Tüzün Erdem, Dalmau Josep
Division of Neuro-Oncology, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Neurologist. 2007 Sep;13(5):261-71. doi: 10.1097/NRL.0b013e31813e34a5.
Recent studies suggest that a substantial number of patients with autoimmune limbic encephalitis may improve if properly diagnosed and treated. This is due, in part, to the increasing recognition of disorders that associate with antibodies to neuronal cell membrane antigens. This review focuses in these disorders, framed in a clinically useful immunologic classification of limbic encephalitis.
Patients with limbic encephalitis usually present with rapidly progressive short-term memory deficits, psychiatric symptoms, and seizures. After excluding viral and systemic autoimmune disorders, many patients with limbic encephalitis (paraneoplastic or not) have cerebrospinal fluid inflammatory findings, EEG or MRI abnormalities in the temporal lobes, and antineuronal antibodies. These antibodies are directed against 2 broad categories of antigens: (1) intracellular or classic paraneoplastic antigens, including Hu, Ma2, CV2/CRMP5, and amphiphysin among others, and (2) cell membrane antigens, including voltage-gated potassium channels, N-methyl-D-aspartate receptor, and others expressed in the neuropil of hippocampus and cerebellum (pending characterization). Whereas the disorders related to the first category of antibodies associate with cancer (lung, testis and other), prominent brain infiltrates of cytotoxic T-cells, and limited response to treatment, the disorders related to the second category of antibodies associate less frequently with cancer (thymoma, teratoma), seem to be antibody-mediated, and respond significantly better to immunotherapy.
Once considered an extremely rare disorder, almost always related to cancer, and refractory to treatment, limbic encephalitis is now regarded as a relatively frequent disorder, often unrelated to cancer, and with clinical-immunologic variants that respond to treatment.
近期研究表明，相当数量的自身免疫性边缘叶脑炎患者若能得到正确诊断和治疗，病情可能会改善。部分原因在于，与神经元细胞膜抗原抗体相关的疾病越来越受到关注。本综述聚焦于这些疾病，采用临床上实用的边缘叶脑炎免疫分类法进行阐述。
边缘叶脑炎患者通常表现为快速进展的短期记忆缺陷、精神症状和癫痫发作。在排除病毒性和全身性自身免疫性疾病后，许多边缘叶脑炎患者（无论是否为副肿瘤性）脑脊液有炎症表现，脑电图或磁共振成像在颞叶有异常，且存在抗神经元抗体。这些抗体针对两大类抗原：（1）细胞内或典型的副肿瘤性抗原，包括Hu、Ma2、CV2/CRMP5和 amphiphysin等；（2）细胞膜抗原，包括电压门控钾通道、N-甲基-D-天冬氨酸受体，以及在海马体和小脑神经纤维网中表达的其他抗原（有待进一步明确）。与第一类抗体相关的疾病与癌症（肺癌、睾丸癌等）相关，有明显的细胞毒性T细胞脑浸润，对治疗反应有限；而与第二类抗体相关的疾病与癌症（胸腺瘤、畸胎瘤）的关联较少，似乎是抗体介导的，对免疫治疗反应明显更好。
边缘叶脑炎曾被认为是一种极其罕见的疾病，几乎总是与癌症相关且治疗难治，现在则被视为一种相对常见的疾病，通常与癌症无关，且有对治疗有反应的临床免疫变异型。
