摘要目的 观察雷帕霉素治疗儿童结节性硬化症(TSC)合并癫痫的临床效果及安全性.方法 开放性、前瞻性、自身对照研究,收集2011年9月至2013年9月解放军总医院儿童医学中心收治的TSC合并癫痫并接受雷帕霉素治疗24周以上的52例患儿.其中男34例,女18例,癫痫发病年龄中位数为4.8个月(4 d～49个月),接受雷帕霉素治疗的年龄是27个月(4.5 ～172.5个月).观察52例患儿雷帕霉素治疗后的癫痫控制发作情况及有效率等.结果 52例患儿中有10例有TSC家族史.24例患儿进行了TSC基因检测,4例为TSC1突变,20例为TSC2突变.入组前59.62％(31/52)患儿服用3种以上的抗癫痫药物,其中10例服用5种以上抗癫痫药物.52例患儿雷帕霉素治疗24周癫痫控制无发作率25.00％(13例)、总有效率73.08％(38例);治疗48周31例患儿癫痫控制无发作率19.35％(6例)、总有效率74.19％(23例);治疗72周17例患儿癫痫控制无发作5例、总有效13例;治疗96周的12例患儿癫痫控制无发作3例、总有效9例.随着患儿发作次数的减少,使用的抗癫痫药物种类也在减少,雷帕霉素治疗前平均发作次数70.27次/d,抗癫痫药物种类1.30种,治疗48 ～96周后,发作次数降至1.94 ～2.80次/d,抗癫痫药物种类0.83～ 0.97种.52例患儿在随诊的各时间点血、尿常规及肝肾功能检查均未见异常;雷帕霉素的药物剂量1 mg/(m2·d),平均0.7(0.35 ～ 1.20) mg/d.雷帕霉素血药浓度维持在10 μg/L以下(平均6.5 μg/L).服用雷帕霉素患儿出现一过性口腔溃疡23.08％(12/52),持续2～3d可以消失;17.31％(9/52)出现上呼吸道感染.结论 雷帕霉素治疗儿童TSC合并癫痫疗效确切,不良反应少.儿童患者每日服用雷帕霉素剂量为1 mg/m2时,有效安全.

abstractsObjective To evaluate the therapeutic effect and safety of rapamycin in treatment of children with tuberous sclerosis complex (TSC) complicated with epilepsy.Method This was an openlabel,prospective,self-controlled study.From Sep.2011 to Sep.2013,52 patients with the diagnosis of tuberous sclerosis complicated with epilepsy receiving rapamycin treatment for at least 24 weeks were enrolled.Result Of the 52 children,34 were male and 18 female.The median age at onset of epilepsy was 4.8 months (4 days-49 months),the median age for treatment with rapamycin was 27 months (4.5-172.5 months).Ten children had a family history of TSC.In 24 children TSC gene detection was carried out,among whom TSC1 mutation was detected in 4 cases and TSC2 mutation in 20.Before rapamycin therapy,59.62％,(31/52) patients took more than 3 antiepileptic drugs,of whom 10 cases even took more than 5 kinds of antiepileptic drugs.Fifty-two patients received rapamycin treatment for 24 weeks,seizure free rate was 25.00％ (13 cases),the total effective rate was 73.08％ (38 cases) ; 31 cases received treatment for 48 weeks,seizure free 6 cases,total effective 23 cases; 17cases accepted treatment for 72 weeks,seizure free 5 cases,total effective 13 cases; 12 cases received treatment for 96 weeks,seizure free 3 cases,total effective 9 cases.With the decrease of seizure attacks,use of antiepileptic drug types were reduced simultaneously,they had a negative correlation.Before rapamycin therapy,the average frequency of seizures was 70.27 times/d,the number of antiepileptic drug kinds was 1.30.After 24,48,72,96 weeks' treatment,the average seizure frequency was reduced to 1.94-2.80 times/d and the antiepileptic drugs were reduced to 0.83-0.97 kinds.On every visit during the follow-up,blood and urine routine tests,liver and kidney function test showed no abnormality in the 52 cases.The drug dosage was 1 mg/(m2 · d),average 0.7 mg/d (0.35-1.20 mg/d).Blood concentrations of rapamycin remained below 10 μg/L (average 6.5 μg/L).The main side effect was oral ulcer which happened in 23.08％ (12/52).The oral ulcer would disappeared 2-3 days later.17.31％ (9/52 cases) had upper respiratory infection.Conclusion Rapamycin was effective in children with tuberous sclerosis and epilepsy with few adverse reactions.The daily dose of rapamycin for children patients is 1 mg/m2,which has a certain effect on seizures and a good safety profile.