儿童抗N-甲基-D-天冬氨酸受体脑炎15例临床分析

Clinical analysis of anti-N-methyl-D-aspartate receptor encephalitis in 15 children

目的探讨儿童抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特点。方法对2015年4月至12月复旦大学附属儿科医院神经内科收治的15例确诊为抗NMDAR脑炎患儿资料进行回顾性分析。结果 15例中男8例、女7例,年龄8个月至12岁,中位发病年龄7岁。临床症状:首发症状意识障碍伴惊厥3例(20.0%),精神行为异常4例(26.7%)。15例均有惊厥发作,睡眠障碍5例(33.3%);发生惊厥持续状态3例;意识障碍10例(66.7%),昏迷3例;肢体或颜面部不自主运动12例(80.0%);尿潴留7例(46.7%)。中枢性低通气3例(20.0%)。继发于感染后2例(13.3%)。辅助检查:均行脑脊液检查,5例(33.3%)白细胞轻度升高,2例(13.3%)蛋白明显升高;脑脊液抗NMDAR抗体均阳性;其中10例行IgG指数检查,4例(40.0%)Ig G指数升高。10例(66.7%)头颅磁共振成像(MRI)异常。脑电图均为背景活动变慢,9例(60.0%)痫样放电,未发现δ刷。仅1例(6.7%)发现卵巢占位性病变。治疗和随访:均应用静脉甲泼尼龙加丙种球蛋白免疫治疗,1例(6.7%)给予血浆置换。随访1~6个月,9例改良Rankin量表评级为0~2级。结论抗NMDAR脑炎临床表现和实验室检查缺乏特异性,初期诊断困难。脑脊液特异性抗NMDAR抗体阳性可确诊该病。儿童抗NMDAR脑炎患者肿瘤发生率低,脑电图δ刷少见。早期诊断和及时应用免疫抑制剂治疗,预后良好。

Objective To explore the clinical characteristics of anti-N-methyl-D-aspartate receptor（anti-NMDAR） encephalitis in children. Methods Between April 2015 and December 2015, fifteen children were diagnosed with this disorder at the Department of Neurology, Children＇ s Hospital of Fudan University. We retrospectively analyzed the data of clinical characteristics and laboratory examinations. Results （1）There were seven females and eight males, the median age of onset was 7 years old, ranging from 8 months to 12 years. （2）Clinical characteristics were as follows： 3/15 （20%） had impaired consciousness along with convulsion, and 4/15 （26.7%） had emotional and behavioral changes at the onset of disease. Seizures occurred in all the 15 children and status epilepticus in 3 cases. Facial and limb involuntary movements occurred in 12/15 （80%）. Seven cases （46.7%） demonstrated uroschesis. Three had hypoventilation. Two （ 13.3% ） were secondary to virus infection. （ 3 ） Imaging and laboratory examination showed that the white blood cell of cerebrospinal fluid （CSF） in 5/15 cases （33.3%） were moderately elevated. The protein of cerebrospinal fluid （CSF） was obviously increased in 2 patient （ 13.3 %）. IgG index was detected in 10 patients and increased in 4/10 （40%）. All had cerebrospinal fluid antibodies. MRI was abnormal in 10/15 （66.7%）. EEG typically showed diffuse background slowing, while no extreme delta brush was observed. One case（6.7%） had a mass in ovary. All patients received intravenous methylprednisolone and immunoglobulins （IVIG）. One case （6.7%） received plasma exchange. Follow-ups lasted for 1 to 6 months. The functional outcomes of 9 patients were favorable, mRS being 0 to 2. Conclusion Due to the lack of specificity of clinical symptoms and laboratory examination, this disorder is difficult to diagnose at the onset. The disease can be diagnosed by the specific anti-NMDAR antibody in the cerebrospinal fluid. Tumors and delt brush are rarely found in children with anti-NMDAR encephalitis. Early diagnosis and timely initiation of immunosuppressive treatment will result in favorable outcome in the majority of the patients.