Atormac
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 1047  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (770 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed2443    
    Printed98    
    Emailed3    
    PDF Downloaded104    
    Comments [Add]    
    Cited by others 1    

Recommend this journal

 


 
Table of Contents    
ORIGINAL ARTICLE
Year : 2014  |  Volume : 62  |  Issue : 2  |  Page : 164-168

Preoperative pulmonary function is strongly related to myasthenic crisis after thymectomy


1 Department of Neurology, Chonnam National University Hwasun Hospital; Department of Neurology, Chonnam National University Medical School, Gwangju, Korea
2 Department of Neurology, Chonnam National University Hwasun Hospital, Gwangju, Korea

Date of Submission04-Jan-2014
Date of Decision13-Apr-2014
Date of Acceptance19-Apr-2014
Date of Web Publication14-May-2014

Correspondence Address:
Tai-Seung Nam
Department of Neurology, Chonnam National University Medical School, Gwangju 501-757
Korea
Login to access the Email id

Source of Support: Supported by grants from the Chonnam National University Hospital Biomedical Research Institute (CRI11058-1), Conflict of Interest: None


DOI: 10.4103/0028-3886.132361

Rights and Permissions

 » Abstract 

Background: Myasthenic crisis can be occasionally a complication after surgery for thymomatous myasthenia gravis (T-MG). Aims: The purpose of this study was to investigate the influence of thymectomy on the subsequent clinical course of T-MG. Study Design: Retrospective study. Materials and Methods: Only T-MG patients with at least 36 months of follow-up after transsternal thymectomy for thymoma was screened, and those with successfully weaned from a ventilator after surgery were included in the study. Results: Forty-eight T-MG patients were enrolled during the study period. Myasthenic crisis after thymectomy (MCAT) occurred in 12 (25%) patients with T-MG. Eight (67%) patients with MCAT experienced respiratory failure within the first 1 and 2 years after disease onset. The ratio of measured forced vital capacity (mFVC) to the predicted FVC (pFVC) preoperatively was the only independent factor affecting the occurrence of MCAT (odds ratio, 0.916; 95% confidence interval [CI], 0.867-0.967; P = 0.002). The area under the curve of the receiver operating characteristic for mFVC/pFVC was 0.881 (95% CI 0.754-0.956, P < 0.001), with sensitivity, specificity, and positive and negative predictive values of 58.3%, 97.2%, 87.5%, and 90%, respectively, at a threshold of ≤65% of mFVC/pFVC. Conclusions: MCAT may occur in patients with T-MG after thymectomy especially within 2 years after disease onset. Preoperative mFVC/pFVC is strongly associated with the occurrence of MCAT postoperatively.


Keywords: Myasthenia gravis, pulmonary function, thymoma


How to cite this article:
Choi KH, Nam TS, Lee SH, Kim MK. Preoperative pulmonary function is strongly related to myasthenic crisis after thymectomy. Neurol India 2014;62:164-8

How to cite this URL:
Choi KH, Nam TS, Lee SH, Kim MK. Preoperative pulmonary function is strongly related to myasthenic crisis after thymectomy. Neurol India [serial online] 2014 [cited 2020 Mar 30];62:164-8. Available from: http://www.neurologyindia.com/text.asp?2014/62/2/164/132361



 » Introduction Top


Myasthenia gravis (MG) is an acquired autoimmune neuromuscular transmission disorder characterized by muscle weakness and fatigue. [1] Approximately, 15-30% of MG patients have thymoma. [2],[3] Thymectomy is recommended in patients with thymomatous MG (T-MG) and is associated with reduced morbidity and mortality. [4] However, myasthenic crisis can occasionally complicate thymectomy, [5],[6] which is the most common cause of death in patients with MG. There is a substantial decrease in the incidence due introduction of intensive care units, immune-modulation therapy, and less invasive surgical approaches including video-assisted thoracoscopic surgery. [7],[8],[9],[10]

The information in regard to short-term prognosis, in particular myasthenic crisis after thymectomy (MCAT) is limited, and the reported rates range between 3.8% and 34% and the predictive factors reported are varied. [11],[12],[13],[14],[15] This may be related to the diversity of surgical indications for thymectomy. [16] This study included only patients with T-MG who had thymectomy and studied the effect of thymectomy on the subsequent clinical course of MG, and also identified the predictive factors for MCAT in the short-term postoperative period.


 » Materials and Methods Top


Data of 49 patients who underwent transsternal thymectomy for T-MG during a 13-year period between January 1996 and December 2009 were retrospectively evaluated. Only T-MG patients with at least 36 months of follow-up after surgery and those without overlapping syndromes or underlying cardiopulmonary diseases were enrolled in the study. Written informed consent was obtained from all patients participating in the study, and the study was approved by the institutional review board. MCAT was defined as neuromuscular respiratory failure occurring several months after surgery in patients with T-MG, who were successfully weaned from a mechanical ventilator after thymectomy. MG patients were grouped into: Group 1 patients with MCAT and Group 2 patients without MCAT.

Data collected included: Age of onset, gender, time interval from disease onset to thymectomy, presence of MG symptoms, history of myasthenic crisis before thymectomy (MCBT), preoperative bulbar symptoms, daily doses of pyridostigmine, and use of corticosteroids before thymectomy, serum level of anti-acetylcholine receptor antibody (anti-AChR), and pulmonary functions: measured forced vital capacity (mFVC), ratio of mFVC to the predicted FVC (mFVC/pFVC), measured forced expiratory volume in 1 s (mFEV1), the ratio of mFEV1 to the predicted FEV1 (mFEV1/pFEV1), and the ratio mFEV1 to mFVC (mFEV1/mFVC), and thymic pathology. AChR antibody level was measured immediate to thymectomy by radioimmunoassay (reference range, <0.2 nmol/L). Pulmonary function tests were done immediate to thymectomy; mFVC - the volume of air that can forcibly be blown out after full inspiration, mFEV1 - the volume of air that can be forced out in 1 s after taking a deep breath, and pFVC and pFEV1 - the reference values of healthy individuals with normal lung function of the same age, sex, and height. The ratios in pulmonary function were expressed as a percentage. Thymic pathology was confirmed by histological examination and classified as Type A, AB, B1, B2, and B3. [17]

Statistical analyses were performed using IBM SPSS 20.0 (IBM Corp., Armonk, NY, USA) for Windows (version 20.0). The normal distribution of all continuous variables was analyzed using the Kolmogorov-Smirov test. For identification of statistically significant independent predictors of MCAT, categorical, and continuous variables were analyzed using Fisher's exact test and Mann-Whitney U-test. Receiver operating characteristic (ROC) analysis of preoperative pulmonary function to predict the occurrence of MCAT was assessed using MedCalc for Windows (version 12.6.0; MedCalc Software, Ostend, Belgium). Clinical factors which were found to have P < 0.20 in the univariate analysis were entered into a stepwise multiple logistic regression analysis. All tests were two-sided, and P < 0.05 was considered s statistically significant.


 » Results Top


Of the 49 T-MG patients who had underwent thymectomy, one patient with an overlapping syndrome (systemic lupus erythematosus) was excluded. Of the 48 patients enrolled, 23 were men, mean age of onset was 50.3 ± 12.4 years, median time interval from disease onset to thymectomy was 3.6 months (range, 0.6-59.6 months), and mean time from thymectomy to the last follow-up was 80.8 ± 39.6 months. Forty-one (85.4%) patients were classified as generalized MG and 7 (14.6%) as ocular MG. Three patients needed mechanical ventilation for >48 h (delayed ventilation weaning) in the postoperative period, and none of the patients had underlying cardiopulmonary complications.

There were 12 (25%) patients in Group 1 (MCAT) and 36 (75%) in Group 2 (no MCAT). Time interval from disease onset to thymectomy was longer in Group 1 compared with Group 2 (5.2 months vs. 3.2 months, P = nonsignificant), MCAT occurred within the first 6 months of surgery in 6 (50%) of patients, 2 (16.7%) patients within 6-12 months, and in 4 (33.3%) patients after 1 year in Group 1. The median time interval from thymectomy to MCAT was 6.7 months (range, 1-40 months), and time from disease onset to MCAT was 17 months (range, 2-46 months).

The ratio of patients with a history of MCBT was significantly higher in Group 1 than in Group 2 (P = 0.002). The mean value of daily doses of pyridostigmine was significantly associated with the occurrence of MCAT (P = 0.045). The mean values of mFVC and mFVC/pFVC in Group 1 were significantly lower compared to those in Group 2 (P = 0.001 and P < 0.001, respectively). The values of mFVC and mFVC/pFVC in Group 1 were 2.28 L (range, 0.9-3.93 L) and 60% (range, 25-91%), respectively. The values of mFEV1 and mFEV1/pFEV1 were also significantly related to the occurrence of MCAT (P = 0.004 and P = 0.002, respectively), but that of mFEV1/mFVC was not. There were no significant differences between the two groups in age of onset, gender, and the existence of generalized MG symptoms, bulbar symptoms, immunotherapy, and the mean value of preoperative anti-AChR titers. After thymectomy, patients with Type A, AB, B1, B2, and B3 were 0, 3, 5, 2, and 2 in number in Group 1, and 5, 4, 10, 15, and 2 in number in Group 2, respectively. The types of thymoma between the two groups were not associated with the occurrence of MCAT. Clinical factors related to the occurrence of MCAT are shown in [Table 1].
Table 1: Clinical factors affecting the occurrence of MCAT in patients with T-MG (n=48)

Click here to view


On univariate analysis, the variables that had P < 0.05 between the two groups were a past history of MCBT, daily doses of pyridostigmine, and preoperative pulmonary function including mFVC, mFEV1, mFVC/pFVC, and mFEV1/pFEV1. On multivariate logistic regression analysis, preoperative mFVC/pFVC just before thymectomy was significantly related with the occurrence of MCAT several months after surgery. The data are shown in [Table 2]. ROC curve area (area under the curve [AUC]) for mFVC/pFVC% was 0.881 (95% confidence interval 0.754-0.956, P < 0.0001), with sensitivity, specificity, positive, and negative predictive values of 58.3%, 97.2%, 87.5%, and 90%, respectively, at a threshold of ≤65%. That is, 7 (87.5%) of eight patients below this score preoperatively had experienced MCAT, but 90% of 40 patients with preoperative mFVC/pFVC >65% had not. The comparisons of the ROC curves for each pulmonary function test are shown in [Figure 1].
Figure 1: The receiver operating characteristic (ROC) curves of four pulmonary function tests predicting the occurrence of myasthenic crisis after thymectomy. The area under the ROC curve of measured forced vital capacity (mFVC)/predicted FVC is 0.881, and mFVC, measured forced expiratory volume in 1 s (mFEV1), mFEV1/predicted FEV1 had area under the curves of 0.796, 0.756, 0.846, in order

Click here to view
Table 2: Predictive factors affecting the occurrence of MCAT in patients with T-MG (n=48)

Click here to view



 » Discussion Top


The primary purpose of this study was to investigate the effect of thymectomy on the occurrence of MCAT, and it was 25%, similar to the earlier studies. [11],[12],[13],[14] We included patients with MCAT occurring several months postoperative, delayed weaning, the diagnostic criteria of MCAT in the earlier studies, can be due to perioperative morbidity related to the surgery and not due to myasthenic crisis. [18] In addition, respiratory failure occurring in the immediate postoperative period can be either to lead to myasthenic crisis or cholinergic crisis, and it may be difficulty to differentiate between them. [14]

It has been reported that time from disease onset to thymectomy of <8 months may be strongly associated with excellent prognosis, clinical remission. [19] In our study of the 29 patients, 8 (27%) patient who received thymectomy within 8 months of the disease onset experienced postoperative respiratory failure, and all experienced MCAT within the first 1 year after surgery. It has been observed that MG is severe during the first 2 years of onset of the disease, [20],[21],[22],[23] and myasthenic crisis occurs in 15% to 20% within the same period. [5],[13] In this study, 25% of patients with T-MG experienced MCAT and in 8 (67%) of patients developed this complication within in the first 2 years of onset of disease, similar to the observation in the earlier studies. The results suggest that thymectomy, within 2 years of disease onset, may not give any protection from developing postoperative respiratory failure. These observations suggests that preoperative immunomodulatory therapy including intravenous immunoglobulin or plasma exchange may deserve careful consideration for the stabilization of unstable MG symptoms during the early phase of T-MG. [24],[25]

The second purpose of this study was to identify predictive factors for MCAT in patients with T-MG. It is important to know, which MG patients are at risk of experiencing postoperative respiratory failure. In this study, preoperative pulmonary function was strongly associated with the occurrence of MCAT, and preoperative mFVC/pFVC in particular was found to be the only single predictive factor. This result suggests that patients with significantly reduced mFVC/pFVC may not be the candidate for thymectomy, and thymectomy may be considered in these patients after stabilization, and these patients should be closely monitored in the postoperative period. It has been observed that preoperatively reduced pulmonary function may not be significantly related to the occurrence of postoperative respiratory failure. [13] In this study, the optimal cut-off point of preoperative pulmonary function to determine the risk of MCAT was 65% of mFVC/pFVC. Earlier studies reported that preoperative vital capacity of >2 L may be unlikely to have postoperative respiratory failure. [26] In this study of the 41 patients, 7 (17%) patients with preoperative mFVC >2 L experienced MCAT. The conflicting results might be due to the heterogeneous nature of the thymic pathologies, thymoma 24% and 43%, [13],[26] respectively. Whereas, in our study all the patients were T-MG.

There are several limitations for this study. This analysis is retrospective with the possible selection bias. The medical and surgical treatment regimens in the study patients were not standardized. In conclusion, thymectomy, within the first 2 years of onset of disease, may be not prevent the occurrence of postoperative MCAT, especially in patients with reduced pulmonary function preoperatively. Preoperative mFVC/pFVC was strongly associated with the occurrence of postoperative respiratory failure. Measurement of pulmonary functions and the stabilization of unstable MG symptoms including reduced pulmonary function may be important before deciding to thymectomy.

 
 » References Top

1.Alshekhlee A, Miles JD, Katirji B, Preston DC, Kaminski HJ. Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals. Neurology 2009;72:1548-54.  Back to cited text no. 1
    
2.Maggi L, Andreetta F, Antozzi C, Baggi F, Bernasconi P, Cavalcante P, et al. Thymoma-associated myasthenia gravis: Outcome, clinical and pathological correlations in 197 patients on a 20-year experience. J Neuroimmunol 2008;201-2:237-44.  Back to cited text no. 2
    
3.Mao ZF, Mo XA, Qin C, Lai YR, Hackett ML. Incidence of thymoma in myasthenia gravis: A systematic review. J Clin Neurol 2012;8:161-9.  Back to cited text no. 3
    
4.Amato AA, Russell JA. Disorders of neuromuscular transmission. In: Amato AA, Russell JA, editors. Neuromuscular Disorders. 1 st ed. New York: McGraw-Hill Medical; 2008. p. 457-528.  Back to cited text no. 4
    
5.Thomas CE, Mayer SA, Gungor Y, Swarup R, Webster EA, Chang I, et al. Myasthenic crisis: Clinical features, mortality, complications, and risk factors for prolonged intubation. Neurology 1997;48:1253-60.  Back to cited text no. 5
    
6.Bedlack RS, Sanders DB. On the concept of myasthenic crisis. J Clin Neuromuscul Dis 2002;4:40-2.  Back to cited text no. 6
    
7.Owe JF, Daltveit AK, Gilhus NE. Causes of death among patients with myasthenia gravis in Norway between 1951 and 2001. J Neurol Neurosurg Psychiatry 2006;77:203-7.  Back to cited text no. 7
    
8.Kim JY, Park KD, Richman DP. Treatment of myasthenia gravis based on its immunopathogenesis. J Clin Neurol 2011;7:173-83.  Back to cited text no. 8
    
9.Yim AP, Kay RL, Izzat MB, Ng SK. Video-assisted thoracoscopic thymectomy for myasthenia gravis. Semin Thorac Cardiovasc Surg 1999;11:65-73.  Back to cited text no. 9
    
10.Mack MJ. Video-assisted thoracoscopy thymectomy for myasthenia gravis. Chest Surg Clin N Am 2001;11:389-405, xi.  Back to cited text no. 10
[PUBMED]    
11.Bulkley GB, Bass KN, Stephenson GR, Diener-West M, George S, Reilly PA, et al. Extended cervicomediastinal thymectomy in the integrated management of myasthenia gravis. Ann Surg 1997;226:324-34.  Back to cited text no. 11
    
12.Kas J, Kiss D, Simon V, Svastics E, Major L, Szobor A. Decade-long experience with surgical therapy of myasthenia gravis: Early complications of 324 transsternal thymectomies. Ann Thorac Surg 2001;72:1691-7.  Back to cited text no. 12
    
13.Watanabe A, Watanabe T, Obama T, Mawatari T, Ohsawa H, Ichimiya Y, et al. Prognostic factors for myasthenic crisis after transsternal thymectomy in patients with myasthenia gravis. J Thorac Cardiovasc Surg 2004;127:868-76.  Back to cited text no. 13
    
14.Prokakis C, Koletsis E, Salakou S, Apostolakis E, Baltayiannis N, Chatzimichalis A, et al. Modified maximal thymectomy for myasthenia gravis: Effect of maximal resection on late neurologic outcome and predictors of disease remission. Ann Thorac Surg 2009;88:1638-45.  Back to cited text no. 14
    
15.Nam TS, Lee SH, Kim BC, Choi KH, Kim JT, Kim MK, et al. Clinical characteristics and predictive factors of myasthenic crisis after thymectomy. J Clin Neurosci 2011;18:1185-8.  Back to cited text no. 15
    
16.Hatton PD, Diehl JT, Daly BD, Rheinlander HF, Johnson H, Schrader JB, et al. Transsternal radical thymectomy for myasthenia gravis: A 15-year review. Ann Thorac Surg 1989;47:838-40.  Back to cited text no. 16
    
17.Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. In: Pathology and Genetics of Tumors of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. 2 nd ed. Lyon: IARC Press; 2004. p. 145-97.  Back to cited text no. 17
    
18.Naguib M, el Dawlatly AA, Ashour M, Bamgboye EA. Multivariate determinants of the need for postoperative ventilation in myasthenia gravis. Can J Anaesth 1996;43:1006-13.  Back to cited text no. 18
    
19.Nieto IP, Robledo JP, Pajuelo MC, Montes JA, Giron JG, Alonso JG, et al. Prognostic factors for myasthenia gravis treated by thymectomy: Review of 61 cases. Ann Thorac Surg 1999;67:1568-71.  Back to cited text no. 19
    
20.Oosterhuis HJ. The natural course of myasthenia gravis: A long term follow up study. J Neurol Neurosurg Psychiatry 1989;52:1121-7.  Back to cited text no. 20
[PUBMED]    
21.Rowland LP, Hoefer PF, Aranow H Jr, Merritt HH. Fatalities in myasthenia gravis; a review of 39 cases with 26 autopsies. Neurology 1956;6:307-26.  Back to cited text no. 21
[PUBMED]    
22.Somnier FE, Keiding N, Paulson OB. Epidemiology of myasthenia gravis in Denmark. A longitudinal and comprehensive population survey. Arch Neurol 1991;48:733-9.  Back to cited text no. 22
    
23.Mantegazza R, Beghi E, Pareyson D, Antozzi C, Peluchetti D, Sghirlanzoni A, et al. A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy. J Neurol 1990;237:339-44.  Back to cited text no. 23
    
24.Huang CS, Hsu HS, Kao KP, Huang MH, Huang BS. Intravenous immunoglobulin in the preparation of thymectomy for myasthenia gravis. Acta Neurol Scand 2003;108:136-8.  Back to cited text no. 24
    
25.Jensen P, Bril V. A comparison of the effectiveness of intravenous immunoglobulin and plasma exchange as preoperative therapy of myasthenia gravis. J Clin Neuromuscul Dis 2008;9:352-5.  Back to cited text no. 25
    
26.Loach AB, Young AC, Spalding JM, Smith AC. Postoperative management after thymectomy. Br Med J 1975;1:309-12.  Back to cited text no. 26
[PUBMED]    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]

This article has been cited by
1 Criteria for Postoperative Mechanical Ventilation After Thymectomy in Patients With Myasthenia Gravis: A Retrospective Analysis
Keerthi Chigurupati,Shrinivas Gadhinglajkar,Rupa Sreedhar,Muraleedharan Nair,Madathipat Unnikrishnan,Manjusha Pillai
Journal of Cardiothoracic and Vascular Anesthesia. 2018; 32(1): 325
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow