儿童抗N-甲基-D-天冬氨酸受体脑炎的临床特征

Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in children

目的:分析抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎患儿的临床特点及预后,为临床早期识别本病提供依据。方法:回顾性分析2015年1月至2018年3月在中南大学湘雅二医院儿科住院的42例抗NMDAR脑炎患儿的临床资料及随访情况,总结其临床特点、治疗效果及预后情况。结果:42例患儿中男15例(35.7%),女27例(64.3%),男女比例1꞉1.8,年龄(9.20±4.66)岁(最小4个月,最大17岁)。首发症状以癫痫发作(47.6%,20/42)和精神行为异常(35.7%,15/42)最为常见;患儿在病程中累积出现精神行为异常(36/42,85.7%)、癫痫发作(36/42,85.7%)、言语障碍(32/42,76.2%)、运动障碍(28/42,66.7%)、意识障碍(28/42,66.7%)、自主神经功能紊乱(26/42,61.9%)及睡眠障碍(24/42,57.1%)等症状。42例患儿脑脊液抗NMDAR抗体均为阳性;50.0%(21/42)的患儿头颅MRI检查结果异常,病变累及顶叶、额叶、颞叶、枕叶、基底节及视神经等部位,1例患儿病变累及视神经合并髓鞘少突胶质细胞糖蛋白(myelin oligodendrocyte glycoprotein,MOG)抗体阳性;40例患儿行脑电图检查,92.5%(37/40)出现异常,以弥漫性慢波为主要表现,1例可见δ刷;合并肠系膜畸胎瘤1例,占2.4%(1/42)。出院时mRS评分为2.14±1.46,较住院期间最高mRS评分(3.88±1.38)显著降低(P<0.05),疗效显著;随访3~39个月,出院后3个月时mRS评分仅为0.81±1.29,与出院时mRS评分比较仍有显著改善,其中76.2%(32/42)mRS评分≤2,预后良好;4.8%(2/42)的患儿复发,无死亡病例。开始免疫治疗时间和病程中最高mRS评分是影响预后的因素,开始免疫治疗时间越早、病程中mRS评分越低,预后越好。结论:癫痫发作、精神行为异常、运动障碍、言语障碍及自主神经功能紊乱是儿童抗NMDAR脑炎的常见临床表现;免疫治疗效果显著,开始免疫治疗的时间和病情严重程度是影响预后的重要因素;抗NMDAR脑炎可合并其他自身抗体,其临床意义及机制有待深入研究。

Objective:To analyze the clinical characteristics and prognosis of children with anti-Nmethyl-D-aspartate receptor(NMDAR)encephalitis and to provide a basis for early clinical identification of this disease.Methods:The clinical data of 42 cases of anti-NMDAR encephalitis at Department of Pediatrics,Second Xiangya Hospital,Central South University from January 2015 to March 2018 were collected.The clinical features and followed-up outcomes were analyzed retrospectively.Results:There were 15 cases(35.7%)of males and 27 cases(64.3%)of females in 42 children,with a ratio of 1꞉1.8.They were aged from 4 months to 17 years,with an average of(9.20±4.66)years.The most common initial symptoms were seizures(47.6%,20/42)and mental behavior disorder(35.7%,15/42).During the course of the disease,85.7%patients(36/42)had mental and behavior disorder,85.7%patients(36/42)had epilepsy,76.2%(32/42)had speech disorder,66.7%patients(28/42)had dyskinesia,66.7%patients(28/42)had the decreased level of consciousness,61.9%patients(26/42)had autonomic instability,and 57.1%(24/42)patients had sleep disorder.All the children had positive antibody against NMDA receptor resistance encephalitis in cerebrospinal fluid.Head MRI showed the abnormal incidence was 50.0%(21/42),and the lesions involved in parietal lobe,frontal lobe,temporal lobe,occipital lobe,midbrain,thalamus,basal ganglia and optic nerve.There was a patient with optic nerve damage combined with myelin oligodendrocyte glycoprotein(MOG)antibody positive.Forty cases were examined by electroencephalogram(EEG),92.5%cases(37/40)were abnormal,mainly showing diffuse slow waves,andδbrushes could be seen in severe cases.And there was 1 patient(2.4%)complicated with mesenteric teratoma.The mRS score(2.14±1.46)at discharge was significantly lower than the highest mRS score(3.88±1.38)during hospitalization(P<0.05).After 3-39 months of follow-up,mRS score at 3 months after discharge was only 0.81±1.29,which was still improved compared with that at discharge,76.2%cases(32/42)experienced complete or near-complete recovery(mRS score≤2),and 4.8%(2/42)cases relapsed.There was no mortality;the initial time of immunotherapy and the highest mRS score in the course of the disease were the factors affecting the prognosis.The earlier the starting time for immunotherapy and the lower mRS score in the course of the disease were,the better the prognosis was.Conclusion:Seizures,mental and behavior disorder,dyskinesias,speech disorder and autonomic instability are common clinical manifestations of anti-NMDAR encephalitis in children.The effect of immunotherapy is significant,and the time to start immunotherapy and the severity of the disease are important factors affecting the prognosis.Anti-NMDAR encephalitis can be combined with other autoantibodies,but its clinical significance and mechanism need further study.