Yuasa Tatsuhiko, Fujita Koji
Department of Neurology, Kamagaya-Chiba Medical Center for Intractable Neurological Disease (KC-MIND), Kamagaya General Hospital, Chiba, Japan.
Brain Nerve. 2010 Aug;62(8):817-26.
The concept of limbic encephalitis has changed over time. Since the introduction of "limbic encephalitis" (LE) in 1968, LE was thought to almost always be associated with carcinoma; this belief led to the coining of the term "paraneoplastic limbic encephalitis" (PLE). In the 1990s, antineuronal antibodies, including anti-Hu and anti-Ta/Ma2, were detected; this supported the hypothesis of an autoimmune mechanism for PLE. The prognosis of patients with PLE was, however, poor. Since 2001, there have been reports of patients with LE exhibiting antibodies to the voltage-gated potassium channel; this observation is intriguing because in such cases the encephalitis was usually independent of carcinoma, and its clinical course was often reversible. Since the 1990s, cases of non-herpetic acute limbic encephalitis have been reported in Japan. In some of these cases, an autoantibody to GluRepsilon2 (NR2B) has been detected; GluRepsilon2 is a subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor found in the limbic forebrain. A postulated pathophysiologic role of this antibody led to the concept of autoantibody-mediated acute reversible LE (AMED-ARLE). In 2007, some patients with ovarian teratoma developed encephalitis and exhibited antibodies to the NMDA receptor; this antibody is thought to recognize NR1/NR2 heteromers. Later, anti-NMDA receptor antibodies were also detected in some Japanese patients who had been previously diagnosed with juvenile acute non-herpetic encephalitis. Currently, limbic encephalitis is categorized into 3 groups: limbic encephalitis caused by virus infection, autoantibody-mediated limbic encephalitis (AMLE), and limbic encephalitis with autoimmune disease. In AMLE, antibodies to cytoplasmic antigens cause classical PLE (type I). In contrast, antibodies to cell membrane antigens often cause reversible limbic encephalitis in patients with (PLE type II) or without tumors (AMED-ARLE).
边缘叶脑炎的概念随时间发生了变化。自1968年引入“边缘叶脑炎”（LE）以来，人们认为LE几乎总是与癌症相关；这种观点导致了“副肿瘤性边缘叶脑炎”（PLE）这一术语的产生。在20世纪90年代，检测到了包括抗Hu和抗Ta/Ma2在内的抗神经元抗体；这支持了PLE的自身免疫机制假说。然而，PLE患者的预后很差。自2001年以来，有报道称LE患者体内存在针对电压门控钾通道的抗体；这一观察结果很有趣，因为在这些病例中，脑炎通常与癌症无关，其临床病程往往是可逆的。自20世纪90年代以来，日本报告了非疱疹性急性边缘叶脑炎病例。在其中一些病例中，检测到了针对GluRepsilon2（NR2B）的自身抗体；GluRepsilon2是边缘前脑N-甲基-D-天冬氨酸（NMDA）谷氨酸受体的一个亚基。这种抗体假定的病理生理作用导致了自身抗体介导的急性可逆性LE（AMED-ARLE）这一概念的产生。2007年，一些患有卵巢畸胎瘤的患者发生了脑炎，并表现出针对NMDA受体的抗体；这种抗体被认为可识别NR1/NR2异聚体。后来，在一些先前被诊断为青少年急性非疱疹性脑炎的日本患者中也检测到了抗NMDA受体抗体。目前，边缘叶脑炎分为3组：病毒感染引起的边缘叶脑炎、自身抗体介导的边缘叶脑炎（AMLE）和伴有自身免疫性疾病的边缘叶脑炎。在AMLE中，针对细胞质抗原的抗体导致典型的PLE（I型）。相比之下，针对细胞膜抗原的抗体通常在有肿瘤（PLE II型）或无肿瘤（AMED-ARLE）的患者中引起可逆性边缘叶脑炎。
