利妥昔单抗治疗12例儿童免疫性脑病的疗效及安全性分析

Efficacy and safety of rituximab in the treatment of 12 children with autoimmune encephalopathy

目的观察利妥昔单抗(rituximab,RTX)对一线免疫治疗及其他免疫抑制剂治疗效果不佳的免疫性脑病患儿的疗效和安全性。方法回顾性分析2016年9月至2018年12月广州市妇女儿童医疗中心神经内科收治的一线免疫治疗方案及其他免疫抑制剂疗效不佳的免疫性脑病患儿,接受RTX治疗后的病情转归及不良反应。患者RTX治疗疗程结束后均随访至少6个月。使用改良Rankin量表(modified Rankin scale,mRS)评分评估患儿免疫治疗前、RTX治疗前及RTX治疗疗程结束后3个月、6个月的神经功能障碍情况。结果使用RTX治疗的患儿共有12例,包括抗N-甲基-D-天冬氨酸受体(anti-N-methyl-D-aspartate receptor,NMDAR)脑炎7例、髓鞘少突胶质细胞糖蛋白抗体相关性疾病(myelin oligodendrocyte glycoprotein antibody associated diseases,MOG-AD)2例、眼阵挛-肌阵挛-共济失调综合征2例及原发性中枢神经系统血管炎1例。一线治疗无效至启动RTX治疗时间为中位数(上、下四分位数)为15.0(10.0,27.5)d。RTX治疗疗程结束后3个月及6个月mRS分别为1.50(1.00,2.00)和1.00(1.00,2.00),与一线免疫治疗后的mRS〔4.00(4.00,4.75)〕比较均明显减低(χ^2=22.947,P<0.001)。所有患儿脑电图及头颅MRI表现均有不同程度改善。治疗过程中发生皮疹及继发感染各2例,分别于抗过敏、抗感染治疗后好转。结论对于一线免疫治疗无效的儿童免疫性脑病,RTX疗效好,且安全性较好。

Objective To evaluate the effectiveness and safety of rituximab(RTX)in children with immunological encephalopathy who had a poor response to the first-line treatment and other immunosuppressive agents.Methods After RTX treatment,outcome and adverse effects of children with immunological encephalopathy who had a poor response to first-line treatment and other immunosuppressive agents in the Department of Neurology in Guangzhou Women and Children's Medical Center from September 2016 to December 2018 were collected retrospectively.A total of 6 months was followed up after RTX treatment.Modified Rankin scale(mRs)was used to evaluate the neurological dysfunction before immunotherapy,before RTX treatment,3 and 6 months after RTX treatment.Results A total of 12 children received RTX treatment.Seven cases were diagnosed as anti-n-methyl-d-aspartate receptor(NMDAR)encephalitis,2 cases as myelin oligodendrocyte glycoprotein antibody associated diseases(MOG-AD),2 cases as opsoclonus-myoclonus-ataxia and 1 case as primary central nervous system vasculitis.The median time from first-line treatment failure to RTX initiation was 15.0(10.0,27.5)days.mRS at 3 months and 6 months after RTX treatment was 1.50(1.00,2.00)and 1.00(1.00,2.00),respectively,which were significantly improved compared with that after first-line immunotherapy 4.00(4.00,4.75)(χ^2=22.947,P<0.001).EEG and brain MRI results of all the children were improved in varying degrees.Adverse reactions during treatment:2 cases had rashes,2 cases had secondary infection,which improved after anti-allergy and anti-infection treatment respectively.Conclusions RTX has a good efficacy and safety profile in children with immunological encephalopathy who had a poor response to first-line immunotherapy.