomy in nonthymomatous myasthenia gravis is unclear, although evidence suggests that thymectomy increases the probability for myasthenic remission or improvement.