소아 뇌전증 환자에서 항경련제 치료 후 재발의 위험인자
The Risk Factors for Relapse of Unprovoked Seizures after Drug Withdrawal in Epileptic Children
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
목적: 제주도에 거주하는 뇌전증 진단을 받은 소아 환자들을 대상으로 항경련제 치료 종결 후 발작의 재발에 영향을 미치는 예측 인자를 살펴보고자 하였다. 방법: 2001년 3월부터 2013년 5월까지 첫 발작으로 제주대학교 병원을 방문한 환자들을 연구 대상으로 하였다. 뇌자기공명영상이 정상이면서 마지막 경련으로부터 2년 이상 경과하고 치료 종결시 뇌파가정상인 환아들을 최종 연구 대상으로 하였다. 그리고 최소 관찰 기간1년 이상인 경우로 제한하였다. 결과: 재발은 전체 68명 중 23명에서 발생하여 치료 종결 후 1년 완치 비율은 66.2%였다. 치료 종결 후 재발 환자들의 평균 재발 간격은6.9±7.1개월이었다. 누적으로 계산시 항경련제 중단 도중 4명, 3개월이내 16.2% (11/68), 6개월 이내 19.1% (13/68), 1년 이내 86.9% (20/ 23), 19개월 1명, 22개월 1명, 24개월 1명으로 대부분의 재발은 1년 이내에 발생하였고 모든 환자는 2년 이내에 재발하였다. 재발에 영향을미치는 인자에 대한 단변량 분석에서 10세 이상에서 첫 발작 발생(P= 0.007), 후기 관해(P=0.020), 2년 이상 항경련제 치료(P=0.018), 복합열성발작(P=0.001)이 통계학적으로 의미있게 재발군에서 높은 빈도로 나타났다. 뇌전증 가족력(P=0.068)은 경계선상의 통계학적인 의미를 보였다. 다변량 분석 결과, 복합열성발작(P=0.009, odds ratio= 24.2, 95% CI 2.23-262.28), 10세 이상 첫 발작 발생(P=0.002, odds ratio= 16.7, 95% CI 2.76-101.31), 후기 관해(P=0.047, odds ratio=4.4, 95% CI 1.02-18.93)에서 뇌전증 환자의 치료 종결 후 재발에 영향을 미치는 인자로 확인되었다. 결론: 복합열성발작, 10세 이상 첫 발작 발생, 항경련제 치료 후 12 개월 이내 경련 조절 실패에 해당하는 변수가 뇌전증 환자의 치료 종결 후 재발에 영향을 미치는 독립 인자로 확인되었다.
Abstract
Purpose: We evaluated the risk factors for relapse of unprovoked seizures after drug withdrawal in epileptic children in Jeju Island, South Korea. Methods: A population-based retrospective study was performed in 632 children whose first unprovoked seizure occurred between March 2001 and May 2013. The study included children experiencing a seizure free-state during a minimum of 2- year treatment period with anti-epileptic drugs (AEDs) with at least 1-year follow-up after AED withdrawal at the Pediatric Department at the Jeju National University Hospital. Results: Sixty-eight children including 36 boys and 32 girls, met the above-mentioned inclusion criteria, and subsequent seizure relapse occurred in 23 patients (33.8%). The mean age at the first unprovoked seizure was 79.1±45.9 months and the mean number of unprovoked seizures was 7.1±4.9. Partial and generalized seizures were observed in 19 and 49 patients, respectively. Several variables such as the age at onset of the first seizure, late remission, duration of AED treatment longer than 2 years, and complex febrile seizures before the first unprovoked seizure affected the risk for relapse. Multivariate analysis identified complex febrile seizure, age at the first seizure onset being more than 10 years, and late remission as significant predictors of relapse. Conclusion: We identified three independent risk factors for relapse following an unprovoked seizure in epileptic children after AED withdrawal : complex febrile seizure, age at the first seizure onset being more than 10 years, and late remission.
참고문헌 (32)
- Altunbaşak S, "Relapse risk analysis after drug withdrawal in epileptic children with uncomplicated seizures", Seizure, 8, pp.384~389 (1999)
- Bouma PA, "Discontinuation of antiepileptic therapy: a prospective study in children", J Neurol Neurosurg Psychiatry, 50, pp.1579~1583 (1987)
- Serra JG, "Antiepileptic drug withdrawal in childhood: does the duration of tapering off matter for seizure recurrence?", J Child Neurol, 20, pp.624~626 (2005)
- Shinnar S, "Discontinuing antiepileptic drugs in children with epilepsy: a prospective study", Ann Neurol, 35, pp.534~545 (1994)
- Olmez A, "Risk of recurrence after drug withdrawal in childhood epilepsy", Seizure, 18, pp.251~256 (2009)
- Todt H., "The late prognosis of epilepsy in childhood: results of a prospective follow-up study", Epilepsia, 25, pp.137~144 (1984)
- Arts WF, "Follow-up of 146 children with epilepsy after withdrawal of antiepileptic therapy", Epilepsia, 29, pp.244~250 (1988)
- Verrotti, A, "Antiepileptic drug withdrawal in childhood epilepsy: what are the risk factors associated with seizure relapse?", Eur J Paediatr Neurol, 16, pp.599~604 (2012)
- Dooley J, "Discontinuation of anticonvulsant therapy in children free of seizures for 1 year: a prospective study", Neurology, 46, pp.969~974 (1996)
- Tennison M, "Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a six-week and a nine-month taper period", N Engl J Med, 330, pp.1407~1410 (1994)
- Camfield P, "The frequency of intractable seizures after stopping AEDs in seizure-free children with epilepsy", Neurology, 64, pp.973~975 (2005)
- Braathen G, "Early discontinuation of treatment in children with uncomplicated epilepsy: a prospective study with a model for prediction of outcome", Epilepsia, 38, pp.561~569 (1997)
- Ramos-Lizana J, "Recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy: a prospective study", Eur J Paediatr Neurol, 14, pp.116~124 (2010)
- 신원섭, "Natural History of Treated New-Onset Epilepsy in Children: A Long-term Follow-up Cohort Study in a Single Center", 대한소아신경학회지, 20(2), pp.98~107 (2012), 대한소아신경학회
- Pavlović M, "Antiepileptic drugs withdrawal in patients with idiopathic generalized epilepsy", Seizure, 20, pp.520~525 (2011)
- "Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy", Epilepsia, 22, pp.489~501 (1981)
- "Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy", Epilepsia, 30, pp.389~399 (1989)
- Peters AC, "Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy", Neurology, 50, pp.724~730 (1988)
- Gherpelli JL, "Discontinuing medication in epileptic children: a study of risk factors related to recurrence", Epilepsia, 33, pp.681~686 (1992)
- Berg AT, "Relapse following discontinuation of antiepileptic drugs: a meta-analysis", Neurology, 44, pp.601~608 (1994)
- Chadwick D, "Outcomes after seizure recurrence in people with well-controlled epilepsy and the factors that influence it", Epilepsia, 37, pp.1043~1050 (1996), The MRC Antiepileptic Drug Withdrawal Group
- Berg AT, "The course of childhood-onset epilepsy over the first two decades: a prospective, longitudinal study", Epilepsia, 56, pp.40~48 (2015)
- Peters AC, "Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy", Neurology, 50, pp.724~730 (1998)
- Mastropaolo C, "Prognosis after therapy discontinuation in children with epilepsy", Eur Neurol, 32, pp.141~145 (1992)
- Matricardi M, "Outcome after discontinuation of antiepileptic drug therapy in children with epilepsy", Epilepsia, 30, pp.582~589 (1989)
- Pavlović M, "Withdrawal of antiepileptic drugs in young patients with cryptogenic focal epilepsies", Seizure, 21, pp.431~436 (2012)
- Verrotti A, "Factors associated with relapse after antiepileptic drug withdrawal in a selected population with partial epilepsy", Dev Med Child Neurol, 41, pp.643~645 (1999)
- Arts WF, "Course and prognosis of childhood epilepsy: 5-year follow-up of the Dutch study of epilepsy in childhood", Brain, 127(8), pp.1774~1784 (2004)
- Overweg J., "Withdrawal of antiepileptic drugs(AEDs) in seizurefree patients, risk factors for relapse with special anttention for the EEG", Seizure, 4, pp.19~36 (1995)
- Grosso S, "Childhood absence epilepsy: evolution and prognostic factors", Epilepsia, 46, pp.1796~1801 (2005)
- Williams GW, "Interobserver variability in EEG interpretation", Neurology, 35, pp.f1714~1719 (1985)
- Hwang G, "Predictors of unprovoked seizure after febrile seizure: short-term outcomes", Brain Dev, 37, pp.315~321 (2015)