title: [Efficacy and safety of rapamycin in treatment of children with epilepsy complicated with tuberous sclerosis].
abstract: OBJECTIVE
  To evaluate the therapeutic effect and safety of rapamycin in treatment of children with tuberous sclerosis complex (TSC) complicated with epilepsy.
  
  
  METHODS
  This was an open-label, 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.
  
  
  RESULTS
  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; 17 cases 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/(m(2)×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.
  
  
  CONCLUSIONS
  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/m(2), which has a certain effect on seizures and a good safety profile.
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Zening
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Junsi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Xiaoqiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pediatrics, General Hospital of China People's Liberation Army, Beijing 100853, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D012640:Seizures / Q000517:prevention & control; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000150:complications* / Q000235:genetics
chemical_list: D000927:Anticonvulsants; D020123:Sirolimus