抗代谢型谷氨酸受体1抗体相关性脑炎一例  

Anti-metabotropic glutamate receptor 1 antibodies associated encephalitis:a case report

作　　者：刘磊[1] 刘建国[2] 张景晓 俞英欣 戚晓昆[2] 王佳伟[1,3] Liu Lei;Liu Jianguo;Zhang Jingxiao;Yu Yingxin;Qi Xiaokun;Wang Jiawei(Department of Neurology,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China;Department of Neurology,People′s Liberation Army General Hospital Accredited to the Sixth Medical Center,Beijing 100048,China;Medical Research Center,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院神经内科,100730 [2]解放军总医院神经内科医学部派驻第六医学中心神经内科,100048 [3]首都医科大学附属北京同仁医院中心实验室,100730

出　　处：《中华神经科杂志》2021年第9期920-927,共8页Chinese Journal of Neurology

基　　金：国家自然科学基金(81771313);国家自然科学基金青年科学基金(81301029);北京市自然科学基金(7192040);北京市医院管理局“青苗”计划专项经费(QML20150206);北京市科技计划课题“首都特色”项目(Z171100001017039);首都卫生发展科研专项(2020-2-2056)。

摘　　要：目的采用基于组织底物实验及实验室内部基于细胞底物实验的抗代谢型谷氨酸受体1抗体联合检测方法,对既往病因不明的1例以小脑性共济失调为主要表现的脑炎病例进行筛查并最终确诊,总结分析其临床和治疗特点。方法对2020年1月9日解放军总医院神经内科医学部派驻第六医学中心神经内科收治的1例以急性头晕伴行走不稳起病,继而出现头部晃动、反复言语、计算力下降的中年女性患者的临床资料进行总结。首先对患者的血清和脑脊液进行常规神经抗体检测。再通过该患者血清及脑脊液分别孵育大鼠海马、小脑以及转染抗代谢型谷氨酸受体1质粒的人胚肾293细胞,使用间接免疫荧光法进行额外抗体筛查。结合文献对代谢性谷氨酸受体1的生理功能及抗代谢性谷氨酸受体1抗体相关性脑炎的临床特点进行总结。结果经常规商品化试剂盒筛查,该患者神经抗体呈阴性,但基于组织底物实验显示其血清及脑脊液结合大鼠脑片均出现"神经毡"样染色,其中小脑浦肯野细胞出现了"美杜莎头"样特征性染色。后续结合患者的特征性头部晃动症状,通过实验室内部基于细胞底物实验明确其存在抗代谢型谷氨酸受体1抗体,进而诊断为抗代谢型谷氨酸受体1抗体相关性脑炎。1年后随访,患者经过皮质类固醇激素、人血免疫球蛋白治疗后血清抗体滴度大幅度下降伴脑脊液抗体转阴,症状虽有所缓解,但仍留有较严重小脑萎缩及共济失调。结论抗代谢型谷氨酸受体1抗体可导致急性脑炎。小脑性共济失调及头部晃动是其特征性临床表现。本病对免疫治疗反应有限,可能会遗留严重后遗症。Objective To establish a tissue based assay and in-house cell based assay combined system to screen anti-metabotropic glutamate receptor 1 antibodies in a case of previously idiopathic encephalitis with prominent cerebellar ataxia and make the final diagnosis,and to summarize and analyze clinical characteristics and treatment response of the disease.Methods A middle-aged woman admitted to Department of Neurology,People's Liberation Army General Hospical Accredited to the Sixth Medical Center in January 9,2020,who presented with acute dizziness,unsteady gait and developed head titubation,repeated language and calculation impairment was reported.The patient′s serum and cerebrospinal fluid were firstly tested with commercial kits for conventional neural antibodies.Then samples were incubated with rat hippocampus,cerebellum and human embryonic kidney 293 cells transfected with metabotropic glutamate receptor 1 plasmid to screen extra antibodies by indirect immunofluorescence method.By reviewing literature,physical functions of metabotropic glutamate receptor 1 and clinical features of anti-metabotropic glutamate receptor 1 antibodies associated encephalitis were summarized.Results The patient was neural antibodies negative with commercial kits.Further investigation showed neuropil staining pattern after her serum and cerebral spinal fluid were incubated with rat brain slices.The characteristic"Medusa head"staining pattern of Purkinje cells in cerebellum was also noticed.Along with her previous head titubation symptom,an in-house cell based assay using human embryonic kidney 293 cells transfected with metabotropic glutamate receptor 1 plasmid was developed and proved the existence of anti-metabotropic glutamate receptor 1 antibodies.The final diagnosis of anti-metabotropic glutamate receptor 1 antibodies associated encephalitis was made.One-year follow-up revealed her serum antibodies titers dramatically decreased and cerebrospinal fluid antibodies were negative after using steroids and intravenous immunoglobulin,bu

关 键 词：受体 谷氨酸 自身免疫疾病 自身抗体 脑炎 小脑共济失调 

分 类 号：R742.9[医药卫生—神经病学与精神病学]