Predictors for seizure relapse in children with epilepsy after antiepileptic drug withdrawal: case-control study

  • Agung Triono RSUP Dr. Sardjito/FKKMK UGM
  • Elisabeth Siti Herini Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia https://orcid.org/0000-0003-2571-8310
  • Irawan Mangunatmaja Faculty of Medicine, Public Health and Nursing, Universitas of Indonesia, Jakarta, Indonesia
Keywords: children, epilepsy, predictor, seizure, relapse

Abstract

Background Epilepsy is defined as a neurologic condition  caused by a pathological brain condition. Epilepsy patients who have stopped treatment and are seizure-free for two years are considered to have achieved complete remission. Relapse occurs when seizures return after anti-epileptic drug (AED) withdrawal. Several studies reported that frequent seizures, prolonged duration to control seizures, number of AEDs consumed, and abnormal electroencephalography (EEG) found during AEDs tapered, were reported as predictors of relapse.

Methods This retrospective, case-control study was carried out from 2012 – 2016 using multisite medical record evaluation, followed by interviews and EEG examinations. The case group included children with epilepsy who had seizure relapse, while the control group included children with complete remission of epilepsy. Bivariate and multivariate analyses were performed to identify predictors of relapse.

Results Relapse predictors in bivariate analysis were symptomatic etiology epilepsy (OR 5.000; 95%CI 2.345 to 10.660; P<0.001), time to seizure control ?1 year (OR 3.689; 95%CI 1.493 to 9.116; P=0.003), and worsened EEG evolution at pre-withdrawal compared to EEG at the time of diagnosis (OR 2.310; 95%CI 1.132 to 4.717; P=0.021). Statistically significant relapse predictors in multivariate analysis were symptomatic etiology epilepsy (OR 4.384; 95%CI 1.985 to 9.681; P<0.001) and slow (?1 year) time to seizure control (OR 4.355; 95%CI 1.753  to 10.817; P 0.002).

Conclusion Symptomatic etiology epilepsy and time to seizure control ?1 year are independent predictive factors for seizure relapse in children with epilepsy. Therefore, children with these conditions require a longer period and careful, gradual dose reduction before antiepileptic drugs withdrawal.

Author Biographies

Elisabeth Siti Herini, Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia

Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia

Irawan Mangunatmaja, Faculty of Medicine, Public Health and Nursing, Universitas of Indonesia, Jakarta, Indonesia

Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas of Indonesia, Jakarta, Indonesia

References

1. Browne TR, Holmes GL. Handbook of Epilepsy. 4th edition. Philadelphia: Lippincott Williams & Wilkins; 2008. p. 278.
2. Panayiotopoulos C. The Epilepsies [Internet]. Bladon Medical Publishing; 2005. [cited 2022 Aug 19]. Available from: www.ncbi.nlm.nih.gov/books/NBK2606/
3. WHO. Epilepsy [Internet]. [cited 2022 Aug 19]. Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy
4. Mlinar S, Petek D, Coti? Ž, Mencin ?eplak M, Zaletel M. Persons with Epilepsy: Between Social Inclusion and Marginalisation. Behav Neurol. 2016;2016:2018509. DOI: https://doi.org/ 10.1155/2016/2018509
5. Pavlovi? M, Jovi? N, Pekmezovi? T. Antiepileptic drugs withdrawal in patients with idiopathic generalized epilepsy. Seizure. 2011 ;20:520–5. DOI: 10.1016/j.seizure.2011.03.007
6. Loy-Gerala MDC, Ibarra-Bravo OM, Márquez-Estudillo MDR, Mena-Barranco F, Rogel-Ortiz FJ, Silva-Sánchez SE, et al. Clinical guide: discontinuing chronic antiepileptic drug treatment. Rev Mex Neurocienc. 2019;20:123-8.DOI: http://dx.doi.org/10.24875/RMN.M19000033
7. Shinnar S, Berg AT, Moshé SL, Kang H, O’Dell C, Alemany M, et al. Discontinuing antiepileptic drugs in children with epilepsy: A prospective study. Ann Neurol. 1994;35:534–45. DOI: 10.1002/ana.410350506
8. Verrotti A, D’Egidio C, Agostinelli S, Parisi P, Spalice A, Chiarelli F, et al. Antiepileptic drug withdrawal in childhood epilepsy: What are the risk factors associated with seizure relapse? Eur J Paediatr Neurol. 2012;16:599–604. DOI: 10.1016/j.ejpn.2012.02.002
9. Contento M, Bertaccini B, Biggi M, Magliani M, Failli Y, Rosati E, et al. Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs. Epilepsia. 2021 ;62:2159–70. DOI: 10.1111/epi.16993
10. Specchio LM, Beghi E. Should Antiepileptic Drugs Be Withdrawn in Seizure-Free Patients? CNS Drugs. 2004;18:201–12. DOI: 10.4045/tidsskr.16.0957
11. Beghi E, Giussani G, Grosso S, Iudice A, La Neve A, Pisani F, et al. Withdrawal of antiepileptic drugs: Guidelines of the Italian League Against Epilepsy. Epilepsia. 2013;54:2–12. DOI: 10.1111/epi.12305
12. Braathen G, Melander H. Early discontinuation of treatment in children with uncomplicated epilepsy: A prospective study with a model for prediction of outcome. Epilepsia. 1997;38:561–9. DOI: https://doi.org/10.1111/j.1528-1157.1997.tb01141.x
13. Hawash KY, Rosman NP. Do Partial Seizures Predict an Increased Risk of Seizure Recurrence After Antiepilepsy Drugs Are Withdrawn? J Child Neurol. 2003 ;18:331–7. DOI: 10.1177/08830738030180050601
14. Callaghan B, Schlesinger M, Rodemer W, Pollard J, Hesdorffer D, Allen Hauser W, et al. Remission and relapse in a drug-resistant epilepsy population followed prospectively: Drug-Resistant Epilepsy Population. Epilepsia. 2011;52:619–26. DOI: 10.1111/j.1528-1167.2010.02929.x
15. Yang H, Zhang J, Yang C, Wu D, Liu X, Lu H, et al. The long-term prognosis and predictors of epilepsy: a retrospective study in 820 patients. Acta Epileptol. 2021 ;3:26. DOI: https://doi.org/10.1186/s42494-021-00060-2
16. Mangunatmadja I. Prediksi luaran klinis pasien epilepsi fokal berusia kurang dari 3 tahun: peran evolusi klinis dan elektroensefalografi serta magnetic resonance imaging = Prediction of clinical outcome of patients below 3 years of age with focal epilepsy: the role of clinical and electroencephalographical evolution and magnetic resonance imaging. [Internet]. [cited 2022 July 21]. 2012. Available from: //perpustakaan.fk.ui.ac.id%2Fnew-opac%2Findex.php%3Fp%3Dshow_detail%26id%3D15102
17. Olmez A, Arslan U, Turanli G, Aysun S. Risk of recurrence after drug withdrawal in childhood epilepsy. Seizure. 2009;18:251–6. DOI: 10.1016/j.seizure.2008.10.011
18. Zhao Y, Ding H, Zhao X, Qiu X, Li B. Risk factors of recurrence after drug withdrawal in children with epilepsy. Front Neurol. 2023;14:1122827. DOI: 10.3389/fneur.2023.1122827
19. Remission of Seizures and Predictors of Intractability in Long?Term Follow?Up - Sillanpää - 1993 - Epilepsia - Wiley Online Library [Internet]. [cited 2022 Jul 25]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1528-1157.1993.tb02114.x?sid=nlm%3Apubmed
20. Ramos-Lizana J, Aguirre-Rodríguez J, Aguilera-López P, Cassinello-García E. Recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy: a prospective study. Eur J Paediatr Neurol. 2010;14:116-24. DOI: https://doi.org/10.1016/j.ejpn.2009.05.006. 21. Lacombe V, Mayes M, Mosseri S, Reed S, Ou T. Distribution and predictive factors of seizure types in 104 cases. Equine Vet J. 2014;46:441-5. DOI: 10.1111/evj.12149
22. Dooley J, Gordon K, Camfield P, Camfield C, Smith E. Discontinuation of anticonvulsant therapy in children free of seizures for 1 year: A prospective study. Neurology. 1996 ;46:969–74. DOI: 10.1212/wnl.46.4.969
23. Beydoun A, Passaro EA. Appropriate use of medications for seizures: Guiding principles on the path of efficacy. Postgrad Med. 2002;111:69–82. DOI: 10.3810/pgm.2002.01.1081
24. Rizvi S, Ladino LD, Hernandez-Ronquillo L, Téllez-Zenteno JF. Epidemiology of early stages of epilepsy: Risk of seizure recurrence after a first seizure. Seizure. 2017;49:46–53. DOI: 10.1016/j.seizure.2017.02.006
25. Thurston JH, Thurston DL, Hixon BB, Keller AJ. Prognosis in childhood epilepsy: additional follow-up of 148 children 15 to 23 years after withdrawal of anticonvulsant therapy. N Engl J Med. 1982;306:831–6. DOI: 10.1056/NEJM198204083061403
26. Holmes GL, Ben-Ari Y. The Neurobiology and Consequences of Epilepsy in the Developing Brain. Pediatr Res. 2001;49:320–5. DOI: 10.1203/00006450-200103000-00004
27. Shen Y, Gong Y, Ruan Y, Chen Z, Xu C. Secondary epileptogenesis: common to see, but possible to treat? Front Neurol. 2021;12:747372. DOI: 10.3389/fneur.2021.747372
28. Sadzot B. Epilepsy: a progressive disease? BMJ. 1997;314:391–391. DOI: 10.1136/bmj.314.7078.391
29. Berkovic SF, Mulley JC, Scheffer IE, Petrou S. Human epilepsies: interaction of genetic and acquired factors. Trends Neurosci. 2006;29:391–7. DOI: 10.1016/j.tins.2006.05.009
30. Andersson T, Braathen G, Persson A, Theorell K. 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. 1997;38:225–32. DOI: https://doi.org/10.1111/j.1528-1157.1997.tb01101.x
31. Marsan CA, Zivin LS. Factors Related to the Occurrence of Typical Paroxysmal Abnormalities in the EEG Records of Epileptic Patients. Epilepsia. 1970;11:361–81. DOI: 10.1111/j.1528-1157.1970.tb03903.x
Published
2024-03-04
How to Cite
1.
Triono A, Herini E, Mangunatmaja I. Predictors for seizure relapse in children with epilepsy after antiepileptic drug withdrawal: case-control study. PI [Internet]. 4Mar.2024 [cited 20May2024];64(2):120-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/3300
Section
Pediatric Neurology
Received 2023-01-03
Accepted 2024-03-04
Published 2024-03-04