International Journal of Neuroscience, 2014; 124(11): 792–798 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 0020-7454 print / 1543-5245 online DOI: 10.3109/00207454.2014.883391
RESEARCH ARTICLE
Risk factors of myasthenic crisis after thymectomy in 178 generalized myasthenia gravis patients in a five-year follow-up study
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
Shanshan Yu,1 Jing Lin,1 Xiangning Fu,2 Jun Li,3 Yue Li,1 Bo Chen,1 Mingshan Yang,1 Min Zhang,1 and Bitao Bu1 1
Department of Neurology; 2 Department of Thoracic Surgery, and 3 Department of Large Vessel Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Purpose: The aims of this study were to assess the clinical characteristics of patients with postoperative myasthenic crisis (PMC) and to identify the risk factors affecting the occurrence of PMC. Method: Extended thymectomy was performed on 178 patients with generalized MG with a mean onset age of 36.8 years. The potentially risk factors were analyzed by binary logistic regression analysis. Result: During the over five-year follow-up, 44 patients (24.7%) experienced 58 episodes of PMC. The mean interval between surgery and the first episodes of PMC was 13.8 months, and for 81.8% of the patients it occurred within the first 2 years after thymectomy. Nine of 16 patients (56.3%) with a history of preoperative MC had recurrent crises. Respiratory tract infection was the most common precipitant of PMC. Univariate analysis showed that age at onset, preoperative MGFA class, preoperative MC, presence of bulbar symptoms, operation duration, amount of intraoperative blood loss, and the presence of thymoma were significantly associated with the occurrence of PMC. However, multivariate logistic regression analysis revealed that a history of preoperative MC (OR = 2.845, p = 0.044), presence of bulbar symptoms (OR = 3.062, p = 0.027), and longer operation duration (OR = 1.026, p = 0.009) were the independent risk factors for PMC. Conclusion: The important risk factors for developing PMC in generalized MG patients include the presence of bulbar symptoms, history of preoperative MC, and longer operation duration. Optimization of the preoperative evaluation and proper perioperative care of MG patients may decrease the frequency of PMC. KEYWORDS: myasthenia gravis, myasthenic crisis, thymectomy, thymoma
Introduction Myasthenia gravis (MG) is an organ-specific, autoimmune disease caused by circulating autoantibodies against components of the nicotinic acetylcholine receptors (AChR) and muscle-specific kinase (MuSK) on the postsynaptic membrane at neuromuscular junctions [1]. The cardinal features of the disease are fatigability and fluctuating weakness of affected muscles. The thymus is considered as the main site for production of anti-AChR antibodies. Thymectomy, combined with corticosteroids, immunosuppressive agents, Received 29 November 2013; revised 2 January 2014; accepted 10 January 2014 Correspondence. Bitao Bu, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. E-mail: [email protected]
792
and cholinesterase inhibitors, have been accepted as the standard treatment for MG patients [2]. Myasthenic crisis (MC) is the most severe clinical condition of MG, characterized by a rapid deterioration in ventilatory muscle weakness requiring ventilation, a situation that corresponds to the MGFA classification V [3]. Postoperative MC (PMC) is a condition in which a patient needs mechanical ventilation support longer than 48 h after thymectomy with no major cardiopulmonary complications or cholinergic crisis [4]. In addition, in the follow-up period after thymectomy, a condition that a patient needs endotracheal intubation because of respiratory muscle weakness belongs to PMC. Repeated episodes of crisis are counted separately if there is a stable interval of at least one month between the episodes. The incidence of PMC varies from 3.1% to 34% [5,6], and approximately one-third of these patients experience a second episode of crisis
Risk factors of myasthenic crisis after thymectomy
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
[7]. Ventilatory support is usually needed to manage the emergency. Sometimes, patients can be managed without intubation as a result of spontaneous improvement or use of plasmapheresis (PP) or high-dose intravenous immunoglobulin (IVIG) [8]. However, the mortality is still a major concern for MC patients, so identifying and managing precipitating factors are key to minimize the occurrence of the emergency. Here, we have analyzed a group of thymectomized patients with generalized MG who experienced PMC to pinpoint the potentially precipitating factors, in order to take proper measures to minimize mortality after thymectomy.
Patients and methods The research protocol was approved by the Scientific Committee of Tongji Medical College, Huazhong University of Science and Technology. The data on 178 generalized MG patients who underwent extended thymectomy from March 1997 to March 2012 at Tongji Hospital were retrospectively evaluated. The diagnosis of MG was made on the fluctuating muscle weakness and fatigability of affected muscles, decremental responses to repetitive nerve stimulation test, and striking responses to intramuscular injection of one bolus of neostigmine sulfate. The serum AChR-Ab titers had been determined using ELISA methods in some cases. The MGFA clinical classification was used to assess the initial severity of the disease [9]. The final follow-up status of patients was assessed according to the MGFA postintervention status classification [9]. Patients were routinely examined for thymic abnormalities with chest CT or MRI. The thymectomy criteria included thymomatous MG and generalized nonthymomatous MG, assessed by a team of neurologists and surgeons. The medial sternotomy or the videoassisted thoracoscopic extended thymectomy (VATES) was used in the hospital. Thymic histopathology was classified into thymoma and nonthymoma. Thymomas were further graded as benign and malignant according to the World Health Organization (WHO) histological classification system. Patients with invasive thymoma had received postoperative radiotherapy and chemotherapy. The enrolled patients were divided into group I who did not develop PMC and group II who experienced PMC. Treatment regimen for MC usually included corticosteroids, cyclophosphamide pulse therapy, intravenous administration of immunoglobulin (IVIG) or plasmapheresis (PP), and administration of robust antibiotics. Intubation, ventilatory support, temporal discontinuation of cholinesterase inhibitors for 72 h C
2014 Informa Healthcare USA, Inc.
793
followed by readministration of pyridostigmine were generally instituted in the Intensive Care Unit. Clinical paradigms had been documented and analyzed in the study, including gender, onset-age, symptom duration before operation, age at operation, preoperative MGFA class, bulbar symptoms, preoperative MC, concomitant disorders, preoperative and postoperative medications and doses, approach of the surgery, operation time, intraoperative blood loss, histology of the thymic gland, postoperative adjuvant therapy, and PMC. The timing for thymectomy was that MG symptoms were significantly improved and daily dosage of prednisone was required less than 20 mg. After operation, all the patients had been followed up at Tongji Hospital and the doses of pyridostigmine and prednisone had been slowly tapered according to MG symptom improvement. During prednisone tapering, the daily doses would be maintained if MG symptoms rebounded. The drugs would be totally discontinued after a patient had been symptom-free for at least 6 months. If the MG symptoms relapsed, the pharmaceutical therapy would be restarted. If a patient did not tolerate corticosteroids or did not respond well, azathioprine at a daily dose of 150 mg would be considered. Tacrolimus at a daily dose of 3 mg would be instituted if a patient could not tolerate azathioprine. All the patients were required to visit expert neurologists every 2 months if the patients’ symptoms did not disappear, or every 6 months if the patients had no symptoms. Online communication and telephone interview were sometimes used to follow up those cases that had no symptoms for years. All statistical analyses were performed with SPSS 19.0 for Windows (SPSS Inc, Chicago, IL, USA). All continuous data were expressed as mean ± SD and analyzed by student’s t-test and categorical data were analyzed by chi squared (X2 ) test or Fisher’s exact test. Univariate regression analysis was used to analyze individual variable risk factor for PMC. The single risk factors suggested in univariate analysis were then entered into stepwise binary logistic regression analysis.
Results The 178 patients (53% females and 47% males) with generalized MG had been followed up for 5.7 ± 3.6 years. The onset age was 36.8 ± 13.6 years. The disease course to thymectomy was 25.8 ± 43.1 months and the age at surgery was 38.4 ± 13.2 years. Bulbar symptoms were evident in 126 (70.8%) patients. Before thymectomy, 173 patients (97.2%) required pyridostigmine bromide to relieve MG symptoms, and 128 patients (71.9%) were on prednisone as well. The daily dosages of pyridostigmine bromide and prednisone were
794
S. Yu et al.
Table 1. 178).
General clinical data of generalized MG patients (n =
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
Overall patients Number of patients 178 Sex (F: M) 95: 83 Age at onset (years) (mean) 36.8 ± 13.6 Time between onset and surgery (months) 25.8 ± 43.1 (mean) Age at thymectomy (years) (mean) 38.4 ± 13.2 MGFA classification preoperation II 112 (IIA: 49 IIB: 63) III 46 (IIIA: 3 IIIB: 43) IV 4 (IVB: 4) V 16 Bulbar symptom (n) 126 MG crisis preoperation (n) 16 Concomitant disorders (n) 22 Surgery approach transsternal: VATS (n) 159:19 Operation time (min) (mean) 130 ± 20 Blood loss (ml) (mean) 106.8 ± 18.8 Radiation therapy (n) 14 Thymoma: nonthymoma (n) 109: 69 Follow-up time (years) (mean) 5.7 ± 3.6
207.3 ± 72.5 mg and 17.2 ± 14.4 mg, respectively. Moreover, 22 patients (12.4%) had concomitant disorders such as hyperthyroidism. Transsternal extended thymectomy was performed in 159 patients (89.3%), and VATES procedure in 19 (10.7%) cases. The average operation duration was 130 ± 20 minutes and intraoperative blood loss was estimated to be 106.8 ± 18.8 ml (Table 1). Thymus histopathology revealed that thymoma were found in 109 patients (61.2%), including type A in 7 cases, type AB in 18 cases, type B1 in 32 cases, type B2 in 27 cases, and type B3 in 25 cases. According to Masaoka-Koga staging system, 22 cases were encapsulated tumors (Masaoka stage I), and 89 cases corresponded to invasive tumors (38, 39, and 10 cases in Masaoka stages II, III, and IV, respectively). In addition, nonthymomatous changes were observed in 69 MG patients (38.8%), which included 56 cases with thymic hyperplasia and 13 cases with other kinds of abnormalities such as thymic atrophy or adipoma. In all, 44 cases (24.7%) developed 58 attacks (33 patients had one episode of crisis, 8 had two episodes, and 3 had three ones) of PMC during the follow-up. Sixteen patients (9%) had episodes of crises before thymectomy, and 9 of them (56.3%) developed PMC. The mean interval between the surgery and the first episodes of PMC was 13.8 ± 28.0 months, and over 80% of PMC occurred within 2 years after thymectomy. Eleven of the 35 patients (31.4%) who had survived the first PMC developed a second crisis at intervals of less than two months to four years after the first attack.
Regarding the treatment of the 58 attacks of PMC, 34 patients (58.6%) were supported by mechanical ventilation, and 15 cases (25.9%) gained improvement only after proper adjustment of medications, administration of antibiotics, and BiPAP mechanical ventilation. However, nine patients died of acute respiratory failure because of some reasons. Tracheostomy was subsequently performed in 13 (29.5%) of the 34 intubated patients. The identified precipitants for developing PMC included upper respiratory tract infection, aspiration pneumonia, improper use of medications, and stress such as surgery or emotional stress, but no certain precipitants were known in 17 PMC patients (29.3%) (Table 2). In order to pinpoint the intrinsic factors which might contribute to occurrence of the PMC, the clinical data between the group I (n = 134) and the group II (n = 44) had been comparatively analyzed. The average onset age in group II was significantly older than that in the group I patients (p = 0.014). There were no significant differences regarding the mean symptom duration before the operation and follow-up time between two groups. Furthermore, The MGFA class and the presence of bulbar symptoms had exerted significant influence on the occurrence of PMC (p = 0.002, and p = 0.009, respectively). Nine (56.25%) of 16 patients who had a history of preoperative MC developed PMC and the comparison between the two groups showed significant association with PMC (5.2% versus 20.5%, p = 0.005, Table 3). The use of medications that may help to prevent or minimize the possibility of developing PMC had been compared, but no significant differences were found in the ratio of the patients who took medications and in the average dosages of the two drugs between the two groups. However, longer operative time and more blood loss during operation were observed in the group
Table 2.
Precipitants of 58 attacks of PMC.
Precipitants Infections Pneumonia, upper airway infection Gastroenteritis Aspiration Treatment associated Adjuvant therapy High-dose methylprednisolone impulsion therapy Withdraw drugs Inappropriate treatment by oneself Stress – surgery, emotional stress, drinking, trauma Idiopathic
Number (n = 58)
Rate
27 1 1
46.6% 1.7% 1.7%
3 1
5.2% 1.7%
1 1 6
1.7% 1.7% 10.3%
17
29.3%
International Journal of Neuroscience
Risk factors of myasthenic crisis after thymectomy
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
Table 3.
The comparison of generalized MG patients with and without PMC. Group I (n = 134)
Group II (n = 44)
72: 62 35.5 ± 14.2 29.2 ± 47.4 37.2 ± 13.7
23: 21 40.7 ± 11.1 15.3 ± 23.3 41.8 ± 11.0
125 9 88 7 129 203.5 ± 74.1 95 16.5 ± 14.4 17
33 11 38 9 44 218.9 ± 66.8 33 19.4 ± 14.4 5
117 169.37 ± 88.42 94 17.10 ± 14.89 19 3 118: 16 127.5 ± 21.0 105.0 ± 19.2 76: 58 12 64 48 10
41 221.59 ± 96.88 35 8.47 ± 9.08 10 9 41: 3 137.5 ± 14.1 112.5 ± 16.5 33: 11 13 20 8 4
0.411 0.001∗ 0.226 0.001∗ 0.183
RESEARCH ARTICLE
Risk factors of myasthenic crisis after thymectomy in 178 generalized myasthenia gravis patients in a five-year follow-up study
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
Shanshan Yu,1 Jing Lin,1 Xiangning Fu,2 Jun Li,3 Yue Li,1 Bo Chen,1 Mingshan Yang,1 Min Zhang,1 and Bitao Bu1 1
Department of Neurology; 2 Department of Thoracic Surgery, and 3 Department of Large Vessel Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Purpose: The aims of this study were to assess the clinical characteristics of patients with postoperative myasthenic crisis (PMC) and to identify the risk factors affecting the occurrence of PMC. Method: Extended thymectomy was performed on 178 patients with generalized MG with a mean onset age of 36.8 years. The potentially risk factors were analyzed by binary logistic regression analysis. Result: During the over five-year follow-up, 44 patients (24.7%) experienced 58 episodes of PMC. The mean interval between surgery and the first episodes of PMC was 13.8 months, and for 81.8% of the patients it occurred within the first 2 years after thymectomy. Nine of 16 patients (56.3%) with a history of preoperative MC had recurrent crises. Respiratory tract infection was the most common precipitant of PMC. Univariate analysis showed that age at onset, preoperative MGFA class, preoperative MC, presence of bulbar symptoms, operation duration, amount of intraoperative blood loss, and the presence of thymoma were significantly associated with the occurrence of PMC. However, multivariate logistic regression analysis revealed that a history of preoperative MC (OR = 2.845, p = 0.044), presence of bulbar symptoms (OR = 3.062, p = 0.027), and longer operation duration (OR = 1.026, p = 0.009) were the independent risk factors for PMC. Conclusion: The important risk factors for developing PMC in generalized MG patients include the presence of bulbar symptoms, history of preoperative MC, and longer operation duration. Optimization of the preoperative evaluation and proper perioperative care of MG patients may decrease the frequency of PMC. KEYWORDS: myasthenia gravis, myasthenic crisis, thymectomy, thymoma
Introduction Myasthenia gravis (MG) is an organ-specific, autoimmune disease caused by circulating autoantibodies against components of the nicotinic acetylcholine receptors (AChR) and muscle-specific kinase (MuSK) on the postsynaptic membrane at neuromuscular junctions [1]. The cardinal features of the disease are fatigability and fluctuating weakness of affected muscles. The thymus is considered as the main site for production of anti-AChR antibodies. Thymectomy, combined with corticosteroids, immunosuppressive agents, Received 29 November 2013; revised 2 January 2014; accepted 10 January 2014 Correspondence. Bitao Bu, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. E-mail: [email protected]
792
and cholinesterase inhibitors, have been accepted as the standard treatment for MG patients [2]. Myasthenic crisis (MC) is the most severe clinical condition of MG, characterized by a rapid deterioration in ventilatory muscle weakness requiring ventilation, a situation that corresponds to the MGFA classification V [3]. Postoperative MC (PMC) is a condition in which a patient needs mechanical ventilation support longer than 48 h after thymectomy with no major cardiopulmonary complications or cholinergic crisis [4]. In addition, in the follow-up period after thymectomy, a condition that a patient needs endotracheal intubation because of respiratory muscle weakness belongs to PMC. Repeated episodes of crisis are counted separately if there is a stable interval of at least one month between the episodes. The incidence of PMC varies from 3.1% to 34% [5,6], and approximately one-third of these patients experience a second episode of crisis
Risk factors of myasthenic crisis after thymectomy
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
[7]. Ventilatory support is usually needed to manage the emergency. Sometimes, patients can be managed without intubation as a result of spontaneous improvement or use of plasmapheresis (PP) or high-dose intravenous immunoglobulin (IVIG) [8]. However, the mortality is still a major concern for MC patients, so identifying and managing precipitating factors are key to minimize the occurrence of the emergency. Here, we have analyzed a group of thymectomized patients with generalized MG who experienced PMC to pinpoint the potentially precipitating factors, in order to take proper measures to minimize mortality after thymectomy.
Patients and methods The research protocol was approved by the Scientific Committee of Tongji Medical College, Huazhong University of Science and Technology. The data on 178 generalized MG patients who underwent extended thymectomy from March 1997 to March 2012 at Tongji Hospital were retrospectively evaluated. The diagnosis of MG was made on the fluctuating muscle weakness and fatigability of affected muscles, decremental responses to repetitive nerve stimulation test, and striking responses to intramuscular injection of one bolus of neostigmine sulfate. The serum AChR-Ab titers had been determined using ELISA methods in some cases. The MGFA clinical classification was used to assess the initial severity of the disease [9]. The final follow-up status of patients was assessed according to the MGFA postintervention status classification [9]. Patients were routinely examined for thymic abnormalities with chest CT or MRI. The thymectomy criteria included thymomatous MG and generalized nonthymomatous MG, assessed by a team of neurologists and surgeons. The medial sternotomy or the videoassisted thoracoscopic extended thymectomy (VATES) was used in the hospital. Thymic histopathology was classified into thymoma and nonthymoma. Thymomas were further graded as benign and malignant according to the World Health Organization (WHO) histological classification system. Patients with invasive thymoma had received postoperative radiotherapy and chemotherapy. The enrolled patients were divided into group I who did not develop PMC and group II who experienced PMC. Treatment regimen for MC usually included corticosteroids, cyclophosphamide pulse therapy, intravenous administration of immunoglobulin (IVIG) or plasmapheresis (PP), and administration of robust antibiotics. Intubation, ventilatory support, temporal discontinuation of cholinesterase inhibitors for 72 h C
2014 Informa Healthcare USA, Inc.
793
followed by readministration of pyridostigmine were generally instituted in the Intensive Care Unit. Clinical paradigms had been documented and analyzed in the study, including gender, onset-age, symptom duration before operation, age at operation, preoperative MGFA class, bulbar symptoms, preoperative MC, concomitant disorders, preoperative and postoperative medications and doses, approach of the surgery, operation time, intraoperative blood loss, histology of the thymic gland, postoperative adjuvant therapy, and PMC. The timing for thymectomy was that MG symptoms were significantly improved and daily dosage of prednisone was required less than 20 mg. After operation, all the patients had been followed up at Tongji Hospital and the doses of pyridostigmine and prednisone had been slowly tapered according to MG symptom improvement. During prednisone tapering, the daily doses would be maintained if MG symptoms rebounded. The drugs would be totally discontinued after a patient had been symptom-free for at least 6 months. If the MG symptoms relapsed, the pharmaceutical therapy would be restarted. If a patient did not tolerate corticosteroids or did not respond well, azathioprine at a daily dose of 150 mg would be considered. Tacrolimus at a daily dose of 3 mg would be instituted if a patient could not tolerate azathioprine. All the patients were required to visit expert neurologists every 2 months if the patients’ symptoms did not disappear, or every 6 months if the patients had no symptoms. Online communication and telephone interview were sometimes used to follow up those cases that had no symptoms for years. All statistical analyses were performed with SPSS 19.0 for Windows (SPSS Inc, Chicago, IL, USA). All continuous data were expressed as mean ± SD and analyzed by student’s t-test and categorical data were analyzed by chi squared (X2 ) test or Fisher’s exact test. Univariate regression analysis was used to analyze individual variable risk factor for PMC. The single risk factors suggested in univariate analysis were then entered into stepwise binary logistic regression analysis.
Results The 178 patients (53% females and 47% males) with generalized MG had been followed up for 5.7 ± 3.6 years. The onset age was 36.8 ± 13.6 years. The disease course to thymectomy was 25.8 ± 43.1 months and the age at surgery was 38.4 ± 13.2 years. Bulbar symptoms were evident in 126 (70.8%) patients. Before thymectomy, 173 patients (97.2%) required pyridostigmine bromide to relieve MG symptoms, and 128 patients (71.9%) were on prednisone as well. The daily dosages of pyridostigmine bromide and prednisone were
794
S. Yu et al.
Table 1. 178).
General clinical data of generalized MG patients (n =
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
Overall patients Number of patients 178 Sex (F: M) 95: 83 Age at onset (years) (mean) 36.8 ± 13.6 Time between onset and surgery (months) 25.8 ± 43.1 (mean) Age at thymectomy (years) (mean) 38.4 ± 13.2 MGFA classification preoperation II 112 (IIA: 49 IIB: 63) III 46 (IIIA: 3 IIIB: 43) IV 4 (IVB: 4) V 16 Bulbar symptom (n) 126 MG crisis preoperation (n) 16 Concomitant disorders (n) 22 Surgery approach transsternal: VATS (n) 159:19 Operation time (min) (mean) 130 ± 20 Blood loss (ml) (mean) 106.8 ± 18.8 Radiation therapy (n) 14 Thymoma: nonthymoma (n) 109: 69 Follow-up time (years) (mean) 5.7 ± 3.6
207.3 ± 72.5 mg and 17.2 ± 14.4 mg, respectively. Moreover, 22 patients (12.4%) had concomitant disorders such as hyperthyroidism. Transsternal extended thymectomy was performed in 159 patients (89.3%), and VATES procedure in 19 (10.7%) cases. The average operation duration was 130 ± 20 minutes and intraoperative blood loss was estimated to be 106.8 ± 18.8 ml (Table 1). Thymus histopathology revealed that thymoma were found in 109 patients (61.2%), including type A in 7 cases, type AB in 18 cases, type B1 in 32 cases, type B2 in 27 cases, and type B3 in 25 cases. According to Masaoka-Koga staging system, 22 cases were encapsulated tumors (Masaoka stage I), and 89 cases corresponded to invasive tumors (38, 39, and 10 cases in Masaoka stages II, III, and IV, respectively). In addition, nonthymomatous changes were observed in 69 MG patients (38.8%), which included 56 cases with thymic hyperplasia and 13 cases with other kinds of abnormalities such as thymic atrophy or adipoma. In all, 44 cases (24.7%) developed 58 attacks (33 patients had one episode of crisis, 8 had two episodes, and 3 had three ones) of PMC during the follow-up. Sixteen patients (9%) had episodes of crises before thymectomy, and 9 of them (56.3%) developed PMC. The mean interval between the surgery and the first episodes of PMC was 13.8 ± 28.0 months, and over 80% of PMC occurred within 2 years after thymectomy. Eleven of the 35 patients (31.4%) who had survived the first PMC developed a second crisis at intervals of less than two months to four years after the first attack.
Regarding the treatment of the 58 attacks of PMC, 34 patients (58.6%) were supported by mechanical ventilation, and 15 cases (25.9%) gained improvement only after proper adjustment of medications, administration of antibiotics, and BiPAP mechanical ventilation. However, nine patients died of acute respiratory failure because of some reasons. Tracheostomy was subsequently performed in 13 (29.5%) of the 34 intubated patients. The identified precipitants for developing PMC included upper respiratory tract infection, aspiration pneumonia, improper use of medications, and stress such as surgery or emotional stress, but no certain precipitants were known in 17 PMC patients (29.3%) (Table 2). In order to pinpoint the intrinsic factors which might contribute to occurrence of the PMC, the clinical data between the group I (n = 134) and the group II (n = 44) had been comparatively analyzed. The average onset age in group II was significantly older than that in the group I patients (p = 0.014). There were no significant differences regarding the mean symptom duration before the operation and follow-up time between two groups. Furthermore, The MGFA class and the presence of bulbar symptoms had exerted significant influence on the occurrence of PMC (p = 0.002, and p = 0.009, respectively). Nine (56.25%) of 16 patients who had a history of preoperative MC developed PMC and the comparison between the two groups showed significant association with PMC (5.2% versus 20.5%, p = 0.005, Table 3). The use of medications that may help to prevent or minimize the possibility of developing PMC had been compared, but no significant differences were found in the ratio of the patients who took medications and in the average dosages of the two drugs between the two groups. However, longer operative time and more blood loss during operation were observed in the group
Table 2.
Precipitants of 58 attacks of PMC.
Precipitants Infections Pneumonia, upper airway infection Gastroenteritis Aspiration Treatment associated Adjuvant therapy High-dose methylprednisolone impulsion therapy Withdraw drugs Inappropriate treatment by oneself Stress – surgery, emotional stress, drinking, trauma Idiopathic
Number (n = 58)
Rate
27 1 1
46.6% 1.7% 1.7%
3 1
5.2% 1.7%
1 1 6
1.7% 1.7% 10.3%
17
29.3%
International Journal of Neuroscience
Risk factors of myasthenic crisis after thymectomy
Int J Neurosci Downloaded from informahealthcare.com by University of Sydney on 03/13/15 For personal use only.
Table 3.
The comparison of generalized MG patients with and without PMC. Group I (n = 134)
Group II (n = 44)
72: 62 35.5 ± 14.2 29.2 ± 47.4 37.2 ± 13.7
23: 21 40.7 ± 11.1 15.3 ± 23.3 41.8 ± 11.0
125 9 88 7 129 203.5 ± 74.1 95 16.5 ± 14.4 17
33 11 38 9 44 218.9 ± 66.8 33 19.4 ± 14.4 5
117 169.37 ± 88.42 94 17.10 ± 14.89 19 3 118: 16 127.5 ± 21.0 105.0 ± 19.2 76: 58 12 64 48 10
41 221.59 ± 96.88 35 8.47 ± 9.08 10 9 41: 3 137.5 ± 14.1 112.5 ± 16.5 33: 11 13 20 8 4
0.411 0.001∗ 0.226 0.001∗ 0.183
