抗体介导的中枢神经系统自身免疫性疾病患儿207例临床分析

Clinical analysis of 207 children with antibody-mediated central nervous system autoimmune diseases

目的:探讨抗体介导的中枢神经系统(CNS)自身免疫性疾病患儿的临床特征、治疗及预后。方法:回顾性收集湖南省儿童医院神经内科自2014年6月至2022年5月收治的经血和(或)脑脊液抗神经抗体检测确诊的207例抗体介导的CNS自身免疫性疾病患儿的临床资料,总结分析其临床特征、实验室和影像学资料、治疗方案和预后。结果:207例抗体介导的CNS自身免疫性疾病患儿中抗N-甲基-D-天冬氨酸受体(NMDAR)抗体阳性117例,抗髓鞘少突胶质细胞糖蛋白(MOG)抗体阳性63例,抗胶质纤维酸性蛋白(GFAP)抗体阳性32例,抗接触蛋白相关蛋白-2(CASPR2)抗体阳性6例,抗水通道蛋白4(AQP4)抗体阳性3例,抗γ-氨基丁酸B型受体(GABABR)抗体阳性2例,抗富亮氨酸胶质瘤失活蛋白1(LGI1)抗体阳性1例;最常见的临床表型是急性播散性脑脊髓炎(ADEM),其次为视神经炎(ON);精神行为异常、癫痫发作及不自主运动是抗NMDAR抗体阳性患儿最常见的临床症状,而发热、头痛、意识障碍及视觉障碍是MOG抗体相关疾病(MOGAD)及自身免疫性GFAP星形胶质细胞病(GFAP-A)病程中最常见的临床症状。207例患儿中17例有多重抗神经抗体共阳性,其中抗NMDAR抗体与抗MOG抗体共存10例(1例同时检测到抗GFAP抗体),抗NMDAR抗体与抗GFAP抗体共存3例,抗MOG抗体与抗GFAP抗体共存3例,抗NMDAR抗体与抗CASPR2抗体共存2例,抗GABABR抗体与抗CASPR2抗体共存1例。202例患儿脑脊液检查结果显示154例出现白细胞增多症,27例蛋白水平升高。203例患儿脑电图检查结果显示179例异常,异常脑电图主要表现为局灶性或全面性慢波,部分患儿脑电图提示痫性放电。205例患儿接受了免疫治疗。所有存活患儿均至少随访6个月,164例患儿完全康复,40例存在不同程度后遗症,3例死亡。随访期间共有28例患儿有1次或多次复发。结论:抗体介导的CNS自身免疫性疾病可发生于儿童各年龄段,免疫治疗有效,大部分患儿对免疫治疗反应良好,死亡率低,但部分患儿存在复发风险。

Objective To investigate the clinical features,treatments and prognoses of children with antibody-mediated central nervous system(CNS)autoimmune diseases.Methods Two hundred and seven children with antibody-mediated CNS autoimmune diseases confirmed by anti-neuronal antibody detection in blood and/or cerebrospinal fluid in Department of Neurology,Children's Hospital of Hunan Province from June 2014 to May 2022 were enrolled.Their clinical features,laboratory and imaging data,treatment regimens and prognoses were retrospectively analyzed.Results Of the 207 children,117 were positive for anti-N-methyl-D-aspartate receptor(NMDAR)antibodies,63 for anti-myelin oligodendrocyte glycoprotein(MOG)antibodies,32 for anti-glial fibrillary acidic protein(GFAP)antibodies,6 for anti-contactin-associated protein-like 2(CNTNAP2)antibodies,3 for anti-aquaporin 4(AQP4)antibodies,2 for anti-gamma-aminobutyric acid type B receptor(GABABR)antibodies,and 1 for anti-anti-leucine-rich glioma-inactivated 1(LGI1)antibodies.Acute disseminated encephalomyelitis(ADEM)was the most common clinical phenotype among the children,followed by optic neuritis(ON).Behavioral abnormalities,seizures,and involuntary movements were the most common clinical presentations of anti-NMDAR encephalitis for these children,while fever,headache,and disturbance of consciousness or vision were the most common symptoms for children with MOG antibody disease or autoimmune GFAP astrocytopathy.The coexistence of multiple anti-neural antibodies was detected in 17 patients,among which 10 had coexistent anti-NMDAR and anti-MOG antibodies(including 1 with anti-GFAP antibody),3 had coexistent anti-NMDAR and anti-GFAP antibodies,3 had coexistent anti-MOG and anti-GFAP antibodies,2 had coexistent anti-NMDAR and anti-CASPR2 antibodies,and 1 had coexistent anti-GABABR and anti-CASPR2 antibodies.In our cohort,of the 202 children examined for cerebrospinal fluid,154 had cerebrospinal fluid leukocytosis and 27 had elevated protein.Of the 203 children had electroencephalography,179 was abnormal;abnormal EEG was mainly manifested as focal or global slow waves,and epileptic discharge in some children;205 patients received immunotherapy.All survivors were followed up for at least 6 months;164 recovered completely,40 had varied sequelae,and 3 died;28 had one or more relapses.Conclusion Antibody-mediated CNS autoimmune diseases occur in children at all ages;most such pediatric patients have good response to immunotherapy,enjoying low mortality rate;however,some survivors have relapsing risk.