儿童抗谷氨酸脱羧酶65抗体相关自身免疫性脑炎二例并文献复习

目的探讨儿童抗谷氨酸脱羧酶65(GAD65)抗体相关自身免疫性脑炎的临床特点及预后。方法对2019年于首都医科大学附属北京儿童医院神经内科住院的2例抗GAD65抗体相关自身免疫性脑炎患儿的临床资料进行回顾性分析。并分别以“抗GAD65抗体”“脑炎”“癫痫”“共济失调”和“anti-GAD65 antibody”“encephalitis”“epilepsy”“cerebellar ataxia”为关键词,对中文期刊全文数据库、万方数据知识服务平台、生物医学文献数据库(Pubmed)建库至2020年1月的文献进行检索,选取临床资料完整的儿童病例,总结临床特点及预后。结果2例抗GAD65抗体相关自身免疫性脑炎的患儿均为女性,例1于4岁9月龄起病,以发热伴意识障碍为主要临床表现,头颅磁共振成像提示颅内弥漫性T2加权序列(T2WI)稍高信号,脑电图提示慢波。例2于6岁8月龄起病,以反复局灶性癫痫发作、记忆力减退、头痛为主要临床表现,头颅磁共振成像提示双侧海马T2WI高信号,脑电图提示累及颞区的异常放电。2例患儿均应用了甲泼尼龙及丙种球蛋白免疫治疗,短期症状均有所改善。分别随访6个月及1年,例1完全恢复,例2仍有局灶性癫痫。文献检索共收集6篇英文文献,报道了6例患儿,结合本组共8例。8例患儿中癫痫发作6例,记忆力下降4例,意识障碍、行为异常各3例,认知障碍、头痛各2例,自主神经功能障碍、共济失调、吞咽困难、失语各1例。急性期或亚急性期5例头颅磁共振成像异常,其中3例累及边缘系统,2例边缘系统外受累为主。慢性期3例出现海马萎缩或硬化。8例均加用免疫治疗,免疫治疗后所有患者均短期获得不同程度的改善。随访6个月至6年,3例边缘叶外脑炎预后良好,5例边缘叶脑炎预后欠佳,其中死亡1例,4例遗留局灶性癫痫。结论儿童抗GAD65抗体相关免疫性脑炎是一种罕见可治疗的疾病,包括边缘叶脑炎及边缘叶以外脑炎,以癫痫发作及记忆力下降为常见临床表现。早期诊断并积极免疫治疗可短期内改善症状。边缘叶脑炎慢性期易出现难治性癫痫,长期预后不佳。

Pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 antibody:two cases report and literature review

Objective To investigate the clinical features and prognosis of pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65(GAD65)antibody.Methods Clinical data of 2 patients diagnosed as autoimmune encephalitis associated with anti-GAD65 antibody at Department of Neurology,Beijing Children′s Hospital in 2019 were analyzed retrospectively.A literature search with“anti-GAD65 antibody”“encephalitis”“epilepsy”or“cerebellar ataxia”as key words was conducted at China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform and PubMed(up to January 2020).The clinical features and prognosis of pediatric cases with complete clinical data were retrieved and summarized.Results Two patients with positive anti-GAD65 antibody of serum and cerebrospinal fluid were both females.The onset age of case 1 was 57 months and her main clinical manifestations were fever and unconsciousness.The cranial magnetic resonance imaging(MRI)showed diffuse T2 weighted imaging(T2WI)abnormal signals,and the electroencephalogram(EEG)showed slow waves.The onset age of case 2 was 80 months and her main clinical manifestations of were recurrent focal seizures,memory loss,and headache.The MRI showed high T2WI signal in bilateral hippocampus,and the EEG showed abnormal discharge involving the temporal area.Both cases were treated with methylprednisolone and intravenous immunoglobulin,the short-term symptoms of them were both improved.They were followed up for 6 months and 1 year respectively,the case 1 recovered completely,and the case 2 still had focal seizures.Six English reports which included 6 cases were retrieved.Together with these 2 cases,a total of 8 cases were analyzed.The clinical symptoms included seizures(6 cases),memory loss(4 cases),loss of consciousness(3 cases),behavioral abnormalities(3 cases),cognitive impairment(2 cases),headache(2 cases),autonomic symptoms(1 case),ataxia(1 case),dysphagia(1 case),and aphasia(1 case).There were 5 cases with cranial MRI abnormalities in the acute phase or sub-acute phase,of whom 3 cases had the limbic system involvement,and 2 cases were mainly had extra limbic area involvement.Three cases had hippocampal atrophy or sclerosis during follow-up.All 8 patients were treated with immunotherapy.After immunotherapy,all patients had short-term improvement.Follow-up for 6 months to 6 years showed that 3 cases with extra limbic encephalitis improved to baseline levels,and 5 limbic encephalitis cases had poor outcomes,including 1 death and 4 cases still had focal epilepsy.Conclusions Pediatric anti-GAD65 antibody associated autoimmune encephalitis is a rare but treatable disease,including limbic encephalitis and extra limbic encephalitis.The most common clinical manifestations are seizures and memory impairment.Early diagnosis and immunotherapy can improve the symptoms in a short time.But patients with limbic encephalitis often had refractory epilepsy in the chronic phase,and have a poor long-term outcome.