Antiepileptikabehandlung bei Hirntumor-bedingten epileptischen Anfällen

Zusammenfassung

Das Lebenszeitrisiko von Patienten mit Hirntumoren für das Auftreten von fokalen epileptischen Anfällen wird mit 20 – 80 % angegeben. Beim derzeitigen Wissensstand unterscheidet sich die medikamentöse Behandlung Hirntumor-bedingter fokaler Anfälle nicht von der Behandlung von Anfällen anderer Ätiologie. Die Auswahl der Antiepileptika richtet sich daher vor allem nach dem Nebenwirkungsspektrum und den pharmakokinetischen Interaktionen mit der Chemotherapie. Das in den deutschen Therapie-Leitlinien bei fokalen Anfällen als Mittel erster Wahl empfohlene Levetiracetam wird auch bei Hirntumor-bedingten Anfällen von zahlreichen Autoren als Mittel erster Wahl bezeichnet. Eine prophylaktische Antiepileptikagabe wird nach der derzeitigen Studienlage in der Regel abgelehnt. Nach einem ersten eindeutigen epileptischen Anfall sollte wegen des Rezidivrisikos in der Regel antiepileptisch behandelt werden.

Abstract

The lifetime risk of patients with brain tumours to have focal epileptic seizures is 20 – 80 %. Based on current evidence the management of tumour-related seizures does not differ substantially from that applied to epilepsies from other aetiologies. Therefore, the choice of an anticonvulsant is based, above all, on tolerability and pharmacokinetic interactions with chemotherapeutic drugs. Levetiracetam is recommended by many authors as first-line therapy in brain tumour-related epilepsy; this corresponds with the recommendation of the German guidelines on the treatment of focal seizures of any aetiology. Based on current evidence, the prophylactic prescription of long-term antiepileptic drugs in brain tumour patients who have not presented with seizures is not justified. Because of the high risk of recurrence, however, antiepileptic treatment should be strongly considered after a single brain tumour-related seizure.

Schlüsselwörter

Hirntumor - Antiepileptika - Epilepsie

Key words

brain tumours - antiepileptic drugs - epilepsy

• Literatur

• 1 Ostrom QT, Gittleman H, Farah P et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 2013; 15 (Suppl. 02) ii1-ii56 DOI: 10.1093/neuonc/not151. Erratum in: Neuro Oncol. 2014; 16:760
• 2 Paulus W, Hasselblatt M. Tumoren. In: Klöppel G, Kreipe HH, Remmele W, Hrsg. Pathologie, Bd. Neuropathologie. 3. Aufl. Berlin – Heidelberg: Springer; 2012: 481-549
• 3 Böker DK, Solymosi L. Röntgen und andere bildgebende Verfahren. In: Fröscher W, Vassella F, , Hrsg. Die Epilepsien. 1.Aufl. Berlin – New York: De Gruyter; 1994: 402-437
• 4 Van Breemen MSM, Wilms EB, Vecht ChJ. Epilepsy in patients with brain tumors: epidemiology, mechanism and management. Lancet Neurol 2007; 6: 421-430
• 5 Hildebrand J, Lecaille C, Perennes J et al. Epileptic seizures during follow-up of patients treated for primary brain tumors. Neurology 2005; 65: 212-215
• 6 Kerkhof M, Vecht ChJ. Seizure characteristics and prognostic factors of gliomas. Epilepsia 2013; 54 (Suppl. 09) 12-17
• 7 Krämer G. Tumorbedingte epileptische Anfälle bei Erwachsenen. Epilepsieblätter 1999; 12: 2-6
• 8 Vecht CJ, Wilms EB. Seizures in low- and high-grade gliomas: current management and future outlook. Expert Rev Anticancer Ther 2010; 10: 663-669
• 9 De Angelis LM. Brain tumors. N Engl J Med 2001; 344: 114-123
• 10 Brogna Ch, Robles G, Duffau H. Brain tumors and epilepsy. Expert Rev Neurother 2008; 8: 941-955
• 11 Rossetti AO, Stupp R. Epilepsy in brain tumor patients. Curr Opin Neurol 2010; 23: 603-609
• 12 Liu XY, Wang XF. Brain-tumor related epilepsy: review of the literature. Cancer Therapy 2012; 8: 130-138
• 13 Patzold U, Haller P. Die Klinik zerebraler Metastasen. Münch med Wschr 1975; 117: 301-306
• 14 Reif PS, Strzelczyk K, Rüegg S et al. Primäre Hirntumoren und Hirnmetastasen. Symptomatische Epilepsie und Fahreignung – Expertenumfrage und systematisches Review. Nervenarzt 2010; 81: 1467-1475
• 15 Govori V, Humolli I, Cepreganov M et al. Brain tumors and epilepsy. Acta Clin Croat 2010; 49: 133-138
• 16 Liigant A, Haldre S, Öun A et al. Seizure disorders in patients with brain tumors. Europ Neurol 2001; 45: 46-51
• 17 Lynam LM, Lyons MK, Drazkowski JF et al. Frequency of seizures in patients with newly diagnosed brain tumors: a retrospective review. Clin Neurol Neurosurg 2007; 109: 634-638
• 18 Stefan H. Hirntumoren und Epilepsien. Z Epileptol 2009; 22: 65-71
• 19 Von Lehe M, Schramm J, Simon M. Chirurgisches Management tumorassoziierter Epilepsie. Z Epileptol 2012; 22: 65-71
• 20 Luyken C, Blümcke I, Fimmers R et al. The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor outcome and neurosurgical aspects. Epilepsia 2003; 44: 822-830
• 21 Prayson RA. Brain tumors in adults with medically intractable epilepsy. Am J Clin Pathol 2011; 136: 557-563
• 22 Klein M, Engelberts NHJ, van der Ploeg HM et al. Epilepsy in low-grade gliomas: The impact on cognitive function and quality of life. Ann Neurol 2003; 54: 514-520
• 23 Rudà R, Bello L, Duffau H et al. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments. Neuro-Oncol 2012; 14: 55-64
• 24 Berg AT, Berkovic SF, Brodie MJ et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE commission on classification and terminology, 2005-2009. Epilepsia 2010a 51: 676-685
• 25 Berg AT, Berkovic SF, Brodie MJ et al. Revidierte Terminologie und Konzept der Einteilung von epileptischen Anfällen und Epilepsien: Bericht der Klassifikations- und Terminologiekommission der Internationalen Liga gegen Epilepsie, 2005–2009 (Übersetzung von G Krämer). Akt Neurol 2010b 37: 120-130
• 26 Michelucci R, Pasini E, Meletti St. Epilepsy in primary cerebral tumors: The characteristics of epilepsy at the onset (results from the PERNO study – Project of Emilia Romagna region on neurooncology). Epilepsia 2013; 54 (Suppl. 07) 86-91
• 27 Avila EK, Graber J. Seizures and epilepsy in cancer patients. Curr Neurol Neurosci Rep 2010; 10: 60-67
• 28 Swisher ChB, Doreswamy M, Gingrich KJ et al. Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors. Neurocrit Care 2012; 16: 109-113
• 29 Beaumont A, Whittle IR. The pathogenesis of tumour associated epilepsy. Acta Neurochir (Wien) 2000; 142: 1-15
• 30 Blümcke I. Epilepsy-associated brain tumors. In: Stefan H, Theodore WH, Eds. Handbook of clinical neurology. Epilepsy, part II. 108. (3rd series) Amsterdam: Elsevier; 2012: 559-568
• 31 De Groot M, Reijneveld JC, Aronica E et al. Epilepsy in patients with a brain tumor: focal epilepsy requires forced treatment. Brain 2012; 135: 1002-1016
• 32 Robert SM, Sontheimer H. Glutamate transporters in the biology of malignant gliomas. Cell Mol Life Sci 2014; 71: 1839-1854
• 33 Vecht ChJ, and van Breemen M. Optimizing therapy of seizures in patients with brain tumors. Neurology 2006; 67 (Suppl. 04) S10-S13
• 34 Ettinger AB. Structural causes of epilepsy. Tumors, cysts, stroke, and vascular malformations. Neurol Clin 1994; 12: 41-57
• 35 Pallud J, Capelle L, Haberfeld G. Tumoral epileptogenicity: how does it happen?. Epilepsia 2013; 54 (Suppl. 09) 30-34
• 36 You G, Sha Z, Jung T. The pathogenesis of tumor-related epilepsy and its implications for clinical treatment. Seizure 2012; 21: 153-159
• 37 Asanuma M, Miyazaki I, Diaz-Corrales FJ et al. Neuroprotective effects of zonisamide target astrocyte. Ann Neurol 2010; 67: 239-249
• 38 Buckingham SC, Campbell SL, Haas BR et al. Glutamate release by primary brain tumors induces epileptic activity. Nat Med 2011; 17: 1269-1274
• 39 Yuen TI, Morokoff AP, Bjorksten A et al. Glutamate is associated with a higher risk of seizures in patients with gliomas. Neurology 2012; 79: 883-889
• 40 Robe PA, Martin DH, Nguyen-Khac MT et al. Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults. BMC Cancer 2009; 9: 372
• 41 Grossman SA, Ye X, Chamberlain M et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol 2009; 27: 4155-4161
• 42 Rosati A, Marconi S, Pollo B et al. Epilepsy in glioblastoma multiforme: correlation with glutamine synthetase levels. J Neurooncol 2009; 93: 319-324
• 43 Rosati A, Poliani PL, Todeschini A et al. Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme. Neuro Oncol 2013; 15: 618-625
• 44 Liubinas SV, D’Abaco GM, Moffat BM et al. IDH I mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas. Epilepsia 2014; 55: 1438-1443
• 45 Stockhammer F, Misch M, Helms HJ et al. IDH 1/2 mutations in WHO grade II astrocytomas associated with localisation and seizure as the initial symptom. Seizure 2012; 21: 194-197
• 46 Conti L, Palma E, Roseti C et al. Anomalous levels of Cl- transporters cause a decrease of GABAergic inhibition in human peritumoral epileptic cortex. Epilepsia 2011; 52: 1635-1644
• 47 Garzon-Muvdi T, Schiapparelli P, Rhys C et al. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation. PLoS Biol 2012; 10: e1001320
• 48 Pallud J, Le Van Quyen M, Bielle F et al. GABAergic excitation contributes to epileptic activities around human glioma. Sci Transl Med 2014; 6: 244ra89
• 49 Lhatoo SD, Meghimi N, Schuele St. Tumor-related epilepsy and epilepsy surgery. Epilepsia 2013; 54 (Suppl. 09) 1-4
• 50 Pallud J, Audureau E, Blonski M et al. Epileptic seizures in diffuse low-grade gliomas in adults. Brain 2014; 137: 449-462
• 51 Perucca E. Optimizing antiepileptic drug treatment in tumoral epilepsy. Epilepsia 2013; 54 (Suppl. 09) 97-104
• 52 Seek M. Surgical treatment of tumoral temporal-lobe epilepsy. Lancet Neurol 2003; 2: 722-723
• 53 Tandon N, Esquenazi Y. Resection strategies in tumoral epilepsy: Is a lesionectomy enough?. Epilepsie 2013; 54 (Suppl. 09) 72-78
• 54 Bruna J, Miro J, Roser V. Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment. Expert Rev Clin Pharmacol 2013; 6: 333-344
• 55 Maschio M. Brain tumor-related epilepsy. Curr Neuropharmacol 2012; 10: 124-133
• 56 Frenay MP, Fontaine D, Vandenbos F et al. First-line nitrosurea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas. Eur J Neurol 2005; 12: 685-690
• 57 Van Breemen MSM, Wilms EB, Vecht CJ. Seizure control in brain tumors. In: Grisold W, Soffietti R, , Eds. Handbook of clinical neurology. Neuro-oncology. 104. (3rd series) Amsterdam: Elsevier; 2012: 381-389
• 58 Wallace EM, O’Reilly M, Twomey M. A review of the use of antiepileptic drugs in high-grade central nervous system tumors. Am J Hosp Palliat Care 2012; 29: 618-621
• 59 Diener HC, Weimar C, Berlit P et al. Hrsg. Leitlinien für Diagnostik und Therapie in der Neurologie. Kap. 76, Gliome. 5. Aufl. Stuttgart: Thieme; 2012: 922-938
• 60 Moots P, Marciunas R, Eisert D et al. The course of seizure disorders in patients with malignant gliomas. Arch Neurol 1995; 52: 717-724
• 61 Rudà R, Trevisan E, Sofietti R. Epilepsy and brain tumors. Curr Opin Oncol 2010; 22: 611-620
• 62 Maschio M, Dinapoli L. Lecture: profile of risks and benefits of new antiepileptic drugs in brain tumor-related epilepsy. Neurol Sci 2011; 32 (Suppl. 02) S259-S262
• 63 Weller M, Stupp R, Wick W. Epilepsy meets cancer: when, why, and what to do about it?. Lancet Oncol 2012; 13: e375-e382
• 64 Jaeckle KA, Ballman K, Furth A et al. Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma. Neurology 2009; 73: 1207-1213
• 65 Kerrigan SJ, Graham C, Stenning S et al. Enzyme inducing antiepileptic drugs and survival of patients with recurrent malignant glioma. Conference abstract. 10th Congress of European Association of Neuro-Oncology Marseille: 2012 Date of publication: September 2012
• 66 Lim D, Tarapore P, Chang E et al. 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 2009; 93: 349-354
• 67 Merrell RT, Anderson SK, Meyer FB et al. Seizures in patients with glioma treated with phenytoin and levetiracetam. J Neurosurg 2010; 113: 1176-1181
• 68 Pruitt AA. Medical management of patients with brain tumors. Curr Treat Options Neurol 2011; 13: 413-426
• 69 Penovich PE, Dickens DL, Gates JR et al. Treating seizures due to brain neoplasms: rational new choices. Epilepsia 2004; 45 (Suppl. 07) 311
• 70 Perry JR, Sawka C. Add-on gabapentin for refractory seizures in patients with brain tumors. Can J Neurol Sci 1996; 23: 128-131
• 71 Dinapoli L, Maschio M, Mingoia M et al. Add-on lacosamide in brain tumor-related epilepsy. Boll Lega Ital Epilessia 2012; 144: 195-197
• 72 Saria MG, Corle C, Hu H et al. Retrospective analysis of the tolerability and activity of lacosamide in patients with brain tumors. J Neurosurg 2013; 118: 1183-1187
• 73 Spitz M, Drees C, Frey L et al. Pharmaco-adherence in patients with epilepsy and neurologic tumors. Epilepsy Curr 2014; 14 (Suppl. 01) 230
• 74 Yamamoto T, Yamazoe T, Fujimoto A et al. Effectiveness and role of lamotrigine in the paradigm shift towards new antiepileptic drugs: a therapeutic strategy proposed after an investigation of a large number of cases at a single hospital. Brain Nerve 2014; 66: 59-66
• 75 Dinapoli L, Maschio M, Jandolo B et al. Quality of life and seizure control in patients with brain-tumor related epilepsy treated with levetiracetam monotherapy: preliminary data of an open label-study. Neurol Sci 2009; 30: 353-359
• 76 Kerkhof M, Dielemans JC, van Breemen MS et al. Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro Oncol 2013; 15: 961-967
• 77 Lee YJ, Kim T, Bae SH et al. Levetiracetam compared with valproic acid for the prevention of postoperative seizures after supratentorial tumor surgery: a retrospective chart review. CNS Drugs 2013; 27: 753-759
• 78 Maschio M, Albani F, Baruzzi A et al. Levetiracetam therapy in patients with brain tumor and epilepsy. J Neuro-Oncol 2006b 80: 97-100
• 79 Milligan TA, Hurwitz S, Bromfield EB. Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery. Neurology 2008; 71: 665-669
• 80 Newton HB, Dalton J, Goldlust S et al. Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients. J Neuro-Oncol 2006; 78: 99-102
• 81 Rosati A, Buttolo L, Stefini R et al. Efficacy and safety of levetiracetam in patients with glioma. Arch Neurol 2010; 67: 343-346
• 82 Rossetti AO, Jeckelmann S, Novy J et al. Levetiracetam and pregabalin for antiepileptic monotherapy in patients with primary brain tumors. A phase II randomized study. Neuro-Oncol 2014; 16: 584-588
• 83 Wagner GL, Wilms EB, van Donselaar CA et al. Levetiracetam: preliminary experience in patients with primary brain tumors. Seizure 2003; 12: 585-596
• 84 Maschio M, Dinapoli L, Vidri A et al. 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 2009; 93: 349-354
• 85 Maschio M, Dinapoli L, Sperati F et al. Oxcarbazepine monotherapy in patients with brain tumor-related epilepsy. Open-label pilot study for assessing the efficacy, tolerability and impact on quality of life. J Neuro-Oncol 2012; 106: 651-656
• 86 Maschio M, Dinapoli L, Sperati F et al. Effect of pregabalin add-on treatment on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy: a pilot study. Epileptic Disord 2012; 14: 388-397
• 87 Novy J, Stupp R, Rossetti AO. Pregabalin in patients with primary brain tumors and seizures: a preliminary observation. Clin Neurol Neurosurg 2009; 11: 171-173
• 88 Maschio M, Dinapoli L, Zarabla A et al. Outcome and tolerability of topiramate in brain tumor associated epilepsy. J Neuro-Oncol 2008; 86: 61-70
• 89 Weller M, Gorlia T, Cairncross JG et al. Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma. Neurology 2011; 77: 1156-1164
• 90 Maschio M, Dinapoli L, Saverian F et al. Efficacy and tolerability of zonisamide as add-on in brain tumor-related epilepsy: preliminary report. Acta Neurol Scand 2009; 120: 210-212
• 91 Reif PS, Strik H, Rosenow F. Therapeutisches Management bei Patienten mit tumorassoziierter Epilepsie – Pharmakotherapie. Z Epileptol 2012; 25: 104-113
• 92 Kargiotis O, Markoula S, Kyritsis AP. Epilepsy in the cancer patient. Cancer Chemother Pharmacol 2011; 67: 489-501
• 93 Kerrigan S, Grant R. Antiepileptic drugs for treating seizures in adults with brain tumors (review). . Cochrane Database Syst Rev 2011; 8
• 94 Maschio M, Dinapoli L. Patients with brain tumor-related epilepsy. J Neurooncol 2012; 109: 1-6
• 95 Ruggiero A, Rizzo D, Mastrangelo S et al. Interactions between antiepileptic and chemotherapeutic drugs in children with brain tumors: Is it time to change treatment?. Pediatr Blood Cancer 2010; 54: 193-198
• 96 De Groot M, Douw L, Sizoo EM et al. Levetiracetam improves verbal memory in high-grade glioma patients. Neuro-Oncology 2013; 15: 216-223
• 97 Oberndorfer S, Piribauer M, Marosi C et al. P450 enzyme inducing and non-enzyme inducing antiepileptics in glioblastoma patients treated with standard chemotherapy. J Neurooncol 2005; 72: 255-260
• 98 Relling MV, Pui CH, Sandlund JT et al. Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia. Lancet 2000; 356: 285-290
• 99 Tibussek D, Distelmaier F, Schönberger S et al. Antiepileptic treatment in paediatric oncology – an interdisciplinary challenge. Klin Pädiatr 2006; 218: 340-349
• 100 Van Breemen MSM, Rijsman RM Tophoorn MJB et al. Efficacy of anti-epileptic drugs in patients with gliomas and seizures. J Neurol 2009; 256: 1519-1526
• 101 Yano H, Nakayama N, Ohe N et al. A review of brain tumor-related epilepsy: the utility of levetiracetam. J Jpn Epil Soc 2013; 31: 2-7
• 102 Barker CA, Bishop AJ, Chang M et al. Valproic acid use during radiation therapy for glioblastoma associated with improved survival. Int J Radiat Oncol Biol Phys 2013; 86: 504-509
• 103 Felix FH, Trompieri NM, de Araujo OL et al. Potential role for valproate in the treatment of high-risk brain tumors of childhood – results from a retrospective observational cohort study. Pediatr Hematol Oncol 2011; 28: 556-570
• 104 Felix FH, de Araujo OL, da Trindade KM et al. Retrospective evaluation of outcomes of children with diffuse intrinsic pontine glioma treated with radiochemotherapy and valproic acid in a single center. J Neurooncol 2014; 116: 261-266
• 105 Guthrie GD, Eljamel S. Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme. J Neurosurg 2013; 118: 859-865
• 106 Masoudi A, Elopre M, Amini E et al. Influence of valproic acid on outcome of high-grade gliomas in children. Anticancer Res 2008; 28: 2437-2442
• 107 Stupp R, Mason WP et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352: 987-996
• 108 Činčárová L, Zdráhal Z, Fajkus J. New perspectives of valproic acid in clinical practice. Expert Opin Investig Drugs 2013; 22: 1435-1447
• 109 Weller M. Are we ready for a randomized trial of valproic acid in newly diagnosed glioblastoma?. Neuro-Oncol 2013; 15: 809-810
• 110 Bobustuc GC, Baker CH, Limaye A et al. Levetiracetam enhances p53-mediated MGMT inhibition and sensitizes glioblastoma cells to temozolomide. Neuro-Oncol 2010; 12: 917-927
• 111 Iwamoto FM, Kreisl TN, Kim L et al. Phase 2 trial of talampanel, a glutamate receptor inhibitor, for adults with recurrent malignant gliomas. Cancer 2010; 1776-1782
• 112 Tönjes M, Barbus S, Park YJ et al. BCAT1 promotes cell proliferation through no acid catabolism in gliomas carrying wild-type IDH1. Nat Med 2013; 19: 901
• 113 Marcuse LV, Lancman G, Demopoulos A et al. Nonconvulsive status epilepticus in patients with brain tumors. Seizure 2014; 23: 542-547
• 114 Diener HC, Weimar C, Berlit P et al. Hrsg. Leitlinien für Diagnostik und Therapie in der Neurologie. Kap. 2, Status epilepticus im Erwachsenenalter. 5. Aufl. Stuttgart: Thieme; 2012: 48-57
• 115 Fröscher W. Drug resistant epilepsy. Epileptologia 2012; 20: 17-23
• 116 Scholly J, Valenti M-P, Staack AM et al. Hypothalamic hamartoma: Is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis. Epilepsia 2013; 54 (Suppl. 09) 123-128
• 117 Guerrini R, Rosati A, Giordano F et al. The medical and surgical treatment of tumoral seizures: Current and future perspectives. Epilepsia 2013; 54 (Suppl. 09) 84-90
• 118 Mamon HJ, Wen PY, Burns AC et al. Allergic skin reactions to anticonvulsant medications in patients receiving cranial radiation therapy. Epilepsia 1999; 40: 341-344
• 119 Bourg V, Lebrun C, Chichmanian RM et al. Nitrosurea-cisplatin based chemotherapy associated with valproate: increase of haematologic toxicity. Ann Oncol 2001; 12: 217-219
• 120 Schlegel U. Hohe Lebensqualität – trotz Hirntumor. Medical Tribune 2011; 46 (43) 21
• 121 Vecht CJ, Wagner GL, Wilms EB. Interactions between antiepileptic and chemotherapeutic drugs. Lancet Neurol 2003; 2: 404-409
• 122 Gerstner T, Teich M, Bell N et al. Valproate-associated coagulopathies are frequent and variable in children. Epilepsia 2006; 47: 1136-1143
• 123 Schabet M, Weinauer E. Therapie primärer Hirntumoren. Fortschr Neurol Psychiat 2003; 71: 607-682
• 124 Kerrigan S. Drug treatment of epilepsy in people with brain tumors. EJOP 2010; 4: 9-10
• 125 Rambeck B, May TW. Enzyminduktion in der Leber durch Antiepileptika. In: Fröscher W, Blankenhorn V, May TW, et al. Pharmakotherapie der Epilepsien. 4. Aufl. Stuttgart-New York: Schattauer; 2008: 128-130
• 126 Rote Liste. Frankfurt/Main: Rote Liste Service GmbH; 2014 54. Ausgabe.
• 127 Baxter K, Preston CL Eds. Stockley’s Drug Interactions. 10th ed. London-Chicago: Pharmaceutical Press; 2013
• 128 Neher KD. Interaktionen: Beeinflussung der Serumkonzentration von Antiepileptika durch andere Medikamente. In: Fröscher W, Blankenhorn V, May TW, et al. Pharmakotherapie der Epilepsien. 4. Aufl. Stuttgart-New York: Schattauer; 2008: 135-177
• 129 Neher KD. Interaktionen: Beeinflussung der Serumkonzentration von Nicht-Antiepileptika durch Antiepileptika. In: Fröscher W, Blankenhorn V, May TW, et al. Pharmakotherapie der Epilepsien. 4. Aufl. Stuttgart-New York: Schattauer; 2008: 128-130
• 130 Patsalos PN. Drug interactions with the newer antiepileptic drugs (AEDs) – Part 2: Pharmacokinetic and pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders. Clin Pharmacokinet 2013; 52: 1045-1061
• 131 Wen PY, Schiff D, Kesari S et al. Medical management of patients with brain tumors. J Neurooncol 2006; 80: 313-332
• 132 Rogers LR. Chemotherapy and immunotherapy of brain tumors: What the epileptologist must know. Epilepsia 2013; 54 (Suppl. 09) 105-108
• 133 Ikeda H, Murakami T, Takano M et al. Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient. Br J Clin Pharmacol 2005; 59: 593-597
• 134 Motl S, Zhuang Y, Waters ChM et al. Pharmacokinetic considerations on the treatment of CNS tumors. Clin Pharmacokinet 2006; 45: 871-903
• 135 Villika K, Kivisto KT, Maenpaa H et al. Cytochrome P450-inducing antiepileptics increase the clearance of vincristine in patients with brain tumors. Clin Pharmacol Ther 1999; 66: 589-593
• 136 Grenader T, Gipps M, Shavit L et al. Significant drug interaction: Phenytoin toxicity due to erlotinib. Lung Cancer 2007; 57: 404-406
• 137 Markoula S, Teotonia R, Ratmaraj N et al. Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs. Ther Drug Monit 2014; 36: 494-498
• 138 Vimpat® Fachinformation. Monheim: UCB Pharma GmbH; 2013
• 139 Wells EM, Gaillard WD, Packer RJ. Pediatric brain tumors and epilepsy. Semin Pediatr Neurol 2012; 19: 3-8
• 140 Kim LG, Johnson TL, Marson AG et al. Prediction of risk of seizure recurrence after a single seizure and early epilepsy: further results from the MESS trial. Lancet Neurol 2006; 5: 317-322
• 141 Glantz MJ, Cole BF, Forsyth PA et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Neurology 2000; 54: 1886-1893
• 142 Lee MH, Kong DS, Seol HJ et al. Risk of seizure and its clinical implication in the patients with cerebral metastasis from lung cancer. Acta Neurochir 2013; 155: 1833-1837
• 143 Wu AS, Trinh VT, Suki D et al. A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors. J Neurosurg 2013; 118: 873-883
• 144 Sayegh ET, Fakurnejad S, Oh T et al. Anticonvulsant prophylaxis for brain tumor surgery: determining the current best available evidence. J Neurosurg 2014; 29: 1-9 [Epub ahead of print]
• 145 Blümcke I, Coras R. Epileptogene Hirntumoren. Z Epileptol 2012; 25: 83-87
• 146 Brainer-Lima PT, Mertens Brainer-Lima A, Azevedo-Filho HR. Ganglioglioma – comparison with other low-grade brain tumors. Arq Neuropsiquiatr 2006; 64: 613-618
• 147 Morris HH, Matkovic Z, Estes ML et al. Ganglioglioma and intractable epilepsy: Clinical and neurophysiologic features and predictions of outcome after surgery. Epilepsia 1998; 39: 307-313
• 148 Stefan H, Blümcke I, Buchfelder M. Hirntumoren und Epilepsie. Nervenarzt 2005; 76: 1196-1208
• 149 Louis DN, Ohgaki H, Wiestler OD et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropatol 2007; 114: 97-109
• 150 Japp A, Gielen GH, Becker AJ. Recent aspects of classification and epidemiology of epilepsy-associated tumors. Epilepsia 2013; 54 (Suppl. 09) 5-11
• 151 Khan RB, Omar A. Seizure recurrence and risk factors after antiepileptic drug withdrawal in children with brain tumors. Epilepsia 2006; 47: 375-379
• 152 Zschocke St, Hansen HC Hrsg. Klinische Elektroenzephalographie. 3. Aufl.. Berlin-Heidelberg: Springer; 2012
• 153 Sharanreddy M, Kulkarni PK. Automated EEG signal analysis for identification of epilepsy seizures and brain tumour. J Med Eng Technol 2013; 37: 511-519
• 154 Schmidt D, Löscher W. Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: a review of current clinical experience. Acta Neurol Scand 2005; 111: 291-300
• 155 Schlegel U, Schramm J. Epileptische Anfälle. In: Schlegel U, Westphal M, Hrsg. Neuroonkologie. Stuttgart-New York: Thieme; 1998: 95-96
• 156 Weller M. Chemotherapie von Hirntumoren bei Erwachsenen. Nervenarzt 2008; 79: 231-241
• 157 Stopschinski BE, Beier D, Beier CP. Medikamentöse Therapie von Hirntumoren. Nervenheilkunde 2012; 31: 621-629
• 158 Hu A, Xu Z, Kim RY et al. Seizure control: A secondary benefit of chemotherapeutic temozolomide in brain cancer patients. Epilepsy Res 2011; 95: 270-272
• 159 Baglia R, Sperling MR, Nei M. Temozolomide chemotherapy, AEDs and surgery for refractory epilepsy in patients with oligodendrogliomas. Abstract Philadelphia: American Epilepsy Society; 2007 Program No 1056
• 160 Ngo L, Nei M, Glass J. Temozolomide treatment of refractory epilepsy in a patient with an oligodendroglioma. Epilepsia 2006; 47: 1237-1238
• 161 Sherman JH, Moldovan K, Yeoh HK et al. Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J Neurosurg 2011; 114: 1617-1621
• 162 Meyer A, Fröscher W. Anfallssteigernde Medikamente und Drogen. In: Fröscher W, Vassella F, Hufnagel A, Hrsg Die Epilepsien. 2. Aufl. Stuttgart-New York: Schattauer; 2004: 523-541
• 163 Bast T, Wiemer-Kruel A. Rationale Epilepsiebehandlung bei tuberöser Sklerose. Nervenheilkunde 2014; 33: 356-361
• 164 Cardamone M, Flanagan D, Mowat D et al. Mammalian target of rapamycin inhibitors for intractable epilepsy and subependymal giant cell astrocytomas in tuberous sclerosis complex. J Pediatr 2014; 164: 1195-2000
• 165 Knuf M, Bach A, Lampe C. Neues zur Therapie der Tuberösen Sklerose. Akt Dermatol 2013; 39: 74-78
• 166 Krueger DA, Carc MM, Holland K et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 2010; 363: 1801-1811
• 167 Votubia® Fachinformation. Nürnberg: Novartis Pharma GmbH; 2013
• 168 Boehmerle W, Huehnchen P, Endres M. Neurologische Nebenwirkungen von Zytostatika. Akt Neurol 2014; 41: 21-34
• 169 Plotkin SR, Wen PY. Neurologic complications of cancer therapy. Neurol Clin 2003; 21: 279-318
• 170 Spitzer M. Chemo-Gehirn – Nebenwirkungen von Chemotherapie in Erleben, Denken, Fühlen und Handeln. Nervenheilkunde 2014; 33: 319-324
• 171 Wychowski T, Wang H, Buniak L et al. Considerations in prophylaxis tumor-associated epilepsy: prevention of status epilepticus and tolerability of newer generation AEDs. Clin Neurol Neurosurg 2013; 115: 2365-2369
• 172 Fröscher W. Beendigung der Pharmakotherapie – warum, wann, wie?. Nervenheilkunde 2010; 29: 204-208