Objective: 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 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.
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; 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.
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/m(2), which has a certain effect on seizures and a good safety profile.