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Journal of Neurology

, Volume 265, Issue 3, pp 500–509 | Cite as

Does early postoperative drug regimen impact seizure control in patients undergoing temporal lobe resections?

  • Barbara Schmeiser
  • Bernhard J. Steinhoff
  • Andreas Schulze-Bonhage
Original Communication

Abstract

Objective

To evaluate the impact of postoperative antiepileptic drug (AED) load on seizure control in patients who underwent surgical treatment for pharmacoresistant mesiotemporal lobe epilepsy during the first two postoperative years.

Patients and methods

532 consecutive patients (48.7% males and 51.7% females) who underwent surgical treatment for mesiotemporal lobe epilepsy were retrospectively evaluated regarding effects of AED load on seizures control during the first 2 years following epilepsy surgery. We analyzed whether postoperative increases in postoperative AED load are associated with better seizure control in patients initially not seizure free, and if postoperative decreases in postoperative AED load would increase the risk for seizure persistence or recurrence. For statistical analyses, Fisher’s exact and Wilcoxon test were applied.

Results

68.9, 64.0 and 59.1% of patients were completely seizure free (Engel Ia) at 3, 12 and 24 months after surgery, respectively. Patients in whom daily drug doses were increased did not have a higher rate of seizure freedom at any of the three follow-up periods. Of 16 patients achieving secondary seizure control at 12 months after surgery, only one did so with an increase in drug load in contrast to 15 patients who experienced a running down of seizures independent of drug load increases. Decreases in drug load did not significantly increase the risk for seizure recurrence. Of postoperatively seizure free patients at 3 months after surgery in whom AED were consequently reduced, 85% remained completely seizure free at 1 year and 76% at 1 year after surgery, respectively, as opposed to 86% each when AED was not reduced (differences n.s.). Mean daily drug load was significantly lower in seizure free patients at 12 and 24 months compared to patients with ongoing seizures.

Conclusion

In this large patient cohort stratified to the epilepsy syndrome neither did a postoperative reduction in drug load significantly increase the risk for seizure relapse nor did increases in drug dosages lead to improved seizure control. Mean drug load was on average lower in seizure free- than non-seizure free patients at 12 and 24 months of follow-up. Secondary seizure control after initial postoperative seizures in > 90% of cases occurred as a running down, independent of an AED increase. Thus, the effect of the surgical intervention rather than the postoperative drug regimen was the key determinant for seizure control. This finding supports a curative role of temporal lobe surgery rather than an effect rendering the majority of patients’ pharmacoresponsive with a critical role of the antiepileptic drug regime for seizure control.

Keywords

Mesiotemporal lobe epilepsy surgery Postoperative antiepileptic drug treatment Seizure outcome 

Notes

Compliance with ethical standards

Funding

This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of interest

There are no conflicts of interest.

Ethical approval

This study was approved by the local ethic committee of the University of Freiburg (EK-Freiburg 263/14).

Publication

The present manuscript has not been submitted for publication elsewhere and will not be submitted elsewhere while under consideration for this journal.

References

  1. 1.
    Wiebe S, Blume WT, Girvin JP et al (2001) A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 345:311–318.  https://doi.org/10.1056/NEJM200108023450501 CrossRefPubMedGoogle Scholar
  2. 2.
    McIntosh AM, Wilson SJ, Berkovic SF (2001) Seizure outcome after temporal lobectomy: current research practice and findings. Epilepsia 42:1288–1307CrossRefPubMedGoogle Scholar
  3. 3.
    Engel J (1993) Clinical neurophysiology, neuroimaging, and the surgical treatment of epilepsy. Curr Opin Neurol Neurosurg 6:240–249PubMedGoogle Scholar
  4. 4.
    Fauser S, Schulze-Bonhage A (2015) In response: long-term seizure outcome in 211 patients with focal cortical dysplasia. Epilepsia 56:1177–1178.  https://doi.org/10.1111/epi.13017 CrossRefPubMedGoogle Scholar
  5. 5.
    Tellez-Zenteno JF, Dhar R, Hernandez-Ronquillo L, Wiebe S (2007) Long-term outcomes in epilepsy surgery: antiepileptic drugs, mortality, cognitive and psychosocial aspects. Brain 130:334–345.  https://doi.org/10.1093/brain/awl316 CrossRefPubMedGoogle Scholar
  6. 6.
    Seiam AH, Dhaliwal H, Wiebe S (2011) Determinants of quality of life after epilepsy surgery: systematic review and evidence summary. Epilepsy Behav 21:441–445.  https://doi.org/10.1016/j.yebeh.2011.05.005 CrossRefPubMedGoogle Scholar
  7. 7.
    Taylor DC, McMacKin D, Staunton H et al (2001) Patients’ aims for epilepsy surgery: desires beyond seizure freedom. Epilepsia 42:629–633CrossRefPubMedGoogle Scholar
  8. 8.
    Berg AT, Langfitt JT, Spencer SS, Vickrey BG (2007) Stopping antiepileptic drugs after epilepsy surgery: a survey of U.S. epilepsy center neurologists. Epilepsy Behav 10:219–222.  https://doi.org/10.1016/j.yebeh.2006.12.001 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Tellez-Zenteno JF, Ronquillo LH, Jette N et al (2012) Discontinuation of antiepileptic drugs after successful epilepsy surgery. A Canadian survey. Epilepsy Res 102:23–33.  https://doi.org/10.1016/j.eplepsyres.2012.04.018 CrossRefPubMedGoogle Scholar
  10. 10.
    Hoppe C, Poepel A, Sassen R, Elger CE (2006) Discontinuation of anticonvulsant medication after epilepsy surgery in children. Epilepsia 47:580–583.  https://doi.org/10.1111/j.1528-1167.2006.00471.x CrossRefPubMedGoogle Scholar
  11. 11.
    Helmstaedter C, Elger CE, Witt JA (2016) The effect of quantitative and qualitative antiepileptic drug changes on cognitive recovery after epilepsy surgery. Seizure 36:63–69.  https://doi.org/10.1016/j.seizure.2016.02.001 CrossRefPubMedGoogle Scholar
  12. 12.
    Aldenkamp AP, Alpherts WC, Sandstedt P et al (1998) Antiepileptic drug-related cognitive complaints in seizure-free children with epilepsy before and after drug discontinuation. Epilepsia 39:1070–1074CrossRefPubMedGoogle Scholar
  13. 13.
    Cramer JA, Mintzer S, Wheless J, Mattson RH (2010) Adverse effects of antiepileptic drugs: a brief overview of important issues. Expert Rev Neurother 10:885–891.  https://doi.org/10.1586/ern.10.71 CrossRefPubMedGoogle Scholar
  14. 14.
    Langfitt JT, Holloway RG, McDermott MP et al (2007) Health care costs decline after successful epilepsy surgery. Neurology 68:1290–1298.  https://doi.org/10.1212/01.wnl.0000259550.87773.3d CrossRefPubMedGoogle Scholar
  15. 15.
    Cole AJ, Wiebe S (2008) Debate: should antiepileptic drugs be stopped after successful epilepsy surgery? Epilepsia 49(Suppl 9):29–34.  https://doi.org/10.1111/j.1528-1167.2008.01924.x CrossRefPubMedGoogle Scholar
  16. 16.
    McIntosh AM, Kalnins RM, Mitchell LA et al (2004) Temporal lobectomy: long-term seizure outcome, late recurrence and risks for seizure recurrence. Brain 127:2018–2030.  https://doi.org/10.1093/brain/awh221 CrossRefPubMedGoogle Scholar
  17. 17.
    Spencer SS, Berg AT, Vickrey BG et al (2005) Predicting long-term seizure outcome after resective epilepsy surgery: the multicenter study. Neurology 65:912–918.  https://doi.org/10.1212/01.wnl.0000176055.45774.71 CrossRefPubMedGoogle Scholar
  18. 18.
    Yardi R, Irwin A, Kayyali H et al (2014) Reducing versus stopping antiepileptic medications after temporal lobe surgery. Ann Clin Transl Neurol 1:115–123.  https://doi.org/10.1002/acn3.35 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lossius MI, Hessen E, Mowinckel P et al (2008) Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study). Epilepsia 49:455–463.  https://doi.org/10.1111/j.1528-1167.2007.01323.x CrossRefPubMedGoogle Scholar
  20. 20.
    Kim YD, Heo K, Park SC et al (2005) Antiepileptic drug withdrawal after successful surgery for intractable temporal lobe epilepsy. Epilepsia 46:251–257.  https://doi.org/10.1111/j.0013-9580.2005.28004.x CrossRefPubMedGoogle Scholar
  21. 21.
    Pimentel J, Peralta AR, Campos A et al (2012) Antiepileptic drugs management and long-term seizure outcome in post surgical mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsy Res 100:55–58.  https://doi.org/10.1016/j.eplepsyres.2012.01.010 CrossRefPubMedGoogle Scholar
  22. 22.
    Berg AT, Vickrey BG, Langfitt JT et al (2006) Reduction of AEDs in postsurgical patients who attain remission. Epilepsia 47:64–71.  https://doi.org/10.1111/j.1528-1167.2006.00371.x CrossRefPubMedGoogle Scholar
  23. 23.
    Lachhwani DK, Loddenkemper T, Holland KD et al (2008) Discontinuation of medications after successful epilepsy surgery in children. Pediatr Neurol 38:340–344.  https://doi.org/10.1016/j.pediatrneurol.2008.01.010 CrossRefPubMedGoogle Scholar
  24. 24.
    Schmidt D, Loscher W (2003) How effective is surgery to cure seizures in drug-resistant temporal lobe epilepsy? Epilepsy Res 56:85–91CrossRefPubMedGoogle Scholar
  25. 25.
    Schiller Y, Cascino GD, So EL, Marsh WR (2000) Discontinuation of antiepileptic drugs after successful epilepsy surgery. Neurology 54:346–349CrossRefPubMedGoogle Scholar
  26. 26.
    Al-Kaylani M, Konrad P, Lazenby B et al (2007) Seizure freedom off antiepileptic drugs after temporal lobe epilepsy surgery. Seizure 16:95–98.  https://doi.org/10.1016/j.seizure.2006.10.007 CrossRefPubMedGoogle Scholar
  27. 27.
    Kwan P, Arzimanoglou A, Berg AT et al (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51:1069–1077.  https://doi.org/10.1111/j.1528-1167.2009.02397.x CrossRefPubMedGoogle Scholar
  28. 28.
    Engel JJ, Van Nes PC, Rasmussen TB, Ojemann LM (1993) Outcome with respect to epileptic seizures in surgical treatment of the epilepsies. N Y Raven Press, New York, pp 609–621Google Scholar
  29. 29.
    WHO (2015) WHO Collaborating Centre for Drug Statistics Methodology, Guidelines for ATC classification and DDD assignmentGoogle Scholar
  30. 30.
    Schmidt D, Baumgartner C, Loscher W (2004) The chance of cure following surgery for drug-resistant temporal lobe epilepsy. What do we know and do we need to revise our expectations? Epilepsy Res 60:187–201.  https://doi.org/10.1016/j.eplepsyres.2004.07.004 PubMedGoogle Scholar
  31. 31.
    Salanova V, Andermann F, Rasmussen T et al (1996) The running down phenomenon in temporal lobe epilepsy. Brain 119(Pt 3):989–996CrossRefPubMedGoogle Scholar
  32. 32.
    Ladino LD, Hernandez-Ronquillo L, Tellez-Zenteno JF (2014) Management of antiepileptic drugs following epilepsy surgery: a meta-analysis. Epilepsy Res 108:765–774.  https://doi.org/10.1016/j.eplepsyres.2014.01.024 CrossRefPubMedGoogle Scholar
  33. 33.
    Kuzniecky R, Rubin ZK, Faught E, Morawetz R (1992) Antiepileptic drug treatment after temporal lobe epilepsy surgery: a randomized study comparing carbamazepine and polytherapy. Epilepsia 33:908–912CrossRefPubMedGoogle Scholar
  34. 34.
    Griffin CT, Abastillas ME, Armon C et al (2004) Early antiepileptic drug reduction following anterior temporal lobectomy for medically intractable complex partial epilepsy. Seizure 13:434–437.  https://doi.org/10.1016/j.seizure.2003.10.004 CrossRefPubMedGoogle Scholar
  35. 35.
    Tanriverdi T, Ajlan A, Poulin N, Olivier A (2009) Morbidity in epilepsy surgery: an experience based on 2449 epilepsy surgery procedures from a single institution. J Neurosurg 110:1111–1123.  https://doi.org/10.3171/2009.8.JNS08338 CrossRefPubMedGoogle Scholar
  36. 36.
    Kerling F, Pauli E, Lorber B et al (2009) Drug withdrawal after successful epilepsy surgery: how safe is it? Epilepsy Behav 15:476–480.  https://doi.org/10.1016/j.yebeh.2009.05.016 CrossRefPubMedGoogle Scholar
  37. 37.
    Boshuisen K, Braams O, Jennekens-Schinkel A et al (2009) Medication policy after epilepsy surgery. Pediatr Neurol 41:332–338.  https://doi.org/10.1016/j.pediatrneurol.2009.04.025 CrossRefPubMedGoogle Scholar
  38. 38.
    Park KI, Lee SK, Chu K et al (2010) Withdrawal of antiepileptic drugs after neocortical epilepsy surgery. Ann Neurol 67:230–238.  https://doi.org/10.1002/ana.21884 CrossRefPubMedGoogle Scholar
  39. 39.
    Rathore C, Sarma SP, Radhakrishnan K (2011) Prognostic importance of serial postoperative EEGs after anterior temporal lobectomy. Neurology 76:1925–1931.  https://doi.org/10.1212/WNL.0b013e31821d74b3 CrossRefPubMedGoogle Scholar
  40. 40.
    Das RR, Artsy E, Hurwitz S et al (2012) Outcomes after discontinuation of antiepileptic drugs after surgery in patients with low grade brain tumors and meningiomas. J Neurooncol 107:565–570.  https://doi.org/10.1007/s11060-011-0779-y CrossRefPubMedGoogle Scholar
  41. 41.
    Menon R, Rathore C, Sarma SP, Radhakrishnan K (2012) Feasibility of antiepileptic drug withdrawal following extratemporal resective epilepsy surgery. Neurology 79:770–776.  https://doi.org/10.1212/WNL.0b013e3182644f7d CrossRefPubMedGoogle Scholar
  42. 42.
    Tanriverdi T, Olivier A, Poulin N et al (2008) Long-term seizure outcome after mesial temporal lobe epilepsy surgery: corticalamygdalohippocampectomy versus selective amygdalohippocampectomy. J Neurosurg 108:517–524.  https://doi.org/10.3171/JNS/2008/108/3/0517 CrossRefPubMedGoogle Scholar
  43. 43.
    Malmgren K, Edelvik A (2017) Long-term outcomes of surgical treatment for epilepsy in adults with regard to seizures, antiepileptic drug treatment and employment. Seizure 44:217–224.  https://doi.org/10.1016/j.seizure.2016.10.015 CrossRefPubMedGoogle Scholar
  44. 44.
    Reinholdson J, Olsson I, Edelvik A et al (2015) Long-term follow-up after epilepsy surgery in infancy and early childhood—a prospective population based observational study. Seizure 30:83–89.  https://doi.org/10.1016/j.seizure.2015.05.019 CrossRefPubMedGoogle Scholar
  45. 45.
    Braathen G, Melander H (1997) Early discontinuation of treatment in children with uncomplicated epilepsy: a prospective study with a model for prediction of outcome. Epilepsia 38:561–569CrossRefPubMedGoogle Scholar
  46. 46.
    Verrotti A, Morresi S, Basciani F et al (2000) Discontinuation of anticonvulsant therapy in children with partial epilepsy. Neurology 55:1393–1395CrossRefPubMedGoogle Scholar
  47. 47.
    Peters AC, Brouwer OF, Geerts AT et al (1998) Randomized prospective study of early discontinuation of antiepileptic drugs in children with epilepsy. Neurology 50:724–730CrossRefPubMedGoogle Scholar
  48. 48.
    Zeng TF, An DM, Li JM et al (2012) Evaluation of different antiepileptic drug strategies in medically refractory epilepsy patients following epilepsy surgery. Epilepsy Res 101:14–21.  https://doi.org/10.1016/j.eplepsyres.2012.02.013 CrossRefPubMedGoogle Scholar
  49. 49.
    Helmstaedter C, Witt JA (2017) How neuropsychology can improve the care of individual patients with epilepsy. Looking back and into the future. Seizure 44:113–120.  https://doi.org/10.1016/j.seizure.2016.09.010 CrossRefPubMedGoogle Scholar
  50. 50.
    Uijl SG, Leijten FS, Arends JB et al (2008) Prognosis after temporal lobe epilepsy surgery: the value of combining predictors. Epilepsia 49:1317–1323.  https://doi.org/10.1111/j.1528-1167.2008.01695.x CrossRefPubMedGoogle Scholar
  51. 51.
    Spencer SS, Spencer DD, Williamson PD, Mattson RH (1981) Ictal effects of anticonvulsant medication withdrawal in epileptic patients. Epilepsia 22:297–307CrossRefPubMedGoogle Scholar
  52. 52.
    Schmidt D, Baumgartner C, Loscher W (2004) Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience. Epilepsia 45:179–186CrossRefPubMedGoogle Scholar
  53. 53.
    van Veelen CW, van Rijen PC, Debets RM et al (2001) Dutch Collaborative Epilepsy Surgery Program: reduction of seizures, operative complications and tapering of medication in 338 patients, 1973–1998. Ned Tijdschr Geneeskd 145:2223–2228PubMedGoogle Scholar
  54. 54.
    Boshuisen K, Arzimanoglou A, Cross JH et al (2012) Timing of antiepileptic drug withdrawal and long-term seizure outcome after paediatric epilepsy surgery (TimeToStop): a retrospective observational study. Lancet Neurol 11:784–791.  https://doi.org/10.1016/S1474-4422(12)70165-5 CrossRefPubMedGoogle Scholar
  55. 55.
    Lee SY, Lee JY, Kim DW et al (2008) Factors related to successful antiepileptic drug withdrawal after anterior temporal lobectomy for medial temporal lobe epilepsy. Seizure 17:11–18.  https://doi.org/10.1016/j.seizure.2007.05.014 CrossRefPubMedGoogle Scholar
  56. 56.
    Janszky J, Janszky I, Schulz R et al (2005) Temporal lobe epilepsy with hippocampal sclerosis: predictors for long-term surgical outcome. Brain 128:395–404.  https://doi.org/10.1093/brain/awh358 CrossRefPubMedGoogle Scholar
  57. 57.
    Englot DJ, Chang EF (2014) Rates and predictors of seizure freedom in resective epilepsy surgery: an update. Neurosurg Rev 37:389–404.  https://doi.org/10.1007/s10143-014-0527-9 (discussion 404–5) CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Grivas A, Schramm J, Kral T et al (2006) Surgical treatment for refractory temporal lobe epilepsy in the elderly: seizure outcome and neuropsychological sequels compared with a younger cohort. Epilepsia 47:1364–1372.  https://doi.org/10.1111/j.1528-1167.2006.00608.x CrossRefPubMedGoogle Scholar
  59. 59.
    Lee YJ, Lee JS (2013) Temporal lobe epilepsy surgery in children versus adults: from etiologies to outcomes. Korean J Pediatr 56:275–281.  https://doi.org/10.3345/kjp.2013.56.7.275 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Tonini C, Beghi E, Berg AT et al (2004) Predictors of epilepsy surgery outcome: a meta-analysis. Epilepsy Res 62:75–87.  https://doi.org/10.1016/j.eplepsyres.2004.08.006 CrossRefPubMedGoogle Scholar
  61. 61.
    Radhakrishnan K, So EL, Silbert PL et al (1998) Predictors of outcome of anterior temporal lobectomy for intractable epilepsy: a multivariate study. Neurology 51:465–471CrossRefPubMedGoogle Scholar
  62. 62.
    Schmeiser B, Zentner J, Steinhoff BJ et al (2017) The role of presurgical EEG parameters and of reoperation for seizure outcome in temporal lobe epilepsy. Seizure 51:174–179.  https://doi.org/10.1016/j.seizure.2017.08.015 CrossRefPubMedGoogle Scholar
  63. 63.
    Grote A, Witt JA, Surges R et al (2015) A second chance-reoperation in patients with failed surgery for intractable epilepsy: long-term outcome, neuropsychology and complications. J Neurol Neurosurg Psychiatry.  https://doi.org/10.1136/jnnp-2015-310322 PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Barbara Schmeiser
    • 1
  • Bernhard J. Steinhoff
    • 2
  • Andreas Schulze-Bonhage
    • 3
  1. 1.Department of Neurosurgery, University HospitalAlbert-Ludwigs-UniversityFreiburgGermany
  2. 2.Kork Epilepsy CenterKehlGermany
  3. 3.Department of EpileptologyUniversity Hospital FreiburgFreiburgGermany

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