利妥昔单抗治疗儿童非肿瘤性抗N-甲基-D-天冬氨酸受体脑炎的4例临床观察及疗效分析
摘要
目的探讨利妥昔单抗用于抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患儿的疗效和安全性。方法收集2014年5月至2017年4月该院收治的经一线免疫治疗无效的4例抗NMDAR脑炎患儿,通过回顾性分析其临床资料,评价利妥昔单抗的疗效及不良反应。结果 4例患儿中女性3例、男性1例,年龄分别为7岁1个月(患儿1)、5岁9个月(患儿2)、5岁3个月(患儿3)、9岁5个月(患儿4),4例患儿均未合并肿瘤,临床上均有精神行为异常及不自主运动等,脑脊液抗NMDAR抗体阳性,对一线免疫治疗(大剂量糖皮质激素和静脉注射丙种球蛋白)疗效不佳,mRS神经功能评分分别为:患儿1、3为4分,患儿2、4为5分。给予妥昔单抗治疗后除患儿2外临床症状均明显好转,症状恢复表现为意识改善,精神症状消失或明显减轻,不自主运动消失或明显减少,睡眠时间正常,情绪平稳。患儿2治疗妥昔单抗治疗4次后可以说单字,肢体抖动轻微减少但并不明显,余症状未见明显好转,10周后给予等剂量第5次利妥昔单抗治疗,至今随访13个月,头颅MRI可见脑萎缩,语言功能逐渐恢复,目前临床遗留有口周部及肢体的不自主运动、情绪冲动、注意力不集中、睡眠不安等表现,mRs4分。4例患儿均无复发。在首次输注利妥昔单抗初,患儿2出现呕吐及轻度腹痛,患儿3出现头痛、一过性皮肤瘙痒,经暂停输注半小时后临床症状均逐渐消失,以原输液速度减半继续完成输注,之后治疗均顺利,余患儿未出现不良反应。结论利妥昔单抗是经一线免疫治疗无效的抗NMDAR脑炎患儿的一有效治疗措施。
引文
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[2]DALMAU J,LANCASTER E,MARTINEZ-HERNAN-DEZ E,et al.Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis[J].Lancet Neurol,2011,10(1):63-74.
[3]TITULAER M J,MCCRACKEN L,GABILONDO I,et al.Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis:an observational cohort study[J].Lancet Neurol,2013,12(2):157-165.
[4]ZEKERIDOU A,KARANTONI E,VIACCOZ A,et al.Treatment and outcome of children and adol-escents with N-methyl-D-aspartate receptor encephalitis[J].J Neurol,2015,262(8):1859-1866.
[5]ELIZA G L,ANUSHA K,DEANNA S,et al.Comparative outcomes in children and adults with anti-N-Meth-ylD-aspartate(anti-NMDA)receptor encephalitis[J].J Child Neurol,2017,32(11):1-6.
[6]MIYA K,TAKAHASHI Y,MORI H.Anti-NMDAR autoimmune encephalitis[J].Brain Dev,2014,36(8):645-652.
[7]ROSENFELD MR,TITULAER MJ,DALMAU J.Paraneoplastic syndromes and autoimmune encephalitis:Five new things[J].Neurol Clin Pract,2012,2(3):215-223.
[8]彭晓音,董静静,高志杰,等.儿童抗N-甲基-D-天冬氨酸受体脑炎的临床特点及治疗随访[J].中华实用儿科临床杂志,2015,30(5):374-378.
[9]牛翠萍.抗N-甲基-D-天冬氨酸受体脑炎的临床分析[J].临床医药文献杂志,2015,2(8):1564-1565.
[10]MOK CC.Rituximab for the treatment of rheumatoid arthritis:an update[J].Drug Des Oevel Ther,2013,8(1):87-100.
[11]MALONEY DG,GRILLO-LOPEZ AJ,WHITE CA,et a1.IDEC.C2B8(Rituximab)anti-CD20monoclonal antibody therapy in patients with relapsed low-grade nonHodgkin,s lymphoma[J].Blood,1997,90(6):2188-2195.
[12]STONE JH,MERKEL PA,SPIERA R,et a1.Rituximab versus cyclophosphamide for ANCA-associated vasculitis[J].N Engl J Med,2010,363(3):221-232.
[13]COHEN SB,EMRRY P,GREENWALD MW.et a1.Rituximab for rbeumatoid arthritis refractory to anti-tumor necrosis factor therapy:Results of a muhicenter,randomized,double-blind,placebo-controlled.phaseⅢtrial evaluating primary efficacy and safety at twenty-four weeks[J].Arthritis Rheum,2006,54(9):2793-2806.
[14]ZHANG Y,LIU G,JIANG M D,et al.Analysis of electroencephalogram characteristics of anti-NMDA receptor encephalitis patients in China[J].Clinical Neurophysiology,2017,128(7):1227-1233.