重症肌无力158例临床分析
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摘要
重症肌无力(MG)是目前影响神经-肌肉接头最常见的疾病,我们对1999年1月至2009年6月曾在我院住院的158例MG患者临床资料进行分析。
目的进一步加深对MG的认识,以期更好的做到早诊断早治疗,改善患者预后,进一步提高广大患者的生存质量。
资料与方法对158例MG患者的临床表现、改良Osserman分型、辅助检查、治疗及预后等情况进行回顾分析。
结果平均发病年龄,女42.27±14.20岁,男43.43±15.89岁,女男比例为1.59:1;首发症状共发现有九种,其中上睑下垂首发最多见;各型患者中以ⅡB型所占比例最高;对合并甲功异常的病例根据甲功三项(FT3、FT4、TSH)化验结果分为“提示甲亢者”和“提示甲低者”两类,前者比后者多见;按胸腺有无异常,将肺部CT分为未见异常和胸腺异常两类,从肺部CT上看,伴有胸腺异常的MG患者性别比例为1.61:1(女:男);MG治疗以药物和胸腺手术为主,绝大部分患者近期预后较好。
结论对MG男女发病年龄情况的研究结果与以往十分不同;MG的首发症状可达十种,发现以眼球运动受限首发者;近十年来MG患者各型分布情况已可能出现了显著变化;MG合并“提示甲亢者”多见;肺部CT有胸腺异常的MG患者性别比例和MG患者总体的性别比例十分相近;MG患者个体病情差异较大,应重视个体化治疗,多数患者近期预后较好,少部分患者病情反复发作,个别患者预后极差,可突发呼吸心跳骤停最终导致死亡。
Myasthenia gravis (MG) is an acquired autoimmune diseases which is mediated by acetylcholine receptor antibody (AChR-Ab) dependent cellular immunity and involved in complement. The lesions mainly involves the postsynaptic membrane acetylcholine receptor in the neuromuscular junction (NMJ) leading to NMJ transmission disorder. Clinical manifestations are weakness and easy fatiguability of skeletal muscle; aggreviated by activity and improved by rest, mild in the morning and severe in the evening. Clinical symptoms will be relieved or disappear by application of cholinesterase inhibitors (ChEI).
Reference to the diagnostic criteria of MG discussed during the Fifth National Conference on Neuroimmunology in 1997 then collated and summarized by XU Xian-hao, a total of 158 cases (97 women) clinical data was collected from Thoracic Surgery and Neurology in our hospital from January 1999 to June 2009. There are 65 cases of Neurology and 93 cases of Thoracic Surgery. The information such as clinical manifestations, modified Osserman classification, assistant investigation, treatment and prognosis were analyzed. From the discussion, MG should be understanded more deeply. Results may prevent the disease efficiently, decrease the frequency of Mysthenia crisis, improve prognosis and get the target of improvement the quality of life of patients with MG.
We can draw the conclusion from the clinical data: 1. Age of onset: The mean age of onset was similar bewteen male patients and female. They were 42.27±14.20 years (women, n=97) and 43.43±15.89 years (men, n=61) respectively. The number of female patients increased with the age and reached to the peak range from 40 to 49 years old. Otherwise, there was no obvious peak of age group in male patients. The number of male patients in each age group between 20 and 69 was similar, and the maximum difference was less than 5%. The difference of patients ratio in each age group deceased in recent five years. 2. First symptom: There were 10 types about first symptoms of MG: ptosis, limb weakness, diplopia, dysphagia, masticatory atonia, limited eyeball movement, dysdipsia, barylalia, inability to lift the head, difficult breathing and facial muscle weakness. There were 9 types didn’t have facial muscle weakness in the research, but including the symptom of limited eyeball movement. In adult group, the patients of ptosis ratio accounted 64.56%, and the ratio of ptosis and limb weakness both accounted near to 80%. 3. Classification variety: The classification of MG had a significant change in recent 10 years and groupⅡB took the highest proportion. We divided the entire time period into two periods from far and near. Comparing the two periods, in recent years, the proportion of groupⅠand groupⅡA both had increased. On the contrary, the proportion of groupⅡB, groupⅢand groupⅣall decreased. The classification experienced a change to some extend. 4. Thyroid function disorder and MG: According to the laboratory reports(freeT3,free T4,TSH)on the cases of merging thyroid function disorder, this part of the patients was divided into two groups " hyperthyroidism or possible " and " hypothyroidism or possible ". The ratio of merging " hyperthyroidism or possible " with MG ranged from 9% to 21%, and the result was obvious higher than the ratio of merging " hypothyroidism or possible " with MG. Our results implied that close relationship may exist between MG and thyroid antibodies. The patients of thyroid function disorders should be payed more attention in clinical work and regularly examine the thyroid function and/or antibodies. As to generalized MG also should be payed attention to the potential tendency of hyperthyroidism. 5. Lung CT and MG: According to whether the thymus was abnormal or not, the lung CT was divided into normal and abnormal group. Sex ratio of abnormal thymus in lung CT with MG was similar to the overall MG patients. The propotion of abnormal thymus in lung CT was increased with age and reached the peak before 50 years old. The groupⅡB took the highest proportion. 6. Diagnostic criteria: MG was not currently found in a unified diagnostic criteria. The previous two of diagnostic criteria which this study followed may be too simple, the other three can not be carried out in the general hospitals even in some large hospitals. The ice test is simple, convenient, safe and easy to spread. This method is suggested to apply in routine clinical work in future and to observe the advantages and disadvantages. 7. Treatment and prognosis: MG patients with large differences between individuals, treatment should be payed attention to be individualized. Most patients got good prognosis in short-term. A small number of patients often had to be hospitalized many times because of some incentives, such as infection, fatigue, mood swings, skipped or irregular medication. Some individual patients got poor prognosis, and the sudden respiratory and cardiac arrest may occur and lead to death.
Compared with previous studies, this study found that patients with MG had significant change in the past decade in many ways such as age of onset, clinical manifestations, Osserman classification, complicating diseases, etc. There was not found a unified diagnostic criteria for MG and MG patients with large differences between individuals. The study suggests that we should have a further in-depth understanding about MG in future clinical work. Earlier diagnosis and treatment should be done and treatment should be payed attention to individuals. Furthermore, it is better to improve the prognosis of patients and improve their quality of life.
目的进一步加深对MG的认识,以期更好的做到早诊断早治疗,改善患者预后,进一步提高广大患者的生存质量。
资料与方法对158例MG患者的临床表现、改良Osserman分型、辅助检查、治疗及预后等情况进行回顾分析。
结果平均发病年龄,女42.27±14.20岁,男43.43±15.89岁,女男比例为1.59:1;首发症状共发现有九种,其中上睑下垂首发最多见;各型患者中以ⅡB型所占比例最高;对合并甲功异常的病例根据甲功三项(FT3、FT4、TSH)化验结果分为“提示甲亢者”和“提示甲低者”两类,前者比后者多见;按胸腺有无异常,将肺部CT分为未见异常和胸腺异常两类,从肺部CT上看,伴有胸腺异常的MG患者性别比例为1.61:1(女:男);MG治疗以药物和胸腺手术为主,绝大部分患者近期预后较好。
结论对MG男女发病年龄情况的研究结果与以往十分不同;MG的首发症状可达十种,发现以眼球运动受限首发者;近十年来MG患者各型分布情况已可能出现了显著变化;MG合并“提示甲亢者”多见;肺部CT有胸腺异常的MG患者性别比例和MG患者总体的性别比例十分相近;MG患者个体病情差异较大,应重视个体化治疗,多数患者近期预后较好,少部分患者病情反复发作,个别患者预后极差,可突发呼吸心跳骤停最终导致死亡。
Myasthenia gravis (MG) is an acquired autoimmune diseases which is mediated by acetylcholine receptor antibody (AChR-Ab) dependent cellular immunity and involved in complement. The lesions mainly involves the postsynaptic membrane acetylcholine receptor in the neuromuscular junction (NMJ) leading to NMJ transmission disorder. Clinical manifestations are weakness and easy fatiguability of skeletal muscle; aggreviated by activity and improved by rest, mild in the morning and severe in the evening. Clinical symptoms will be relieved or disappear by application of cholinesterase inhibitors (ChEI).
Reference to the diagnostic criteria of MG discussed during the Fifth National Conference on Neuroimmunology in 1997 then collated and summarized by XU Xian-hao, a total of 158 cases (97 women) clinical data was collected from Thoracic Surgery and Neurology in our hospital from January 1999 to June 2009. There are 65 cases of Neurology and 93 cases of Thoracic Surgery. The information such as clinical manifestations, modified Osserman classification, assistant investigation, treatment and prognosis were analyzed. From the discussion, MG should be understanded more deeply. Results may prevent the disease efficiently, decrease the frequency of Mysthenia crisis, improve prognosis and get the target of improvement the quality of life of patients with MG.
We can draw the conclusion from the clinical data: 1. Age of onset: The mean age of onset was similar bewteen male patients and female. They were 42.27±14.20 years (women, n=97) and 43.43±15.89 years (men, n=61) respectively. The number of female patients increased with the age and reached to the peak range from 40 to 49 years old. Otherwise, there was no obvious peak of age group in male patients. The number of male patients in each age group between 20 and 69 was similar, and the maximum difference was less than 5%. The difference of patients ratio in each age group deceased in recent five years. 2. First symptom: There were 10 types about first symptoms of MG: ptosis, limb weakness, diplopia, dysphagia, masticatory atonia, limited eyeball movement, dysdipsia, barylalia, inability to lift the head, difficult breathing and facial muscle weakness. There were 9 types didn’t have facial muscle weakness in the research, but including the symptom of limited eyeball movement. In adult group, the patients of ptosis ratio accounted 64.56%, and the ratio of ptosis and limb weakness both accounted near to 80%. 3. Classification variety: The classification of MG had a significant change in recent 10 years and groupⅡB took the highest proportion. We divided the entire time period into two periods from far and near. Comparing the two periods, in recent years, the proportion of groupⅠand groupⅡA both had increased. On the contrary, the proportion of groupⅡB, groupⅢand groupⅣall decreased. The classification experienced a change to some extend. 4. Thyroid function disorder and MG: According to the laboratory reports(freeT3,free T4,TSH)on the cases of merging thyroid function disorder, this part of the patients was divided into two groups " hyperthyroidism or possible " and " hypothyroidism or possible ". The ratio of merging " hyperthyroidism or possible " with MG ranged from 9% to 21%, and the result was obvious higher than the ratio of merging " hypothyroidism or possible " with MG. Our results implied that close relationship may exist between MG and thyroid antibodies. The patients of thyroid function disorders should be payed more attention in clinical work and regularly examine the thyroid function and/or antibodies. As to generalized MG also should be payed attention to the potential tendency of hyperthyroidism. 5. Lung CT and MG: According to whether the thymus was abnormal or not, the lung CT was divided into normal and abnormal group. Sex ratio of abnormal thymus in lung CT with MG was similar to the overall MG patients. The propotion of abnormal thymus in lung CT was increased with age and reached the peak before 50 years old. The groupⅡB took the highest proportion. 6. Diagnostic criteria: MG was not currently found in a unified diagnostic criteria. The previous two of diagnostic criteria which this study followed may be too simple, the other three can not be carried out in the general hospitals even in some large hospitals. The ice test is simple, convenient, safe and easy to spread. This method is suggested to apply in routine clinical work in future and to observe the advantages and disadvantages. 7. Treatment and prognosis: MG patients with large differences between individuals, treatment should be payed attention to be individualized. Most patients got good prognosis in short-term. A small number of patients often had to be hospitalized many times because of some incentives, such as infection, fatigue, mood swings, skipped or irregular medication. Some individual patients got poor prognosis, and the sudden respiratory and cardiac arrest may occur and lead to death.
Compared with previous studies, this study found that patients with MG had significant change in the past decade in many ways such as age of onset, clinical manifestations, Osserman classification, complicating diseases, etc. There was not found a unified diagnostic criteria for MG and MG patients with large differences between individuals. The study suggests that we should have a further in-depth understanding about MG in future clinical work. Earlier diagnosis and treatment should be done and treatment should be payed attention to individuals. Furthermore, it is better to improve the prognosis of patients and improve their quality of life.
引文
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[2] Whiting P, Lindstrom J. Purification and characterization of anticotinic acetylcholine receptor from rat brain[J]. Proc Natl Acad Sci USA, 1987,84:595.
[3] Skeie GO, Lunde PK, Sejersted OM, et al. Autoimmunity against the ryanodine receptor in myasthenia gravis[J]. Acta Physiol Scand, 2001,171(3):379-384.
[4] Hoch W, McConville J, Helms S, et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies[J]. Nat Med,2001,7: 365-368.
[5]李海峰,丛志强.合并多发性硬化或视神经炎的重症肌无力临床分析[J].中华神经科杂志, 2005,38(4):261-264.
[6]王志宏,刘敏,宋敬卉,等.干燥综合征合并重症肌无力1例报告[J].临床神经病学杂志, 2006,19(6):424.
[7]吕瑞娟,张博爱,贾延劼,等.吉兰-巴雷综合征合并重症肌无力1例报告并文献复习[J].中国实用神经疾病杂志, 2007,10(2):62-63.
[8]韩晓凤,韩洁英,陈芳源.重症肌无力、胸腺瘤、重型再生障碍性贫血一例[J].中华血液学杂志, 2005,26(3):132.
[9]崔淑芳.神经肌肉传递失常[M]//余宗颐.神经内科学.北京:北京大学医学出版社, 2003:391-397.
[10]吴江.神经病学[M].北京:人民卫生出版社, 2005:341-346.
[11]许贤豪.肌无力-临床与基础[M].北京:中国协和医科大学出版社, 2003:24-102.
[12] Joern P Sieb. Myasthenia gravis: emerging new therapy options [J]. Current Opinion in Pharmacology, 2005,5(3):303-307.
[13] Chris Turner. A review of myasthenia gravis: Pathogenesis, clinical features and treatment[J]. Curr Anaesth Crit Care, 2007,18(1):15-23.
[14] Bianca M, Conti-Fine, Monica Milani, et al. Myasthenia gravis: past, present, and future[J]. J Clin Invest, 2006,116(11):2843-2854.
[15] Richaud-Patin Y, Vega-Boada F, Vidaller A, et al. Multidrug resistance-1 (MDR-1) in autoimmune disorders IV. Pglycoprotein overfunction in lymphocytes from myasthenia gravis patients[J]. Biomed Pharmacother, 2004,58:320-324.
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