Sipos Ildiko
Neurológiai Klinika, Semmelweis Egyetem, Budapest, Hungary.
Neuropsychopharmacol Hung. 2018 Mar;20(1):18-25.
The recognition of the antibody-mediated encephalitis as a separate entity among the immune disorders of the central nervous system was one of the greatest breakthroughs of the last two decades in neurology. Unlike viral or tumor-related encephalitis, the antibody-mediated form has a good response to immunotherapy, which gives a special clinical importance to the discovery. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the first fully characterized antibody-mediated encephalitises. This article attempts to summarize the clinical features of this complex neuropsychiatric disorder with the aim to help its early recognition and to report the clinical course and the outcome of our six seropositive anti-NMDAR cases. The disease appears typically in young females and often combined with ovarian teratoma. However, the antibody production could develop without any malignancy. The course of the illness is usually monophasic, but 10% of the cases are relapsing. The anti-NMDAR encephalitis is the result of disturbed glutamatergic neurotransmission due to the internalization of the receptor-antibody complexes. The disease usually develops after a common viral infection, but recent data proved that anti-NMDAR encephalitis could also develop after herpes simplex virus-1 encephalitis. The Janus-faced clinical course of the disease is the obstacle of the early recognition. Psychiatric symptoms - like delusion, hallucination and agitation - dominate in the first, cortical phase of the illness, which are indistinguishable from the signs of primary psychosis. The true nature of the disease only reveals later, with the appearance of the basal ganglia territory and brainstem sings, such as perioral hyperkinesia and bradycardia. Further delays the diagnosis that the leading symptoms of the second phase could be interpreted as the side effects of the initial treatment. According to expert psychiatrists, the unusual dynamic of the psychotic symptoms and the lack of response to the neuroleptic drugs could lead toward the idea of the anti-NMDAR encephalitis. The final diagnosis depends on the detection of the anti-NMDAR antibody from the cerebrospinal fluid or the serum, respectively. Haloperidol is the most potent drug to treat the psychotic symptoms of the cortical phase; however due to its antidopaminergic side effect atypical neuroleptics are recommended by the experts. The immunological treatment is the administration of intravenous corticosteroid combined with plasma exchange or with intravenous IgG infusion. The immunotherapy in most of the cases is successful, but the recovery is long and it requires strong cooperation between the psychiatrists, neurologists and intensive care therapists.
在过去二十年的神经病学领域,将抗体介导的脑炎识别为中枢神经系统免疫疾病中的一个独立病种是最重大的突破之一。与病毒性或肿瘤相关性脑炎不同,抗体介导型脑炎对免疫治疗反应良好,这赋予了该发现特殊的临床重要性。抗N-甲基-D-天冬氨酸受体(抗NMDAR)脑炎是首批得到充分特征描述的抗体介导性脑炎之一。本文试图总结这种复杂的神经精神疾病的临床特征,以助于早期识别,并报告我们6例血清学阳性抗NMDAR病例的临床病程及转归。该疾病通常见于年轻女性,常合并卵巢畸胎瘤。然而,抗体产生也可能在无任何恶性肿瘤的情况下发生。疾病病程通常为单相性,但10%的病例会复发。抗NMDAR脑炎是受体-抗体复合物内化导致谷氨酸能神经传递紊乱的结果。该疾病通常在普通病毒感染后发生,但最近的数据证明,抗NMDAR脑炎也可能在单纯疱疹病毒1型脑炎后发生。该疾病双面性的临床病程是早期识别的障碍。在疾病的首个皮层期,精神症状如妄想、幻觉和激越占主导,这些症状与原发性精神病的体征难以区分。疾病的真正本质只有在后期基底节区和脑干体征如口周多动症和心动过缓出现时才会显现。进一步延误诊断的是第二阶段的主要症状可能被解释为初始治疗的副作用。据专家精神科医生称,精神病症状的异常动态变化以及对抗精神病药物缺乏反应可能使人想到抗NMDAR脑炎。最终诊断分别取决于脑脊液或血清中抗NMDAR抗体的检测。氟哌啶醇是治疗皮层期精神病症状最有效的药物;然而,由于其抗多巴胺能副作用,专家推荐使用非典型抗精神病药物。免疫治疗是静脉注射皮质类固醇联合血浆置换或静脉注射免疫球蛋白。大多数情况下免疫治疗是成功的,但恢复过程漫长,需要精神科医生、神经科医生和重症监护治疗师之间密切合作。