利司扑兰治疗儿童脊髓性肌萎缩症的临床分析

Clinical analysis of risdiplam in the treatment of spinal muscular atrophy in children

目的探讨利司扑兰治疗儿童脊髓性肌萎缩症(SMA)患者的临床效果,以期更好地制定中国治疗方案。方法选取符合国际SMA协会定义的临床诊断标准的6例中国儿童SMA患者。多重连接探针扩增技术检测患者SMN1基因和SMN2基因。SMA患者口服利司扑兰进行治疗,在利司扑兰治疗过程中均辅以康复训练,治疗后评估日常生活活动能力、呼吸和饮食情况,及治疗后神经系统查体,监测药物不良反应。结果6例SMN1基因纯合缺失的SMA患者包括Ⅰ型1例,Ⅱ型4例,Ⅲ型1例,SMN2基因拷贝数在2~3之间。在利司扑兰治疗过程中联合康复训练,所有患者短期内均有运动功能改善,最短起效时间为1 d。运动功能改善方面包括上肢远端力量、头部转动、独坐能力、下肢远端力量、步行、蹲起、姿势、平衡能力等,运动功能改善部位以上肢远端改善最明显。肌张力以腰部肌张力改善为主。各有1例患者呼吸肌力改善和食欲改善。联合康复训练较单纯利司扑兰治疗更有助于运动功能改善。未发现药物不良反应。结论国内首次报道利司扑兰治疗儿童SMA疗效确切,辅以康复训练,患者运动功能及日常生活能力可获得明显改善,是可供选择的方便安全治疗方法。

Objective To explore the clinical efficacy of risdiplam in the treatment of pediatric spinal muscular atrophy(SMA)patients for better making treatment plans in China.Methods Six Chinese children,who were diagnosed as SMA according to the defined criteria of the International SMA Consortium,were recruited.SMN1 and SMN2 genes were detected by multiplex ligation-dependent probe amplification.SMA patients were treated with oral risdiplam combined with rehabilitation.Activities of daily living and respiratory and dietary conditions were evaluated,the neurological examinations were conducted after treatment,and the adverse events were monitored.Results Six patients were found homozygous deletion of SMN1,including one case of typeⅠ,four cases of typeⅡ,and one case of typeⅢ,and SMN2 copies were 2-3.During the treatment of risdiplam combined with rehabilitation,the motor function was improved in all patients in the short term.The minimum effective time of risdiplam treatment was one day.Motor function was improved on the aspects of distal upper limb strength,head rotation,solitary sitting ability,distal lower limb strength,walking,squatting,posture,and balance ability,etc.The most obvious areas of improved motor function were in the distal upper limbs.Muscle tension was mainly improved in the lower back.There was one patient with improved respiratory muscle strength and one patient with improved appetite.The efficiency of risdiplam combined with rehabilitation was better to improve the motor function than that of risdiplam therapy.No adverse drug reactions were found.Conclusion In China,it is first reported that risdiplam is convenient,effective,and safe in the treatment of pediatric SMA,and the motor function and the daily living ability of patients can be obviously improved by risdiplam combined with rehabilitation.