Motomura Masakatsu, Fukuda Taku
Department of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Brain Nerve. 2011 Jul;63(7):745-54.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction, and approximately 60% of patients with LEMS have a tumor, mostly small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical data of Japanese patients in the present study are as follows: the ratio of men to women is 3: 1 (mean age, 62 years; age range, 17-80 years). Of the patients with LEMS, 61% have SCLC, whereas the others do not have cancer. Clinical symptoms are usually characterized by proximal muscle weakness and dysautonomia. In less than 10% of the patients, there are signs of cerebellar dysfunctions (paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS), and these are usually associated with SCLC. The diagnosis can be confirmed by detecting a specific antibody in a radioimmunoprecipitation assay and finding reduced amplitude of compound muscle action potential that increases by over 100% after maximum voluntary activation or 50Hz of nerve stimulation. The pathomechanism of LEMS is characterized by impaired transmission across the neuromuscular junction because of autoantibodies directed against the presynaptic P/Q-type voltage-gated calcium channels (P/Q-VGCCs). Histopathologic evaluation of the cerebellum in patients with PCD-LEMS showed a reduced number of P/Q-type VGCCs in the molecular layer. Therefore, it was hypothesized that P/Q-VGCC antibodies may induce cerebellar dysfunction after entering the CNS in patients with PCD-LEMS. Specific tumor therapy in patients with LEMS as well as cancer often improves the neurologic deficit. Tumor removal is the primary treatment for LEMS. If the result of the primary screening is negative, screening should be repeated after 3-6 months and thereafter every 6 months for up to 2 years. Most patients benefit from 3, 4-diaminopyridine administered with pyridostigmine. In those with severe weakness, intravenous gamma globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone when administered alone or in combination with immunosuppressive drugs can achieve long-term control of the disorder.
兰伯特-伊顿肌无力综合征（LEMS）是一种神经肌肉接头处的自身免疫性疾病，约60%的LEMS患者患有肿瘤，其中大多数为小细胞肺癌（SCLC），属于副肿瘤性神经综合征。本研究中日本患者的临床数据如下：男女比例为3:1（平均年龄62岁；年龄范围17 - 80岁）。在LEMS患者中，61%患有SCLC，其余患者无癌症。临床症状通常以近端肌无力和自主神经功能障碍为特征。不到10%的患者有小脑功能障碍的体征（LEMS伴副肿瘤性小脑变性；PCD - LEMS），且这些通常与SCLC相关。通过在放射免疫沉淀试验中检测特异性抗体以及发现复合肌肉动作电位幅度降低，而在最大自主激活或50Hz神经刺激后增加超过100%，可确诊。LEMS的发病机制特点是由于针对突触前P/Q型电压门控钙通道（P/Q - VGCCs）的自身抗体导致神经肌肉接头处传递受损。对PCD - LEMS患者小脑的组织病理学评估显示分子层中P/Q型VGCCs数量减少。因此，推测在PCD - LEMS患者中，P/Q - VGCC抗体进入中枢神经系统后可能诱发小脑功能障碍。对LEMS患者以及癌症患者进行特异性肿瘤治疗通常可改善神经功能缺损。肿瘤切除是LEMS的主要治疗方法。如果初次筛查结果为阴性，应在3 - 6个月后重复筛查，此后每6个月筛查一次，持续2年。大多数患者受益于与吡啶斯的明联合使用的3,4 - 二氨基吡啶。对于严重肌无力患者，静脉注射丙种球蛋白（IVIg）或血浆置换可带来短期益处。单独使用泼尼松或与免疫抑制药物联合使用可实现对该疾病的长期控制。
