Kitanosono Hiroko, Shiraishi Hirokazu, Motomura Masakatsu
Department of Neurology and Strokology, Nagasaki University Hospital.
Brain Nerve. 2018 Apr;70(4):341-355. doi: 10.11477/mf.1416201007.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction. Approximately 50-60% of patients with LEMS have a tumor, most often small cell lung cancer (SCLC), making LEMS a paraneoplastic neurological syndrome. In Japan, the clinical picture is a male: female ratio of 3:1; mean age, 62 years (17-80 years); and 61% of LEMS patients have SCLC (SCLC-LEMS), with the remainder of patients having no cancer. Patients with LEMS develop a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes with post-tetanic potentiation, and autonomic symptoms. Interestingly, less than 10% of patients with LEMS have cerebellar ataxia (LEMS with paraneoplastic cerebellar degeneration). Considering its pathomechanisms, LEMS is a presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine is impaired by autoantibodies against P/Q-type voltage-gated calcium channels (P/Q-VGCCs) at active zones reducing quantal release of acetylcholine, although an animal model using immunization with purified P/Q-VGCCs has not yet been established. The diagnosis can be confirmed by finding a reduced compound muscle action potential amplitude that increases by over 60% following maximum voluntary activation or 50 Hz nerve stimulation. Approximately 90% of patients who satisfy the above electrophysiological diagnostic criteria are positive for P/Q-VGCC antibodies have their diagnosis confirmed. Specific tumor therapy in SCLC-LEMS will often improve the neurologic deficit. Tumor removal is the primary treatment for LEMS. If primary tumor screening is negative, screening should be repeated after 3-6 months, followed by screening every 6 months until 2 years post diagnosis. Most patients benefit from 3,4-diaminopyridine being administered with pyridostigmine. In those with severe weakness, high-dose intravenous gamma-globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone, alone or combined with immunosuppressive drugs, can achieve long-term control of the disorder. The results of a prospective cohort study showed that the presence of LEMS with SCLC had a significant survival advantage independent of other prognostic factors including disease extent, age, sex, performance status, and serum sodium values.
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50%-60%的LEMS患者患有肿瘤，最常见的是小细胞肺癌（SCLC），这使得LEMS成为一种副肿瘤性神经综合征。在日本，临床表现为男性与女性比例为3:1；平均年龄62岁（17-80岁）；61%的LEMS患者患有SCLC（SCLC-LEMS），其余患者无癌症。LEMS患者会出现一系列独特的临床特征，包括近端肌无力、强直后增强导致的腱反射减弱以及自主神经症状。有趣的是，不到10%的LEMS患者有小脑共济失调（伴副肿瘤性小脑变性的LEMS）。考虑到其发病机制，LEMS是一种神经肌肉传递的突触前疾病，其中乙酰胆碱的量子释放因针对活性区P/Q型电压门控钙通道（P/Q-VGCCs）的自身抗体而受损，从而减少乙酰胆碱的量子释放，尽管尚未建立使用纯化P/Q-VGCCs免疫的动物模型。通过发现复合肌肉动作电位幅度降低，在最大自主激活或50Hz神经刺激后增加超过60%，可确诊。满足上述电生理诊断标准的患者中，约90%的P/Q-VGCC抗体呈阳性，其诊断得以确认。SCLC-LEMS的特异性肿瘤治疗通常会改善神经功能缺损。肿瘤切除是LEMS的主要治疗方法。如果初次肿瘤筛查为阴性，应在3-6个月后重复筛查，然后每6个月筛查一次，直至诊断后2年。大多数患者受益于3,4-二氨基吡啶与吡啶斯的明联合使用。对于严重肌无力患者，大剂量静脉注射丙种球蛋白（IVIg）或血浆置换可带来短期益处。泼尼松单独使用或与免疫抑制药物联合使用，可实现对该疾病的长期控制。一项前瞻性队列研究结果表明，SCLC合并LEMS的存在具有显著的生存优势，独立于其他预后因素，包括疾病范围、年龄、性别、体能状态和血清钠值。
