吗替麦考酚酯治疗儿童神经系统自身免疫性疾病的疗效

Efficacy and safety of mycophenolate mofetil in treatment of pediatric immune-mediated disease of the nervous system

目的探讨吗替麦考酚酯(MMF)治疗儿童神经系统自身免疫性疾病的疗效及安全性。方法收集并分析12例被诊断为神经系统自身免疫性疾病且使用MMF治疗的患儿的临床资料、辅助检查结果、治疗及预后的资料。结果12例的诊断分别为神经系统炎性脱髓鞘病8例,其中髓鞘少突胶质细胞糖蛋白(MOG)IgG相关疾病5例、水通道蛋白-4(AQP4)抗体阳性的视神经脊髓炎谱系疾病(NMOSD)1例、多发性硬化(MS)1例、慢性炎性脱髓鞘性多发性神经根神经病(CIDP)1例,自身免疫性脑炎(AE,抗体阴性)2例,免疫性小脑共济失调1例,眼阵挛肌阵挛综合征(OMS)1例。MMF起始剂量为0.25 g/d,维持剂量为0.25~0.5 g/d。每1~3个月定期随诊,根据临床症状和检验结果调整MMF的剂量。使用MMF前共复发39次,用药后8例患儿无复发,分别为MOG IgG相关疾病3例、AE 2例、MS 1例、CIDP 1例、免疫性小脑共济失调1例。4例患儿复发,分别为MOG IgG相关疾病2例、AQP4 IgG NMOSD 1例、OMS 1例。MMF治疗后年平均复发率较治疗前下降(中位数1.92次/年vs.0.00次/年,P=0.034)。MMF治疗前、后的改良Rankin评分比较差异有统计学意义(中位数3.00分vs.1.00分,P=0.002)。治疗过程中2例患儿出现严重不良反应,分别为结核潜伏感染和重症肺炎,个别患儿仅表现为轻度胃肠反应,给予对症治疗后症状消失。结论MMF或可降低儿童神经系统炎性脱髓鞘病及AE的复发率以及改善神经功能障碍,MMF治疗仍有复发的OMS患儿需启动其他免疫治疗,MMF治疗有可能会出现严重不良反应。

Objective To evaluate the efficacy and safety of mycophenolate mofetil(MMF)in the treatment of pediatric immune-mediated disease of the nervous system.Methods Clinical data,auxiliary examination results,treatment and clinical prognosis of 12 children diagnosed with immune-mediated disease of the nervous system were collected and retrospectively analyzed.Results Among 12 children,8 cases were diagnosed with inflammatory demyelinating disease including myelin oligodendrocyte-glycoprotein(MOGIgG)-associated disease(n=5),aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder(NMOSD-AQP4)(n=1),multiple sclerosis(MS)(n=1),chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)(n=1);two children were diagnosed with autoimmune encephalitis(AE,negative antibody),one child was diagnosed with autoimmune cerebellar ataxia and one child of oculomotor myoclonus syndrome(OMS).The initial dose of MMF was 0.25 g/d and the maintenance dose was ranged from 0.25 to 0.5 g/d.All children were followed up every 1-3 months.The dose of MMF was adjusted according to clinical symptoms and examination results.Before MMF treatment,all patients developed 39 times of episode,whereas 8 children had no episode after MMF treatment including 3 cases of MOG-IgG-associated disease,2 cases of AE,1 case of MS,1 case of CIDP and 1 case of autoimmune cerebellar ataxia.Four patients recurred including 2 cases of MOG-IgG-associated disease,1 case of NMOSD-AQP4 and 1 case of OMS.The median annual recurrence rate after MMF treatment was 0.00,significantly lower than 1.92 times/year before MMF treatment(P=0.034).The median modified Rankin score significantly differed before and after MMF treatment(3.00 vs.1.00,P=0.002).During MMF treatment,2 children experienced severe adverse events including latent tuberculosis infection and severe pneumonia.Two patients developed mild gastrointestinal symptoms,which were alleviated after symptomatic treatment.Conclusions MMF probably could reduce the recurrence of pediatric inflammatory demyelinating disease and AE and mitigate neurological dysfunction.Immunotherapy should be considered for OMS children with recurrence after MMF treatment.However,MMF treatment might induce severe adverse events.