老年人重症肌无力研究进展
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摘要
重症肌无力(MG)是一种神经肌肉传递障碍的获得性自身免疫性疾病,主要发生于中青年,50岁以后很少出现新发病例。但随着人口的老龄化和诊断技术的不断提高,老年人MG发病率逐渐升高。老年人的免疫功能较弱,且常合并其他疾病(如心脑血管疾病、呼吸系统疾病、肿瘤等),这会加重或掩盖MG病情,给临床诊断和治疗带来困难。关于老年人MG临床特点以及对药物和手术治疗反应的研究结果不尽相同,正确认识MG的临床特点有助于临床医生及早做出正确诊断,提高疗效并改善预后。
Myasthenia gravis( MG) is an acquired autoimmune disease caused by neuromuscular transmission dysfunction. It mainly occurs in young and middle-aged people. However, with the growing population aging and continuous improvement of diagnostic technology, the incidence of MG is increasing in elderly people. The elderly are more vulnerable to cardiovascular and cerebrovascular diseases, respiratory diseases and tumors, which may aggravate or cover MG condition, causing difficulties in clinical diagnosis and treatment. This paper summarized the research progress of immunologic and clinical features, drugs and surgical treatments of MG in elderly patients.
Myasthenia gravis( MG) is an acquired autoimmune disease caused by neuromuscular transmission dysfunction. It mainly occurs in young and middle-aged people. However, with the growing population aging and continuous improvement of diagnostic technology, the incidence of MG is increasing in elderly people. The elderly are more vulnerable to cardiovascular and cerebrovascular diseases, respiratory diseases and tumors, which may aggravate or cover MG condition, causing difficulties in clinical diagnosis and treatment. This paper summarized the research progress of immunologic and clinical features, drugs and surgical treatments of MG in elderly patients.
引文
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[2] Aragonès JM, Bolíbar I,Bonfill X,et al. Myasthenia gravis:a higher than expected incidence in the elderly[J]. Neurology,2003,60(6):1024-1026.
[3] Matsuda M, Dohi-Iijima N, Nakamura A, et al. Increase in incidence of elderly-onset patients with myasthenia gravis in Nagano Prefecture, Japan[J]. Intern Med, 2005,44(6):572-577.
[4] Pakzad Z, Aziz T, Oger J. Increasing incidence of myasthenia gravis among elderly in British Columbia, Canada[J]. Neurology,2011,76(17):1526-1528. DOI:10.1212/WNL.0b013e3182l7e735.
[5] Limburg PC, The TH, Hummel-Tappel E, et al. Anti-acetylcholine recetor antibodies in myasthenia gravis. Part 1. Relation to clinical parameters in 250 patients[J]. J Neurol Sci, 1983,58(3):357-370.
[6] Aarli JA. Myasthenia gravis in the elderly:Is it different?[J].Ann N Y Acad Sci, 2008(1132):238-243. DOI:10. 1196/annals. 1405.040.
[7] Hellmann MA, Mosberg-Galili R, Steiner I. Myasthenia gravis in the elderly[J]. J Neurol Sci, 2013,325(1-2):1-5. DOI:10.1016/j.jns.2012.10.028.
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[9] Yamamoto AM, Gajdos P, Eymard B, et al. Anti-titin antibodies in myasthenia gravis:tight association with thymoma and heterogeneity of nonthymoma patients[J]. Arch Neurol, 2001,58(6):885-890.
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[11] Skeie GO, Mygland A, Aarli JA, et al. Titin antibodies in patients with late onset myasthenia gravis:clinical correlations[J].Autoimmunity, 1995,20(2):99-104.
[12] Evoli A, Tonali PA, Padua L, et al. Clinical correlates with antiMuSK antibodies in generalized seronegative myasthenia gravis[J].Brain, 2003,126(Pt 10):2304-2311.
[13] Stickler DE, Massey JM, Sanders DB. MuSK-antibody positive myasthenia gravis:clinical and electrodiagncstic patterns[J]. Clin Neurophysiol, 2005,116(9):2065-2068.
[14] Murai H, Yamashita N, Watanabe M, et al. Characteristics of myasthenia gravis according to onset-age:Japanese nationwide survey[J]. J Neurol Sci, 2011,305(1-2):97-102. DOI:10.1016/j.jns.2011.03.004.
[15] Ishii W, Matsuda M, Hanyuda M, et al. Comparison of the histological and immunohistochemical features of the thymus in youngand elderly-onset myasthenia gravis without thymoma[J].J Clin Neurosci, 2007,14(2):110-115.
[16] Evoli A, Batocchi AP, Minisci C, et al. Clinical characteristics and prognosis of myasthenia gravis in older people[J]. J Am Geriatr Soc, 2000,48(11):1442-1448. DOI:10.1111/j. 1532-5415.2000.tb02635. x.
[17] Donaldson DH, Ansher M, Horan S, et al. The relationship of age to outcome in myasthenia gravis[J]. Neurology, 1990,40(5):786-790.
[18] Suzuki S,Utsugisawa K,Nagane Y, et al. Clinical and immunological differences between early and late-onset myasthenia gravis in Japan[J]. J Neuroimmunol, 2011,230(1-2):148-152. DOI:10.1016/j. jneuroim. 2010.10.023.
[19] Sommer N, Melms A, Weller M, et al. Ocular myasthenia gravis.A critical review of clinical and pathophysiological aspects[J].Doc Ophthalmol, 1993,84(4):309-333.
[20] Lavrnic D, Jarebinski M, Rakocevid-Stojanovic V, et al. Epidemiological and clinical characteristics of myasthenia gravis in Belgrade, Yugoslavia(1983-1992)[J]. Acta Neurol Scand,1999,100(3):168-174. DOI:10. 1111/j. 1600-0404. 1999.tb00733. x.
[21] Alshekhlee A, Miles JD, Katirji B, et al. Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals[J].Neurology, 2009,72(18):1548-1554. DOI:10. 1212/WNL.0b013e3181a41211.
[22] Romi F, Gilhus NE, Varhaug JE, et al. Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis[J]. Eur J Neurol, 2002,9(1):55-61.
[23] Lazarus AH, Crow AR. Mechanism of action of IVIG and anti-D in ITP[J]. Transfus Apher Sci, 2003,28(3):249-255.
[24] Chua E, McLoughlin C, Sharma AK. Myasthenia gravis and recurrent falls in an elderly patient[J]. Age Ageing, 2000,29(1):93-94.
[25] Punga AR, Sawada M, Stalberg EV. Electrophysiological signs and the prevalence of adverse effects of acetylcholinesterase inhibitors in patients with myasthenia gravis[J]. Muscle Nerve, 2008,37(3):300-307.
[26] Antonini G, Morino S, Gragnani F, et al. Myasthenia gravis in the elderly:a hospital based study[J]. Acta Neurol Scand, 1996,93(4):260-262.
[27] Ponseti JM, Gamez J, Azem J, et al. Tacrolimus for myasthenia gravis:a clinical study of 212 patients[J]. Ann N Y Acad Sci,2008,1132:254-263.
[28] Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis[J]. Cochrane Database Syst Rev, 2012(12):CD002277. DOI:10.1002/14651858. CD002277. pub4.
[29] Tsuchida M, Yamato Y, Souma T, et al. Efficacy and safety of extended thymectomy for eldesrly patients with myasthenia gravis[J].Ann Thorac Surg, 1999,67(6):1563-1567.
[30] Abt PL, Patel HJ, Marsh A, et al. Analysis of thymectomy for myasthenia gravis in older patients:a 20-year single institution experience[J]. J Am Coll Surg, 2001,192(4):459-464.
[31] Kawaguchi N, Kuwabara S, Nemoto Y, et al. Effects of thymectomy on late-onset myasthenia gravis without thymoma[J]. Clin Neurol Neurosurg, 2007,109(10):858-861.
[2] Aragonès JM, Bolíbar I,Bonfill X,et al. Myasthenia gravis:a higher than expected incidence in the elderly[J]. Neurology,2003,60(6):1024-1026.
[3] Matsuda M, Dohi-Iijima N, Nakamura A, et al. Increase in incidence of elderly-onset patients with myasthenia gravis in Nagano Prefecture, Japan[J]. Intern Med, 2005,44(6):572-577.
[4] Pakzad Z, Aziz T, Oger J. Increasing incidence of myasthenia gravis among elderly in British Columbia, Canada[J]. Neurology,2011,76(17):1526-1528. DOI:10.1212/WNL.0b013e3182l7e735.
[5] Limburg PC, The TH, Hummel-Tappel E, et al. Anti-acetylcholine recetor antibodies in myasthenia gravis. Part 1. Relation to clinical parameters in 250 patients[J]. J Neurol Sci, 1983,58(3):357-370.
[6] Aarli JA. Myasthenia gravis in the elderly:Is it different?[J].Ann N Y Acad Sci, 2008(1132):238-243. DOI:10. 1196/annals. 1405.040.
[7] Hellmann MA, Mosberg-Galili R, Steiner I. Myasthenia gravis in the elderly[J]. J Neurol Sci, 2013,325(1-2):1-5. DOI:10.1016/j.jns.2012.10.028.
[8] Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis:emerging clinical and biological heterogeneity[J]. Lancet Neurol,2009,8(5):475-490. DOI:10.1016/S1474-4422(09)70063,8.
[9] Yamamoto AM, Gajdos P, Eymard B, et al. Anti-titin antibodies in myasthenia gravis:tight association with thymoma and heterogeneity of nonthymoma patients[J]. Arch Neurol, 2001,58(6):885-890.
[10] Somnier FE. Exacerbation of myasthenia gravis after removal of thymomas[J]. Acta Neurol Scand, 1994,90(1):56-66.
[11] Skeie GO, Mygland A, Aarli JA, et al. Titin antibodies in patients with late onset myasthenia gravis:clinical correlations[J].Autoimmunity, 1995,20(2):99-104.
[12] Evoli A, Tonali PA, Padua L, et al. Clinical correlates with antiMuSK antibodies in generalized seronegative myasthenia gravis[J].Brain, 2003,126(Pt 10):2304-2311.
[13] Stickler DE, Massey JM, Sanders DB. MuSK-antibody positive myasthenia gravis:clinical and electrodiagncstic patterns[J]. Clin Neurophysiol, 2005,116(9):2065-2068.
[14] Murai H, Yamashita N, Watanabe M, et al. Characteristics of myasthenia gravis according to onset-age:Japanese nationwide survey[J]. J Neurol Sci, 2011,305(1-2):97-102. DOI:10.1016/j.jns.2011.03.004.
[15] Ishii W, Matsuda M, Hanyuda M, et al. Comparison of the histological and immunohistochemical features of the thymus in youngand elderly-onset myasthenia gravis without thymoma[J].J Clin Neurosci, 2007,14(2):110-115.
[16] Evoli A, Batocchi AP, Minisci C, et al. Clinical characteristics and prognosis of myasthenia gravis in older people[J]. J Am Geriatr Soc, 2000,48(11):1442-1448. DOI:10.1111/j. 1532-5415.2000.tb02635. x.
[17] Donaldson DH, Ansher M, Horan S, et al. The relationship of age to outcome in myasthenia gravis[J]. Neurology, 1990,40(5):786-790.
[18] Suzuki S,Utsugisawa K,Nagane Y, et al. Clinical and immunological differences between early and late-onset myasthenia gravis in Japan[J]. J Neuroimmunol, 2011,230(1-2):148-152. DOI:10.1016/j. jneuroim. 2010.10.023.
[19] Sommer N, Melms A, Weller M, et al. Ocular myasthenia gravis.A critical review of clinical and pathophysiological aspects[J].Doc Ophthalmol, 1993,84(4):309-333.
[20] Lavrnic D, Jarebinski M, Rakocevid-Stojanovic V, et al. Epidemiological and clinical characteristics of myasthenia gravis in Belgrade, Yugoslavia(1983-1992)[J]. Acta Neurol Scand,1999,100(3):168-174. DOI:10. 1111/j. 1600-0404. 1999.tb00733. x.
[21] Alshekhlee A, Miles JD, Katirji B, et al. Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals[J].Neurology, 2009,72(18):1548-1554. DOI:10. 1212/WNL.0b013e3181a41211.
[22] Romi F, Gilhus NE, Varhaug JE, et al. Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis[J]. Eur J Neurol, 2002,9(1):55-61.
[23] Lazarus AH, Crow AR. Mechanism of action of IVIG and anti-D in ITP[J]. Transfus Apher Sci, 2003,28(3):249-255.
[24] Chua E, McLoughlin C, Sharma AK. Myasthenia gravis and recurrent falls in an elderly patient[J]. Age Ageing, 2000,29(1):93-94.
[25] Punga AR, Sawada M, Stalberg EV. Electrophysiological signs and the prevalence of adverse effects of acetylcholinesterase inhibitors in patients with myasthenia gravis[J]. Muscle Nerve, 2008,37(3):300-307.
[26] Antonini G, Morino S, Gragnani F, et al. Myasthenia gravis in the elderly:a hospital based study[J]. Acta Neurol Scand, 1996,93(4):260-262.
[27] Ponseti JM, Gamez J, Azem J, et al. Tacrolimus for myasthenia gravis:a clinical study of 212 patients[J]. Ann N Y Acad Sci,2008,1132:254-263.
[28] Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis[J]. Cochrane Database Syst Rev, 2012(12):CD002277. DOI:10.1002/14651858. CD002277. pub4.
[29] Tsuchida M, Yamato Y, Souma T, et al. Efficacy and safety of extended thymectomy for eldesrly patients with myasthenia gravis[J].Ann Thorac Surg, 1999,67(6):1563-1567.
[30] Abt PL, Patel HJ, Marsh A, et al. Analysis of thymectomy for myasthenia gravis in older patients:a 20-year single institution experience[J]. J Am Coll Surg, 2001,192(4):459-464.
[31] Kawaguchi N, Kuwabara S, Nemoto Y, et al. Effects of thymectomy on late-onset myasthenia gravis without thymoma[J]. Clin Neurol Neurosurg, 2007,109(10):858-861.