多重抗神经元抗体阳性自身免疫性脑炎临床特点分析

Clinical analysis of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies

目的分析多重抗神经元抗体阳性自身免疫性脑炎临床特点及多重抗体阳性临床意义。方法回顾性总结2015年1月至2019年12月于空军军医大学唐都医院诊治的多重抗神经元抗体阳性自身免疫性脑炎患者的临床资料,对其临床表现、辅助检查、治疗及预后进行分析。结果收集的64例自身免疫性脑炎患者中,有多重抗神经元抗体阳性患者7例,占10.9%,包括:3例抗γ氨基丁酸B型受体抗体相关脑炎,其中1例同时伴抗谷氨酸脱羧酶抗体、抗Hu抗体阳性,另外2例分别合并抗N-甲基-D-天冬氨酸受体(NMDAR)抗体、抗Hu抗体阳性;2例抗NMDAR脑炎,1例合并抗Yo抗体阳性,1例抗NMDAR脑炎发病初期合并抗Hu抗体阳性,复发时抗接触蛋白相关蛋白2(CASPR2)抗体合并抗Hu抗体、抗CV2抗体阳性;1例抗富亮氨酸胶质瘤失活蛋白1抗体脑炎合并抗Ma2抗体阳性;1例抗CASPR2抗体脑炎合并抗Tr抗体阳性。有2例患者头颅磁共振成像异常。7例患者经免疫治疗后症状均得到缓解,其中3例在随访中筛查出肿瘤(经病理或影像检查证实),均在1年内死亡,余4例患者中有1例复发。结论多重抗神经元抗体阳性自身免疫性脑炎患者少见,多重抗体可导致临床症状变化或叠加,可能影响预后,尤其是合并副肿瘤抗体时需密切随访。

Objective To analyse the clinical features and significance of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies.Methods Patients of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies hospitalized in Tangdu Hospital,the Air Force Military Medical University from January 2015 to December 2019 were reviewed retrospectively.The clinical symptoms,supplementary examination,treatment options and outcomes were summarized in this study.Results Among 64 patients with positive antibodies related to autoimmune encephalitis,there were seven patients with co-existence of multiple anti-neuronal antibodies,all of whom were male,aging from 44 to 66 years.Antibodies were detected against gamma-aminobutyric acid beta receptor in three patients,one patient having coexisting antibodies against glutamic acid decarboxylase and Hu,two other patients having coexisting antibodies against N-methyl-D-aspartate receptor(NMDAR)and Hu respectively;against NMDAR in two patients,of which one patient had coexisting antibody against Yo,another one had coexisting antibody against Hu in early stage,against contactin assocaited protein 2(CASPR2),Hu and neuronal nuclear antibody type 2 when relapsing;against leucine-rich glioma-inactived 1 in one patient who had coexisting antibody against Ma2;against CASPR2 in one patient who had coexisting antibody against Tr.All of the patients were responded to immunotherapy in the early treatment.Three patients were detected with tumor(confirmed by pathology or imaging),including two cases of lung cancer(one of them with multiple metastasis),one case with mediastinal malignant small cell carcinoma,all died within one year.One of the other four patients was recurrent during the follow-up.Conclusions Patients of autoimmune encephalitis with co-existence of multiple anti-neuronal antidodies are rare.Concurrent antibodies can lead to change or overlap of clinical symptoms,which may affect prognosis.Close follow-up is needed in patients with paraneoplastic antibodies.