Motomura Masakatsu
Department of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki University.
Rinsho Shinkeigaku. 2011 Nov;51(11):872-6. doi: 10.5692/clinicalneurol.51.872.
The neuromuscular junction lacks the protection of the blood-nerve barrier and is vulnerable to antibody-mediated disorders. Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies against acetylcholine receptors (AChR) and muscle-specific receptor tyrosine kinase (MuSK)/LDL-receptor related protein 4 which are AChR-associated transmembrane post-synaptic proteins involved in AChR aggregation. The seropositivity rates for AChR positive and MuSK positive MG in Japan are 80-85% and 5-10%/less than 1%,respectively. The incidence of late-onset MG, defined as onset after age 50 years, has been increasing worldwide. A nationwide epidemiological survey in Japan also revealed that the rates of late-onset MG had increased from 20% in 1987 to 42% in 2006. In 2010, a guideline for standard treatments of late-onset MG was published by the Japanese Society of Neurological Therapeutics. Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction and approximately 60% of LEMS patients have a tumor, mostly small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical pictures of Japanese LEMS patients are as follows; male dominant sex ratio (3 : 1), mean age 62 years (17-80 years), 61% of LEMS have SCLC, and the remaining are without cancer. In less than 10% of cases there are signs of cerebellar dysfunctions (paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS) as well, often associated with SCLC. Most patients benefit from 3, 4-diaminopyridine plus pyridostigmine. In paraneoplastic LEMS, treatment of the tumor often results in neurological improvement. In non-paraneoplastic LEMS, prednisone alone or combined with immunosuppressants are treatment options. In both MG and LEMS, where weakness is severe, plasma exchange or intravenous immunoglobulin treatment may provide short-term benefit.
神经肌肉接头缺乏血神经屏障的保护，易受抗体介导疾病的影响。重症肌无力（MG）是由针对乙酰胆碱受体（AChR）和肌肉特异性受体酪氨酸激酶（MuSK）/低密度脂蛋白受体相关蛋白4的自身抗体介导的神经肌肉传递失败所致，这些蛋白是参与AChR聚集的AChR相关跨膜突触后蛋白。在日本，AChR阳性和MuSK阳性MG的血清阳性率分别为80 - 85%和5 - 10%/低于1%。晚发型MG（定义为50岁以后发病）的发病率在全球范围内一直在上升。日本的一项全国性流行病学调查还显示，晚发型MG的发病率已从1987年的20%上升至2006年的42%。2010年，日本神经治疗学会发布了晚发型MG的标准治疗指南。兰伯特 - 伊顿肌无力综合征（LEMS）是一种神经肌肉接头的自身免疫性疾病，约60%的LEMS患者患有肿瘤，大多数为小细胞肺癌（SCLC），作为一种副肿瘤性神经综合征。日本LEMS患者的临床表现如下：男女比例以男性为主（3∶1），平均年龄62岁（17 - 80岁），61%的LEMS患者患有SCLC，其余患者无癌症。不到10%的病例也有小脑功能障碍的迹象（LEMS伴副肿瘤性小脑变性；PCD - LEMS），通常与SCLC相关。大多数患者受益于3,4 - 二氨基吡啶加吡啶斯的明。在副肿瘤性LEMS中，肿瘤治疗通常会使神经功能得到改善。在非副肿瘤性LEMS中，单独使用泼尼松或联合免疫抑制剂是治疗选择。在MG和LEMS中，当肌无力严重时，血浆置换或静脉注射免疫球蛋白治疗可能会提供短期益处。
