Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Efficacy of levetiracetam in refractory childhood epilepsy

난치성 소아 간질에서 levetiracetam의 효과

  • Lee, Keon-Su (Institute for Brain Research, Chungnam National University, Department of Pediatrics, College of Medicine, Chungnam National University) ;
  • Kang, Joon-Won (Institute for Brain Research, Chungnam National University, Department of Pediatrics, College of Medicine, Chungnam National University)
  • 이건수 (충남대학교 의학전문대학원 소아과학교실, 뇌과학연구소) ;
  • 강준원 (충남대학교 의학전문대학원 소아과학교실, 뇌과학연구소)
  • Received : 2009.09.25
  • Accepted : 2010.02.15
  • Published : 2010.04.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : To evaluate the efficacy and safety of levetiracetam adjunctive therapy for reducing the rate of seizure frequency in children with intractable pediatric epilepsy. Methods : We reviewed the medical records of 86 patients with intractable pediatric epilepsy who visited our hospital between March 1989 and February 2009. Levetiracetam was included in the previous anticonvulsant regimen for at least 6 months and the reduction in the rate of seizure frequency was determined in follow-up examinations. We analyzed demographic data, seizure types, antiepileptic drug history, levetiracetam dose, adverse effects of levetiracetam therapy, treatment outcome, electroencephalogram findings, etc. Results : More than 50% reduction in the seizure frequency was observed in 62 of the 86 (72.1%) patients; 44 patients (51.1%) became seizure free, while the seizure frequency increased in 5.8% patients. The associations between seizure reduction rate and age, associated diseases, seizure types, and seizure frequency before treatment were not significant. However, the duration of disease, dose of levetiracetam, duration and frequency of anticonvulsant administration before levetiracetam therapy were significantly correlated. Electroencephalogram findings and the cause of epilepsy showed partial correlation. Forty (46%) patients showed adverse symptoms; the symptoms in the order of their frequency were somnolence, hyperactivity, irritability, aggressiveness, tiredness, etc. Conclusion : The findings of our study provide the evidence that levetiracetam adjunctive therapy is efficacious and well tolerated in various refractory childhood epilepsy cases.

목 적: 간질 환자의 20-30%는 난치성 간질로 알려졌는데, 기존의 항경련제나 새로운 항경련제에 반응하지 않는 난치성 간질환자에게 LEV를 부가요법으로 투여 후 효과와 부작용을 알아보고자 본 연구를 시행하였다. 방 법: 1989년 3월부터 2009년 3월까지 충남대학교병원 소아청소년과를 방문하여 난치성 간질로 진단받은 환자 중 6개월 이상 추적 관찰한 86명을 대상으로, LEV 투여 전 6개월간의 평균 경련 횟수를 기준으로 LEV외에 다른 항경련제를 추가하기 전까지의 평균 경련 감소 정도를 백분율로 분석하였다. 결 과: 86명의 환자 중 남자는 47명, 여자는 39명이었고, 발작 소실은 86명 중 44명(51.1%), 50% 이상 발작 감소는 86명 중 62명(72.1%)이었고, 19.8%는 변화가 없었으며, 5.8%는 발작이 증가했다. 나이, 동반질환, 발작형 및 치료 전 6개월간 발작 횟수는 발작 소실이나 50% 이상 발작 감소율과 관계가 없었다. 통계적으로 의미 있는 발작 소실과 50% 이상 발작 감소를 보인 경우는, 질병기간, LEV 투여 전 치료기간, LEV의 용량과 치료 전 사용한 항경련제의 숫자였으며, LEV 치료 기간과 뇌파는 발작 소실에만 의의가 있었고, 원인은 50% 이상 감소율에만 의의가 있었다. 부작용은 86명 중 40명(46%)에서 나타났고, 부작용은 기면, 과잉 행동, 과민성, 공격성, 피로 등이었으며, 대부분 일시적이거나 경미하여 치료 도중 소실되었다. 결 론: 난치성 소아 간질의 치료에 LEV의 부가 요법은 부분 발작뿐만 아니라 전신발작에도 효과와 반응이 좋고, 심각한 부작용도 없었다.

Keywords

References

  1. Berg AT, Kelly MM. Defining intractability: comparisons among published definitions. Epilepsia 2006;47:431-6. https://doi.org/10.1111/j.1528-1167.2006.00440.x
  2. Shorvon SD. Medical assesment and treatment of chronic epilepsy. BMJ 1991;302:363-6. https://doi.org/10.1136/bmj.302.6773.363
  3. Vigevano F. Levetiracetam in pediatrics. J Child Neurol 2005; 20:87-93. https://doi.org/10.1177/08830738050200020101
  4. Glauser TA, Ayala R, Elterman RD, Mitchell WG, Van Orman CB, Glauer LJ, et al. Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology 2006;66:1654-60. https://doi.org/10.1212/01.wnl.0000217916.00225.3a
  5. Lynch BA, Lambeng N, Nocka K. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA 2004;101:9861-6. https://doi.org/10.1073/pnas.0308208101
  6. Vaisleib II, Neft RA. Rapid dosge titration of levetiracetam in children. Pharmacotherapy 2008;28:393-6. https://doi.org/10.1592/phco.28.3.393
  7. Park JS, Kang HC, You SJ. Clinical experience with levetiracetam adjunctive therapy for pediatric intractable epilepsy. J Korean Child Neurol Soc 2008;16:36-41.
  8. Radtke RA. Pharmacokinetics of levetiracetam. Epilepsia. 2001;42;24-7.
  9. Otoul C, Smedt HD, Stockis A. Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy. Epilepsia 2007;48:2111-5. https://doi.org/10.1111/j.1528-1167.2007.01201.x
  10. Glauser TA, Mitchell WG, Weinstock A, Bebin M, Chen D, Coupez R, et al. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia 2007;48:1117- 22. https://doi.org/10.1111/j.1528-1167.2007.01090.x
  11. Pellock JM, Glauser TA, Bebin EM. Pharmacokinetic study of levetiracetam in children. Epilepsia 2001;42:1574-9.
  12. Goraya JS, Khurana DS, Valencia I, Melvin JJ, Cruz M, Legido A, et al. Intravenous levetiracetam in children with epilepsy. Pediatr Neurol 2008;38;177-80. https://doi.org/10.1016/j.pediatrneurol.2007.11.003
  13. Perry MS, Benatar M. Efficacy and tolerability of levetiracetam in children younger than 4 years: A retrospective review. Epilepsia 2007;48:1123-7. https://doi.org/10.1111/j.1528-1167.2007.01003.x
  14. Pina-Garza JE, Nordli DR, Rating D, Yang H, Jimmy SD, Duncan B, et al. Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures. Epilepsia 2009;50:1141-9. https://doi.org/10.1111/j.1528-1167.2008.01981.x
  15. Coppola G, Mangano S, Tortorella G, Pelliccia A, Fels A, Romano A, et al. Levetiracetam during 1-year follow-up in children, adolescents, and young adults with refractory epilepsy. Epilepsy Res 2004;59:35-42. https://doi.org/10.1016/j.eplepsyres.2004.03.006
  16. Opp J, Tuxhorn I, May T, Kluger G, Wiemer-Kruel A, Kurlemann G, et al. Levetiracetam in children with refractory epilepsy: A multicenter open label study in Germany. Seizure 2005;14:476-84. https://doi.org/10.1016/j.seizure.2005.08.002
  17. Grosso S, Cordelli DM, Franzoni E, Coppola G, Capovilla G, Zamponi N, et al. Efficacy and safty of levetiracetam in infants and young children with refractory epilepsy. Seizure 2007;16:345-50. https://doi.org/10.1016/j.seizure.2007.02.004
  18. Lagae L, Buyse G, Ceulemans B. Clinical experience with levetiracetam in childhood epilepsy: an add-on and monotherapy trial. Seizure 2005;14:66-71. https://doi.org/10.1016/j.seizure.2004.10.004
  19. Bourgeois BFD, Holder DL, Valencia I. Open-label assesment of levetiracetam efficacy and adverse effects in a pediatric population. Epilepsia 2001;42:53-4.
  20. Glauser TA, Pellock JM, Bebin EM. Efficacy and safty of levetiracetam in children with partial seizures: An open-lavel trial. Epilepsia 2002;43:518-24. https://doi.org/10.1046/j.1528-1157.2002.13101.x
  21. Kossoff EH, Los JG, Boatman DF. A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy. Epilepsy & Behavior 2007;11:514-7. https://doi.org/10.1016/j.yebeh.2007.07.011
  22. Berkovic SF, Knowlton RC, Leroy RF, Schiemann J, Falter U. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology 2007;69:1751-60.
  23. Striano P, Coppola A, Pezzella M, Ciampa C, Specchio N, Ragona F, et al. An open-label trial of levetiracetam in severe myoclonic epilepsy of infancy. Neurology 2007;69:250- 4. https://doi.org/10.1212/01.wnl.0000265222.24102.db
  24. Verrotti A, Cerminara C, Coppola G, Franzoni E, Parisi P, Iannetti P, et al. Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents. Developmental medicine & child neurology 2008;50:29-32.
  25. Mikati MA, Banna DEI, Sinno D, Mroueh S. Response of infantile spasms to levetiracetam. Neurology 2008;70:574-5. https://doi.org/10.1212/01.wnl.0000279379.32754.8b
  26. Barron TF, Faircloth VC, Yuncker LA, Hunt SL. Levetiracetam adjunctive therapy for refractory pediatric generalized epilepsies. Epilepsia 2001;42(7 Suppl):S53.
  27. Buyse G, Ceulemans B, Lagae L. Add-on levetiracetam on refractory generalized childhood epilepsy syndromes. Epilepsia 2002;43(8 Suppl):S154. https://doi.org/10.1046/j.1528-1157.2002.25001.x
  28. Berg J, Wruk M, Baeumel C, Kluger G, Holthausen H. Addon therapy with levetiracetam in difficult-to-treat, idiopathic focal epilepsies of childhood. Epilepsia 2003;44(8 Suppl):S79. https://doi.org/10.1046/j.1528-1157.44.s6.32.x