Skip to main content

Advertisement

SpringerLink
Log in

Treatment of epileptic seizures in brain tumors: a critical review

  • Review
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Epileptic seizures represent a common signal of intracranial tumors, frequently the presenting symptom and the main factor influencing quality of life. Treatment of tumors concentrates on survival; antiepileptic drug (AED) treatment frequently is prescribed in a stereotyped way. A differentiated approach according to epileptic syndromes can improve seizure control and minimize unwarranted AED effects. Prophylactic use of AEDs is to be discouraged in patients without seizures. Acutely provoked seizures do not need long-term medication except for patients with high recurrence risk indicated by distinct EEG patterns, auras, and several other parameters. With chronically repeated seizures (epilepsies), long-term AED treatment is indicated. Non-enzyme-inducing AEDs might be preferred. Valproic acid exerts effects against progression of gliomatous tumors. In low-grade astrocytomas with epilepsy, a comprehensive presurgical epilepsy work-up including EEG-video monitoring is advisable; in static non-progressive tumors, it is mandatory. In these cases, the neurosurgical approach has to include the removal of the seizure-onset zone frequently located outside the lesion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Al-Kaylani M, Konrad P, Lazenby B et al (2007) Seizure freedom off antiepileptic drugs after temporal lobe epilepsy surgery. Seizure 16:95–98

    Article  PubMed  Google Scholar 

  2. Anderson GD, Lin Y-X, Berge C, Ojemann GA (1997) Absence of bleeding complications in patients undergoing cortical surgery while receiving valproate treatment. J Neurosurg 87:251–256

    Article  Google Scholar 

  3. Baayen JC, de Jongh A, Stam CJ et al (2003) Localization of slow wave activity in patients with tumor-associated epilepsy. Brain Topogr 16:85–93

    Article  PubMed  Google Scholar 

  4. Bähr O, Hermisson M, Rona S et al (2012) Intravenous and oral levetiracetam in patients with a suspected primary tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial. Acta Neurochir 154:229–235

    Article  PubMed  Google Scholar 

  5. Bartolomei F, Bosma I, Klein M et al (2006) How do brain tumors alter functional connectivity? A magnetoencephalography study. Ann Neurol 59:128–138

    Article  PubMed  Google Scholar 

  6. Bauer G, Bauer R (2011) EEG, drug effects, and central nervous system poisoning. In: Schomer DL, Lopes da Silva F (eds.): Niedermeyer’s electroencephalography, 6th ed. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo, pp 901–922

  7. Bauer R, Dobesberger J, Unterhofer C et al (2007) Outcome of adult patients with temporal lobe tumours and medically refractory focal epilepsy. Acta Neurochir 149:1211–1216

    Article  CAS  PubMed  Google Scholar 

  8. Beaumont A, Whittle IR (2000) The pathogenesis of tumour associated epilepsy. Acta Neurochir 142:1–15

    Article  CAS  PubMed  Google Scholar 

  9. Berg AT, Vickrey BG, Langfitt JT et al (2006) Reduction of AEDs in postsurgical patients who attain remission. Epilepsia 47:64–71

    Article  PubMed  Google Scholar 

  10. Beyenburg S, Stavem K, Schmidt D (2010) Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy: systematic review and meta-analysis. Epilepsia 51:7–26

    Article  CAS  PubMed  Google Scholar 

  11. Blaheta RA, Michaelis M, Hernáiz Driever P, Cinatl J (2005) Evolving anticancer drug valproic acid: Insights into mechanism and clinical studies. Med Res Rev 25:383–397

    Article  CAS  PubMed  Google Scholar 

  12. Boarini DJ, Beck DW, VanGilder JC (1985) Postoperative prophylactic anticonvulsant therapy in cerebral gliomas. Neurosurgery 16:290–292

    Article  CAS  PubMed  Google Scholar 

  13. Bobustuc GC, Baker CH, Limaye A et al (2010) Levetiracetam enhances p53-mediated MGMT inhibition and sensitizes glioblastoma cells to temozolomide. Neuro-Oncology 12:917–927

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Boon PA, Williamson PD, Fried I et al (1991) Intracranial, intraaxial, space-occupying lesions in patients with intractable partial seizures: an anatomoclinical, neuropsychological, and surgical correlation. Epilepsia 32:467–476

    Article  CAS  PubMed  Google Scholar 

  15. Cavaliere R, Farace E, Schiff D (2006) Clinical implications of status epilepticus in patients with neoplasms. Arch Neurol 63:1746–1749

    Article  PubMed  Google Scholar 

  16. Chaichana KL, Parker SL, Olivi A, Quinones-Hinojosa A (2009) Long-term seizure outcomes in adult patients undergoing primary resection of malignant brain astrocytomas. J Neurosurg 111:282–292

    Article  PubMed  Google Scholar 

  17. Chang SM, Parney IF, Huang W et al (2005) Patterns of care for adults with newly diagnosed malignant glioma. JAMA 293:557–564

    Article  CAS  PubMed  Google Scholar 

  18. Chang EF, Potts MB, Keles GE et al (2008) Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg 108:227–235

    Article  PubMed  Google Scholar 

  19. Chassoux F, Rodrigo S, Mellerio C et al (2012) Dysembryoplastic neuroepithelial tumors: an MRI-based scheme for epilepsy surgery. Neurology 79:1699–1707

    Article  PubMed  Google Scholar 

  20. Chozik BS, Reinert S, Greenblatt SH (1996) Incidence of seizures after surgery for supratentorial meningiomas: a modern analysis. J Neurosurg 84:382–386

    Article  Google Scholar 

  21. Cosgrove GR (2001) Epilepsy surgery for tumors, vascular malformations, trauma, and cerebrovascular disease. In: Lüders HO, Comair YG (eds) Epilepsy surgery, 2nd edn. Lippincott, Philadelphia, pp 793–799

    Google Scholar 

  22. De Groot M, Aronica E, Heimans JJ, Reijneveld JC (2011) Synaptic vesicle protein 2A predicts response to levetiracetam in patients with glioma. Neurology 77:532–539

    Article  PubMed  Google Scholar 

  23. De Groot M, Reijneveld JC, Aronica E, Heimans JJ (2012) Epilepsy in patients with a brain tumour: focal epilepsy requires focused treatment. Brain 135:1002–1016

    Article  PubMed  Google Scholar 

  24. De Santis A, Villani R, Sinisi M et al (2002) Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study. Epilepsia 43:175–182

    Article  PubMed  Google Scholar 

  25. Englot DJ, Berger MS, Barbaro NM, Chang EF (2011) Predictors of seizure freedom after resection of supratentorial low-grade gliomas. J Neurosurg 115:240–244

    Article  PubMed  Google Scholar 

  26. Englot DJ, Berger MS, Barbaro NM, Chang EF (2012) Factors associated with seizure freedom in the surgical resection of glioneuronal tumors. Epilepsia 253:51–57

    Article  Google Scholar 

  27. Eyal S, Yagen B, Sobol E et al (2004) The activity of antiepileptic drugs as histone deacetylase inhibitors. Epilepsia 45:737–744

    Article  CAS  PubMed  Google Scholar 

  28. Ferrier CH, Aronica E, Leijten FSS et al (2006) Electrographic discharge patterns in glioneural tumors and focal cortical dysplasia. Epilepsia 47:1477–1486

    Article  PubMed  Google Scholar 

  29. Forsyth PA, Weaver S, Fulton D et al (2003) Prophylactic anticonvulsants in patients with brain tumour. Can J Neurol Sci 30:106–112

    PubMed  Google Scholar 

  30. Franceschetti S, Binelli S, Casazza M et al (1990) Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumors. Acta Neurochir 103:47–51

    Article  CAS  PubMed  Google Scholar 

  31. Genton P, Gelisse P (2002) Valproic acid. Adverse effects. In: Levy RH, Mattson RH, Meldrum BS, Perucca E (eds) Antiepileptic drugs, 5th edn. Lippincott, Philadelphia, pp 837–851

    Google Scholar 

  32. Glantz MJ, Cole BF, Forsyth PA et al (2000) Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 54:1886–1894

    Article  CAS  PubMed  Google Scholar 

  33. Goldring S, Rich KM, Picker S (1986) Experience with gliomas in patients presenting with a chronic seizure disorder. Clin Neurosurg 33:15–42

    CAS  PubMed  Google Scholar 

  34. Hartman AL, Lesser RP (2011) Brain tumors and other space-occupying lesions. In: Schomer DL, Lopes da Silva F (eds.): Niedermeyer’s electroencephalography, 6th ed. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo, pp 321–330

  35. Hesdorffer DC, Benn EKT, Cascino GD, Hauser WA (2009) Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia 50:1102–1108

    Article  PubMed  Google Scholar 

  36. Hess R (1970) Die epileptogenen Hirntumoren. In: Niedermeyer E (ed.): Epilepsy. Mod Probl Pharmacopsychiat. 1970;4: pp 200–231

  37. Hwang S-L, Lin C-L, Lee K-S et al (2004) Factors influencing seizures in adult patients with supratentorial astrocytic tumors. Acta Neurochir 146:589–594

    Article  PubMed  Google Scholar 

  38. Ianelli A, Guzzetta F, Battaglia D et al (2000) Surgical treatment of temporal tumors associated with epilepsy in children. Pediatr Neurosurg 32:248–254

    Article  Google Scholar 

  39. Jaeckle KA, Ballman K, Furth A, Buckner JC (2009) Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma. Neurology 73:1207–1213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Khalenberg CA, Fadul CE, Roberts DW et al (2012) Seizure prognosis of patients with low-grade tumors. Seizure 21:540–545

    Article  Google Scholar 

  41. Kilbride RD, Costello DJ, Chiappa KH (2009) How seizure detection by continuous electroencephalographic monitoring affects the prescribing of antiepileptic medications. Arch Neurol 66:723–728

    Article  PubMed  Google Scholar 

  42. Kilpatrick CJ (2004) Withdrawal of antiepileptic drugs in seizure-free adults. Aust Prescr 27:114–117

    Google Scholar 

  43. Kim YD, Heo K, Park SC et al (2005) Antiepileptic drug withdrawal after successful surgery for intractable temporal lobe epilepsy. Epilepsia 46:251–257

    Article  CAS  PubMed  Google Scholar 

  44. Klein M, Engelberts NHJ, van der Ploeg HM et al (2003) Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life. Ann Neurol 54:514–520

    Article  PubMed  Google Scholar 

  45. Kvuam DA, Loftus CM, Copeland B, Quest DO (1983) Seizures during the immediate postoperative period. Neurosurgery 12:14–17

    Article  Google Scholar 

  46. Lee S-Y, Lee J-Y, 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

    Article  PubMed  Google Scholar 

  47. Lee JW, Wen PY, Hurwitz S et al (2010) Morphological characteristics of brain tumors causing seizures. Arch Neurol 67:336–342

    PubMed Central  PubMed  Google Scholar 

  48. Lee S-T, Lui T-N, Chang C-N et al (1989) Prophylactic anticonvulsants for prevention of immediate and early postcraniotomy seizures. Surg Neurol 31:361–364

    Article  CAS  PubMed  Google Scholar 

  49. Lieu A-S, Howng S-L (2000) Intracranial meningiomas and epilepsy: incidence, prognosis and influencing factors. Epilepsy Res 38:45–52

    Article  CAS  PubMed  Google Scholar 

  50. Liigant A, Haldre S, Öun A et al (2001) Seizure disorders in patients with brain tumors. Eur Neurol 45:46–51

    Article  CAS  PubMed  Google Scholar 

  51. Lim DA, Tarapore P, Chang E et al (2009) Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized phase II pilot study. J Neurooncol 93:349–354

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Lossius MI, Hessen E, Mohwinckel P et al (2008) Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study). Epilepsia 49:455–463

    Article  PubMed  Google Scholar 

  53. Lote K, Stenwig AE, Skullerud K, Hirschberg H (1998) Prevalence and prognostic significance of epilepsy in patients with gliomas. Eur J Cancer 34:98–102

    Article  CAS  PubMed  Google Scholar 

  54. Lund M (1952) Epilepsy in association with intracranial tumour. Acta psychiat (Kbh) Suppl 81

  55. Luyken C, Blümcke I, Fimmers R et al (2003) The spectrum of long-term epilepsy-associated tumors: long-term seizure outcome and tumor outcome and neurosurgical aspects. Epilepsia 44:822–830

    Article  PubMed  Google Scholar 

  56. Lwu S, Hamilton MG, Forsyth PA et al (2010) Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience. J Neurooncol 96:403–408

    Article  PubMed  Google Scholar 

  57. Lynam LM, Lyons MK, Drazkowski JF et al (2007) Frequency of seizures in patients with newly diagnosed brain tumors: a retrospective review. Clin Neurol Neurosurg 109:634–638

    Article  PubMed  Google Scholar 

  58. Maschio M, Albani F, Baruzzi A et al (2006) Levetiracetam therapy in patients with brain tumour and epilepsy. Neurooncol 80:97–100

    Article  CAS  Google Scholar 

  59. Maschio M, Dinapoli L, Mingoia M et al (2011) Lacosamide as add-on in brain tumor-related epilepsy. J Neurol 258:2100–2104

    Article  CAS  PubMed  Google Scholar 

  60. Maschio M, Dinapoli L, Vidiri L et al (2009) The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine. J Exp Clin Cancer Res 28:60–66

    Article  PubMed Central  PubMed  Google Scholar 

  61. Maschio M, Dinapoli L, Zarabla A et al (2008) Outcome and tolerability of topiramate in brain tumor associated epilepsy. J Neurooncol 86:61–70

    Article  CAS  PubMed  Google Scholar 

  62. Matthew E, Sherwin AL, Welner SA et al (1980) Seizures following intracranial surgery: incidence in the first post-operative week. Can J Neurol Sci 7:285–290

    CAS  PubMed  Google Scholar 

  63. Mauro AM, Bomprezzi C, Morresi S et al (2007) Prevention of early postoperative seizures in patients with primary brain tumors: preliminary experience with oxcarbazepine. J Neurooncol 81:279–285

    Article  CAS  PubMed  Google Scholar 

  64. Menon R, Rathore C, Sarma S, Radhakrishan K (2012) Feasibility of antiepileptic drug withdrawal following extratemporal respective epilepsy surgery. Neurology 79:770–776

    Article  CAS  PubMed  Google Scholar 

  65. Merrell RT, Anderson K, Meyer FB, Lachance DH (2010) Seizures in patients with glioma treated with phenytoin and levetiracetam. J Neurosurg 113:1176–1181

    Article  CAS  PubMed  Google Scholar 

  66. Michaelis M, Doerr HW, Cinatl J (2007) Valproic acid as anti-cancer drug. Curr Pharm Des 13:3378–3393

    Article  CAS  PubMed  Google Scholar 

  67. Milligan TA, Hurwitz S, Bromfield EB (2008) Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery. Neurology 71:665–669

    Article  CAS  PubMed  Google Scholar 

  68. Morris HH III (2001) Lesionectomy as a treatment for chronic epilepsies: is it sufficient for a good outcome? In: Lüders HO, Comair YG (eds) Epilepsy surgery, 2nd edn. Lippincott, Philadelphia, pp 967–971

    Google Scholar 

  69. Morris HH, Estes ML, Gilmore R et al (1993) Chronic intractable epilepsy as the only symptom of primary brain tumor. Epilepsia 34:1038–1043

    Article  CAS  PubMed  Google Scholar 

  70. Newton HB, Goldlust SA, Pearl D (2006) Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients. J Neuro-Oncol 78:99–102

    Article  CAS  Google Scholar 

  71. Novy J, Stupp R, Rossetti AO (2009) Pregabalin in patients with primary brain tumors and seizures: a preliminary observation. Clin Neurol Neurosurg 111:171–173

    Article  PubMed  Google Scholar 

  72. Oberndorfer S, Piribauer M, Marosi C et al (2005) P450 enzyme inducing and non-enzyme inducing antiepileptics in glioblastoma patients treated with standard chemotherapy. J Neuro-Oncol 72:255–260

    Article  CAS  Google Scholar 

  73. Pedersen C, Romner B (2013) Current treatment of low grade astrocytoma: a review. Clin Neurol Neurosurg 115:1–8

    Article  PubMed  Google Scholar 

  74. Raganathan C, Verma NP, Diaz FG (1993) Valproate and epilepsy surgery. J Epilepsy 6:142–144

    Article  Google Scholar 

  75. Rathore C, Panda S, Sarma PS, Radhakrishnan K (2011) How safe is it to withdraw antiepileptic drugs following successful surgery for mesial temporal lobe epilepsy? Epilepsia 52:627–635

    Article  PubMed  Google Scholar 

  76. Riva M (2005) Brain tumoral epilepsy: a review. Neurol Sci 26:S40–S42

    Article  PubMed  Google Scholar 

  77. Rosati A, Buttolo L, Stefini R et al (2010) Efficacy and safety of levetiracetam in patients with glioma. Arch Neurol 67:343–346

    Article  PubMed  Google Scholar 

  78. Rossetti A, Stupp R (2010) Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioma. Neurology 74:1329

    Article  PubMed  Google Scholar 

  79. Schaller B, Rüegg S (2003) Brain tumor and seizures: pathophysiology and its implications for treatment revisited. Epilepsia 44:1223–1232

    Article  PubMed  Google Scholar 

  80. Schiller Y, Cascino GD, So EL et al (2000) Discontinuation of antiepileptic drugs after successful epilepsy surgery. Neurology 54:346–349

    Article  CAS  PubMed  Google Scholar 

  81. Shamij MF, Fric-Shamij EC, Benoit BG (2009) Brain tumors and epilepsy: pathophysiology of peritumoral changes. Neurosurg Rev 32:275–285

    Article  Google Scholar 

  82. Sherman JH, Moldovan K, Yeoh HK et al (2011) Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J Neurosurg 114:1617–1621

    Article  PubMed  Google Scholar 

  83. Shughrue ME, Rutkowski MJ, Chang EF et al (2011) Postoperative seizures following the resection of convexity meningiomas: are prophylactic anticonvulsants indicated? J Neurosurg 114:705–709

    Article  Google Scholar 

  84. Siomin V, Angelov L, Li L, Vogelbaum MA (2005) Results of a survey of neurosurgical practice patterns regarding the prophylactic use of anti-epilepsy drugs in patients with brain tumors. J Neuro-Oncol 74:211–215

    Article  CAS  Google Scholar 

  85. Sirven JI, Wingerchuk DM, Drazkowski JF et al (2004) Seizure prophylaxis in patients with brain tumors: a meta-analysis. Mayo Clin Proc 79:1489–1494

    Article  PubMed  Google Scholar 

  86. Striano S, Striano P, Bocella P et al (2002) Tiagabine in glial tumors. Epileps Res 49:81–85

    Article  CAS  Google Scholar 

  87. Temkin NR, Dikmen SS, Wilensky AJ et al (1990) A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. NEJM 323:497–502

    Article  CAS  PubMed  Google Scholar 

  88. Tremont-Lukats W, Ratilal BO, Armstrong T, Gilbert MR (2008) Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database Syst Rev 18:CD004424

    Google Scholar 

  89. Van Breemen MSM, Rijsman RM, Taphoorn MJB et al (2009) Efficacy of anti-epileptic drugs in patients with gliomas and seizures. J Neurol 256:1519–1526

    Article  PubMed  Google Scholar 

  90. Van Breemen MSM, Wilms EB, Vecht CJ (2007) Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol 6:421–430

    Article  PubMed  Google Scholar 

  91. Vecht CJ, van Breemen MSM (2006) Optimizing therapy of seizures in patients with brain tumors. Neurology 67(Suppl 4):S10–S13

    Article  PubMed  Google Scholar 

  92. Vecht CJ, Wagner LG, Wilms EB (2003) Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol 2:404–409

    Article  CAS  PubMed  Google Scholar 

  93. Wagner GL, Wilms EB, van Donselaar CA, Vecht CJ (2003) Levetiracetam: preliminary experience in patients with primary brain tumours. Seizure 12:585–586

    Article  CAS  PubMed  Google Scholar 

  94. Ward MM, Barbaro NM, Laxer KD, Rampil IJ (1996) Preoperative valproate administration does not increase blood loss during temporal lobectomy. Epilepsia 37:98–101

    Article  CAS  PubMed  Google Scholar 

  95. Weller M, Gorlia T, Cairncross JG et al (2011) Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology 77:1156–1164

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Wick W, Menna O, Meisner C et al (2005) Pharmacotherapy of epileptic seizures in glioma patients: who, when, why and how long? Onkologie 28:391–396

    Article  CAS  PubMed  Google Scholar 

  97. Wieser H-G, Häne A (2001) Antiepileptic drug treatment before and after selective amygdalohippocampectomy. Epil Res 200155:211–223

    Google Scholar 

  98. Yuen TI, Morokoff AP, Bjorksten A et al (2012) Glutamate is associated with a higher risk of seizures in patients with gliomas. Neurology 79:883–889

    Article  CAS  PubMed  Google Scholar 

  99. Zaatreh MM, Firlik KS, Spencer DD, Spencer SS (2003) Temporal lobe tumoral epilepsy. Characteristics and predictors of surgical outcome. Neurology 61:636–641

    Article  PubMed  Google Scholar 

  100. Zentner J, Hufnagel A, Wolf KK et al (1997) Surgical treatment of neoplasms associated with medically intractable epilepsy. Neurosurgery 41:378–387

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurosurgery, Landeskrankenhaus Feldkirch, Feldkirch, Austria

    R. Bauer

  2. Neurosurgery, Medical University Innsbruck, Innsbruck, Austria

    M. Ortler

  3. Neurosurgery, Medical University Mannheim, Mannheim, Germany

    M. Seiz-Rosenhagen

  4. Radio-Oncology, Landeskrankenhaus Feldkirch, Feldkirch, Austria

    R. Maier

  5. Neurosurgery, University Hospital Salzburg, Salzburg, Austria

    J. V. Anton

  6. Neurology, Medical University Innsbruck, Innsbruck, Austria

    I. Unterberger

Authors
  1. R. Bauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Ortler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Seiz-Rosenhagen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. V. Anton
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I. Unterberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Bauer.

Additional information

Comments

Krasimir Minkin, Sofia, Bulgaria

This review is focused on the epilepsy problems of oncological neurosurgery. The authors raised the question about the contradictions between evidence-based medicine and practical medicine regarding prophylactic antiepileptic drug treatment of patients with newly diagnosed brain tumors without history of seizures. The review of the risks for early and late acute postoperative seizures provides some insights for the perioperative and continuous AED treatment in patients with brain tumors. An important positive feature of this paper is the attempt to review all antiepileptic treatment options in patients with brain tumor-related epilepsy: drugs, surgery, radiotherapy, and chemotherapy.

Bowen Jiang, Alfredo Quinones-Hinojosa, Baltimore, USA.

Seizures represent a major symptomatology in the brain tumor population and have significant implications on a patient’s quality of life. The use of antiepileptic drugs (AED) for brain tumor patients is an area of ongoing controversy and debate. Bauer and colleagues are commended for their critical review of the existing literature on this topic. The authors suggest that prophylactic use of AEDs is unwarranted in patients without preoperative seizures. They provide evidence that acutely provoked seizures, for the most part, do not require long-term AED treatment. The authors are applauded for their attempt to summarize the vast literature on evidence-driven guidelines. Yet, the question of when an AED is indicated and for how long is nuanced and complex. The answer is likely dependent upon a combination of pre/intra/postoperative factors, with a patient’s unique tumor history paramount to sophisticated decision-making.

For instance, the authors included meta-analysis from Sirven et al. [1] and Tremont-Lukats et al. [2] to support the conclusion that prophylactic AED treatment has no evidence in brain tumor patients without seizures. Within the benign brain tumor literature, Sughrue et al. evaluated 180 patients who underwent resection for convexity meningiomas. Although none of these patients had preoperative seizures, 129 were treated with AED postoperatively without any statistical difference in seizure control (0 vs 1.9 %) [3]. These data are confirmed by a meta-analysis from Komotar et al. [4] on 19 studies with a total of 689 supratentorial meningioma patients, which concluded no difference in the rate of early or late seizures between AED-treated and not treated groups. It would appear that the routine use of prophylactic AEDs for patients undergoing supratentorial meningioma resection provides no benefit, a sentiment many clinicians would be inclined to agree.

However, as we become more sophisticated and granular with our research, the neurosurgical community is now increasingly able to identify factors associated with higher seizure risk and thus better select patients ideal for AED management. Our institution has previously studied risk factors associated with seizures in WHO grade 1 meningiomas and found that patients with poor functional status, absence of signs of increased ICP, and MRI findings with significant cerebral edema are at higher risk for seizures [5]. Parasagittal and sphenoid wing meningioma are associated with continued seizures despite surgery and therapeutic AED. Likewise, for patients with high-grade gliomas (WHO III and IV), our institution previously found preoperative uncontrolled seizures and parietal lobe involvement to be negative predictors of seizure control [6]. In the era of individualized medicine, patient-specific disease characteristics should be factored into a potential AED therapeutic course. For these patients, a unified shotgun recommendation may not be appropriate, and in fact, many of these patients may benefit from AED therapy despite the guidelines.

At our institution, the use of levetiracetam is routine in the postoperative period and often maintained until the patient returns for first follow-up visit at 14–21 days. Since levetiracetam is a newer AED, its efficacy and side effect profile is frequently debated with that of phenytoin. Lim et al. conducted a randomized phase II pilot study on 29 patients who received either levetiracetam or phenytoin for postoperative seizure control [7]. The authors report better seizure control (87 vs 75 %) and fewer side effects (dizziness, depression, lethargy, insomnia) with levetiracetam. Indeed, this has been our institutional experience as well.

Finally, the authors astutely recognized that the initial data was from Temkin et al. [8] in the traumatic brain injury literature, in which phenytoin was utilized for the prevention of posttraumatic seizures. This literature has since then been extrapolated into the brain tumor armamentarium. Clearly, studies focused on seizure frequency, duration, and severity in the postoperative period will continue to advance the current literature. This study by Bauer et al. succinctly summarizes the vast literature on this topic and suggests treatment paradigms that will help neurosurgeons and neurologists alike in managing seizures for the brain tumor population.

References

1. Sirven JI, Wingerchuk DM, Drazkowski JF et al. (2004) Seizure prophylaxis in patients with brain tumors: a meta-analysis. Mayo Clin Proc 79:1,489–1,494

2. Tremont-Lukats W, Ratilal BO, Armstrong T, Gilbert MR (2008) Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database Syst Rev 18:CD004424

3. Seghrue ME, Rutkowski MJ, Chang EF, Shangari G, Kane AJ, McDermott MW, Berger MS, Parsa AT (2011) Postoperative seizures following the resection of convexity meningiomas: are prophylactic anticonvulsants indicated? J Neurosurg 114: 705–709.

4. Komotar RJ, Raper DM, Starke RM, Iorgulescu JB, Gutin PH (2011) Prophylactic antiepileptic drug therapy in patients undergoing supratentorial meningioma resection: a systematic analysis of efficacy. J Neurosurg 115: 483–490

5. Chaichana KL, Pendleton C, Zaidi H, Olivi A, Weingart JD, Gallia GL, Lim M, Brem H, Quinones-Hinojosa A (2013) Seizure control for patients undergoing meningioma surgery. World Neurosurg 90(3–4):512–524

6. Chaichana KL, Parker SL, Olivi A, Quinones-Hinojosa A (2009) Long-term seizure outcomes in adult patients undergoing primary resection of malignant brain astrocytoma. J Neurosurg 111(2):282–292

7. Lim DA, Tarapore P, Chang EF, Burt M, Chakalian L, Barbaro N, Chang S, Lamborn KR, McDermott MW (2009). Safety and feasibility of switching from phenytoin to levetiracetam monotherapy for glioma-related seizure control following craniotomy: a randomized phase II pilot study. J Neurooncol 93:349–354.

8. Temkin NR, Dikmen SS, Wilensky AJ et al. (1990) A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. NEJM 323:497–502

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bauer, R., Ortler, M., Seiz-Rosenhagen, M. et al. Treatment of epileptic seizures in brain tumors: a critical review. Neurosurg Rev 37, 381–388 (2014). https://doi.org/10.1007/s10143-014-0538-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-014-0538-6

Keywords

Search

Navigation