Thymectomy in Myasthenia Gravis: Response, Complications, and Associated Conditions

doi:10.1016/S0188-4409(02)00405-8

Archives of Medical Research

Volume 33, Issue 6, November–December 2002, Pages 545-551

https://doi.org/10.1016/S0188-4409(02)00405-8 Get rights and content

Abstract

Background

Thymectomy is considered the most effective treatment for achieving sustained improvement as well as remission in patients with myasthenia gravis (MG), and most neurologists favor the use of this procedure. The main focus of many current studies is to determine response-predicting factors.

Methods

Clinical records of 152 patients with an established diagnosis of MG who underwent thymectomy at our institution were reviewed. The purpose was to evaluate outcome of surgical management for MG and prognostic factors that influence that outcome.

Results

The majority of patients were women (119 of 152); mean age was 32.10 ± 14.42 years, while time elapsed from diagnosis to surgery was 20.67 ± 19.7 months. Transsternal thymectomy was performed on 113 patients and transcervical on 39. Forty percent of patients achieved remission and 28% showed improvement; with this, a good response to thymectomy was seen in 68% of patients (n = 103). The most important variables associated with remission were <60 years of age, <2 years of preoperative symptoms, and use of pyridostigmine at low doses. Factors related with poor response were >60 years of age, preoperative Osserman stage other than II, use of high doses of pyridostigmine, use of corticosteroids, and presence of thymic atrophy or thymoma in histopathologic analyses. There was no mortality, although 20 patients (13%) presented complications.

Conclusions

Mexican patients with MG undergoing thymectomies show improvement and remission rates similar to those reported by other studies. Age, length of symptoms, thymic pathology, and medications appear to be predictors of response to thymectomy for MG.

Introduction

Myasthenia gravis (MG) (from: my, muscle; asthenia, weakness, and gravis, severe) is a prototype for both synaptic and autoimmune disorders. In the majority of patients, it is caused by autoantibodies specific for human nicotinic acetylcholine receptor (AChR) that are concentrated at postsynaptic region of the neuromuscular junction (1). These antibodies reduce the number of AChRs, causing impaired neuromuscular transmission that gives rise to fluctuating weakness and fatigue of voluntary muscles during continuous exercise (1). Medical treatments include use of anticholinesterase agents, immunosuppressive drugs, and plasmapheresis, but remission is low and achievable only at a high cost in side effects 2, 3. Thymectomy is considered the most effective treatment for sustained improvement as well as remission (as high as 80%) 4, 5, 6, 7, 8, 9. Current indications for surgical treatment in MG include early, generalized, moderate to severe disease stabilized with medication and resistant ocular disease (10). Several studies have reported factors affecting patient response to thymectomy 11, 12, 13, 14, 15. Among these, mild preoperative Osserman stage, thymic histology (absence of thymoma, presence of germinal center), and short symptom duration have been identified as better prognosis predictors 15, 16, 17. However, due to the heterogeneous populations of these studies, results do not entirely agree. To optimize future selection of patients who would benefit the most with thymectomy, we evaluated results obtained with surgical management of MG at our institution as well as response rates (improvement and remission) and main prognostic factors that influence outcome. Additionally, we analyzed sociodemographic characteristics, associated diseases, complications, and clinical course in our population.

Section snippets

Patients and Methods

We reviewed clinical records from 257 patients with an established diagnosis of MG at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City from January 1989 to December 2000. Diagnosis was established on clinical grounds and confirmed by edrophonium chloride and electromyographic tests (39). Of these 257 patients with MG, surgery was not performed on 78 patients because of a) significant improvement achieved with medical therapy, b) spontaneous remission, c)

Results

One hundred nineteen patients (78%) were women and 33 (22%) were men. Age range was 12–77 years (average 32.10 ± 14.42 years) with only 11 patients >60 years of age. Patients experienced symptoms for an average 24.71 ± 31.76 months prior to surgery. The most common symptom was bilateral palpebral ptosis (93%) followed by extremity weakness (88%). Swallowing complaints were present in 36 (24%) patients. Presurgical distribution of patients by Osserman classification was as follows: stage I, nine

Discussion

MG affects individuals in any age group with peak incidence in women between the ages of 30 and 40 and in men between 60 and 70 years of age (16). In our population, nearly 80% of cases were women between 20 and 30 years of age. Onset of MG is characteristically ill defined with weakness and fatigue of muscles, exacerbation of symptoms caused by stress, exercise, and menstruation. The site most often involved in early disease stages is the eye, but approximately 80% of patients will eventually

References (39)

A Vincent et al.
Myasthenia gravis
Lancet
(2001)
D.B Sanders et al.
The treatment of patients with myasthenia gravis
Neurol Clin North Am
(1994)
A Jaretzki et al.
Maximal thymectomy for myasthenia gravis
J Thorac Cardiovasc Surg
(1988)
A Masaoka et al.
Extended thymectomy for myasthenia gravis patientsa 20-year review
Ann Thorac Surg
(1996)
V Bril et al.
Long-term clinical outcome after transcervical thymectomy for myasthenia gravis
Ann Thorac Surg
(1998)
J.M Budde et al.
Predictor of outcome in thymectomy for myasthenia gravis
Ann Thorac Surg
(2001)
A Jaretzki et al.
Myasthenia gravisrecommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America
Ann Thorac Surg
(2000)
V.J DeFilippi et al.
Transcervical thymectomy for myasthenia gravis
Ann Thorac Surg
(1994)
I.P Nieto et al.
Prognostic factors for myasthenia gravis treated by thymectomyreview of 61 cases
Ann Thorac Surg
(1999)
M Tsuchida et al.
Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis
Ann Thorac Surg
(1999)

J.F Téllez-Zenteno et al.

Patogénesis de la miastenia gravis

Rev Invest Clin

(2000)

Adams RD, Victor M. Myasthenia gravis and episodic forms of muscular weakness. In: Principles of neurology. 5th ed. New...

C Busch et al.

Long-term outcome and quality of life after thymectomy for myasthenia gravis

Ann Surg

(1996)

P Hatton et al.

Transsternal radical thymectomy for myasthenia gravis; a 15-year review

Ann Thorac Surg

(1988)

M Klein et al.

Early and late results after thymectomy in myasthenia gravisa retrospective analysis

Thorac Cardiovasc Surg

(1999)

D.J Lanska

Indications for thymectomy in myasthenia gravis

Neurology

(1990)

A.K Papatestas et al.

Trans- cervical thymectomy in myasthenia gravis

Surg Gynecol Obstet

(1975)

A.E Papatestas et al.

Effects of thymectomy in myasthenia gravis

Ann Surg

(1987)

W Frist et al.

Thymectomy for the myasthenia gravis patientfactors influencing outcome

J Neurol Neurosurg Psychiatry

(1991)

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Thymic Parenchymal Hyperplasia
2023, Modern Pathology
Thymic hyperplasia is a rare condition generally caused by lymphoid follicular hyperplasia associated with autoimmune disorders. True thymic parenchymal hyperplasia unassociated with lymphoid follicular hyperplasia is extremely rare and may give rise to difficulties in diagnosis. We have studied 44 patients with true thymic hyperplasia (38 females and 6 males) aged 7 months to 64 years (mean, 36 years). Eighteen patients presented with symptoms of chest discomfort or shortness of breath; in 20 patients, the lesions were discovered incidentally. Imaging studies demonstrated enlargement of the mediastinum by a mass lesion suspicious for malignancy. All patients were treated with complete surgical excision. The tumors measured from 3.5 to 24 cm (median, 10 cm; mean, 10.46 cm). Histologic examination showed lobules of thymic tissue displaying well-developed corticomedullary architecture, with scattered Hassall corpuscles separated by mature adipose tissue and bounded by a thin fibrous capsule. No cases showed evidence of lymphoid follicular hyperplasia, cytologic atypia, or confluence of the lobules. Immunohistochemical studies showed a normal pattern of distribution for keratin-positive thymic epithelial cells against a background rich in CD3/TdT/CD1a⁺ lymphocytes. Twenty-nine cases had an initial clinical or pathological diagnosis of thymoma or thymoma vs thymic hyperplasia. Clinical follow-up in 26 cases showed that all patients were alive and well between 5 and 15 years after diagnosis (mean, 9 years). Thymic parenchymal hyperplasia causing significant enlargement of the normal thymus that is sufficient to cause symptoms or worrisome imaging findings should be considered in the differential diagnosis of anterior mediastinal masses. The criteria for distinguishing such lesions from lymphocyte-rich thymoma are presented.
Criteria for Postoperative Mechanical Ventilation After Thymectomy in Patients With Myasthenia Gravis: A Retrospective Analysis
2018, Journal of Cardiothoracic and Vascular Anesthesia
Citation Excerpt :
Acute fulminant onset of muscle weakness may precipitate myasthenic crisis that would mandate mechanical ventilation before thymectomy.13 MG grade also was recognized as a risk factor for prolonged ventilatory therapy by other investigators.14,15 Chu et al14 proposed that the MG grade and presence of thymoma were independent predictors of postoperative myasthenic crisis, consistent with this study’s results.
To determine the criteria for postoperative mechanical ventilation after thymectomy in patients with Myasthenia Gravis.
Retrospective study.
Teritiary care centre.
77 Myasthenia gravis patients operated for thymectomy were studied.
After obtaining clearance from Institutional ethics committee, medical records of 77 patients with MG, who were operated for thymectomy between January 2005 and December 2015 were reviewed in a retrospective manner. Perioperative variables collected from the patient records were demographic data, duration of the disease, Osserman and Genkin classification, Anti-acetylcholine antibody (AChR) positivity, preoperative daily dose of drug, history of preoperative myasthenic crisis, preoperative vital capacity, technique of anesthesia, drugs used for anesthesia, perioperative complications, and duration of postoperative mechanical ventilation. The patients were divided into two groups, group I and group II consisting of those who required postoperative ventilation for < 300 minutes and > 300 minutes, respectively. The determinants of prolonged postoperative ventilation were studied.
The requirement of mechanical ventilation was higher in patients with higher Osserman’s grade of myasthenia gravis. Duration of the disease had no effect on the duration of mechanical ventilation in myasthenic patients post thymectomy (p = 0.89). The patients with a preoperative history of myasthenic crisis had a requirement for prolonged mechanical ventilation (p = 0.03). Patients with preoperative vital capacity < 2.9 litres and preoperative CT scan showing thymoma had a requirement for prolonged mechanical ventilation with p values < 0.001 and 0.035, respectively. Patients who showed positivity for anti-acetylcholine antibodies had a prolonged mechanical ventilation (p = 0.026). Preoperative dose of pyridostigmine and the choice of continuation or discontinuation of antcholinesterases on the day of surgery had no influence on the duration of mechanical ventilation (p value of 0.19 and 0.36 respectively). Epidural analgesia intra and postoperatively significantly reduced the requirement of mechanical ventilation (p = 0.006).
The predictors of postoperative ventilation in myasthenic patients undergoing thymectomy as per our study are: 1. Grade of myasthenia; 2. History of preoperative myasthenic crisis; 3. Anti-acetylcholine antibodies positivity; 4. Presence of thymoma; and 5. a vital capacity < 2.9 litres. Use of thoracic epidural as a part of combined anesthetic technique helps to reduce the need of mechanical ventilation in these patients.
Thymic TFH cells involved in the pathogenesis of myasthenia gravis with thymoma
2014, Experimental Neurology
Citation Excerpt :
Furthermore, 80–90% of MG patients manifest thymic pathology, showing strong association between thymic alteration and clinical symptoms of MG (Marx et al., 1997). Standard treatment shows that thymectomy leads to a satisfactory improvement of clinical symptoms for MG patients and a suppression of both cellular and humoral immunity, and reduction in AChR antibodies (Remes-Troche et al., 2002). Although the generally accepted hypothesis in MG establishes the thymus as the disease initiating site, the differential immunological responses in thymoma from distinct clinical manifestations of OMG and GMG are still unknown.
Follicular helper CD4 + T (TFH) cells are the specialized providers of B cell help in germinal centers (GCs). Formation of GCs in thymi is the primary thymi characteristic in MG patients. TFH cells are involved in the pathogenic process of many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and autoimmune thyroid disease. The role thymic TFH cells played in MG with thymoma has not been elucidated. Here, we analyzed surface markers CXCR5, Bcl-6, ICOS and IL-21 on TFH cells in thymus derived from thymoma patients with ocular MG (OMG), generalized MG (GMG) or without MG using immunohistochemical staining, immunofluorescence, western blotting, and real-time PCR analysis. We show that clinical severity of MG is correlated with higher mRNA expression of the four markers. Indeed, results show higher expression of all four markers in thymoma with GMG patients compared with both OMG and non-MG patients. We found no significant difference in the expression of CXCR5, Bcl-6 and ICOS in OMG compared with non-MG patients. Regression analysis shows a positive correlation between thymic CXCR5, BCL-6, ICOS and IL-21 levels and quantitative MG score (QMGS) in GMG patients. In addition, we found no significant correlation between TFH cell expression and QMGS in OMG patients. Our findings show that higher expression of TFH cells in the thymoma is related to the clinical severity of MG and suggests a role in the pathogenesis of MG. However, the real source of these TFH cells is still uncertain and needs further study.
The ageing and myasthenic thymus: A morphometric study validating a standard procedure in the histological workup of thymic specimens
2008, Journal of Neuroimmunology
The thymus is believed to play an important role in the pathogenesis of myasthenia gravis (MG). The 80% of MG patients with anti-acetylcholine receptor autoantibodies fall into three clinical subgroups: 1) thymoma; 2) early-onset MG (< age of 40; EOMG) and 3) late-onset (LOMG; onset after 40). Thymectomy is widely used in EOMG, but its benefits have not been established in randomized controlled trials. A multicenter international trial (MGTX) currently seeks to determine whether thymectomy reduces corticosteroid requirements, and to look for correlations with thymic histology. We here describe the validated, standardized histological workup and reporting system used in this trial.
A review of myasthenia gravis: Pathogenesis, clinical features and treatment
2007, Current Anaesthesia and Critical Care
Myasthenia gravis is an organ-specific autoimmune disease characterised by fatigable weakness of voluntary muscles. It is associated with antibodies to the post-synaptic nicotinic acetylcholine receptor in the neuromuscular junction. It peaks in the 20s especially in women and in the 50s in men. Patients may present with a wide range of neurological symptoms but usually develop ptosis and/or diplopia at some point in their illness. Some patients may present with neuromuscular respiratory failure from the onset. Management is aimed at firstly treating the symptoms with acetylcholine esterase inhibitors, such as pyridostigmine, secondly treating the underlying disease process with immunosuppressants and thirdly considering thymectomy in patients with a thymoma and patients with generalised myasthenia. In this review, the important aspects of pathogenesis, diagnosis, investigation and management are discussed.
Does perioperative high-dose prednisolone have clinical benefits for generalized myasthenia gravis?
2006, European Journal of Cardio-thoracic Surgery

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ClinicalThymectomy in Myasthenia Gravis: Response, Complications, and Associated Conditions

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients and Methods

Results

Discussion

Lancet

Neurol Clin North Am

J Thorac Cardiovasc Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Patogénesis de la miastenia gravis

Rev Invest Clin

Long-term outcome and quality of life after thymectomy for myasthenia gravis

Ann Surg

Transsternal radical thymectomy for myasthenia gravis; a 15-year review

Ann Thorac Surg

Early and late results after thymectomy in myasthenia gravisa retrospective analysis

Thorac Cardiovasc Surg

Indications for thymectomy in myasthenia gravis

Neurology

Trans- cervical thymectomy in myasthenia gravis

Surg Gynecol Obstet

Effects of thymectomy in myasthenia gravis

Ann Surg

Thymectomy for the myasthenia gravis patientfactors influencing outcome

J Neurol Neurosurg Psychiatry

Clinical
Thymectomy in Myasthenia Gravis: Response, Complications, and Associated Conditions