以癫痫发作为首发症状的抗谷氨酸脱羧酶65抗体病患者的临床特点及预后

Clinical characteristics and prognosis of patients with anti-glutamate decarboxylase 65 antibody disease and the seizure as the onset symptom

目的探讨以癫痫发作为首发症状的抗谷氨酸脱羧酶65(GAD65)抗体病的临床特点及预后。方法回顾性分析2018年1月至2021年7月期间就诊于吉林大学第一医院的11例以癫痫发作为首发症状的GAD65抗体病患者的临床资料并随访。结果11例患者的中位发病年龄为49岁,平均(18~76岁),男女比例为1∶2,分别诊断为自身免疫性脑炎8例,免疫检查点抑制剂诱发的脑炎2例,自身免疫相关癫痫1例。9例患者有前驱症状。患者均以癫痫发作为首发症状,以全面性强直阵挛发作类型为主。脑脊液异常主要表现为白细胞增多和(或)蛋白水平升高;颅脑核磁共振(MRI)主要表现为颞叶和海马T2加权和FLAIR高信号;脑电图监测到发作间期以颞区、额区为主的尖波、尖慢波或慢波放电。2例患者筛查到潜在肿瘤,3例患者筛查到胸腺异常。6例患者免疫治疗后再无癫痫发作,5例患者因肿瘤的存在意识水平下降或癫痫持续状态而死亡,1例合并肿瘤的幸存患者6个月后出现了复发。结论以癫痫发作为首发症状的GAD65抗体病以中年女性最为常见,常伴有前驱症状、认知障碍及精神障碍。主要引起脑脊液、颞叶及海马的炎性改变,抗体滴度与病情严重程度及免疫治疗效果无关,早期免疫治疗可改善患者预后,肿瘤的存在对预后影响较大。

Objective To investigate the clinical characteristics and prognosis of patients with anti-glutamate decarboxylase 65(GAD65)antibody disease and the seizure as the onset symptom.Methods From January 2018 to July 2021,eleven GAD65 patients with seizure as the onset symptom in the First Hospital of Jilin University were retrospectively analyzed.Clinical data were collected and the patients were followed up.Results The median age of onset disease of 11 patients was 49 years old,with the patients'age from 18 to 76 years old.The ratio of male to female patients was 1∶2.Eight patients were diagnosed as autoimmune encephalitis,two patients as immune checkpoint inhibitor-induced encephalitis and one patient as autoimmune-associated epilepsy.Nine patients had prodromal symptoms.All patients had epileptic seizures as the onset symptom.The major seizure type was the generalized tonic-clonic seizure.Cerebrospinal fluid abnormalities were mainly manifested as leukocytosis and/or elevated protein levels.Brain magnetic resonance imaging(MRI)was mainly T2WI/FLAIR-high-signal in the temporal lobe and hippocampus.During seizures,spike-wave,spike-slow-wave or slow-wave discharges were detected by EEG monitoring mainly in the temporal and frontal regions.Two patients Were screened to have potential tumors,and Three patients were screened to have thymus abnormalities.Six patients had no seizures after immunotherapy.Five patients died due to tumor presence,decreased level of consciousness or persistent seizures.One of survivors had tumor and relapsed 6 months later.Conclusion Anti-GAD65 antibody disease with seizures as the onset symptom is very common in middle-aged women,often accompanied by prodromal symptoms,cognitive impairment and mental disorders.It mainly leads to inflammation changes in cerebrospinal fluid,temporal lobe and hippocampus.Antibody titer has no relation to the severity of the disease and the effect of immunotherapy.Early immunotherapy can improve the prognosis of patients,and the presence of tumor has a great impact on the prognosis.