Clinical Outcome of Juvenile Myasthenia Gravis After Extended Transsternal Thymectomy in a Chinese Cohort

Clinical Outcome of Juvenile Myasthenia Gravis After Extended Transsternal Thymectomy in a Chinese Cohort Chao Cheng, MD, PhD, Zhenguo Liu, MD, Fenghua Xu, MD, Zhensheng Deng, MD, Huiyu Feng, MD, Yiyan Lei, MD, Jianyong Zou, MD, and Sai-Ching J. Yeung, MD, PhD Departments of Thoracic Surgery, and Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Peoples Republic of China; and Departments of Emergency Medicine and Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas Background. The role of surgical treatment for juvenile myasthenia gravis (MG) remains unclear. Here, we performed a retrospective study to evaluate the predictors of clinical outcome of juvenile MG treated with extended transsternal thymectomy. Methods. A total of 141 consecutive juvenile MG patients underwent extended transsternal thymectomy at an academic hospital over a 20-year period were reviewed. Thymectomy was performed in patients resistant to pyridostigmine therapy, with generalized symptoms or ocular MG with partial response to pyridostigmine for more than 2 years. Variables potentially affecting responses to extended transsternal thymectomy were evaluated using Kaplan-Meier analysis and Cox regression modeling. Complete stable remission (CSR) is defined as asymptomatic without medication for more than 12 months. Results. There were 96 patients with ocular MG and 45 generalized MG, the median age at disease onset was 6 years and that at operation was 12 years. Among 135 patients with complete postoperative follow-up, 34 (25.2%) achieved CSR, 28 (20.7%) experienced pharmacologic remission, 61 (45.2%) improved, 5 (3.7%) remained stable, and 7 (5.2%) deteriorated. The results indicated the disease-onset age greater than 6 years and age at operation greater than 12 years were both positively associated with CSR responses. Postoperative steroid treatments in ocular MG and preoperative disease duration in generalized MG (>12 months) were negatively associated with CSR responses. Conclusions. Extended transsternal thymectomy for Chinese juvenile MG patients has an efficacy comparable with reports from other ethnicities. Juvenile patients with disease-onset age greater than 6 years, age at operation greater than 12 years, and shorter disease duration of generalized MG are associated with favorable clinical outcomes. (Ann Thorac Surg 2013;95:1035 42) 2013 by The Society of Thoracic Surgeons Myasthenia gravis (MG) is an autoimmune disease with antibodies against the postsynaptic nicotinic acetylcholine receptors causing a neuromuscular transmission disorder characterized by relapsing voluntary muscle weakness [1]. Acquired juvenile myasthenia gravis (JMG) with MG signs and symptoms before 18 years of age account for 10% to 43% of all MG patients [2, 3]. The prevalence of JMG in Chinese children may actually be higher than that in Caucasians [3, 4]. It was well recognized that the thymus was pathogenetically linked to MG, and thymectomy as an important treatment of MG was widely accepted in adult patients [5, 6]. However, the information about the efficacy and the appropriate timing of thymectomy in JMG patients are still limited [4, 7 9]. To address this gap in kwledge, we conducted a retrospective review of 141consecutive cases of JMG treated with extended transsternal thymectomy Accepted for publication Nov 19, 2012. Address correspondence to Dr Cheng, Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Rd, Guangzhou 510080, P. R. China; e-mail: drchengchao@yahoo.com.cn. (ETT) at our MG research center from 1990 to 2010. In this study, we analyzed the preoperative and long-term postoperative follow-up data to evaluate the efficacy of ETT and potential predictors of clinical outcomes in these JMG patients. Patients and Methods Patients A retrospective review of JMG patients was conducted according to a protocol approved by the Ethic Committee and Institutional Review Board of the First Affiliated Hospital of Sun Yat-sen University. We reviewed a total of 141 consecutive patients with JMG who underwent ETT at the MG Research Center of the First Affiliated Hospital of Sun Yat-sen University from January 1990 to December 2010. Experienced neurologists, specializing in MG in our research center, diagsed JMG based on all 4 diagstic criteria as in our previous report [10]: (1) typical clinical manifestation; (2) pharmacologic testing with edrophonium chloride that elicits unequivocal im- 2013 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc http://dx.doi.org/10.1016/j.athoracsur.2012.11.074

1036 CHENG ET AL Ann Thorac Surg EXTENDED TRANSSTERNAL THYMECTOMY FOR JUVENILE MG 2013;95:1035 42 Abbreviations and Acronyms AChRs acetylcholine receptors CSR compete stable remission ETT extended transsternal thymectomy GCR general complete remission GMG generalized myasthenia gravis JMG juvenile myasthenia gravis MGFA Myasthenia Gravis Foundation of America OMG ocular myasthenia gravis PR pharmacologic remission SFEMG single-fiber electromyography provement in strength; (3) electrophysiologic testing with repetitive nerve stimulation studies or single-fiber electromyography, or both, demonstrating a primary postsynaptic neuromuscular junction disorder; and (4) therapeutic benefits from anticholinesterase drugs or corticosteroids, or both. In patients 2 or less years old, the diagsis should be further confirmed by the positive AChR-Ab test [11] and absence of family history to exclude the congenital myasthenia gravis. Osserman classification was used to evaluate the severity of the disease: class I (ocular MG [OMG]); class II (mild generalized MG); class III (moderate generalized MG); class IV (severe generalized MG). The JMG patients were treated with ETT, if they had the following: (1) resistance to pyridostigmine and immusuppressive therapy; (2) generalized myasthenia gravis (GMG); and (3) ocular JMG with partial response to pyridostigmine but absence of complete stable remission (CSR) more than 2 years. The ETT treatment classified as T-3b according to the Myasthenia Gravis Foundation of America was performed as previously reported [12]. All patients received anti-cholinesterase inhibitors; 88 patients (62.4%) received corticosteroids and 2 patients (1.4 %) received azathioprine. Oral corticosteroids were usually started at 0.25 to 1.0 mg/kg per day; the doses were gradually reduced to the minimum effective dose during remission [13]. After ETT, these medications were weaned off if the patient was symptom free; otherwise, the medications were managed by neurologists. Follow-up was continued through routine ambulatory treatment, clinic visits, or telephone interviews. Clinical Responses The Myasthenia Gravis Foundation of America postintervention status and quantitative MG scores were used to evaluate the response to treatment by experienced neurologists in our research center [14]. Exacerbation of MG symptoms or increased requirement of medical therapy postoperatively indicated clinical deterioration. Patients were considered clinically stable or unchanged if the postoperative symptoms and drug dose requirements were similar to the preoperative conditions. A substantial decrease in MG symptoms or a sustained substantial reduction in MG medications was considered clinical improvement. Patients who were asymptomatic with or without low-dose single-drug therapy were considered to be in general complete remission [12]. If the patients were asymptomatic for at least 12 months, those who were still on medications were in pharmacologic remission, and those who were on medications were in CSR. Statistical Analysis Statistical analysis was performed with SPSS 18.0 software (SPSS, Chicago, IL). Continuous quantitative data are presented as median and range. Categoric variables are expressed as counts and proportions. Ratios of categoric variables were compared by the 2 test. Of the 141 patients in the study, 135 had follow-up visits and were included in the neurologic outcome analysis. The Kaplan-Meier analysis and log-rank test were used to estimate the time to CSR, which was defined as the time from surgery to the date when CSR was first documented. Univariate analysis and multivariate Cox regression analysis were performed to determine the impact of various preoperative and operative factors on the probability of CSR. The results from the multivariable regression model were further refined by using the bootstrap technique, which performed 1,000 random resamplings to evaluate the stability and validity of the original model [15]. Statistical significance was set at a p value less than 0.05. Results Patient Profile Of the 141 patients in our study, 135 patients were available for complete follow-up evaluation, and ather 6 patients lost to follow-up were t included in the neurologic outcome analysis. Preoperative clinical characteristics of 141 patients with JMG are shown in Table 1. There were 96 patients (68.1%) with OMG (ie, Osserman class I) and 45 (31.9%) with GMG (37 [26.2%] in class II, 3 [2.1%] in class III, and 5 [3.6%] in class IV). There were 70 boys and 71 girls. The median age of JMG onset was 6 years (range, 1 to 18 years), and the median age of ETT was 12 years (range, 3 to 18 years). All 141 patients received the cholinesterase inhibitor pyridostigmine, and 88 patients received corticosteroids after ETT. In addition, there were 7 patients with concurrent hyperthyroidism in this cohort (Table 1). Follow-up information was available in 135 patients (95.7%). Results of ETT in JMG Patients Pathologic analysis of the resected thymus revealed hyperplasia in 140 patients (99.3%) and rmal thymus in 1 patient (0.7%) (Table 1); thymoma was in our cohort. The presence of ectopic thymic tissue was examined in 93 cases (after July 2006) and in 6 cases ectopic thymic foci were identified in (Table 1): the aortopulmonary window (4 cases, 66.7%), the pericardial fat (1 case, 16.7%), and the pretracheal infrathyroid fat (1 case, 16.7%). The overall perioperative complication rate was 6.4%,

Ann Thorac Surg CHENG ET AL 2013;95:1035 42 EXTENDED TRANSSTERNAL THYMECTOMY FOR JUVENILE MG 1037 Table 1. Clinical Characteristics of 141 Patients With Juvenile Myasthenia Gravis Characteristics Numerical Value Sex Male 70 (49.6%) Female 71 (50.4%) Age at disease onset, years (range) 6 (1 18) a Age at operation, years (range) 12 (3 18) a Hyperthyroidism No 134 (95.0%) Yes 7 (5.2%) Osserman classification I 96 (68.1%) II 37 (26.2%) III 3 (2.1%) IV 5 (3.6%) Follow-up, months (range) 49 (11 123) a Postoperative treatment Anticholinesterase agents 141 (100.0%) Steroids 88 (62.4%) Histopathology Normal 1 (0.7%) Hyperplasia 140 (99.3%) Ectopic thymus b 6 (6.5%) a Median (range). 93 cases. b The search for ectopic thymus was performed in Table 2. Clinical Outcomes of the Juvenile Myasthenia Gravis Patients After Extended Transsternal Thymectomy Category of Response Patients n (%) 12 years a 12 years a Complete remission 34 (25.2%) 11 (16.2%) 23 (34.3%) Pharmacologic 28 (20.7%) 17 (25.0%) 11 (16.4%) remission Improved 61 (45.2%) 33 (48.5%) 28 (41.8%) Unchanged 5 (3.7%) 3 (4.4%) 2 (3.0%) Worsened 7 (5.2%) 4 (5.9%) 3 (4.5%) a Age at operation (years). dosages of pyridostigmine and corticosteroid and 3 patients experienced aggravation of ptosis or diplopia. Overall, the response rate of ETT in JMG patients was 91.1%. Comparison of CSR rates across different patient groups in this study is shown in Table 3. Patients with later disease onset ( 6 years) revealed higher CSR rates (p 0.002). Similarly, between the groups divided by the median age of ETT, the older children ( 12 years) also showed significantly higher CSR rates (p 0.015). Eightyfive patients received corticosteroid treatment postoperatively. Only 15 out of these 85 patients (17.6%) achieved CSR, while in the 50 patients without postoperative corticosteroid administration, 19 (38.0%) achieved CSR and the common complications were pneumonia and postoperative atelectasis. Myasthenia gravis crisis occurred in 10 patients after ETT, among which the preoperative Osserman classification was the following: 1 patient in class I; 4 patients in class II; 3 in class III; and 1 in class IV. Furthermore, in 9 of these 10 patients, there was resistance to pyridostigmine or progression of disease despite corticosteroid and other immusuppressive therapy. Among them, 9 patients underwent MG crisis once after the operation, and 1 patient suffered MG crisis 4 times within the first 6 months postoperatively. The time from the operation to the first crisis ranged from 2 months to 2 years. All patients in this group were treated with anticholinesterase agents and corticosteroids postoperatively. When a crisis happened, the patients received plasma exchange or intraveus immuglobulin infusion by neurology specialists. At the end of last follow-up, 7 patients showed improvement, 2 achieved pharmacologic remissions, and 1 had complete remission. None of the 135 JMG patients died in the period of our follow-up. Neurological Outcomes Clinical outcomes of the 135 patients with complete follow-up are shown in Table 2. There were 34 patients (25.2%) in complete remission (CSR), 28 patients (20.7%) in pharmacologic remission, 61 (45.2%) had improved, 5 (3.7%) patients had an unchanged status, and 7 (5.2%) patients had worsened. Among the 7 patients who deteriorated clinically after ETT, 4 patients needed higher Table 3. Univariate Analysis of Complete Stable Remissions by Characteristics in 135 Patients With Juvenile Myasthenia Gravis Variable No. CSR n (%) p a HR (95% CI) b p b Sex 0.518 0.995 Male 65 18 (27.7%) Ref Female 70 16 (22.9%) 0.99 (0.51 1.96) Age at disease onset (years) 0.002 0.001 6 71 10 (14.1%) Ref 6 18 64 24 (37.5%) 3.52 (1.67 7.43) Age at operation (years) 0.015 0.007 12 68 11 (16.2%) Ref 12 18 67 23 (34.3%) 2.71 (1.31 5.57) Hyperthyroidism 0.814 0.562 No 128 33 (25.8%) Ref Yes 7 1 (14.3%) 0.56 (0.08 4.08) Postoperative corticosteroid treatment 0.009 0.009 No 50 19 (38.0%) Ref Yes 85 15 (17.6%) 0.40 (0.20 0.79) Ectopic thymus 0.863 0.805 No 87 17 (19.5%) Ref Yes 6 1 (16.7%) 1.29 (0.17 9.89) a 2 test. b Univariate proportional hazard analysis. CI confidence interval; CSR complete stable remission; HR hazard ratio.

1038 CHENG ET AL Ann Thorac Surg EXTENDED TRANSSTERNAL THYMECTOMY FOR JUVENILE MG 2013;95:1035 42 Table 4. Univariate Analysis of Complete Stable Remissions by Characteristics in Subgroups of Ocular Myasthenia Gravis and Generalized Myasthenia Gravis patients Ocular Myasthenia Gravis Generalized Myasthenia Gravis Variables No. CSR n (%) p a HR (95% CI) b p b No. CSR n (%) p a HR (95% CI) b p b Sex 0.239 0.489 0.714 0.249 Male 47 15 (31.9%) Ref 18 3 (16.7%) Ref Female 43 9 (20.9%) 0.75 (0.33 1.71) 27 7 (25.9%) 2.24 (0.57 8.84) Age disease onset (years) 0.013 0.013 0.028 0.041 6 53 9 (17.0%) Ref 18 1 (0.06%) Ref 6 18 37 15 (40.5%) 2.85 (1.24 6.53) 27 9 (33.3%) 8.88 (1.10 71.8) Age at operation (years) 0.110 0.152 0.028 0.016 12 50 10 (20.0%) Ref 18 1 (0.06%) Ref 12 18 40 14 (35.0%) 1.81 (0.80 4.08) 27 9 (33.3%) 13.7 (1.64 115) Hyperthyroidism 0.288 0.623 0.890 0.868 No 87 24 (27.6%) Ref 41 9 (22.0%) Ref Yes 3 0 4 1 (25.0%) 0.84 (0.11 6.71) Postoperative corticosteroid treatment 0.001 0.002 0.486 0.510 No 45 9 (20.0%) Ref 5 0 Ref Yes 45 15 (33.3%) 0.18 (0.06 0.52) 40 10 (25.0%) Ectopic thymus 0.729 0.715 0.476 0.861 No 85 23 (27.1%) Ref 44 10 (22.7%) Ref Yes 5 1 (20.0%) 1.46 (0.19 11.1) 1 0 a 2 test. b Univariate proportional hazard analysis. CI confidence interval; CSR complete stable remission; HR hazard ratio. responses to ETT (p 0.009). In our subgroup analysis of OMG and GMG patients, corticosteroid treatment was negatively associated with CSR after ETT (p 0.001) for OMG patients, but there was association with CSR rate in GMG patients (Table 4). Early thymectomy (within 12 months of the onset of symptoms) was a positive predictive factor of the good responses to ETT for OMG patients (51 adults and 59 children) in our previous report [12]. In this study, we found that early thymectomy within 12 months of GMG onset was associated with favorable clinical responses to ETT (p 0.014) (data t shown). Other factors, sex (p 0.518), concurrent hyperthyroidism (p 0.814), MG type (OMG or GMG) (p 0.575), or ectopic thymus status (p 0.863), were t associated significantly with CSR (Table 3). The cumulative incidence of CSR in the postoperative period was 25.1% during the first 3 year period, and 43.2% during the 10 years postoperatively (Fig 1A). The log-rank test revealed significant differences between subgroups based on age at disease onset and operation, the status of postoperative corticosteroid treatment (Fig 1B;C;D). Patients with an older age at operation (12 to 18 years) and corticosteroid treatment had significantly better responses to ETT. In addition, a shorter preoperative duration ( 12 months) was positively associated with good outcomes of ETT in GMG patients (Fig 1E). Multivariate Cox regression analysis revealed that the age at operation and the status of postoperative corticosteroid treatment were independent factors predicting the outcome after ETT (Table 5). The multivariable model was further validated and refined by using the bootstrap technique. The HR confidence interval and p values between the original regression model and the bootstrap model were of a high degree of similarity (Table 5), and this result confirmed the stability and validity of the predictors. Comment Juvenile myasthenia gravis is a rare pediatric disease with many clinical features that are distinct from adult MG. The benefit of surgical treatment in JMG is still controversial [16]. Several studies indicate a wide variation in complete remission rates ranging from 18.1% to 60%, which might be due to small cohort sizes and different racial backgrounds [16 20]. The major series of thymectomized JMG patients from different areas of the world were reviewed and compared with our current results (Table 6). To our kwledge, this is the largest series for Chinese JMG patients. The general complete remissions were comparable across different series (Table 6). Importantly, the cumulative percentage of remission in our series reached 43.2% at 10-year follow-up, which was higher than the previously reported rates ranging from 15% to 34.7% after a variety of nsurgical treatments [19, 21, 22]. Complications of ETT are uncommon and our results strongly suggest that ETT is a safe and effective treatment option for some JMG patients. Data regarding the natural history and response to ETT in prepubertal JMG are limited. While a few reports

Ann Thorac Surg CHENG ET AL 2013;95:1035 42 EXTENDED TRANSSTERNAL THYMECTOMY FOR JUVENILE MG 1039 Fig 1. Kaplan-Meier curves of complete remission (CR) in patients with juvenile myasthenia gravis (JMG) undergoing extended transsternal thymectomy (ETT). The CR was defined using a strict standard (CSR, complete stable remission) (A) (D) and a broader standard (GCR, general complete remission, including asymptomatic patients with low-dose single-drug immusuppression) (E), respectively. Patients in (B) and (C) were grouped according to the age at disease onset (6 years) or the age at operation (12 years), respectively. Patients in (D) were divided by the status of postoperative steroid treatments; those who were treated with steroid had poorer responses after operation. In (F), the outcome of ETT was evaluated by GCR. In generalized JMG patients, those who had duration of symptoms equal to or less than 12 months had a better improvement after operation. A p value less than 0.05 was considered to be significant. found that thymectomy may be beneficial for prepubertal patients with JMG [18], other researchers argued against the surgical intervention because of the importance of the thymus in maintaining the integrity of T cell immunity during adult life [23] and the relative high spontaneous remission rate [22,24]. Our results suggest that the efficacy of ETT was lower in prepubertal patients 12 or less years old at the time of ETT than JMG patients greater than 12 years old (Table 2). In Cox multivariate analysis, whether the JMG patient was younger than 12 years at the time of ETT was an independent predictor of CSR after ETT (Table 5). Therefore, the selection of surgical intervention in prepubertal JMG patients should be made very cautiously. Corticosteroids play an important role in the treatment for adult MG patients. In contrast, corticosteroid treatment in JMG does t influence the likelihood of remission after thymectomy [1]. In our study, postoperative Table 5. Multivariate Cox Regression Analysis of Complete Stable Remissions by Characteristics in Juvenile Myasthenia Gravis Patients from the Original Regression Model and the Bootstrap Model Original Model Bootstrap Model Variable HR (95% CI) p HR (95% CI) p Female gender 0.91 (0.45 1.85) 0.797 0.91 (0.41 1.80) 0.796 Age at operation (12 18 years) 2.43 (1.17 5.05) 0.017 2.43 (1.11 5.56) 0.009 Hyperthyroidism 0.53 (0.07 4.11) 0.547 0.53 (0.00 3.00) 0.313 Osserman class II or higher 1.68 (0.70 4.01) 0.242 1.68 (0.72 4.10) 0.194 Postoperative steroid treatment 0.37 (0.17 0.81) 0.013 0.37 (0.16 0.69) 0.004 Ectopic thymus 1.45 (0.18 11.4) 0.724 1.45 (0.00 6.87) 0.389 CI confidence interval; HR hazard ratio.

1040 CHENG ET AL Ann Thorac Surg EXTENDED TRANSSTERNAL THYMECTOMY FOR JUVENILE MG 2013;95:1035 42 Table 6. Comparison of Major Series of Patients With Juvenile Myasthenia Gravis Who Underwent Thymectomy From Different Areas of the World Seybold et al [18] Lindner et al [17] Ashraf et al [19] Essa et al [16] Heckmann et al [20] Present Study Areas America Germany India Saudi Arabia South Africa China Year 1971 1997 2006 2003 2012 2012 Number of thymectomized patients 49 65 11 30 60 135 Outcome of thymectomy (%) GCR (or CSR) 37.5 60 ND (18.1) 43.4 55 45.9 (25.2) Clinically Improved 33 15 ND 46.6 ND 45.2 CSR complete stable remission, patients who were asymptomatic in the absence of medications for at least 12 months postoperatively; general complete remission, patients who were asymptomatic with or without low-dose single-drug therapy; ND data available. corticosteroid treatment was an independent negative predictor of the CSR rate after ETT in OMG children, but significant difference was found between subgroups with or without postoperative steroid treatment in GMG patients (Table 4). During the follow-up by our neurologists, corticosteroids were added for the patients with symptoms. However, the optimal dosing and timing of GCR corticosteroids in postoperative JMG patients remain unclear. The association of corticosteroids with poor JMG clinical outcome after ETT was most likely due to the need to use corticosteroids to control symptoms in patients with poor clinical outcomes. The duration between disease onset and ETT was a significant predictor of the efficacy of ETT in GMG Fig 2. An algorithm for treatment of juvenile myasthenia gravis (JMG) patients. (CSR complete stable remission.) JMG Diagsis Cholinesterase Inhibitors CSR Wean medica ons as tolerated Con nue Follow Up op onal Age >12 years Add/increase dose of cor costeroid or azathioprine Add/increase dose of cor costeroid or azathioprine CSR CSR Thymectomy? Osserman Class > I Par al Response to Meds. 24 months dura on Thymectomy y

Ann Thorac Surg CHENG ET AL 2013;95:1035 42 EXTENDED TRANSSTERNAL THYMECTOMY FOR JUVENILE MG 1041 patients. A shorter duration of 12 months or less was associated with better clinical outcomes than the group with a duration of greater than 12 months (Fig 1E). Therefore, early thymectomy may be more effective than delayed thymectomy in GMG patients. Several other independent studies also advocated early thymectomy (with the preoperative duration 12 months) [24 26]. As an uncontrolled retrospective study, our results have certain limitations. First, in the absence of the comparison of different treatments without thymectomy, it is hard to determine the real benefits of ETT without the exclusion of spontaneous remission. Second, this study spanned a period with varying clinicians grading and recording the clinical responses. Nevertheless, it is a large cohort of JMG patients from a single medical school-based center in China, with detailed long-term follow-up. Our study indicated that JMG patients with age at operation greater than 12 years, disease-onset age greater than 6 years, and preoperative disease duration 12 months or less in generalized JMG are characteristics associated with favorable neurologic outcomes from ETT. The efficacy of ETT in prepubertal JMG is poor. Due to the high spontaneous remission rate in OMG patients, at least 24 months of medical therapy and observation before ETT should be considered for those who have partial response to medication, but early thymectomy ( 12 months) would be recommended for those who are resistant to medication [12]. Based on our findings, we propose a treatment algorithm for JMG patients in Figure 2. A randomized controlled trial is urgently needed to clarify the role and timing of ETT in JMG. This work was supported by grants from the China National Natural Sciences Foundation (No.30801136 to C. Cheng) and (No.81171125 to C. Cheng) and the Research and Development Program of Sun Yat-sen University (10YKPY09 to C. Cheng). References 1. Andrews PI. Autoimmune myasthenia gravis in childhood. Semin Neurol 2004;24:101 10. 2. Phillips LH II, Torner JC, Anderson MS, Cox GM. The epidemiology of myasthenia gravis in central and western Virginia. Neurology 1992;42:1888 93. 3. Chiu HC, Vincent A, Newsom-Davis J, Hsieh KH, Hung T. The epidemiology of myasthenia gravis in central and western Virginia. Neurology 1987;37:1854 7. 4. Zhang X, Yang M, Xu J, et al. Clinical and serological study of myasthenia gravis in HuBei Province, China. J Neurol Neurosurg Psychiatry 2007;78:386 90. 5. Raica M, Cimpean AM, Ribatti D. Myasthenia gravis and the thymus gland. A historical review. Clin Exp Med 2008;8: 61 4. 6. Drachman DB. Myasthenia gravis. N Engl J Med 1994;330: 1797 810. 7. Adams C, Theodorescu D, Murphy EG, Shandling B. Thymectomy in juvenile myasthenia gravis. J Child Neurol 1990;5:215 8. 8. 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Evoli A, Batocchi AP, Bartoccioni E, Li MM, Minisci C, Tonali P. Juvenile myasthenia gravis with prepubertal onset. Neuromuscul Disord 1998;8:561 7. 22. Rodriguez M, Gomez MR, Howard FM Jr, Taylor WF. Myasthenia gravis in children: long-term follow-up. Ann Neurol 1983;13:504 10. 23. Sauce D, Larsen M, Fastenackels S, et al. Evidence of premature immune aging in patients thymectomized during early childhood. J Clin Invest 2009;119:3070 8. 24. Andrews PI, Massey JM, Howard JF Jr, Sanders DB. Race, sex, and puberty influence onset, severity, and outcome in juvenile myasthenia gravis. Neurology 1994;44:1208 14. 25. Venuta F, Rendina EA, De Giacomo T, et al. Thymectomy for myasthenia gravis: a 27-year experience. Eur J Cardiothorac Surg 1999;15:621 5. 26. Youssef S. Thymectomy for myasthenia gravis in children. J Pediatr Surg 1983;18:537 41. INVITED COMMENTARY Juvenile myasthenia gravis (JMG) is a form of MG presenting before age 19 years and more common in Asian populations. The report from Cheng and colleagues [1] is a retrospective analysis of 141 patients who underwent extended transsternal thymectomy in a Chinese hospital. The objective of the report was to identify factors associated with complete or pharmacologic remission, which occurred in approximately 46% of patients. The authors found that older age at operation ( 12 years) and a short waiting time from diagsis ( 12 months) 2013 by The Society of Thoracic Surgeons 0003-4975/$36.00 Published by Elsevier Inc http://dx.doi.org/10.1016/j.athoracsur.2012.12.012