Brain Tumor Related Epilepsy: Pathophysiological Approaches and Rational Management of Antiseizure Medication

Overview

Journal Neurol Res Pract

Specialty Neurology

Date 2022 Sep 4

PMID 36059029

Authors

Sabine Seidel

Tim Wehner

Dorothea Miller

Jorg Wellmer

Uwe Schlegel

Wenke Gronheit

Affiliations

Soon will be listed here.

Abstract

Background: Brain tumor related epilepsy (BTRE) is a common complication of cerebral tumors and its incidence is highly dependent on the type of tumor, ranging from 10-15% in brain metastases to > 80% in low grade gliomas. Clinical management is challenging and has to take into account aspects beyond the treatment of non-tumoral epilepsy.

Main Body: Increasing knowledge about the pathophysiology of BTRE, particularly on glutamatergic mechanisms of oncogenesis and epileptogenesis, might influence management of anti-tumor and BTRE treatment in the future. The first seizure implies the diagnosis of epilepsy in patients with brain tumors. Due to the lack of prospective randomized trials in BTRE, general recommendations for focal epilepsies currently apply concerning the initiation of antiseizure medication (ASM). Non-enzyme inducing ASM is preferable. Prospective trials are needed to evaluate, if AMPA inhibitors like perampanel possess anti-tumor effects. ASM withdrawal has to be weighed very carefully against the risk of seizure recurrence, but can be achievable in selected patients. Permission to drive is possible for some patients with BTRE under well-defined conditions, but requires thorough neurological, radiological, ophthalmological and neuropsychological examination.

Conclusion: An evolving knowledge on pathophysiology of BTRE might influence future therapy. Randomized trials on ASM in BTRE with reliable endpoints are needed. Management of withdrawal of ASMs and permission to drive demands thorough diagnostic as well as neurooncological and epileptological expertise.

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References

Kim Y, Kim T, Joo J, Han J, Kim Y, Kim I . Survival benefit of levetiracetam in patients treated with concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma multiforme. Cancer. 2015; 121(17):2926-32. DOI: 10.1002/cncr.29439. View

Koekkoek J, Dirven L, Taphoorn M . The withdrawal of antiepileptic drugs in patients with low-grade and anaplastic glioma. Expert Rev Neurother. 2016; 17(2):193-202. DOI: 10.1080/14737175.2016.1219250. View

Maschio M, Zarabla A, Maialetti A, Fabi A, Vidiri A, Villani V . Quality of life, mood and seizure control in patients with brain tumor related epilepsy treated with lacosamide as add-on therapy: A prospective explorative study with a historical control group. Epilepsy Behav. 2017; 73:83-89. DOI: 10.1016/j.yebeh.2017.05.031. View

Valencia-Sanchez C, Gorelkin V, Mrugala M, Sharma A, Vora S, Ashman J . Clinical evaluation of fitness to drive in patients with brain metastases. Neurooncol Pract. 2019; 6(6):484-489. PMC: 6899051. DOI: 10.1093/nop/npz027. View

Venkataramani V, Tanev D, Kuner T, Wick W, Winkler F . Synaptic input to brain tumors: clinical implications. Neuro Oncol. 2020; 23(1):23-33. PMC: 7850064. DOI: 10.1093/neuonc/noaa158. View

Cardona A, Rojas L, Wills B, Bernal L, Ruiz-Patino A, Arrieta O . Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma. J Neurooncol. 2017; 136(2):363-371. DOI: 10.1007/s11060-017-2660-0. View

Belcastro V, Rosa Pisani L, Bellocchi S, Casiraghi P, Gorgone G, Mula M . Brain tumor location influences the onset of acute psychiatric adverse events of levetiracetam therapy: an observational study. J Neurol. 2017; 264(5):921-927. DOI: 10.1007/s00415-017-8463-6. View

Fisher R, Acevedo C, Arzimanoglou A, Bogacz A, Cross J, Elger C . ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014; 55(4):475-82. DOI: 10.1111/epi.12550. View

Lieu A, Howng S . Intracranial meningiomas and epilepsy: incidence, prognosis and influencing factors. Epilepsy Res. 1999; 38(1):45-52. DOI: 10.1016/s0920-1211(99)00066-2. View

10.

Lange F, Hornschemeyer J, Hornschemeyer M, Kirschstein T . Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy. Cells. 2021; 10(5). PMC: 8156732. DOI: 10.3390/cells10051226. View

11.

Huberfeld G, Vecht C . Seizures and gliomas--towards a single therapeutic approach. Nat Rev Neurol. 2016; 12(4):204-16. DOI: 10.1038/nrneurol.2016.26. View

12.

Urban H, Willems L, Ronellenfitsch M, Rosenow F, Steinbach J, Strzelczyk A . Increased occurrence of status epilepticus in patients with brain metastases and checkpoint inhibition. Oncoimmunology. 2020; 9(1):1851517. PMC: 7714514. DOI: 10.1080/2162402X.2020.1851517. View

13.

Shen S, Bai Y, Zhang B, Liu T, Yu X, Feng S . Correlation of preoperative seizures with a wide range of tumor molecular markers in gliomas: An analysis of 442 glioma patients from China. Epilepsy Res. 2020; 166:106430. DOI: 10.1016/j.eplepsyres.2020.106430. View

14.

Vezzani A, French J, Bartfai T, Baram T . The role of inflammation in epilepsy. Nat Rev Neurol. 2010; 7(1):31-40. PMC: 3378051. DOI: 10.1038/nrneurol.2010.178. View

15.

Rosenow F, Luders H . Presurgical evaluation of epilepsy. Brain. 2001; 124(Pt 9):1683-700. DOI: 10.1093/brain/124.9.1683. View

16.

van der Meer P, Dirven L, Fiocco M, Vos M, Kouwenhoven M, van den Bent M . First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid. Epilepsia. 2021; 62(5):1119-1129. PMC: 8251728. DOI: 10.1111/epi.16880. View

17.

Gonen T, Grossman R, Sitt R, Nossek E, Yanaki R, Cagnano E . Tumor location and IDH1 mutation may predict intraoperative seizures during awake craniotomy. J Neurosurg. 2014; 121(5):1133-8. DOI: 10.3171/2014.7.JNS132657. View

18.

Bond K, Rea E, Lawthom C . Seizures in palliative medicine: brivaracetam. BMJ Support Palliat Care. 2021; 13(e2):e308-e310. DOI: 10.1136/bmjspcare-2021-003228. View

19.

Mo F, Meletti S, Belcastro V, Quadri S, Napolitano M, Bello L . Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study. J Neurooncol. 2022; 157(3):551-559. DOI: 10.1007/s11060-022-03998-6. View

20.

Venkataramani V, Tanev D, Strahle C, Studier-Fischer A, Fankhauser L, Kessler T . Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature. 2019; 573(7775):532-538. DOI: 10.1038/s41586-019-1564-x. View