Cervical thymectomy in the treatment of myasthenia gravis

Treatment modalities in myasthenia gravis consist of surgery, chemotherapy and plasmapheresis. Thymectomy can be accomplished either through a median sternotomy or through a small, transverse cervical incision. Forty patients who underwent cervical thymectomy for non-thymomatous myasthenia gravis were studied retrospectively. Twenty-six patients (65%) showed a favourable response to thymectomy and there were statistically significant improvements in myasthenic symptoms and reductions in medication requirements. Age, sex, duration of symptoms and thymic histology were not predictive of response to thymectomy. Operative mortality was zero and operative morbidity was minimal. During the last 6 years, only two of 22 patients required admission to the intensive care unit postoperatively. The postoperative hospital stay ranged from 2 to 23 days. Cervical thymectomy does not preclude later sternotomy in those patients who fail to respond favourably. We therefore recommend cervical thymectomy as the initial surgical procedure in the treatment of non-thymomatous myasthenia gravis.     

Long-term outcome and quality of life after open and thoracoscopic thymectomy for myasthenia gravis: analysis of 131 patients

Background  Myasthenia gravis is an autoimmune disease with a great impact on quality of life. Besides conservative treatment with mestinon and immunosuppressive medication, thymectomy is an established intervention that offers substantial improvements of the disease. Since the past decade, minimally invasive procedures have been performed. This study aimed to report on the long-term results for all the patients who underwent thymectomy for myasthenia gravis, paying special attention to postoperative disease-related outcome, quality of life, and differences regarding the operative approach. Methods  This report describes a series of 131 patients with generalized myasthenia gravis who underwent thymectomy between 1980 and 2005. The clinical course data during the hospitalization and consultation in our outpatient clinic were reviewed, and survival data were generated. The patients were seen in the outpatient clinic, where a modified Osserman and quality-of-life score was evaluated at the end of the follow-up period for all surviving patients. Results  A total of 106 patients with myasthenia gravis were followed up after thymectomy for a median time of 8 years (range, 1–27 years). Eight patients died during this period. The perioperative mortality rate was 0%, and the morbidity rate was 19.8%. The patients with thymoma and a high preoperative Osserman score had a significantly shorter survival. With minimally invasive procedures, the hospital stay was significantly shorter, and the rate for improvement of myasthenia gravis-associated symptoms was significantly higher. The rate of perioperative complications and myasthenia-related complications during the follow-up period showed no significant differences. Conclusions  Transsternal and minimally invasive thymectomy contribute to an improvement in myasthenia gravis symptoms for all subgroups. Surgery can be performed with low individual risks. In our trial, minimally invasive surgery was found to be superior in terms of improvement in myasthenia gravis-associated symptoms. Additionally, the hospital stay was shorter, and the patients felt less disturbed by direct effects of the operation. Therefore, minimally invasive thymectomy can be regarded as the treatment of choice for patients undergoing surgery for myasthenia gravis.     

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.     

Trans-sternal thymectomy in myasthenia gravis

Between 1986 and 1989 27 patients with myasthenia gravis underwent radical thymectomy: 24 patients without and two patients with thymoma through a trans-sternal incision, another with thymomatous myasthenia through a left-sided thoracotomy. The patients were staged according to the modified Ossermann classification. The results were evaluated prospectively according to the Disability Status Scale of Oosterhuis. During a mean follow up of 22.4 months, 21 patients (77%) benefited from the operation with complete remission achieved in 9 (33%) and significant improvement noted in 12 (44%). There were no operative deaths and no hospital morbidity. The mean operation time was 88 minutes, the mean postoperative hospital stay 10.5 days. These results support the recommendation for radical trans-sternal thymectomy in the treatment of patients with myasthenia gravis as a safe procedure.     

Thymectomy for myasthenia gravis in children

Myasthenia gravis is rare in childhood. In the last 12 years, we have treated eight children under 16 years of age for this disease. There were six girls and two boys, a ratio of 3:1. Age of presentation of symptoms ranged from 10 to 16 years (mean 11 3/4). There was no significant family history and there were no significant associated diseases. Antibodies were measured in six patients and were all negative. All patients were given cholinergic drugs and five had corticosteroids as well. Three underwent tracheostomies because of severe respiratory insufficiency. There was clinical deterioration or no improvement in spite of increasing doses of medication; hence, thymectomy was performed in all after an average duration of symptoms of 12 months (range 4 to 17). All thymectomies were done through median sternotomy. There was no postoperative morbidity or mortality. No thymoma was found. Four had lymphoid hyperplasia, in three, the thymus looked normal and in one it looked very atrophic. Dramatic amelioration with eventual complete recovery was seen in six, with an average follow-up of 7.3 years (3 to 11) after thymectomy. Two patients are only one year after thymectomy and are improving progressively. We recommend early thymectomy in myasthenia gravis of childhood on the basis of very encouraging results.     

The current role of thymectomy for myasthenia gravis

Myasthenia gravis is an autoimmune disease characterized by muscle weakness and fatigability due to a reduction in available acetylcholine receptors at the neuromuscular junction. Treatment with anticholinesterase drugs and corticosteroids has improved the prognosis for patients with this disease. However, controversy continues concerning the indications for thymectomy. During a 9 year period, 27 patients who underwent thymectomy by median sternotomy were reviewed. Eighty-one percent of these patients benefited from the procedure. Clinical improvement did not correlate with age, sex, duration of symptoms, severity of disease or thymic histology. This suggests that the indications for thymectomy should be liberalized to include most patients with generalized myasthenia who fail to respond readily to conventional medical therapy. The importance of immunosuppression and plasmapheresis in the therapy of myasthenia gravis awaits further delineation of the immune defect associated with the disease.     

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.     

The transcervical approach to the superior mediastinum.

We describe our experience with the transcervical approach for the surgical treatment of nonthyroidal superior mediastinal masses. With careful patient selection, proper preoperative workup, and proper operative positioning and technique, the entire superior mediastinum may be explored, thus avoiding the significant morbidity associated with the transsternal route. The transcervical approach requires a thorough knowledge of the surgical anatomy. Nine patients underwent transcervical exploration of the superior mediastinum. The indications included parathyroid adenoma, thymoma, congenital cyst, hemangioma, adenocarcinoma, and thymectomy for myasthenia gravis. We specifically discuss the role of thymectomy in the treatment of myasthenia gravis.     

Thymectomy by partial sternotomy for the treatment of myasthenia gravis

BACKGROUND: Myasthenia gravis is an autoimmune disease characterized by weakness and fatigue of voluntary muscles. Surgical treatment of choice for myasthenia gravis has been thymectomy. However, thymectomy indications and surgical approach are still controversial. The purpose of this study is to evaluate the efficacy of partial median sternotomy approach to the thymus. METHODS: From 1973 to 1999, 478 patients with myasthenia gravis underwent thymectomy through a partial median sternotomy. RESULTS: Sixty-one patients (12.7%) had complete remission of symptoms, 299 (62.5%) had a significant improvement, and 83 (17.4%), a mild improvement; whereas 35 patients (7.4%) had no improvement of clinical symptoms. CONCLUSIONS: Partial median sternotomy has shown to be a useful surgical approach to the thymus, as demonstrated by the good functional and aesthetic results, associated with low morbidity and no mortality.     

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.     

Surgical outcome of thymectomy for myasthenia gravis

Background The medical treatment for myasthenia gravis has been reported to have remission rates as low as 15%. Thymectomy on the other hand has been reported to have clinical remission rates up to 80% and therefore has become the accepted mode of treatment. Methods 57 patients diagnosed with myasthenia gravis underwent thymectomy at the Christian Medical College and Hospital, Vellore from January 1994 to December 2003. The aim of this study was to determine the outcome for myasthenia gravis after thymectomy. Results Our results indicated that female sex had a better over all prognosis, Ossermann stage, I, IIA, & III was associated with higher incidence of complete clinical remission and the response to thymectomy decreased with increasing Ossermann stage. Post operative medication requirement reduced significantly as compared to the preoperative requirement. Conclusion We therefore conclude that trans-sternal thymectomy was found to be beneficial to all patients of mild to moderate myasthenia gravis, with 70.2% patients showing improvement postoperatively. We also advocate thymectomy for ocular myasthenia gravis.     

A case of a small thymoma associated with myasthenia gravis in which the tumor was reduced by corticosteroid therapy]

The case in this study was a 34-year-old male with a small thymoma associated with myasthenia gravis. The patient had been treated with corticosteroids for 10 months against myasthenia gravis. During the course of the treatment a chest CT revealed that the tumor had reduced. Thereafter the extended thymectomy was performed. A close examination of the excised thymus revealed the presence of a flat cystic tumor measuring 1.5 x 0.8 x 0.5 cm at the site corresponding to the CT image. This tumor was histologically ascertained to be a thymoma. The thymoma is sensitive to corticosteroids, which can effectively reduce it. As conclusion, it is necessary to check thoroughly on the presence of thymoma prior to the initiation of corticosteroid therapy to treat myasthenia gravis.     

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.     

A case report of extended thymectomy in an elderly patient with myasthenia gravis associated with Hashimoto's disease

We experienced a case of late-onset myasthenia gravis associated with Hashimoto's disease. A 74-year-old female with chief complaints of extremities acratia and hypohidrosis was diagnosed as having myasthenia gravis by the Tensilon test. In addition severe hypothyroidism was noted, and histological examination of a thyroid biopsy revealed Hashimoto's thyroiditis. Extended thymectomy was carried out, and the postoperative course was uneventful due to administration of an anti-ChE drug and a thyroid hormone. This case is extremely rare because only 10 patients with late-onset (over 70 years old) myasthenia gravis have been reported in the literature in Japan, and only three of them were associated with Hashimoto's disease. It was suggested that, in cases of myasthenia gravis in elderly patients, we should take into consideration radical therapy including thymectomy as a positive approach to treatment.     

Video-assisted thymectomy for myasthenia gravis: an update of a single institution experience

Objective: Video-assisted thymectomy was introduced in 1992 as a minimally invasive alternative for the treatment of myasthenia gravis. As experience with this technique is limited and follow-up short, we present this expanded and updated experience for purposes of validation of the technique. Methods: Thirty-eight video-assisted thymectomies for myasthenia gravis were performed in our institution between March 1992 and March 2002. Two patients were lost to follow-up. We analyzed clinical results of 36 patients (14 males and 22 females) with a mean age of 41.2 years. Preoperative clinical staging was assessed by the newly recommended Myasthenia Gravis Foundation of America Clinical Classification. Clinical status at follow-up was assessed by the Myasthenia Gravis Foundation of America Postintervention Status classification. Results: There was no perioperative mortality or long-term morbidity. One of 38 (2.6%) patients required conversion to limited thoracotomy for bleeding. The mean length of hospital stay was 1.64 days (range 0–8 days) with a median stay of 1 day. The mean length of follow-up is 53.24 months (range 4–126 months). Overall clinical improvement at follow-up was observed in 30 of 36 (83.0%) patients, with five of 36 (14.0%) patients in complete stable remission. Conclusions: Video-assisted thymectomy for myasthenia gravis provides acceptable clinical long-term results by a minimally invasive approach comparable to standard surgical approaches to the disease. The presented data is reported in accordance with the new guidelines by Myasthenia Gravis Foundation of America Task Force for valid comparison with future studies.     

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.     

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.     

Video-assisted thoracoscopic thymectomy--preliminary results

Video-assisted thoracoscopic surgery (VATS) provides a new approach to thymectomy. From April 1999 to December 1999, we performed a total of 10 video-assisted thoracoscopic thymectomies for myasthenia gravis (MG). There were one male and nine female patients with ages ranging from 8 to 59 years. Thymoma was present in one of the ten patients. We considered that complete thymectomy was accomplished in all cases by examination of the thymic bed and of the resected specimen. There was no mortality or intraoperative complications. The median postoperative hospital stay was 4 days. Clinical improvement was observed in all patients after this short follow-up. Compared with a similar historical group of patients with MG who underwent transsternal thymectomy, the VATS group was associated with significantly less analgesic requirement and shortened hospital stay. We conclude that VAT thymectomy is technically feasible and is associated with a favorable postoperative course compared with the transsternal approach. We believe that complete thymectomy can be achieved by this approach. Further investigation with long-term follow-up is needed to further clarify the role of VAT thymectomy in thoracic surgery.     

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.     

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.