诺西那生钠修正治疗儿童脊髓性肌萎缩症随访分析  

Clinical follow-up analysis of nusinersen in the disease-modifying treatment of pediatric spinal muscular atrophy

作　　者：毛姗姗[1] 冯艺杰 徐璐[1] 姚妹 夏雨 金佳宁 王灵双 陈婷婷 陈晓阳[2] 章毅[1] 张欢[1] 姜源[3] 李海冰 隆琦[5] 高峰[1] Mao Shanshan;Feng Yijie;Xu Lu;Yao Mei;Xia Yu;Jin Jianing;Wang Lingshuang;Chen Tingting;Chen Xiaoyang;Zhang Yi;Zhang Huan;Jiang Yuan;Li Haibing;Long Qi;Gao Feng(Department of Neurology,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China;Department of Developmental Behavior,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China;Department of Pulmonary,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China;Department of Orthopedics,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China;Department of Clinical Nutrition,the Children′s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China)

机构地区：[1]浙江大学医学院附属儿童医院神经内科国家儿童健康与疾病临床医学研究中心,杭州310052 [2]浙江大学医学院附属儿童医院发育行为儿科国家儿童健康与疾病临床医学研究中心,杭州310052 [3]浙江大学医学院附属儿童医院呼吸内科国家儿童健康与疾病临床医学研究中心,杭州310052 [4]浙江大学医学院附属儿童医院骨科国家儿童健康与疾病临床医学研究中心,杭州310052 [5]浙江大学医学院附属儿童医院临床营养科国家儿童健康与疾病临床医学研究中心,杭州310052

出　　处：《中华儿科杂志》2022年第7期688-693,共6页Chinese Journal of Pediatrics

基　　金：浙江省“尖兵”“领雁”研发攻关计划(2022C03167);浙江省基础公益分析测试项目(LGC21H090001);浙江省重点研发计划(2021C03099)。

摘　　要：目的探索疾病修正药物诺西那生钠治疗儿童脊髓性肌萎缩症的临床效果。方法回顾性研究,收集2019年10月至2021年10月浙江大学医学院附属儿童医院接受诺西那生钠注射治疗的15例5q脊髓性肌萎缩症患儿的临床基线及随访资料,对一般资料(性别、年龄、基因型、临床分型等)、运动功能、营养状态、脊柱侧弯以及呼吸功能等多系统状况进行分析。治疗前后比较采用Wilcoxon配对秩和检验。结果15例患儿中男7例、女8例,年龄6.8(2.8,8.3)岁,1、2、3型各有2、6、7例,病程55.0(21.0,69.0)个月。诺西那生钠治疗随访9.0(9.0,24.0)个月后,运动量表评估显示患儿Hammersmith婴儿神经学检查第2部分[13.0(7.0,23.0)比18.0(10.0,25.0)分],2、3型患儿Hammersmith功能性运动量表扩展版[38.0(18.5,45.5)比42.0(23.0,51.0)分]及上肢模块修订版量表分数[27.0(19.5,32.0)比33.0(22.5,35.5)分]均较基线明显提高(Z=-2.67、-2.38、-2.52,P=0.018、0.018、0.012)。13例患儿获得临床意义的运动功能改善,2例量表分数保持稳定。主观报告亦提示治疗后患儿肌肉力量、运动能力等有所提升,治疗期间未报告严重不良反应。辅以多学科管理后患儿脊柱侧弯Cobbs角、用力呼气肺活量等指标均改善(均P<0.05)。结论诺西那生钠药物治疗可提升5q脊髓性肌萎缩症患儿的运动功能,安全性良好,药物治疗辅以多学科管理有助于改善多系统功能损伤。Objective To explore the clinical efficacy of disease-modifying drug nusinersen on children with spinal muscular atrophy.Methods The baseline and longitudinal clinical data of 15 children who were treated with nusinersen in the Children′s Hospital,Zhejiang University School of Medicine from October 2019 to October 2021 were retrospectively collected.The general data(gender,age,genotype,and clinical classification,etc.),motor function,nutritional status,scoliosis and respiratory function were analyzed.Wilcoxon rank-sum test was used for comparing multi-system conditions before and after treatment.Results The age of 15 cases(7 males,8 females)was 6.8(2.8,8.3)years,with 2 cases of type 1,6 cases of type 2,and 7 cases of type 3 respectively,and the course of disease was 55.0(21.0,69.0)months.After 9.0(9.0,24.0)months of treatment,the motor function scale evaluations of the Hammersmith neurological examination section 2(13.0(7.0,23.0)vs.18.0(10.0,25.0)scores,Z=-2.67,P=0.018)of 15 children,the Hammersmith functional motor scale expanded(38.0(18.5,45.5)vs.42.0(23.0,51.0)scores,Z=-2.38,P=0.018),and the revised upper limb module(27.0(19.5,32.0)vs.33.0(22.5,35.5)scores,Z=-2.52,P=0.012)of children with type 2 and 3 had significantly improved.Thirteen patients achieved clinically significant motor function improvement,and 2 of them had kept stable scale scores.Subjective reports also indicated that the muscle strength and daily exercise ability of these children improved after treatment,and no serious adverse reactions were reported.Supplemented by the multi-disciplinary team management,the levels of some indicators such as Cobbs angle of scoliosis and forced vital capacity all had significantly improved(all P<0.05).Conclusions Nusinersen can improve the motor function of patients with 5q spinal muscular atrophy,which is also proved safe to be used in children.The drug treatment supplemented by the multi-disciplinary team management is helpful to improve the multi-system function of the children with spinal muscular atroph

关 键 词：脊髓性肌萎缩 儿童 诺西那生钠 疾病修正治疗 临床疗效 

分 类 号：R744.8[医药卫生—神经病学与精神病学]