|
|
儿童癫痫停用抗发作药物的临床研究进展
|
Abstract:
本文深入探讨了儿童癫痫停药复发的相关研究现状。文章首先概述了癫痫在儿童中的发病率以及抗发作药物(ASMs)治疗的普遍性和局限性。重点分析了停药策略，包括无发作时间的确定、药物减量过程，以及单一药物与多药联合治疗的考量。进一步讨论了停药后复发的多种危险因素，如人口统计学因素、癫痫发作的严重程度、癫痫综合征、发作类型、病因、脑电图(EEG)异常、热性惊厥史和家族史，以及其他相关疾病或并发症。此外，综述了儿童癫痫复发预测模型的研究进展，评估了不同模型的贡献与局限性。最后，强调了停药后管理的重要性，包括随访策略和复发后的治疗调整。本综述旨在为临床医生提供停药决策的参考，并指出未来的研究方向，以优化停药策略，降低复发风险，改善患儿预后。
This article explores in depth the current research status of drug withdrawal recurrence in children with epilepsy. This article first summarized the incidence rate of epilepsy in children and the universality and limitations of antiseizure medications (ASMs) treatment. The key analysis focuses on the cessation strategy, including the determination of seizure-free time, the process of drug reduction, and the consideration of single-drug and multi-drug combination therapy. Further discussion was conducted on various risk factors for relapse after discontinuation of medication, such as demographic factors, severity of seizures, epilepsy syndrome, seizure type, etiology, abnormal electroencephalogram (EEG), history of febrile seizures and family history, as well as other related diseases or complications. In addition, the research progress of predictive models for childhood epilepsy recurrence was reviewed, and the contributions and limitations of different models were evaluated. Finally, the importance of post-discontinuation management was emphasized, including follow-up strategies and treatment adjustments after relapse. This review aims to provide clinical doctors with reference for drug discontinuation decisions and point out future research directions to optimize discontinuation strategies, reduce the risk of recurrence, and improve the prognosis of pediatric patients.
| [1] | Fisher, R.S., Acevedo, C., Arzimanoglou, A., Bogacz, A., Cross, J.H., Elger, C.E., et al. (2014) ILAE Official Report: A Practical Clinical Definition of Epilepsy. Epilepsia, 55, 475-482. https://doi.org/10.1111/epi.12550 |
| [2] | Shorvon, S.D. and Goodridge, D.M.G. (2013) Longitudinal Cohort Studies of the Prognosis of Epilepsy: Contribution of the National General Practice Study of Epilepsy and Other Studies. Brain, 136, 3497-3510. https://doi.org/10.1093/brain/awt223 |
| [3] | Baker, G.A., Jacoby, A., Buck, D., Stalgis, C. and Monnet, D. (1997) Quality of Life of People with Epilepsy: A European Study. Epilepsia, 38, 353-362. https://doi.org/10.1111/j.1528-1157.1997.tb01128.x |
| [4] | Perucca, P., Carter, J., Vahle, V. and Gilliam, F.G. (2009) Adverse Antiepileptic Drug Effects. Neurology, 72, 1223-1229. https://doi.org/10.1212/01.wnl.0000345667.45642.61 |
| [5] | Gloss, D., Pargeon, K., Pack, A., Varma, J., French, J.A., Tolchin, B., et al. (2021) Antiseizure Medication Withdrawal in Seizure-Free Patients: Practice Advisory Update Summary. Neurology, 97, 1072-1081. https://doi.org/10.1212/wnl.0000000000012944 |
| [6] | Strozzi, I., Nolan, S.J., Sperling, M.R., Wingerchuk, D.M. and Sirven, J. (2015) Early versus Late Antiepileptic Drug Withdrawal for People with Epilepsy in Remission. Cochrane Database of Systematic Reviews, 2015, CD001902. https://doi.org/10.1002/14651858.cd001902.pub2 |
| [7] | 王萍, 虞培敏, 洪震. 使用抗癫痫药患者的撤药问题[J]. 上海医药, 2015, 36(9): 16-20. |
| [8] | 马融, 范家应. 儿童癫痫“撤停药方案”的临床研究[J]. 中国中西医结合儿科学, 2019, 11(3): 185-187. |
| [9] | 周晓华, 林广裕. 儿童癫痫撤药的研究进展[J]. 汕头大学医学院学报, 2022, 35(1): 62-64. |
| [10] | 董维佳. 259例癫痫患者药物控制3年无发作后复发的因素分析[D]: [硕士学位论文]. 太原: 山西医科大学, 2012. |
| [11] | Ramos-Lizana, J., Aguirre-Rodríguez, J., Aguilera-López, P. and Cassinello-García, E. (2010) Recurrence Risk after Withdrawal of Antiepileptic Drugs in Children with Epilepsy: A Prospective Study. European Journal of Paediatric Neurology, 14, 116-124. https://doi.org/10.1016/j.ejpn.2009.05.006 |
| [12] | Incecik, F., Herguner, O., Altunbasak, S., Mert, G. and Kiris, N. (2014) Risk of Recurrence after Discontinuation of Antiepileptic Drug Therapy in Children with Epilepsy. Journal of Pediatric Neurosciences, 9, 100-104. https://doi.org/10.4103/1817-1745.139262 |
| [13] | Tennison, M., Greenwood, R., Lewis, D. and Thorn, M. (1994) Discontinuing Antiepileptic Drugs in Children with Epilepsy: A Comparison of a Six-Week and a Nine-Month Taper Period. New England Journal of Medicine, 330, 1407-1410. https://doi.org/10.1056/nejm199405193302002 |
| [14] | Serra, J.G., Montenegro, M.A. and Guerreiro, M.M. (2005) Antiepileptic Drug Withdrawal in Childhood: Does the Duration of Tapering off Matter for Seizure Recurrence? Journal of Child Neurology, 20, 624-626. https://doi.org/10.1177/08830738050200071901 |
| [15] | Ayuga Loro, F., Gisbert Tijeras, E. and Brigo, F. (2022) Rapid versus Slow Withdrawal of Antiepileptic Drugs. Cochrane Database of Systematic Reviews, 2022, CD005003. https://doi.org/10.1002/14651858.cd005003.pub4 |
| [16] | Altunbasak, S., Artar, Ö., Burgut, R. and Yildiztas, D. (1999) Relapse Risk Analysis after Drug Withdrawal in Epileptic Children with Uncomplicated Seizures. Seizure, 8, 384-389. https://doi.org/10.1053/seiz.1999.0330 |
| [17] | Smith, R.L. (2006) Withdrawing Antiepileptic Drugs from Seizure-Free Children. Australian Prescriber, 29, 18-21. https://doi.org/10.18773/austprescr.2006.010 |
| [18] | 蒋颖, 狄晴. 癫患者撤药的研究现状[J]. 临床神经病学杂志, 2010, 23(3): 232-234. |
| [19] | Vurucu, S., Saldir, M., Unay, B. and Akin, R. (2010) Determination of Risk Factors Associated with Seizure Relapse after Antiepileptic Drug Withdrawal. Open Medicine, 5, 251-256. https://doi.org/10.2478/s11536-009-0049-y |
| [20] | Lee, I., Li, S. and Chen, Y. (2017) Seizure Recurrence in Children after Stopping Antiepileptic Medication: 5-Year Follow-Up. Pediatrics & Neonatology, 58, 338-343. https://doi.org/10.1016/j.pedneo.2016.08.005 |
| [21] | Holmes, G.L. (1991) The Long-Term Effects of Seizures on the Developing Brain: Clinical and Laboratory Issues. Brain and Development, 13, 393-409. https://doi.org/10.1016/s0387-7604(12)80037-4 |
| [22] | Lamberink, H.J., Otte, W.M., Geerts, A.T., Pavlovic, M., Ramos-Lizana, J., Marson, A.G., et al. (2017) Individualised Prediction Model of Seizure Recurrence and Long-Term Outcomes after Withdrawal of Antiepileptic Drugs in Seizure-Free Patients: A Systematic Review and Individual Participant Data Meta-Analysis. The Lancet Neurology, 16, 523-531. https://doi.org/10.1016/s1474-4422(17)30114-x |
| [23] | Andersson, T., Braathen, G., Persson, A. and Theorell, K. (1997) A Comparison between One and Three Years of Treatment in Uncomplicated Childhood Epilepsy: A Prospective Study. II. the EEG as Predictor of Outcome after Withdrawal of Treatment. Epilepsia, 38, 225-232. https://doi.org/10.1111/j.1528-1157.1997.tb01101.x |
| [24] | Dooley, J., Gordon, K., Camfield, P., Camfield, C. and Smith, E. (1996) Discontinuation of Anticonvulsant Therapy in Children Free of Seizures for 1 Year. Neurology, 46, 969-974. https://doi.org/10.1212/wnl.46.4.969 |
| [25] | Stevelink, R., Al-Toma, D., Jansen, F.E., Lamberink, H.J., Asadi-Pooya, A.A., Farazdaghi, M., et al. (2022) Individualised Prediction of Drug Resistance and Seizure Recurrence after Medication Withdrawal in People with Juvenile Myoclonic Epilepsy: A Systematic Review and Individual Participant Data Meta-Analysis. eClinicalMedicine, 53, Article ID: 101732. https://doi.org/10.1016/j.eclinm.2022.101732 |
| [26] | 陈宏杏, 刘安祥, 徐祖才, 等. 癫痫患者撤药方法的研究进展[J]. 医学综述, 2021, 27(11): 2168-2172. |
| [27] | Gherpelli, J.L.D., Kok, F., Forno, S.D., Elkis, L.C., Lefevre, B.H.W. and Diament, A.J. (1992) Discontinuing Medication in Epileptic Children: A Study of Risk Factors Related to Recurrence. Epilepsia, 33, 681-686. https://doi.org/10.1111/j.1528-1157.1992.tb02347.x |
| [28] | Zhao, Y., Ding, H., Zhao, X., Qiu, X. and Li, B. (2023) Risk Factors of Recurrence after Drug Withdrawal in Children with Epilepsy. Frontiers in Neurology, 14, Article 1122827. https://doi.org/10.3389/fneur.2023.1122827 |
| [29] | Scheffer, I.E., Berkovic, S., Capovilla, G., Connolly, M.B., French, J., Guilhoto, L., et al. (2017) ILAE Classification of the Epilepsies: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia, 58, 512-521. https://doi.org/10.1111/epi.13709 |
| [30] | Kanner, A.M., Ashman, E., Gloss, D., Harden, C., Bourgeois, B., Bautista, J.F., et al. (2018) Practice Guideline Update Summary: Efficacy and Tolerability of the New Antiepileptic Drugs I: Treatment of New-Onset Epilepsy. Neurology, 91, 74-81. https://doi.org/10.1212/wnl.0000000000005755 |
| [31] | 李亚东, 马融. 癫痫撤药的研究进展[J]. 中医儿科杂志, 2015, 11(3): 85-88. |
| [32] | Odero, N., Oyieke, K., Gwer, S. and Samia, P. (2023) Risk Factors for Seizure Recurrence after Initial Withdrawal of Anti-Seizure Medications in Children with Epilepsy at Aga Khan University Hospital, Nairobi, Kenya. Epilepsy & Behavior Reports, 22, Article 100596. https://doi.org/10.1016/j.ebr.2023.100596 |
| [33] | Kanmaz, S., Toprak, D.E., Olculu, C.B., Dokurel, I., Simsek, E., Serin, H.M., et al. (2023) What Are the Predominant Predictors of Seizure Relapse Following Discontinuation of Anti-Seizure Medication in Epileptic Children? Epileptic Disorders, 25, 218-228. https://doi.org/10.1002/epd2.20019 |
| [34] | Matricardi, M., Brinciotti, M. and Benedetti, P. (1989) Outcome after Discontinuation of Antiepileptic Drug Therapy in Children with Epilepsy. Epilepsia, 30, 582-589. https://doi.org/10.1111/j.1528-1157.1989.tb05476.x |
| [35] | Schachter, S.C. (2018) Determining When to Stop Antiepileptic Drug Treatment. Current Opinion in Neurology, 31, 211-215. https://doi.org/10.1097/wco.0000000000000530 |
| [36] | Verrotti, A., Trotta, D., Salladini, C., Morgese, G. and Chiarelli, F. (2003) Risk Factors for Recurrence of Epilepsy and Withdrawal of Antiepileptic Therapy: A Practical Approach. Annals of Medicine, 35, 207-215. https://doi.org/10.1080/07853890310008260 |
| [37] | Berg, A.T. and Shinnar, S. (1994) Relapse Following Discontinuation of Antiepileptic Drugs. Neurology, 44, 601-608. https://doi.org/10.1212/wnl.44.4.601 |
| [38] | 齐自娟, 黎振声, 董李, 等. 抗癫痫药物减停及停药后癫痫复发风险的研究进展[J]. 解放军医学院学报, 2021, 42(9): 983-987. |
| [39] | Shinnar, S., Berg, A.T., Moshé, S.L., Kang, H., O'Dell, C., Alemany, M., et al. (1994) Discontinuing Antiepileptic Drugs in Children with Epilepsy: A Prospective Study. Annals of Neurology, 35, 534-545. https://doi.org/10.1002/ana.410350506 |
| [40] | Vestergaard, M., Pedersen, C.B., Sidenius, P., Olsen, J. and Christensen, J. (2007) The Long-Term Risk of Epilepsy after Febrile Seizures in Susceptible Subgroups. American Journal of Epidemiology, 165, 911-918. https://doi.org/10.1093/aje/kwk086 |
| [41] | Rheims, S. and Auvin, S. (2021) Attention Deficit/hyperactivity Disorder and Epilepsy. Current Opinion in Neurology, 34, 219-225. https://doi.org/10.1097/wco.0000000000000903 |
| [42] | Strasser, L., Downes, M., Kung, J., Cross, J.H. and De Haan, M. (2017) Prevalence and Risk Factors for Autism Spectrum Disorder in Epilepsy: A Systematic Review and Meta-Analysis. Developmental Medicine & Child Neurology, 60, 19-29. https://doi.org/10.1111/dmcn.13598 |
| [43] | Braathen, G. and Melander, H. (1997) Early Discontinuation of Treatment in Children with Uncomplicated Epilepsy: A Prospective Study with a Model for Prediction of Outcome. Epilepsia, 38, 561-569. https://doi.org/10.1111/j.1528-1157.1997.tb01141.x |
| [44] | Geerts, A.T., Niermeijer, J.M.F., Peters, A.C.B., Arts, W.F.M., Brouwer, O.F., Stroink, H., et al. (2005) Four-Year Outcome after Early Withdrawal of Antiepileptic Drugs in Childhood Epilepsy. Neurology, 64, 2136-2138. https://doi.org/10.1212/01.wnl.0000166035.26217.61 |
| [45] | Contento, M., Bertaccini, B., Biggi, M., Magliani, M., Failli, Y., Rosati, E., et al. (2021) Prediction of Seizure Recurrence Risk Following Discontinuation of Antiepileptic Drugs. Epilepsia, 62, 2159-2170. https://doi.org/10.1111/epi.16993 |
| [46] | 李娥, 王亚超, 杜文娟, 等. 优质护理对改善癫痫患儿治疗效果的研究[J]. 国际精神病学杂志, 2016, 43(2): 358-360+363. |
| [47] | 屈会霞, 朱彩华. 小儿癫痫停用抗癫痫药物后复发因素分析[J]. 儿科药学杂志, 2019, 25(5): 22-24. |
| [48] | 王艳. 癫痫患儿的优质护理[J]. 临床医药文献电子杂志, 2019, 6(60): 144. |
| [49] | Goh, S.L., Harding, K.E., Lewis, A.K., Taylor, N.F. and Carney, P.W. (2024) Self-Management Strategies for People with Epilepsy: An Overview of Reviews. Epilepsy & Behavior, 150, Article 109569. https://doi.org/10.1016/j.yebeh.2023.109569 |
| [50] | Sillanpää, M. and Schmidt, D. (2006) Prognosis of Seizure Recurrence after Stopping Antiepileptic Drugs in Seizure-Free Patients: A Long-Term Population-Based Study of Childhood-Onset Epilepsy. Epilepsy & Behavior, 8, 713-719. https://doi.org/10.1016/j.yebeh.2006.02.014 |
| [51] | Marson, A.G., Al-Kharusi, A.M., Alwaidh, M., Appleton, R., Baker, G.A., Chadwick, D.W., et al. (2007) The SANAD Study of Effectiveness of Valproate, Lamotrigine, or Topiramate for Generalised and Unclassifiable Epilepsy: An Unblinded Randomised Controlled Trial. The Lancet, 369, 1016-1026. https://doi.org/10.1016/s0140-6736(07)60461-9 |
| [52] | 徐寿成, 狄晴. 癫痫患者撤药及撤药后复发的研究进展[J]. 临床神经病学杂志, 2021, 34(2): 153-157. |
| [53] | Armijo Simón, J.A. and Adín Ibarra, J. (2000) Bases farmacológicas de la retirada de antiepilépticos. Revista de Neurología, 30, 336-350. https://doi.org/10.33588/rn.3004.99437 |
| [54] | Schulze-Bonhage, A. and Elger, C.E. (1997) Reply. Epilepsia, 38, 1155-1155. https://doi.org/10.1111/j.1528-1157.1997.tb01209.x |
| [55] | Marson, A., Jacoby, A., Johnson, A., Kim, L., Gamble, C. and Chadwick, D. (2005) Immediate versus Deferred Antiepileptic Drug Treatment for Early Epilepsy and Single Seizures: A Randomised Controlled Trial. The Lancet, 365, 2007-2013. https://doi.org/10.1016/s0140-6736(05)66694-9 |
| [56] | Takami, Y. and Nakagawa, T. (2021) Risk of Seizure Recurrence after a First Unprovoked Seizure in Childhood. Brain and Development, 43, 843-850. https://doi.org/10.1016/j.braindev.2021.04.005 |
| [57] | Kwan, P. and Brodie, M.J. (2000) Early Identification of Refractory Epilepsy. New England Journal of Medicine, 342, 314-319. https://doi.org/10.1056/nejm200002033420503 |
| [58] | Camfield, C.S. and Camfield, P.R. (2007) Long-Term Social Outcomes for Children with Epilepsy. Epilepsia, 48, 3-5. https://doi.org/10.1111/j.1528-1167.2007.01390.x |
| [59] | Huo, Q., Luo, X., Xu, Z. and Yang, X. (2024) Machine Learning Applied to Epilepsy: Bibliometric and Visual Analysis from 2004 to 2023. Frontiers in Neurology, 15, Article 1374443. https://doi.org/10.3389/fneur.2024.1374443 |
