抗谷氨酸脱羧酶抗体阳性自身免疫性脑炎三例临床特征分析

目的探讨抗谷氨酸脱羧酶(glutamic acid decarboxylase,GAD)抗体阳性自身免疫性脑炎的临床症状及相关辅助检查特点,为临床正确诊疗抗GAD相关脑炎提供依据。方法对作者医院自2016年1月至2018年8月期间明确诊断的3例抗GAD抗体阳性自身免疫性脑炎患者进行回顾性研究,分析其一般人口学、临床症状学、脑脊液细胞学、影像学、脑电图、治疗及预后等特征。结果3例患者均为女性,发病年龄分别为44岁、26岁、27岁,其中2例患者以难治性癫痫状态起病,1例以头痛起病,病程中均出现一定程度意识障碍及显著认知功能下降,其中1例患者病情恢复期出现类似吉兰-巴雷综合征样周围神经损害;头颅MRI均表现为双侧海马、颞叶等边缘叶系统核异常信号,且进行性加重。3例均检测到GAD65抗体,其中1例发病初期即检测到该抗体,2例患者发病初期神经元抗体检测为阴性,分别于发病43 d、79 d脑脊液检测到;3例患者发病初期脑电图表现中-重度广泛性、多灶样异常,中-高波幅3~5 Hz慢波阵发,杂有稍多量尖棘波发放。1例患者发病初期脑脊液白细胞计数增高(淋巴细胞97%),10 d后复查恢复正常,余2例患者脑脊液常规生化免疫及细胞学未见明显异常。三例患者经甲泼尼龙及大剂量免疫球蛋白治疗后认知功能较症状高峰期基本恢复,未再有癫痫发作。结论此3例抗GAD抗体阳性自身免疫性脑炎患者均为女性,中青年发病,初期表现难治性癫痫持续状态或者耐药性癫痫,恢复期出现认知功能减退,病程中均无显著精神症状;影像学以双侧额颞叶、海马受累较为明显;病程中脑脊液抗GAD 65抗体均阳性,且脑脊液中该抗体发病初期可为阴性。

Analysis of clinical characteristics of three cases with anti-glutamate decarboxylase antibody-positive autoimmune encephalitis

Objective This study was to investigate the clinical symptoms and auxiliary examination of anti-glutamic acid decarboxylase(GAD)-positive autoimmune encephalitis(AE)and provide clinical evidence for its diagnosis and treatment.Methods Three patients with anti-GAD-positive AE diagnosed in our hospital from Jan 2016 to Aug 2018 were retrospectively analyzed for their general demographics,clinical symptoms,cerebrospinal fluid(CSF)cytology,imaging findings,EEG and the clinical outcome of treatment.Results All the 3 patients were female.Their ages at onset were 44,26 and 27 years old,respectively.Among them,2 patients presented with refractory status epilepticus,and 1 patient presented with headache.Consciousness disturbance and cognitive decline occurred in all the 3 patients during the disease course.One case manifested with Guillain-Barrésyndrome-like peripheral neuropathy in the recovery period.There were some common brain MRI findings,which showed progressively abnormal signals of bilateral limbic system,including the hippocampus and the temporal lobe.Of them,two patients had negative neuronal antibody detection at the early stage.Finally,the GAD antibody was positive in the CSF at the 43th and 79th day after onset,respectively.However,anti-GAD of the other case was detective at the onset stage.EEG of all the patients at the early stage showed extensive,multi-focal and moderate-severe abnormal EEG,with moderate-high amplitude 3-5 Hz slow waves and spikes.In one patient,the leucocyte count of CSF increased in the early stage and lymphocytes were 97%.After 10 days,the results returned to normal.In the other 2 patients,there was no obvious abnormality the in routine test and cytology of CSF.All the three patients were well responsive to immunotherapy.After two years of follow-up,epileptic seizures were well controlled and cognitive function profoundly recovered in all of them,but the peripheral nerve damage of case 2 did not fully recover,and case 3 showed extrapyramidal symptoms.Conclusions Anti-GAD antibody-positive AE may be more common in young and middle-aged women,with initial manifestations of refractory status epilepticus or drug-resistant epilepsy,and cognitive decline during disease progression,but without psychiatric symptoms in our current cases.The brain MRI shows obvious abnormality in bilateral frontal lobe,temporal lobe,and hippocampus.CSF routine and cytopathology examinations are generally normal.Anti-GAD antibody production in this AE type has a certain incubation period,and can be negative in the early stage.The antibody can be detected during disease progression.