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Treatment Outcomes of Newly Diagnosed Epilepsy: A Systematic Review and Meta-analysis

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Abstract

Background and Objectives

Understanding the multi-faceted treatment outcomes of newly diagnosed epilepsy is critical for developing rational therapeutic strategies. A meta-analysis was conducted to derive pooled estimates of a range of seizure outcomes in children and adults with newly diagnosed epilepsy commenced on antiseizure medication treatment, and to identify factors associated with different outcomes.

Methods

PubMed/EMBASE were screened for eligible articles between 1 January, 1995 and 1 May, 2021 to include unselected cohort studies with a ≥ 12-month follow-up of seizure outcomes. Proportions of patients seizure free at different follow-up timepoints and their characteristics at the study population level were extracted. The patients were group-wise aggregated using a random-effects model. Primary outcomes were proportions of patients with cumulative 1-year seizure freedom (C1YSF), and 1-year and 5-year terminal seizure freedom (T1YSF and T5YSF). Secondary outcomes included the proportions of patients with early sustained seizure freedom, drug-resistant epilepsy and seizure-free off antiseizure medication at the last follow-up (off antiseizure medications). A separate random-effects meta-analysis was performed for nine predictors of importance.

Results

In total, 39 cohorts (total n = 21,139) met eligibility criteria. They included 15 predominantly adult cohorts (n = 12,024), 19 children (n = 6569), and 5 of mixed-age groups (n = 2546). The pooled C1YSF was 79% (95% confidence interval [CI] 74–83). T1YSF was 68% (95% CI 63–72) and T5YSF was 69% (95% CI 62–75). Children had higher C1YSF (85% vs 68%, p < 0.001) and T1YSF than adult cohorts (74% vs 61%, p = 0.007). For secondary outcomes, 33% (95% CI 27–39) of patients achieved early sustained seizure freedom, 17% (95% CI 13–21) developed drug resistance, and 39% (95% CI 30–50) were off antiseizure medications at the last follow-up. Studies with a longer follow-up duration correlated with higher C1YSF (p < 0.001) and being off antiseizure medications (p = 0.045). Outcomes were not associated with study design (prospective vs retrospective), cohort size, publication year, or the earliest date of recruitment. Predictors of importance in newly diagnosed epilepsy include etiology, epilepsy type, abnormal diagnostics (neuroimaging, examination, and electroencephalogram findings), number of seizure types, and pre-treatment seizure burden.

Conclusions

Seizure freedom is achieved with currently available antiseizure medications in most patients with newly diagnosed epilepsy, yet this is often not immediate, may not be sustainable, and has not improved over recent decades. Symptomatic etiology, abnormal neuro-diagnostics, and increased pre-treatment seizure burden and seizure types are important predictors for unfavorable outcomes in newly diagnosed epilepsy. The study findings may be used as a quantitative benchmark on the efficacy of future antiseizure medication therapy for this patient population.

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References

  1. Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon C-S, Dykeman J, et al. Prevalence and incidence of epilepsy. Neurology. 2017;88:296–303.

    Google Scholar 

  2. Simpson HD, Foster E, Ademi Z, Lawn N, Brodie MJ, Chen Z, et al. Markov modelling of treatment response in a 30-year cohort study of newly diagnosed epilepsy. Brain. 2022;145:1326–37.

    Google Scholar 

  3. Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75:279.

    Google Scholar 

  4. Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1016–26.

    CAS  Google Scholar 

  5. Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1000–15.

    CAS  Google Scholar 

  6. Sharma S, Chen Z, Rychkova M, Dunne J, Lee J, Lawn N, et al. Short- and long-term outcomes of immediate and delayed treatment in epilepsy diagnosed after one or multiple seizures. Epilepsy Behav. 2021;117: 107880.

    Google Scholar 

  7. Brodie MJ, Barry SJE, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78:1548–54.

    CAS  Google Scholar 

  8. Bell GS, Neligan A, Giavasi C, Keezer MR, Novy J, Peacock JL, et al. Outcome of seizures in the general population after 25 years: a prospective follow-up, observational cohort study. J Neurol Neurosurg Psychiatry. 2016;87:843–50.

    Google Scholar 

  9. Berg AT, Rychlik K. The course of childhood-onset epilepsy over the first two decades: a prospective, longitudinal study. Epilepsia. 2015;56:40–8.

    Google Scholar 

  10. Geerts A, Brouwer O, Stroink H, van Donselaar C, Peters B, Peeters E, et al. Onset of intractability and its course over time: the Dutch study of epilepsy in childhood. Epilepsia. 2012;53:741–51.

    Google Scholar 

  11. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–9.

    CAS  Google Scholar 

  12. Perucca E, Brodie MJ, Kwan P, Tomson T. 30 years of second-generation antiseizure medications: impact and future perspectives. Lancet Neurol. 2020;19:544–56.

    CAS  Google Scholar 

  13. Allers K, Essue BM, Hackett ML, Muhunthan J, Anderson CS, Pickles K, et al. The economic impact of epilepsy: a systematic review. BMC Neurol. 2015;15:245.

    Google Scholar 

  14. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies: definition of drug resistant epilepsy. Epilepsia. 2010;51:1069–77.

    CAS  Google Scholar 

  15. Bruun E, Kälviäinen R, Keränen T. Outcome of initial antiepileptic drug treatment in elderly patients with newly diagnosed epilepsy. Epilepsy Res. 2016;127:60–5.

    CAS  Google Scholar 

  16. Ashmawi A, Hosny H, Abdelalim A, Bianchi E, Beghi E. The long-term prognosis of newly diagnosed epilepsy in Egypt: a retrospective cohort study from an epilepsy center in Greater Cairo. Seizure. 2016;41:86–95.

    Google Scholar 

  17. Shackleton DP, Kasteleijn-Nolst Trenite DGA, de Craen AJM, Vandenbroucke JP, Westendorp RGJ. Living with epilepsy: long-term prognosis and psychosocial outcomes. Neurology. 2003;61:64–70.

    CAS  Google Scholar 

  18. Zhang Y, Yu N, Su L, Di Q. A prospective cohort study of prognosis for newly diagnosed epilepsy in east China. BMC Neurol. 2013;13:116.

    Google Scholar 

  19. Su L, Di Q, Kwan P, Yu N, Zhang Y, Hu Y, et al. Prediction for relapse and prognosis of newly diagnosed epilepsy. Acta Neurol Scand. 2013;127:141–7.

    CAS  Google Scholar 

  20. Yao L, Cai M, Chen Y, Shen C, Shi L, Guo Y. Prediction of antiepileptic drug treatment outcomes of patients with newly diagnosed epilepsy by machine learning. Epilepsy Behav. 2019;96:92–7.

    Google Scholar 

  21. Del Felice A, Beghi E, Boero G, La Neve A, Bogliun G, De Palo A, et al. Early versus late remission in a cohort of patients with newly diagnosed epilepsy. Epilepsia. 2010;51:37–42.

    Google Scholar 

  22. Shen C, Du Y, Lu R, Zhang Y, Jin B, Ding Y, et al. Factors predictive of late remission in a cohort of Chinese patients with newly diagnosed epilepsy. Seizure. 2016;37:20–4.

    Google Scholar 

  23. Powell G, Logan J, Kiri V, Borghs S. Trends in antiepileptic drug treatment and effectiveness in clinical practice in England from 2003 to 2016: a retrospective cohort study using electronic medical records. BMJ Open. 2019;9: e032551.

    Google Scholar 

  24. Deeks J, Higgins J, Altman D. Chapter 10: analysing data and undertaking meta-analyses. Version 6.3. Cochrane; 2022. https://training.cochrane.org/handbook/current/chapter-10. Accessed 3 Nov 2022.

  25. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health. 2014;72:39.

    Google Scholar 

  26. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475–82.

    Google Scholar 

  27. Jiang Y, Yuan F, Yang F, Sun X, Yang X, Song L, et al. Prognostic analysis for short- and long-term outcomes of newly diagnosed epilepsy. Seizure. 2017;47:92–8.

    Google Scholar 

  28. Brorson L-O, Eriksson M, Blomberg K, Stenninger E. Fifty years’ follow-up of childhood epilepsy: medical outcome, morbidity, and medication. Epilepsia. 2019;60:381–92.

    Google Scholar 

  29. Sillanpaa M, Schmidt D. Delayed time to first remission identifies poor long-term drug response of childhood-onset epilepsy: a prospective population-based study. Epilepsy Behav. 2009;16:507–11.

    Google Scholar 

  30. Wakamoto H, Nagao H, Hayashi M, Morimoto T. Long-term medical, educational, and social prognoses of childhood-onset epilepsy: a population-based study in a rural district of Japan. Brain Dev. 2000;22:246–55.

    CAS  Google Scholar 

  31. Hauser E, Freilinger M, Seidl R, Groh C. Prognosis of childhood epilepsy in newly referred patients. J Child Neurol. 1996;11:201–4.

    CAS  Google Scholar 

  32. Sillanpaa M, Schmidt D. Seizure clustering during drug treatment affects seizure outcome and mortality of childhood-onset epilepsy. Brain. 2008;131:938–44.

    Google Scholar 

  33. Jallon P, Latour P. Epidemiology of idiopathic generalized epilepsies. Epilepsia. 2005;46:10–4.

    Google Scholar 

  34. Camfield P, Camfield C. Epileptic syndromes in childhood: clinical features, outcomes, and treatment. Epilepsia. 2002;43:27–32.

    Google Scholar 

  35. Hakeem H, Feng W, Chen Z, Choong J, Brodie MJ, Fong S-L, et al. Development and validation of a deep learning model for predicting treatment response in patients with newly diagnosed epilepsy. JAMA Neurol. 2022;79:986.

    Google Scholar 

  36. Marson A, Burnside G, Appleton R, Smith D, Leach JP, Sills G, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial. Lancet. 2021;397:1375–86.

    CAS  Google Scholar 

  37. Beghi E, Beretta S, Colombo M, Bianchi E, Carone D, Zanchi C, et al. Discontinuation of antiseizure medications in seizure-free patients with long-term follow-up: patients’ profile, seizure recurrence, and risk factors. Epilepsy Behav. 2021;117: 107871.

    Google Scholar 

  38. Berg AT, Rychlik K, Levy SR, Testa FM. Complete remission of childhood-onset epilepsy: stability and prediction over two decades. Brain. 2014;137:3213–22.

    Google Scholar 

  39. Camfield C, Camfield P, Gordon K, Dooley J. Does the number of seizures before treatment influence ease of control or remission of childhood epilepsy? Not if the number is 10 or less. Neurology. 1996;46:41–4.

    CAS  Google Scholar 

  40. Henning O, Medalen TEM, Nakken KO, Lossius MI. How often do doctors discuss drug withdrawal with their seizure-free patients with epilepsy? Epilepsy Behav. 2020;108: 107095.

    Google Scholar 

  41. Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia. 2018. https://doi.org/10.1111/epi.14596. (Accessed 17 Nov 2018).

    Article  Google Scholar 

  42. Geerts A, Arts WF, Stroink H, Peeters E, Brouwer O, Peters B, et al. Course and outcome of childhood epilepsy: a 15-year follow-up of the Dutch Study of Epilepsy in Childhood. Epilepsia. 2010;51:1189–97.

    Google Scholar 

  43. Beghi E, Beretta S, Carone D, Zanchi C, Bianchi E, Pirovano M, et al. Prognostic patterns and predictors in epilepsy: a multicentre study (PRO-LONG). J Neurol Neurosurg Psychiatry. 2019;90:1276–85.

    Google Scholar 

  44. Xia L, Ou S, Pan S. Initial response to antiepileptic drugs in patients with newly diagnosed epilepsy as a predictor of long-term outcome. Front Neurol. 2017;8:658.

    Google Scholar 

  45. Besocke AG, Rosso B, Cristiano E, Valiensi SM, del García MC, Gonorazky SE, et al. Outcome of newly-diagnosed epilepsy in older patients. Epilepsy Behav. 2013;27:29–35.

    CAS  Google Scholar 

  46. Bonnett L, Smith CT, Smith D, Williamson P, Chadwick D, Marson AG. Prognostic factors for time to treatment failure and time to 12 months of remission for patients with focal epilepsy: post-hoc, subgroup analyses of data from the SANAD trial. Lancet Neurol. 2012;11:331–40.

    Google Scholar 

  47. Huang L, Li S, He D, Bao W, Li L. A predictive risk model for medical intractability in epilepsy. Epilepsy Behav. 2014;37:282–6.

    Google Scholar 

  48. Oskoui M, Webster RI, Zhang X, Shevell MI. Factors predictive of outcome in childhood epilepsy. J Child Neurol. 2005;20:898–904.

    Google Scholar 

  49. Modi AC, Rausch JR, Glauser TA. Early pediatric antiepileptic drug nonadherence is related to lower long-term seizure freedom. Neurology. 2014;82:671–3.

    CAS  Google Scholar 

  50. Obiako OR, Sheikh TL, Kehinde JA, Iwuozo EU, Ekele N, Elonu CC, et al. Factors affecting epilepsy treatment outcomes in Nigeria. Acta Neurol Scand. 2014;130:360–7.

    CAS  Google Scholar 

  51. Simard-Tremblay E, Shevell M. A profile of adolescent-onset epilepsy. J Child Neurol. 2009;24:1243–9.

    Google Scholar 

  52. Caprara ALF, Rissardo JP, Leite MTB, Silveira JOF, Jauris PGM, Arend J, et al. Course and prognosis of adult-onset epilepsy in Brazil: a cohort study. Epilepsy Behav. 2020;105: 106969.

    Google Scholar 

  53. Huang C, Feng L, Li Y, Wang Y, Chi X, Wang W, et al. Clinical features and prognosis of epilepsy in the elderly in western China. Seizure. 2016;38:26–31.

    Google Scholar 

  54. Gidey K, Chelkeba L, Gemechu TD, Daba FB. Treatment response and predictors in patients with newly diagnosed epilepsy in Ethiopia: a retrospective cohort study. Sci Rep. 2019;9:16254.

    Google Scholar 

  55. Lindsten H, Stenlund H, Forsgren L. Remission of seizures in a population-based adult cohort with a newly diagnosed unprovoked epileptic seizure. Epilepsia. 2002;42:1025–30.

    Google Scholar 

  56. Badawy RAB, Macdonell RAL, Berkovic SF, Newton MR, Jackson GD. Predicting seizure control: cortical excitability and antiepileptic medication. Ann Neurol. 2010;67:64–73.

    Google Scholar 

  57. Petrovski S. Neuropsychiatric symptomatology predicts seizure recurrence in newly treated patients. Neurology. 2010;75:1015–21.

    CAS  Google Scholar 

  58. Aaberg KM, Bakken IJ, Lossius MI, Lund Søraas C, Tallur KK, Stoltenberg C, et al. Short-term seizure outcomes in childhood epilepsy. Pediatrics. 2018;141: e20174016.

    Google Scholar 

  59. Ramos-Lizana J, Rodriguez-Lucenilla MI, Aguilera-López P, Aguirre-Rodríguez J, Cassinello-García E. A study of drug-resistant childhood epilepsy testing the new ILAE criteria. Seizure. 2012;21:266–72.

    Google Scholar 

  60. Nickels KC, Grossardt BR, Wirrell EC. Epilepsy-related mortality is low in children: a 30-year population-based study in Olmsted County. MN Epilepsia. 2012;53:2164–71.

    Google Scholar 

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Authors and Affiliations

  1. Department of Neuroscience, Central Clinical School, The Alfred Centre, Monash University, Level 6, 99 Commercial Road, Melbourne, VIC, 3004, Australia

    Mubeen Janmohamed, Haris Hakeem, Suhailah Hakami, Piero Perucca, Terence J. O’Brien, Ana Antonic-Baker, Zhibin Chen & Patrick Kwan

  2. Department of Neurology, Alfred Hospital, Melbourne, VIC, Australia

    Mubeen Janmohamed, Haris Hakeem, Piero Perucca, Terence J. O’Brien & Patrick Kwan

  3. Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia

    Suyi Ooi, Piero Perucca, Terence J. O’Brien & Patrick Kwan

  4. Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia

    Lily Vu, Piero Perucca, Terence J. O’Brien, Zhibin Chen & Patrick Kwan

  5. Bladin-Berkovic Comprehensive Epilepsy Program, Austin Health, Melbourne, VIC, Australia

    Piero Perucca

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  1. Mubeen Janmohamed
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Correspondence to Mubeen Janmohamed.

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Funding

This study did not receive any specific funding.

Conflicts of Interest/Competing Interests

MJ and HH are supported by the Monash University RTP Stipend scholarship. PP is supported by the National Health and Medical Research Council (APP1163708), the Epilepsy Foundation, The University of Melbourne, Monash University, Brain Australia, the Weary Dunlop Medical Research Foundation, and the Norman Beischer Medical Research Foundation and has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. TJO is supported by an NHMRC Investigator Grant (APP1176426) and his institution has received research grants, speaker honoraria, or consultancy fees from Chiesi, Eisai, UCB Pharma, Zynerba Pharmaceuticals, ES Pharmaceuticals, Supernus, and LivaNova, outside the submitted work. ZC is supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia (GNT1156444), and he/his institution has received consultancy fees and/or research grants from Arvelle Therapeutics and UCB Pharma. PK is supported by a Medical Research Future Fund Practitioner Fellowship (MRF1136427). He/his institution has received research grants, speaker honoraria, or consultancy fees from Chiesi, Eisai, UCB Pharma, and LivaNova, outside the submitted work. The other authors have no disclosures to declare.

Ethics Approval

No ethical approval was required for this study. All data were study-level characteristics and outcomes for a meta-analysis. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines

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Availability of Data and Material

All data extracted have been made available in the online supplementary material. Further cohort data information can be obtained through request to the corresponding author.

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Authors’ Contributions

MJ was the first author involved in the design, systematic search protocol, conceptualization, screening, data extraction, quality rating, statistical contribution, and authoring of the manuscript. HH was involved in the screening, data extraction, quality rating, and editing of the manuscript. SO, LV, and SH were involved in the screening and editing of the manuscript. A-AB was involved in the design, quality rating, and editing of the manuscript. ZC was involved in the design, statistical analysis, and editing of the manuscript. PP and TO were involved in the editing of the manuscript. PK was the senior author in the conceptualizing, design, statistical contribution, and editing of the manuscript.

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Janmohamed, M., Hakeem, H., Ooi, S. et al. Treatment Outcomes of Newly Diagnosed Epilepsy: A Systematic Review and Meta-analysis. CNS Drugs 37, 13–30 (2023). https://doi.org/10.1007/s40263-022-00979-1

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