Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.
Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.
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DOI：
10.1016/s1474-4422(10)70253-2
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发表时间：
2011-01
期刊：
影响因子：
48
通讯作者：
Balice-Gordon, Rita
中科院分区：
文献类型：
--
作者：
Dalmau, Josep;Lancaster, Eric;Martinez-Hernandez, Eugenia;Rosenfeld, Myrna R.;Balice-Gordon, Rita
自2007年发现以来，与N-甲基-D-天冬氨酸受体（NMDAR）抗体相关的脑炎已进入神经病学和其他学科的主流。大多数患有抗NMDAR脑炎的患者发展为多阶段疾病，其从精神病、记忆缺陷、癫痫发作和语言解体进展为具有紧张性特征的无反应状态，通常与异常运动、自主神经和呼吸不稳定相关。这种疾病主要影响儿童和年轻人，发生或不发生肿瘤相关性，对治疗有反应，但可能复发。肿瘤（通常是卵巢畸胎瘤）的存在取决于年龄、性别和种族，在18岁以上的女性中更常见，在黑人女性中比在白色女性中略多。与接受类似初始免疫治疗的无肿瘤患者相比，接受肿瘤切除术和免疫治疗（皮质类固醇、静脉注射免疫球蛋白或血浆置换）的患者对治疗的反应更快，需要二线免疫治疗（环磷酰胺或利妥昔单抗或两者）的频率更低。超过75%的患者有实质性的恢复，发生在症状发展的逆序，并与抗体滴度下降。患者的抗体通过交联和内化机制引起突触NMDAR的滴度依赖性可逆降低。基于NMDAR的药理学或遗传破坏模型，这些抗体效应揭示了受体耗竭与抗NMDAR脑炎的临床特征之间可能的致病关系。
Since its discovery in 2007, the encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) has entered the mainstream of neurology and other disciplines. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. The disorder predominantly affects children and young adults, occurs with or without tumour association, and responds to treatment but can relapse. The presence of a tumour (usually an ovarian teratoma) is dependent on age, sex, and ethnicity, being more frequent in women older than 18 years, and slightly more predominant in black women than it is in white women. Patients treated with tumour resection and immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) respond faster to treatment and less frequently need second-line immunotherapy (cyclophosphamide or rituximab, or both) than do patients without a tumour who receive similar initial immunotherapy. More than 75% of all patients have substantial recovery that occurs in inverse order of symptom development and is associated with a decline of antibody titres. Patients’ antibodies cause a titre-dependent, reversible decrease of synaptic NMDAR by a mechanism of crosslinking and internalisation. On the basis of models of pharmacological or genetic disruption of NMDAR, these antibody effects reveal a probable pathogenic relation between the depletion of receptors and the clinical features of anti-NMDAR encephalitis.