Efficacy And Tolerability Of Different Protocols Of Prednisone Combined For Infantile Spasms In Children

Background and Objective: Infantile spasms (IS) is a refractory epilepsysyndrome,which is assorted into epileptic encephalopathy.Most guidelines and expertconsensuses recommended that adrenocorticotropic hormone (ACTH) was thefirst-line agent for IS. However, the incidence of adverse effects of ACTH is higher,which is also difficult to be available in our country,and the antiepileptic drugs(AEDs)are poor outcome for IS. In2004,Lux et al and Kossoff et al. found that theeffectiveness of high dose prednisolone was equivalent to that of synthetic ACTH,and that prednisolone was more low-cost, more convenient in operation than ACTH.That our team has employed prednisone combined with topiramate(TPM) to treat ISachieved a similar effect. We also found most children with IS had responded at thefirst week and initial dose continued till the end of the second week for unrespondersin the first week unlike higher doses for the second week in the previous studies.Theobjective of this study is to evaluate the clinical efficacy and safety of differentprotocols of prednisone combined with topiramate (TPM) in the treatment of IS, andto provide a new choice of the therapy of IS.Methods: Sixty cases were collected and divided into test and control groups.The control group took prednisone tablet of40mg a day for2weeks.and the testgroup also took prednisone tablet of40mg a day for the first week,if spasms were outof control, the dose of prednisone increased to60mg a day for the second week, Inaddition, TPM was combined in both groups.Prednisone was then reduced by degreesuntil the withdrawal. The assessment of spasms seizure and video-electroencep-halogram (VEEG) monitoring including wake and sleep states were performedbefore treatment, after two weeks of therapy and the end of the courses respectively.And the side effects of the drugs during the treatment were also evaluated.TheGessel’s developmental quotient (DQ) tests were performed before treatment andafter six months of therapy. All patients have been followed-up for more than6months. Results:1、In the first week of therapy，the rate of cessation of spasms in the test groupwas50.00%(15/30),which was similar to46.47%(14/30) in the control group(2=0.067,P=0.796). For the cases without cessation of spasms in the first week oftherapy,the rate of spasms under control in test group at the end of the second weekwas46.47%(7/15),which was higher than31.25%(5/16) in controlgroup(P=0.473).And the rate of complete resolution of hypsarrhythmia in the testgroup was46.47%(7/15), which was also higher than25.00%(4/16) in control group(P=0.273). At the end of treatment, the rate of cessation of spasms in the test groupwas60.00%(9/15), which was higher than37.50%(6/16) in control group(P=0.289).And the rate of complete resolution of hypsarrhythmia in the test groupwas53.33%(8/15), which was also higher than37.50%(6/16) in control group(P=0.479). All the above showed no statistical difference.2、If the statistical analysis included all cases，at the end of2weeks of thetherapy, the rate of cessation of spasms in test group was73.33%(22/30), which wasthe same as63.33%(19/30) in control group (2=0.693,P=0.405). And the rate ofcomplete resolution of hypsarrhythmia in test group was70.00%, as resemble60.00%(18/30) in control group (2=0.659,P=0.589). At the end of treatment, the rateof cessation of spasms in test group was70.00%(21/30), like63.33%(19/30) incontrol group (2=0.300,P=0.785). And the rate of complete resolution ofhypsarrhythmia was63.33%(19/30) similar to60.00%(18/30) in control group(2=0.071,P=0.791).3、At the end of2weeks of the therapy,the rate of cessation of spasms of thecases with the course of less than2months was85.71%(18/21), which wassignificantly higher than44.44%(4/9) in the cases with the course of more than2months in test group (P=0.032). At the end of treatment, the rate of cessation ofspasms of the cases with the course of less than2months was85.71%(18/21), as issignificantly higher than33.33%(3/9) in the cases with the course of more than2months in test group (P=0.008). In the control group,the rate of cessation of spasmsof the cases with the course of the less than2months was80.00%(16/20), which wassignificantly higher than30.00%(3/10)(P=0.015). at the end of treatment,the rate of cessation of spasms of the course of less than2months was75.00%(15/20),as was40.00%(4/10)(P=0.108).4、The incidence of side effects were83.33%(25/30) and80.00%(24/30) in thetest group and hypsarhythmiarol group, respectively (2=0.111,P=0.739).Cushing andappetite increased were the most frequent side effects in our study.Nore children dropout from the study owing to the adverse events. Up to now, the recurrence rate of thetestrial group and the control group were39.14%(9/24) and40.00%(8/20), and therewere not statistically significances between two groups(2=0.003,P=0.954).5、At the end of2weeks of the therapy, Correlation analysis showed that therewas no obvious correlation between the rate of complete resolution of hypsarrhythmiaand the rate of cessation of spasms in both groups(rt=0.099,P=0.666;rc=0.376,P=0.063). However, at the end of treatment, the rate of complete resolution ofhypsarrhythmia was positive correlation with the cessation of spasms in two groups(rt=0.408,P=0.042;rc=0.649,P=0.001).Conclusions:1、 For the cases without cessation of spasms in the first week of therapy,the rateof spasms under control in test group was higher than in control group. the incidenceof side effects and the relapse rate in the both groups were similar. It is indicated thatthe protocols of the test group maybe better than that of the control group.2、The rate of cessation of spasms in the cases with the course of less than2months was significantly higher than that in the cases with the course of more than2months in both groups. It is suggested that early diagnosis and early treatment havean important influence on the prognosis of infantile spasms.3、Although the hypsarrhythmia EEG would be improved with the control of thespasms,there is a delayed effect between the two.