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Review article: Biomedical intelligence

Vol. 146 No. 2526 (2016)

Modern management of seizures and epilepsy

  • Markus Gschwind
  • Margitta Seeck
Cite this as:
Swiss Med Wkly. 2016;146:w14310


Complete seizure control is achieved in 40–50% of all epileptic patients with drug treatment, as reported in most epidemiological studies. Many effective antiepileptic drugs with a favourable profile are available in Switzerland, allowing treatment tailored to the patient’s needs. Unfortunately, up to 40–50% of all patients will eventually relapse (pharmacoresistant epilepsy). These patients run a high risk of additional morbidity and mortality. Possible pharmacoresistant epilepsy should be considered early in the disease, when there is a lack of response to the first antiepileptic drug, since only 14% of those will respond to a second drug, and only 2% to a third drug if the second fails too.

Epilepsy surgery is a viable option for these patients. It requires in-depth evaluation in specialized centres, and is related to complete seizure control in 50–90% of the patients, depending on the lesion type and site. Only for patients in whom surgery cannot be offered should neuromodulation treatments be considered. Today, two different approaches are approved, vagal nerve stimulation (VNS) and deep brain stimulation in the anterior thalamic nuclei (DBS-ANT). Although only a minority of patients become totally seizure-free. Both VNS and DBS-ANT represent an important adjunct in the therapeutic armamentarium.

In the present review, we outline a practical approach for the different steps in therapeutic decisions and we summarise the profiles of modern antiepileptic drugs as well outcome of surgical and neuromodulatory therapies. The goal of any approach should be to obtain complete seizure control.  In general, if two antiepileptic drugs are not successful, in-depth evaluation of the patient in a specialised center is strongly recommended.


  1. Beleza P. Acute symptomatic seizures: a clinically oriented review. Neurologist. 2012;18:109–19.
  2. Delanty N, Vaughan CJ, French JA. Medical causes of seizures. Lancet. 1998;352:383–90.
  3. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46:470–2.
  4. Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475–82.
  6. Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: Management of an unprovoked first seizure in adults: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;84:1705–13.
  7. Cole AJ, Cascino GD. First seizure management: I can see clearly now? Neurol Clin Pract. 2015;5:278–80.
  8. Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78:1548–54.
  9. Marson A, Jacoby A, Johnson A, et al. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial. Lancet. 2005;365:2007–13.
  10. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–9.
  11. Jacoby A, Lane S, Marson A, et al. Relationship of clinical and quality of life trajectories following the onset of seizures: findings from the UK MESS Study. Epilepsia. 2011;52:965–74.
  12. McCormack M, Alfirevic A, Bourgeois S, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364:1134–43.
  13. Ozeki T, Mushiroda T, Yowang A, et al. Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet. 2011;20:1034–41.
  14. Vajda FJ, O'Brien TJ, Lander CM, et al. The teratogenicity of the newer antiepileptic drugs - an update. Acta Neurol Scand. 2014;130:234–8.
  15. Campbell E, Kennedy F, Russell A, et al. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry. 2014;85:1029–34.
  17. Errington AC, Coyne L, Stohr T, et al. Seeking a mechanism of action for the novel anticonvulsant lacosamide. Neuropharmacology. 2006;50:1016–29.
  18. Sutter R, Marsch S, Ruegg S. Safety and efficacy of intravenous lacosamide for adjunctive treatment of refractory status epilepticus: a comparative cohort study. CNS Drugs. 2013;27:–9.
  19. Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48:1308–17.
  20. Halasz P, Kalviainen R, Mazurkiewicz-Beldzinska M, et al. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50:443–53.
  21. Chung S, Sperling MR, Biton V, et al. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010;51:958–67.
  22. Doty P, Hebert D, Mathy FX, et al. Development of lacosamide for the treatment of partial-onset seizures. Ann N Y Acad Sci. 2013;1291:56–68.
  23. Cross SA, Curran MP. Lacosamide: in partial-onset seizures. Drugs. 2009;69:449–59.
  24. Rudd GD, Haverkamp W, Mason JW, et al. Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures. Acta Neurol Scand. 2015;132:355–63.
  25. Vogl C, Mochida S, Wolff C, et al. The synaptic vesicle glycoprotein 2A ligand levetiracetam inhibits presynaptic Ca2+ channels through an intracellular pathway. Mol Pharmacol. 2012;82:199–208.
  26. Lynch BA, Lambeng N, Nocka K, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004;101:9861–6.
  27. Ruegg S, Naegelin Y, Hardmeier M, et al. Intravenous levetiracetam: treatment experience with the first 50 critically ill patients. Epilepsy Behav. 2008;12:477–80.
  28. Jaques L, Rossetti AO. Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis. Epilepsy Behav. 2012;24:70–3.
  29. Patsalos PN. The pharmacokinetic characteristics of levetiracetam. Methods Find Exp Clin Pharmacol. 2003;25:123–9.
  30. Contin M, Albani F, Riva R, et al. Levetiracetam therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2004;26:375–9.
  31. Ragueneau-Majlessi I, Levy RH, Meyerhoff C. Lack of effect of repeated administration of levetiracetam on the pharmacodynamic and pharmacokinetic profiles of warfarin. Epilepsy Res. 2001;47:55–63.
  32. Weintraub D, Buchsbaum R, Resor SR, Jr., et al. Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2007;10:105–10.
  33. Dinkelacker V, Dietl T, Widman G, et al. Aggressive behavior of epilepsy patients in the course of levetiracetam add-on therapy: report of 33 mild to severe cases. Epilepsy Behav. 2003;4:537–47.
  34. Szucs A, Clemens Z, Jakus R, et al. The risk of paradoxical levetiracetam effect is increased in mentally retarded patients. Epilepsia. 2008;49:1174–9.
  35. Schachter SC, Vazquez B, Fisher RS, et al. Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for partial seizures. Neurology. 1999;52:732–7.
  36. Sachdeo R, Beydoun A, Schachter S, et al. Oxcarbazepine (Trileptal) as monotherapy in patients with partial seizures. Neurology. 2001;57:864–71.
  37. Beydoun A, Sachdeo RC, Rosenfeld WE, et al. Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial. Neurology. 2000;54:2245–51.
  38. Schmidt D, Sachdeo R. Oxcarbazepine for Treatment of Partial Epilepsy: A Review and Recommendations for Clinical Use. Epilepsy Behav. 2000;1:396–405.
  39. Beydoun A, Sachdeo RC, Kutluay E, et al. Sustained efficacy and long-term safety of oxcarbazepine: one-year open-label extension of a study in refractory partial epilepsy. Epilepsia. 2003;44:1160–5.
  40. Glauser TA, Nigro M, Sachdeo R, et al. Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group. Neurology. 2000;54:2237–44.
  41. Coppola G. Treatment of partial seizures in childhood : an overview. CNS Drugs. 2004;18:133–56.
  42. Christe W, Kramer G, Vigonius U, et al. A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy. Epilepsy Res. 1997;26:451–60.
  43. Bill PA, Vigonius U, Pohlmann H, et al. A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy. Epilepsy Res. 1997;27:195–204.
  44. Albani F, Grassi B, Ferrara R, et al. Immediate (overnight) switching from carbamazepine to oxcarbazepine monotherapy is equivalent to a progressive switch. Seizure. 2004;13:254–63.
  45. Gonzalez-Esquivel DF, Ortega-Gavilan M, Alcantara-Lopez G, et al. Plasma level monitoring of oxcarbazepine in epileptic patients. Arch Med Res. 2000;31:202–5.
  46. Hwang H, Kim KJ. New antiepileptic drugs in pediatric epilepsy. Brain Dev. 2008;30:549–55.
  47. Gelisse P, Genton P, Kuate C, et al. Worsening of seizures by oxcarbazepine in juvenile idiopathic generalized epilepsies. Epilepsia. 2004;45:1282–6.
  48. Ferrendelli JA. Concerns with antiepileptic drug initiation: safety, tolerability, and efficacy. Epilepsia. 2001;42(Suppl 4):28–30.
  49. Perucca E. Clinical pharmacology and therapeutic use of the new antiepileptic drugs. Fundam Clin Pharmacol. 2001;15:405–17.
  50. Glauser TA. Oxcarbazepine in the treatment of epilepsy. Pharmacotherapy. 2001;21:904–19.
  51. Krauss GL, Perucca E, Ben-Menachem E, et al. Perampanel, a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia. 2013;54:126–34.
  52. French JA, Krauss GL, Steinhoff BJ, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013;54:117–25.
  53. French JA, Krauss GL, Biton V, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012;79:589–96.
  54. Krauss GL, Serratosa JM, Villanueva V, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012;78:1408–15.
  55. French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology. 2015;85:950–7.
  56. Gidal BE, Laurenza A, Hussein Z, et al. Perampanel efficacy and tolerability with enzyme-inducing AEDs in patients with epilepsy. Neurology. 2015;84:1972–80.
  57. Novy J, Rothuizen LE, Buclin T, et al. Perampanel: a significant liver enzyme inducer in some patients? Eur Neurol. 2014;72:213–6.
  58. Krauss GL, Bar M, Biton V, et al. Tolerability and safety of perampanel: two randomized dose-escalation studies. Acta Neurol Scand. 2012;125:8–15.
  59. Krauss GL, Perucca E, Ben-Menachem E, et al. Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: results from phase III extension study 307. Epilepsia. 2014;55:1058–68.
  60. Schulze-Bonhage A, Hintz M. Perampanel in the management of partial-onset seizures: a review of safety, efficacy, and patient acceptability. Patient Prefer Adherence. 2015;9:1143–51.
  61. Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007;73:137–50.
  62. Dooley DJ, Taylor CP, Donevan S, et al. Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci. 2007;28:75–82.
  63. Brodie MJ, Wilson EA, Wesche DL, et al. Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Epilepsia. 2005;46:1407–13.
  64. Deeks ED, Scott LJ. Rufinamide. CNS Drugs. 2006;20:751–60; discussion 61.
  65. Glauser T, Kluger G, Sachdeo R, et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology. 2008;70:1950–8.
  66. Brodie MJ, Rosenfeld WE, Vazquez B, et al. Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial. Epilepsia. 2009;50:1899–909.
  67. Aldenkamp AP, Alpherts WCJ. The Effect of the New Antiepileptic Drug Rufinamide on Cognitive Functions. Epilepsia. 2006;47:1153–9.
  68. Kawai M, Hiramatsu M, Endo A, et al. Effect of zonisamide on release of aspartic acid and gamma-aminobutyric acid from hippocampal slices of E1 mice. Neurosciences. 1994;20:115–9.
  69. Rock DM, Macdonald RL, Taylor CP. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 1989;3:138–43.
  70. Okada M, Kawata Y, Mizuno K, et al. Interaction between Ca2+, K+, carbamazepine and zonisamide on hippocampal extracellular glutamate monitored with a microdialysis electrode. Br J Pharmacol. 1998;124:1277–85.
  71. Suzuki S, Kawakami K, Nishimura S, et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 1992;12:21–7.
  72. Thone J, Leniger T, Splettstosser F, et al. Antiepileptic activity of zonisamide on hippocampal CA3 neurons does not depend on carbonic anhydrase inhibition. Epilepsy Res. 2008;79:105–11.
  73. Masuda Y, Karasawa T. Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. Arzneimittelforschung. 1993;43:416–8.
  74. Masuda Y, Noguchi H, Karasawa T. Evidence against a significant implication of carbonic anhydrase inhibitory activity of zonisamide in its anticonvulsive effects. Arzneimittelforschung. 1994;44:267–9.
  75. Leppik IE, Willmore LJ, Homan RW, et al. Efficacy and safety of zonisamide: results of a multicenter study. Epilepsy Research. 1993;14:165–73.
  76. Ohtahara S. Zonisamide in the management of epilepsy – Japanese experience. Epilepsy Res. 2006;68(Suppl 2):S25–33.
  77. Sills GJ, Brodie MJ. Pharmacokinetics and Drug Interactions with Zonisamide. Epilepsia. 2007;48:435–41.
  78. Faught E, Ayala R, Montouris GG, et al. Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures. Neurology. 2001;57:1774–9.
  79. Kondo T, Kaneko S, Amano Y, et al. Preliminary Report on Teratogenic Effects of Zonisamide in the Offspring of Treated Women with Epilepsy. Epilepsia. 1996;37:1242–4.
  80. Soares-da-Silva P, Pires N, Bonifacio MJ, et al. Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action. Pharmacol Res Perspect. 2015;3:e00124.
  81. Elger C, Bialer M, Cramer JA, et al. Eslicarbazepine acetate: a double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia. 2007;48:497–504.
  82. Almeida L, Potgieter JH, Maia J, et al. Pharmacokinetics of eslicarbazepine acetate in patients with moderate hepatic impairment. Eur J Clin Pharmacol. 2007;64:267–73.
  83. Sperling MR, Abou-Khalil B, Harvey J, et al. Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial. Epilepsia. 2015;56:244–53.
  84. Sperling MR, Harvey J, Grinnell T, et al. Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a randomized historical-control phase III study based in North America. Epilepsia. 2015;56:546–55.
  85. Maia J, Almeida L, Falcão A, et al. Effect of renal impairment on the pharmacokinetics of eslicarbazepine acetate. Int J Clin Pharmacol Ther. 2008;46:119–30.
  86. Margolis JM, Chu BC, Wang ZJ, et al. Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action. JAMA Neurol. 2014;71:985–93.
  87. Deckers CL, Hekster YA, Keyser A, et al. Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study. Epilepsia. 2001;42:1387–94.
  88. Brodie MJ, Yuen AW. Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 Study Group. Epilepsy Res. 1997;26:423–32.
  89. Stephen LJ, Forsyth M, Kelly K, et al. Antiepileptic drug combinations – have newer agents altered clinical outcomes? Epilepsy Res. 2012;98:194–8.
  90. Lamberts RJ, Thijs RD, Laffan A, et al. Sudden unexpected death in epilepsy: people with nocturnal seizures may be at highest risk. Epilepsia. 2012;53:253–7.
  91. Tomson T, Walczak T, Sillanpaa M, et al. Sudden unexpected death in epilepsy: a review of incidence and risk factors. Epilepsia 2005;46(Suppl 11):54–61.
  92. Sperling MR, Feldman H, Kinman J, et al. Seizure control and mortality in epilepsy. Ann Neurol. 1999;46:45–50.
  93. Hennessy MJ, Langan Y, Elwes RD, et al. A study of mortality after temporal lobe epilepsy surgery. Neurology. 1999;53:1276–83.
  94. Hakimi AS, Spanaki MV, Schuh LA, et al. A survey of neurologists’ views on epilepsy surgery and medically refractory epilepsy. Epilepsy Behav. 2008;13:96–101.
  95. Uijl SG, Leijten FS, Moons KG, et al. Epilepsy surgery can help many more adult patients with intractable seizures. Epilepsy Res. 2012;101:210–6.
  96. Lascano AM, Perneger T, Vulliemoz S, et al. Yield of MRI, high-density electric source imaging (HD-ESI), SPECT and PET in epilepsy surgery candidates. Clin Neurophysiol. 2015.
  97. Kurian M, Spinelli L, Delavelle J, et al. Multimodality imaging for focus localization in pediatric pharmacoresistant epilepsy. Epileptic Disord. 2007;9:20–31.
  98. Woermann FG, Vollmar C. Clinical MRI in children and adults with focal epilepsy: a critical review. Epilepsy Behav. 2009;15:40–9.
  99. Martin P, Bender B, Focke NK. Post-processing of structural MRI for individualized diagnostics. Quant Imaging Med Surg. 2015;5:188–203.
  100. Wilke M, Kassubek J, Ziyeh S, et al. Automated detection of gray matter malformations using optimized voxel-based morphometry: a systematic approach. Neuroimage. 2003;20:330–43.
  101. Elger CE, Schmidt D. Modern management of epilepsy: a practical approach. Epilepsy Behav. 2008;12:501–39.
  102. Tellez-Zenteno JF, Hernandez Ronquillo L, Moien-Afshari F, et al. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review and meta-analysis. Epilepsy Res. 2010;89:310–8.
  103. Brodbeck V, Spinelli L, Lascano AM, et al. Electrical source imaging for presurgical focus localization in epilepsy patients with normal MRI. Epilepsia. 2010;51:583–91.
  104. Engel J, Jr., McDermott MP, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012;307:922–30.
  105. Simasathien T, Vadera S, Najm I, et al. Improved outcomes with earlier surgery for intractable frontal lobe epilepsy. Ann Neurol. 2013;73:646–54.
  106. Fisher RS, Velasco AL. Electrical brain stimulation for epilepsy. Nat Rev Neurol. 2014;10:261–70.
  107. Englot DJ, Chang EF, Auguste KI. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg. 2011;115:1248–55.
  108. Orosz I, McCormick D, Zamponi N, et al. Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia. 2014;55:1576–84.
  109. Uthman BM, Reichl AM, Dean JC, et al. Effectiveness of vagus nerve stimulation in epilepsy patients: a 12-year observation. Neurology. 2004;63:1124–6.
  110. Wheless JW, Baumgartner J. Vagus nerve stimulation therapy. Drugs Today (Barc) 2004;40:501–15.
  111. Heath RG. Electrical Self-Stimulation of the Brain in Man. Am J Psychiatry. 1963;120:571–7.
  112. Cooper IS, Amin I, Gilman S, et al. The Effect of Chronic Stimulation of Cerebellar Cortex on Epilepsy in Man. The Cerebellum, Epilepsy, and Behavior: Springer Science + Business Media; 1974. p. 119–71.
  113. Van Buren JM, Wood JH, Oakley J, et al. Preliminary evaluation of cerebellar stimulation by double-blind stimulation and biological criteria in the treatment of epilepsy. J Neurosurg. 1978;48:407–16.
  114. Velasco F, Carrillo-Ruiz JD, Brito F, et al. Double-blind, randomized controlled pilot study of bilateral cerebellar stimulation for treatment of intractable motor seizures. Epilepsia. 2005;46:1071–81.
  115. Velasco F, Velasco M, Ogarrio C, et al. Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report. Epilepsia. 1987;28:421–30.
  116. Velasco F, Velasco M, Velasco AL, et al. Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies. Epilepsia. 1995;36:63–71.
  117. Valentin A, Nguyen HQ, Skupenova AM, et al. Centromedian thalamic nuclei deep brain stimulation in refractory status epilepticus. Brain Stimul. 2012;5:594–8.
  118. Valentin A, Garcia Navarrete E, Chelvarajah R, et al. Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies. Epilepsia. 2013;54:1823–33.
  119. Sramka M, Fritz G, Galanda M, et al. Some Observations in Treatment Stimulation of Epilepsy. Stereotactic Treatment of Epilepsy: Springer Science + Business Media; 1976. p. 257–62.
  120. Velasco M, Velasco F, Velasco AL, et al. Subacute electrical stimulation of the hippocampus blocks intractable temporal lobe seizures and paroxysmal EEG activities. Epilepsia. 2000;41:158–69.
  121. Boex C, Seeck M, Vulliemoz S, et al. Chronic deep brain stimulation in mesial temporal lobe epilepsy. Seizure. 2011;20:485–90.
  122. Cukiert A, Cukiert CM, Burattini JA, et al. Seizure outcome after hippocampal deep brain stimulation in a prospective cohort of patients with refractory temporal lobe epilepsy. Seizure. 2014;23:6–9.
  123. Vonck K, Boon P, Achten E, et al. Long-term amygdalohippocampal stimulation for refractory temporal lobe epilepsy. Ann Neurol. 2002;52:556–65.
  124. Elisevich K, Jenrow K, Schuh L, et al. Long-term electrical stimulation-induced inhibition of partial epilepsy. Case report. J Neurosurg. 2006;105:894–7.
  125. Velasco AL, Velasco F, Velasco M, et al. Neuromodulation of epileptic foci in patients with non-lesional refractory motor epilepsy. Int J Neural Syst. 2009;19:139–47.
  126. Sun FT, Morrell MJ, Wharen RE, Jr. Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics. 2008;5:68–74.
  127. Chkhenkeli SA, Sramka M, Lortkipanidze GS, et al. Electrophysiological effects and clinical results of direct brain stimulation for intractable epilepsy. Clin Neurol Neurosurg. 2004;106:318–29.
  128. Capecci M, Ricciuti RA, Ortenzi A, et al. Chronic bilateral subthalamic stimulation after anterior callosotomy in drug-resistant epilepsy: long-term clinical and functional outcome of two cases. Epilepsy Res. 2012;98:135–9.
  129. Handforth A, DeSalles AA, Krahl SE. Deep brain stimulation of the subthalamic nucleus as adjunct treatment for refractory epilepsy. Epilepsia. 2006;47:1239–41.
  130. Heck CN, King-Stephens D, Massey AD, et al. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia. 2014;55:432–41.
  131. Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010;51:899–908.
  132. Salanova V, Witt T, Worth R, et al. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015;84:1017–25.