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Discontinuing antiepileptic drugs in long-standing idiopathic generalised epilepsy

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Abstract

Background

Once adults with long-standing idiopathic generalised epilepsy have achieved stable seizure remission, patients or physicians may attempt to discontinue their antiepileptic drug treatment. To date, risk of subsequent seizure relapse across the four idiopathic generalised epilepsy syndromes is largely unknown, and so are the clinical variables associated.

Methods

For this retrospective observational study, 256 adult outpatients with idiopathic generalised epilepsy were evaluated. Data were obtained from outpatient charts and, if possible, from additional telephone or mail interviews.

Results

In 84 patients (33%), antiepileptic medication was discontinued at least once. Median patient age at antiepileptic drug withdrawal was 33 years, and median duration of subsequent follow-up was 20 years. Seizures recurred in 46% of patients after a median latency of 11 months. Following multivariable analysis, seizure relapse was independently associated with short duration of seizure remission beforehand. If medication was withdrawn after < 5 years of seizure freedom, two-thirds of patients had a seizure relapse, while among those in remission for ≥ 5 years, only one-third relapsed.

Conclusions

Discontinuation of antiepileptic drug treatment can be successful in every other adult with long-standing idiopathic generalised epilepsy. Short duration of prior seizure remission appears to be a relevant predictor of seizure recurrence.

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References

  1. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshe SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM (2017) ILAE classification of the epilepsies: position paper of the ILAE Commission for Class Terminol. Epilepsia 58(4):512–521. https://doi.org/10.1111/epi.13709

    Article  PubMed  PubMed Central  Google Scholar 

  2. Grosso S, Galimberti D, Vezzosi P, Farnetani M, Di Bartolo RM, Bazzotti S, Morgese G, Balestri P (2005) Childhood absence epilepsy: evolution and prognostic factors. Epilepsia 46(11):1796–1801. https://doi.org/10.1111/j.1528-1167.2005.00277.x

    Article  PubMed  Google Scholar 

  3. Berg AT, Levy SR, Testa FM, Blumenfeld H (2014) Long-term seizure remission in childhood absence epilepsy: might initial treatment matter? Epilepsia 55(4):551–557. https://doi.org/10.1111/epi.12551

    Article  PubMed  PubMed Central  Google Scholar 

  4. Callenbach PM, Bouma PA, Geerts AT, Arts WF, Stroink H, Peeters EA, van Donselaar CA, Peters AC, Brouwer OF (2009) Long-term outcome of childhood absence epilepsy: Dutch Study of Epilepsy in Childhood. Epilepsy Res 83(2–3):249–256. https://doi.org/10.1016/j.eplepsyres.2008.11.011

    Article  PubMed  Google Scholar 

  5. Beghi M, Beghi E, Cornaggia CM, Gobbi G (2006) Idiopathic generalized epilepsies of adolescence. Epilepsia 47(Suppl 2):107–110. https://doi.org/10.1111/j.1528-1167.2006.00706.x

    Article  PubMed  Google Scholar 

  6. Vorderwulbecke BJ, Kowski AB, Kirschbaum A, Merkle H, Senf P, Janz D, Holtkamp M (2017) Long-term outcome in adolescent-onset generalized genetic epilepsies. Epilepsia 58(7):1244–1250. https://doi.org/10.1111/epi.13761

    Article  PubMed  Google Scholar 

  7. Syvertsen M, Flogstad I, Enger U, Landmark CJ, Koht J (2019) Antiepileptic drug withdrawal in juvenile myoclonic epilepsy. Acta Neurol Scand 139(2):192–198. https://doi.org/10.1111/ane.13042

    Article  PubMed  Google Scholar 

  8. Hofler J, Unterberger I, Dobesberger J, Kuchukhidze G, Walser G, Trinka E (2014) Seizure outcome in 175 patients with juvenile myoclonic epilepsy—a long-term observational study. Epilepsy Res 108(10):1817–1824. https://doi.org/10.1016/j.eplepsyres.2014.09.008

    Article  PubMed  Google Scholar 

  9. Stevelink R, Koeleman BP, Sander JW, Jansen FE, Braun KP (2018) Refractory juvenile myoclonic epilepsy: a meta-analysis of prevalence and risk factors. Eur J Neurol. https://doi.org/10.1111/ene.13811

    Article  PubMed  PubMed Central  Google Scholar 

  10. Senf P, Schmitz B, Holtkamp M, Janz D (2013) Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors. Neurology 81(24):2128–2133. https://doi.org/10.1212/01.wnl.0000437303.36064.f8

    Article  PubMed  Google Scholar 

  11. Holtkamp M, Senf P, Kirschbaum A, Janz D (2014) Psychosocial long-term outcome in juvenile myoclonic epilepsy. Epilepsia 55(11):1732–1738. https://doi.org/10.1111/epi.12751

    Article  PubMed  Google Scholar 

  12. Holtkamp M, Kowski AB, Merkle H, Janz D (2014) Long-term outcome in epilepsy with grand mal on awakening: forty years of follow-up. Ann Neurol 75(2):298–302. https://doi.org/10.1002/ana.24103

    Article  PubMed  Google Scholar 

  13. Holtkamp M, Janz D, Kirschbaum A, Kowski AB, Vorderwulbecke BJ (2018) Absence epilepsy beyond adolescence: an outcome analysis after 45 years of follow-up. J Neurol Neurosurg Psychiatry 89(6):603–610. https://doi.org/10.1136/jnnp-2017-317052

    Article  PubMed  Google Scholar 

  14. Trinka E, Baumgartner S, Unterberger I, Unterrainer J, Luef G, Haberlandt E, Bauer G (2004) Long-term prognosis for childhood and juvenile absence epilepsy. J Neurol 251(10):1235–1241. https://doi.org/10.1007/s00415-004-0521-1

    Article  PubMed  Google Scholar 

  15. Nicolson A, Appleton RE, Chadwick DW, Smith DF (2004) The relationship between treatment with valproate, lamotrigine, and topiramate and the prognosis of the idiopathic generalised epilepsies. J Neurol Neurosurg Psychiatry 75(1):75–79

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Pavlovic M, Jovic N, Pekmezovic T (2011) Antiepileptic drugs withdrawal in patients with idiopathic generalized epilepsy. Seizure 20(7):520–525. https://doi.org/10.1016/j.seizure.2011.03.007

    Article  PubMed  Google Scholar 

  17. Lamberink HJ, Otte WM, Geerts AT, Pavlovic M, Ramos-Lizana J, Marson AG, Overweg J, Sauma L, Specchio LM, Tennison M, Cardoso TMO, Shinnar S, Schmidt D, Geleijns K, Braun KPJ (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. Lancet Neurol 16(7):523–531. https://doi.org/10.1016/S1474-4422(17)30114-X

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are most grateful to Dieter Janz who dedicated his work life to epilepsy and, in particular, to delineation, classification and treatment of IGE. For more than half a century, he collected respective patient data which provided the basis for this and previous studies. Dieter Janz passed away in 2016 aged 96 years. Bernd J Vorderwülbecke was funded by grants from von Bodelschwingh Foundation and Deutsche Forschungsgemeinschaft (DFG 422589384). Philine Senf was funded by grants from Else Kröner Fresenius Foundation and Heidehof Foundation. Martin Holtkamp holds the “Friedrich-von-Bodelschwingh Endowed Professorship for Clinical and Experimental Epileptology” at the Department of Neurology, Charité–Universitätsmedizin Berlin.

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Authors and Affiliations

  1. Department of Neurology, Epilepsy-Center Berlin-Brandenburg, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Bernd J. Vorderwülbecke, Andrea Kirschbaum, Hannah Merkle, Philine Senf & Martin Holtkamp

  2. Department of Psychosomatic Medicine, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Philine Senf

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  1. Bernd J. Vorderwülbecke
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  2. Andrea Kirschbaum
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  3. Hannah Merkle
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  4. Philine Senf
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  5. Martin Holtkamp
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Corresponding author

Correspondence to Bernd J. Vorderwülbecke.

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Conflicts of interest

Martin Holtkamp received speaker’s honoraria and/or consultancy fees from Bial, Desitin, Eisai, LivaNova, Novartis, and UCB. All the other authors declare that they have no conflicts of interest.

Ethical standards

The study was approved by the institutional review board at Charité–Universitätsmedizin Berlin and was, therefore, conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All interviewed patients or their next-of-kin gave written informed consent.

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Vorderwülbecke, B.J., Kirschbaum, A., Merkle, H. et al. Discontinuing antiepileptic drugs in long-standing idiopathic generalised epilepsy. J Neurol 266, 2554–2559 (2019). https://doi.org/10.1007/s00415-019-09457-z

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  • DOI: https://doi.org/10.1007/s00415-019-09457-z

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