ObjectiveTo optimize the therapy protocols of high dose prednisone combined with topiramate (TPM) in children with infantile spasms (IS). MethodsSixty cases were collected in our hospital from September 2012 to September 2013 and randomly divided into two groups(n=30) and followed-up for more than 6 months.The spasms were assesses by video-electroencephalogram (VEEG) monitoring including awake and asleep states before treatment, after two weeks of therapy and the end of the courses respectively.And the Gessel developmental quotient (DQ) scores were performed before treatment and after six months of therapy. ResultsFor the unresponders to high dose prednisone in one week of therapy, there were 46.67%and 60.00% in test group higher than 31.25% and 37.50% in control group respectively in 2 week and in the end of treatment.And the rate of complete resolution of hypsarrhythmia in the test group was 46.67% and 60.00% higher than 25.00% and 37.50% in control group respectively in 2 week and in the end of treatment.But there were no statistical significances between two groups(P >0.05).The incidence of side effects(83.33% vs. 80.00%) and the relapse rate(39.14% vs. 40.00%), were not statistically significant between two groups(P >0.05).The responsive rates for the cases with the lead time within 2 months higher than beyond 2 months in two groups respectively in 2 weeks and in the end of treatment. ConclusionsThe protocol of the test group was superior to that of the control group.The responsive rates of children within 2 months of lead time were higher than beyond 2 months, which indicates that early diagnosis and early treatment would improve efficacy and have an important influence on the prognosis of IS.