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Pharmacoresistance and the role of surgery in difficult to treat epilepsy

Abstract

Pharmacoresistance occurs in up to 30% of patients with epilepsy, and is most commonly associated with epilepsy of structural or metabolic origin, abnormal findings on brain imaging or examination, and failure to respond to the first two antiepileptic drugs. However, in patients presumed to have difficult to treat epilepsy, factors that might result in apparent treatment resistance (misdiagnosis of epilepsy, incorrect drug and/or dose, and lifestyle issues) must first be excluded and the diagnosis re-examined. Epilepsy is commonly misdiagnosed, especially in patients with syncope and psychogenic events. The initial steps in confirming the diagnoses of both epilepsy and pharmacoresistance are to obtain a detailed, reliable history and to conduct a careful review of all prior trials of antiepileptic drug therapy. Once the diagnoses of epilepsy and pharmacoresistance are confirmed, the seizure type, epilepsy syndrome, and expected course of the disorder dictate its medical and surgical management. Epilepsy surgery should be considered promptly in these patients, since few interventions are as effective as brain surgery in this setting, particularly in patients with focal pharmacoresistant epilepsy. This Review discusses the concept of pharmacoresistance and describes the approach to management of the patient with difficult to treat epilepsy, focusing on the important role of epilepsy surgery.

Key Points

  • About 25% of patients identified as having difficult to treat epilepsy do not have pharmacoresistance and/or epilepsy

  • Pharmacoresistance occurs in up to 30% of patients with epilepsy, and is usually identified after patients fail to respond to two antiepileptic drugs

  • The diagnosis of pharmacoresistant epilepsy should be confirmed and acted on promptly to control seizures

  • Surgery is a highly effective treatment for pharmacoresistant epilepsy—65% of patients with pharmacoresistant focal epilepsy achieve sustained seizure remission after surgical therapy

  • Despite robust evidence of its efficacy and safety, surgical treatment for epilepsy remains underutilized

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Figure 1: The outcome of surgical treatment in patients with epilepsy.

References

  1. Annegers, J. F., Hauser, W. A. & Elveback, L. R. Remission of seizures and relapse in patients with epilepsy. Epilepsia 20, 729–737 (1979).

    Article  CAS  PubMed  Google Scholar 

  2. Shafer, S. Q., Hauser, W. A., Annegers, J. F. & Klass, D. W. EEG and other early predictors of epilepsy remission: a community study. Epilepsia 29, 590–600 (1988).

    Article  CAS  PubMed  Google Scholar 

  3. Cockerell, O. C., Johnson, A. L., Sander, J. W., Hart, Y. M. & Shorvon, S. D. Remission of epilepsy: results from the National General Practice Study of Epilepsy. Lancet 346, 140–144 (1995).

    Article  CAS  PubMed  Google Scholar 

  4. Cockerell, O. C., Johnson, A. L., Sander, J. W. & Shorvon, S. D. Prognosis of epilepsy: a review and further analysis of the first nine years of the British National General Practice Study of Epilepsy, a prospective population-based study. Epilepsia 38, 31–46 (1997).

    Article  CAS  PubMed  Google Scholar 

  5. Lindsten, H., Stenlund, H. & Forsgren, L. Remission of seizures in a population-based adult cohort with a newly diagnosed unprovoked epileptic seizure. Epilepsia 42, 1025–1030 (2001).

    Article  CAS  PubMed  Google Scholar 

  6. Sillanpaa, M., Jalava, M., Kaleva, O. & Shinnar, S. Long-term prognosis of seizures with onset in childhood. N. Engl. J. Med. 338, 1715–1722 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Banerjee, P. N., Filippi, D. & Allen Hauser, W. The descriptive epidemiology of epilepsy—a review. Epilepsy Res. 85, 31–45 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Schuele, S. U. & Lüders, H. O. Intractable epilepsy: management and therapeutic alternatives. Lancet Neurol. 7, 514–524 (2008).

    Article  PubMed  Google Scholar 

  9. Wiebe, S. & Hesdorffer, D. C. Epilepsy: being ill in more ways than one. Epilepsy Curr. 7, 145–148 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hamiwka, L. D. et al. Social outcomes after temporal or extra-temporal epilepsy surgery: a systematic review. Epilepsia 52, 870–879 (2011).

    Article  PubMed  Google Scholar 

  11. Kwon, C. S. et al. The incidence of injuries in persons with and without epilepsy—a population-based study. Epilepsia 51, 2247–2253 (2010).

    Article  PubMed  Google Scholar 

  12. Sperling, M. R., Feldman, H., Kinman, J., Liporace, J. D. & O'Connor, M. J. Seizure control and mortality in epilepsy. Ann. Neurol. 46, 45–50 (1999).

    Article  CAS  PubMed  Google Scholar 

  13. Leach, J. P., Lauder, R., Nicolson, A. & Smith, D. F. Epilepsy in the UK: misdiagnosis, mistreatment, and undertreatment? The Wrexham area epilepsy project. Seizure 14, 514–520 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Hamiwka, L. D., Singh, N., Niosi, J. & Wirrell, E. C. Diagnostic inaccuracy in children referred with “first seizure”: role for a first seizure clinic. Epilepsia 48, 1062–1066 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Beach, R. & Reading, R. The importance of acknowledging clinical uncertainty in the diagnosis of epilepsy and non-epileptic events. Arch. Dis. Child. 90, 1219–1222 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Scheepers, B., Clough, P. & Pickles, C. The misdiagnosis of epilepsy: findings of a population study. Seizure 7, 403–406 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Smith, D., Defalla, B. A. & Chadwick, D. W. The misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic. QJM 92, 15–23 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Josephson, C. B., Rahey, S. & Sadler, R. M. Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy. Can. J. Neurol. Sci. 34, 221–224 (2007).

    Article  PubMed  Google Scholar 

  19. Uldall, P., Alving, J., Hansen, L. K., Kibaek, M. & Buchholt, J. The misdiagnosis of epilepsy in children admitted to a tertiary epilepsy centre with paroxysmal events. Arch. Dis. Child. 91, 219–221 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zaidi, A., Clough, P., Cooper, P., Scheepers, B. & Fitzpatrick, A. P. Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause. J. Am. Coll. Cardiol. 36, 181–184 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Boesebeck, F., Freermann, S., Kellinghaus, C. & Evers, S. Misdiagnosis of epileptic and non-epileptic seizures in a neurological intensive care unit. Acta Neurol. Scand. 122, 189–195 (2010).

    Article  CAS  PubMed  Google Scholar 

  22. Sarkar, U. et al. Challenges of making a diagnosis in the outpatient setting: a multi-site survey of primary care physicians. BMJ Qual. Saf. http://dx.doi.org/10.1136/bmjqs-2011-000541.

  23. Stephen, L. J. & Brodie, M. J. Antiepileptic drug monotherapy versus polytherapy: pursuing seizure freedom and tolerability in adults. Curr. Opin. Neurol. 25, 164–172 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Kwan, P., Schachter, S. C. & Brodie, M. J. Drug-resistant epilepsy. N. Engl. J. Med. 365, 919–926 (2011).

    Article  CAS  PubMed  Google Scholar 

  25. Levy, R. G., Cooper, P. N. & Giri, P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD001903. http://dx.doi.org/10.1002/14651858.CD001903.pub2.

  26. Fisher, R. S. Therapeutic devices for epilepsy. Ann. Neurol. 71, 157–168 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tellez-Zenteno, J. F., Dhar, R. & Wiebe, S. Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain 128, 1188–1198 (2005).

    Article  PubMed  Google Scholar 

  28. Wiebe, S. & Jette, N. Epilepsy surgery utilization: who, when, where, and why? Curr. Opin. Neurol. 25, 187–193 (2012).

    Article  PubMed  Google Scholar 

  29. Wiebe, S. Still an elusive target: guiding practice for epilepsy surgery. Neurology 75, 678–679 (2010).

    Article  PubMed  Google Scholar 

  30. Engel, J. Jr et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 60, 538–547 (2003).

    Article  PubMed  Google Scholar 

  31. NHS National Institute for Health and Clinical Excellence. The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. NICE Clinical Guidelines [online], (2012).

  32. Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults. A national clinical guideline [online], (2003).

  33. Labiner, D. M. et al. Essential services, personnel, and facilities in specialized epilepsy centers—revised 2010 guidelines. Epilepsia 51, 2322–2333 (2010).

    Article  PubMed  Google Scholar 

  34. Benbadis, S. R. Errors in EEGs and the misdiagnosis of epilepsy: importance, causes, consequences, and proposed remedies. Epilepsy Behav. 11, 257–262 (2007).

    Article  PubMed  Google Scholar 

  35. Krauss, G. L., Abdallah, A., Lesser, R., Thompson, R. E. & Niedermeyer, E. Clinical and EEG features of patients with EEG wicket rhythms misdiagnosed with epilepsy. Neurology 64, 1879–1883 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Falip, M., Gil-Nagel, A., Viteri Torres, C. & Gomez-Alonso, J. Diagnostic problems in the initial assessment of epilepsy. Neurologist 13 (Suppl. 1), S2–S10 (2007).

    Article  PubMed  Google Scholar 

  37. Rugg-Gunn, F. J., Harrison, N. A. & Duncan, J. S. Evaluation of the accuracy of seizure descriptions by the relatives of patients with epilepsy. Epilepsy Res. 43, 193–199 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Heo, J. H. et al. Reliability of semiology description. Neurologist 14, 7–11 (2008).

    Article  PubMed  Google Scholar 

  39. Sheldon, R. et al. Historical criteria that distinguish syncope from seizures. J. Am. Coll. Cardiol. 40, 142–148 (2002).

    Article  PubMed  Google Scholar 

  40. Krumholz, A. et al. Practice parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 69, 1996–2007 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Aylward, R. L. Epilepsy: a review of reports, guidelines, recommendations and models for the provision of care for patients with epilepsy. Clin. Med. 8, 433–438 (2008).

    Article  Google Scholar 

  42. Yogarajah, M. et al. Long term monitoring in refractory epilepsy: the Gowers Unit experience. J. Neurol. Neurosurg. Psychiatry 80, 305–310 (2009).

    Article  CAS  PubMed  Google Scholar 

  43. Kwan, P. & Brodie, M. J. Early identification of refractory epilepsy. N. Engl. J. Med. 342, 314–319 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Schiller, Y. & Najjar, Y. Quantifying the response to antiepileptic drugs: effect of past treatment history. Neurology 70, 54–65 (2008).

    Article  PubMed  Google Scholar 

  45. Berg, A. T., Levy, S. R., Testa, F. M. & D'Souza, R. Remission of epilepsy after two drug failures in children: a prospective study. Ann. Neurol. 65, 510–519 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sillanpaa, M. & Schmidt, D. Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study. Brain 129, 617–624 (2006).

    Article  PubMed  Google Scholar 

  47. Choi, H. et al. Seizure remission and relapse in adults with intractable epilepsy: a cohort study. Epilepsia 49, 1440–1445 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Callaghan, B. et al. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia 52, 619–626 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Brodie, M. J., Barry, S. J., Bamagous, G. A., Norrie, J. D. & Kwan, P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 78, 1548–1554 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Schmidt, D. & Sillanpaa, M. Evidence-based review on the natural history of the epilepsies. Curr. Opin. Neurol. 25, 159–163 (2012).

    Article  PubMed  Google Scholar 

  51. Kwan, P. et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51, 1069–1077 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Jette, N. et al. A literature review of the natural history, epidemiology and surgical outcomes of epilepsy, with a focus on localization-related epilepsy [online], (2009).

  53. Berg, A. T. et al. Early development of intractable epilepsy in children: a prospective study. Neurology 56, 1445–1452 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Ramos-Lizana, J., Aguilera-Lopez, P., Aguirre-Rodriguez, J. & Cassinello-Garcia, E. Early prediction of refractory epilepsy in childhood. Seizure 18, 412–416 (2009).

    Article  CAS  PubMed  Google Scholar 

  55. Semah, F. et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology 51, 1256–1262 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Camfield, P. & Camfield, C. Childhood epilepsy: what is the evidence for what we think and what we do? J. Child. Neurol. 18, 272–287 (2003).

    Article  PubMed  Google Scholar 

  57. Berg, A. T. et al. Defining early seizure outcomes in pediatric epilepsy: the good, the bad and the in-between. Epilepsy Res. 43, 75–84 (2001).

    Article  CAS  PubMed  Google Scholar 

  58. Casetta, I. et al. Early predictors of intractability in childhood epilepsy: a community-based case–control study in Copparo, Italy. Acta Neurol. Scand. 99, 329–333 (1999).

    Article  CAS  PubMed  Google Scholar 

  59. Brorson, L. O. & Wranne, L. Long-term prognosis in childhood epilepsy: survival and seizure prognosis. Epilepsia 28, 324–330 (1987).

    Article  CAS  PubMed  Google Scholar 

  60. Elwes, R. D., Johnson, A. L., Shorvon, S. D. & Reynolds, E. H. The prognosis for seizure control in newly diagnosed epilepsy. N. Engl. J. Med. 311, 944–947 (1984).

    Article  CAS  PubMed  Google Scholar 

  61. [No authors listed] Prognosis of epilepsy in newly referred patients: a multicenter prospective study of the effects of monotherapy on the long-term course of epilepsy. Collaborative Group for the Study of Epilepsy. Epilepsia 33, 45–51 (1992).

  62. Arts, W. F. et al. The early prognosis of epilepsy in childhood: the prediction of a poor outcome. The Dutch study of epilepsy in childhood. Epilepsia 40, 726–734 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Altunbasak, S., Herguner, O. & Burgut, H. R. Risk factors predicting refractoriness in epileptic children with partial seizures. J. Child. Neurol. 22, 195–199 (2007).

    Article  PubMed  Google Scholar 

  64. Gilioli, I. et al. Focal epilepsies in adult patients attending two epilepsy centers: classification of drug-resistance, assessment of risk factors, and usefulness of “new” antiepileptic drugs. Epilepsia 53, 733–740 (2012).

    Article  PubMed  Google Scholar 

  65. Brodie, M. J. & Kwan, P. Staged approach to epilepsy management. Neurology 58 (Suppl. 5), S2–S8 (2002).

    Article  PubMed  Google Scholar 

  66. Mohanraj, R. & Brodie, M. J. Diagnosing refractory epilepsy: response to sequential treatment schedules. Eur. J. Neurol. 13, 277–282 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Hitiris, N., Mohanraj, R., Norrie, J., Sills, G. J. & Brodie, M. J. Predictors of pharmacoresistant epilepsy. Epilepsy Res. 75, 192–196 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Sillanpaa, M. Remission of seizures and predictors of intractability in long-term follow-up. Epilepsia 34, 930–936 (1993).

    Article  CAS  PubMed  Google Scholar 

  69. Hauser, E., Freilinger, M., Seidl, R. & Groh, C. Prognosis of childhood epilepsy in newly referred patients. J. Child. Neurol. 11, 201–204 (1996).

    Article  CAS  PubMed  Google Scholar 

  70. Holowach, J., Thurston, D. L. & O'Leary, J. Prognosis in childhood epilepsy. Follow-up study of 148 cases in which therapy had been suspended after prolonged anticonvulsant control. N. Engl. J. Med. 286, 169–174 (1972).

    Article  CAS  PubMed  Google Scholar 

  71. Shorvon, S. D. & Reynolds, E. H. Early prognosis of epilepsy. Br. Med. J. (Clin. Res. Ed.) 285, 1699–1701 (1982).

    Article  CAS  Google Scholar 

  72. Stephen, L. J., Kwan, P. & Brodie, M. J. Does the cause of localisation-related epilepsy influence the response to antiepileptic drug treatment? Epilepsia 42, 357–362 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Dlugos, D. J. The early identification of candidates for epilepsy surgery. Arch. Neurol. 58, 1543–1546 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. Callaghan, B. C., Anand, K., Hesdorffer, D., Hauser, W. A. & French, J. A. Likelihood of seizure remission in an adult population with refractory epilepsy. Ann. Neurol. 62, 382–389 (2007).

    Article  PubMed  Google Scholar 

  75. Spooner, C. G., Berkovic, S. F., Mitchell, L. A., Wrennall, J. A. & Harvey, A. S. New-onset temporal lobe epilepsy in children: lesion on MRI predicts poor seizure outcome. Neurology 67, 2147–2153 (2006).

    Article  CAS  PubMed  Google Scholar 

  76. Schmidt, D., Baumgartner, C. & Loscher, W. 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 (2004).

    PubMed  Google Scholar 

  77. Schmidt, D. & Loscher, W. How effective is surgery to cure seizures in drug-resistant temporal lobe epilepsy? Epilepsy Res. 56, 85–91 (2003).

    Article  PubMed  Google Scholar 

  78. Tellez-Zenteno, J. F. et al. Discontinuation of antiepileptic drugs after successful epilepsy surgery. A Canadian survey. Epilepsy Res. http://dx.doi.org/10.1016/j.eplepsyres.2012.04.018.

  79. Duncan, J. S. Imaging in the surgical treatment of epilepsy. Nat. Rev. Neurol. 6, 537–550 (2010).

    Article  PubMed  Google Scholar 

  80. Blanco, J. A. et al. Data mining neocortical high-frequency oscillations in epilepsy and controls. Brain 134, 2948–2959 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Andrade-Valenca, L. P., Dubeau, F., Mari, F., Zelmann, R. & Gotman, J. Interictal scalp fast oscillations as a marker of the seizure onset zone. Neurology 77, 524–531 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jacobs, J. et al. High-frequency electroencephalographic oscillations correlate with outcome of epilepsy surgery. Ann. Neurol. 67, 209–220 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Tellez-Zenteno, J. F., Dhar, R., Hernandez-Ronquillo, L. & Wiebe, S. Long-term outcomes in epilepsy surgery: antiepileptic drugs, mortality, cognitive and psychosocial aspects. Brain 130, 334–345 (2007).

    Article  PubMed  Google Scholar 

  84. Wiebe, S., Blume, W. T., Girvin, J. P. & Eliasziw, M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N. Engl. J. Med. 345, 311–318 (2001).

    Article  CAS  PubMed  Google Scholar 

  85. Engel, J. Jr et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA 307, 922–930 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. de Tisi, J. et al. The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet 378, 1388–1395 (2011).

    Article  PubMed  Google Scholar 

  87. Englot, D. J., Ouyang, D., Garcia, P. A., Barbaro, N. M. & Chang, E. F. Epilepsy surgery trends in the United States, 1990–2008. Neurology 78, 1200–1206 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Haneef, Z., Stern, J., Dewar, S., Engel, J. Jr. Referral pattern for epilepsy surgery after evidence-based recommendations: a retrospective study. Neurology 75, 699–704 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Uijl, S. G. et al. Epilepsy surgery can help many more adult patients with intractable seizures. Epilepsy Res. http://dx.doi.org/10.1016/j.eplepsyres.2012.04.002.

  90. de Flon, P., Kumlien, E., Reuterwall, C. & Mattsson, P. Empirical evidence of underutilization of referrals for epilepsy surgery evaluation. Eur. J. Neurol. 17, 619–625 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Bell, G. S. et al. Premature mortality in refractory partial epilepsy: does surgical treatment make a difference? J. Neurol. Neurosurg. Psychiatry 81, 716–718 (2010).

    Article  CAS  PubMed  Google Scholar 

  92. Choi, H. et al. Epilepsy surgery for pharmacoresistant temporal lobe epilepsy: a decision analysis. JAMA 300, 2497–2505 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Seiam, A. H., Dhaliwal, H. & Wiebe, S. Determinants of quality of life after epilepsy surgery: systematic review and evidence summary. Epilepsy Behav. 21, 441–445 (2011).

    Article  PubMed  Google Scholar 

  94. Macrodimitris, S. et al. Psychiatric outcomes of epilepsy surgery: a systematic review. Epilepsia 52, 880–890 (2011).

    Article  PubMed  Google Scholar 

  95. Sherman, E. M. et al. Neuropsychological outcomes after epilepsy surgery: systematic review and pooled estimates of cognitive change. Epilepsia 52, 857–869 (2011).

    Article  PubMed  Google Scholar 

  96. Langfitt, J. T. et al. Worsening of quality of life after epilepsy surgery: effect of seizures and memory decline. Neurology 68, 1988–1994 (2007).

    Article  CAS  PubMed  Google Scholar 

  97. Macrodimitris, S., Sherman, E. M., Williams, T. S., Bigras, C. & Wiebe, S. Measuring patient satisfaction following epilepsy surgery. Epilepsia 52, 1409–1417 (2011).

    Article  PubMed  Google Scholar 

  98. Tellez-Zenteno, J. F., Hernandez Ronquillo, L., Moien-Afshari, F. & Wiebe, S. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review and meta-analysis. Epilepsy Res. 89, 310–318 (2010).

    Article  PubMed  Google Scholar 

  99. Hong, S. C. et al. Surgical treatment of intractable epilepsy accompanying cortical dysplasia. J. Neurosurg. 93, 766–773 (2000).

    Article  CAS  PubMed  Google Scholar 

  100. Tonini, C. et al. Predictors of epilepsy surgery outcome: a meta-analysis. Epilepsy Res. 62, 75–87 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. McIntosh, A. M., Kalnins, R. M., Mitchell, L. A. & Berkovic, S. F. Early seizures after temporal lobectomy predict subsequent seizure recurrence. Ann. Neurol. 57, 283–288 (2005).

    Article  PubMed  Google Scholar 

  102. Schmidt, D., Baumgartner, C. & Loscher, W. Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience. Epilepsia 45, 179–186 (2004).

    Article  PubMed  Google Scholar 

  103. Salanova, V., Markand, O. & Worth, R. Temporal lobe surgery: analysis of failures and the role of reoperation. Acta Neurol. Scand. 111, 126–133 (2005).

    Article  CAS  PubMed  Google Scholar 

  104. Awad, I. A., Nayel, M. H. & Lüders, H. Second operation after failure of previous resection for epilepsy. Neurosurgery 28, 510–518 (1991).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

S. Wiebe has received grants from the Canadian Institutes of Health Research, the National Institutes of Neurological Disorders and Stroke, the Public Health Agency of Canada, Alberta Innovates Health Solutions, Alberta Health Services, the University of Calgary Faculty of Medicine and Hotchkiss Brain Institute. N. Jette holds a Population Health Investigator Award from Alberta Innovates Health Solutions and a Canada Research Chair Tier 2 in Neuroscience Health Services Research. She has received grants or research support from the Canadian Institutes of Health Research, the Public Health Agency of Canada, Alberta Innovates Health Solutions, Alberta Health Services, the University of Calgary Faculty of Medicine and Hotchkiss Brain Institute and Alberta Health and Wellness. The authors thank Dr Elaine Wirrell for giving permission to use some of her data from a literature review written with N. Jette on predictors of remission and intractability in patients with epilepsy.

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S. Wiebe and N. Jette contributed equally to researching the data for the article, discussions of its content, writing the article and review and/or editing of the manuscript before submission.

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Correspondence to Samuel Wiebe.

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Wiebe, S., Jette, N. Pharmacoresistance and the role of surgery in difficult to treat epilepsy. Nat Rev Neurol 8, 669–677 (2012). https://doi.org/10.1038/nrneurol.2012.181

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