Postoperative outcomes of tumor-associated epileptic seizures in glioma patients

Background. Epileptic seizures occur in 50–90 % of patients with low‑grade glioma and in 20–60 % of patients with glioblastoma. The presence of tumor‑associated epilepsy is one of the leading criteria affecting the quality of life of this cohort of patients. The study of risk factors for the formation and persistence of tumor‑associated epilepsy after surgical resection can contribute to the most adequate care for such patients in terms of freedom from seizures and the duration of the relapse‑free period.

Aim. To study the features of epileptic seizures before surgical treatment, in remote cases of the postoperative period in patients with glioma.

Materials and methods. Patients (n = 184) with histologically verified gliomas underwent total or non‑total microsur‑ gical removal of the tumor. The radicality of resection was assessed 1 month after the operation. The observation was carried out for 5 years.

Results. All patients were divided into 4 groups. The 1st group consisted of 102 (55.42 %) patients whose seizures regressed after surgery; the 2nd group included 2 patients with the first seizures after surgery – 1 (0.54 %) in the early and 1 (0.54 %) in the late postoperative period; the 3rd group – 23 (12.5 %) patients with seizures both before and after surgery; the 4th group – 57 (31 %) patients without seizures. Total resection was performed significantly more often in the group with regressed seizures – in 79 (77.4 %) patients. The dynamics of the course of seizures did not depend on their initial nature and frequency. Twenty four (70,6 %) patients with new seizures had tumor recurrence, of which 15 (62.5 %) patients had seizure recurrence earlier than tumor recurrence based on RANO criteria.

Conclusion. Tumor‑associated epilepsy is most common in low‑grade gliomas. Total resection allows to increase life expectancy and improve its quality by controlling seizures. The effectiveness of adjuvant treatment of this cohort of patients is directly related to the results of treatment of tumor‑associated epilepsy.

1. Huang C., Chi X.S., Hu X. et al. Predictors and mechanisms of epilepsy occurrence in cerebral gliomas: what to look for in clinicopathology. Exp Mol Pathol 2017;102(1):115–22. DOI: 10.1016/j.yexmp.2017.01.005

2. Chen H., Judkins J., Thomas C. et al. Mutant IDH1 and seizures in patients with glioma. Neurology 2017;88(19):1805–13. DOI: 10.1212/WNL.0000000000003911

3. Li L., Li G., Fang S. et al. New-Onset postoperative seizures in patients with diffuse gliomas: a risk assessment analysis. Front Neurol 2021;12:682535. DOI: 10.3389/fneur.2021.682535

4. Chang E.F., Potts M.B., Keles G.E. et al. Seizure characteristics and control following resection in 332 patients with low-grade gliomas. J Neurosurg 2008;108(2):227–35. DOI: 10.3171/JNS/2008/108/2/0227

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

6. Savaskan N.E., Heckel A., Hahnen E. et al. Small interfering RNAmediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema. Nat Med 2008;14(6):629–32. DOI: 10.1038/nm1772

7. Vecht C.J., Kerkhof M., Duran-Pena A. Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist 2014;19(7):751–9. DOI: 10.1634/theoncologist.2014-0060

8. Pallud J., McKhann G.M. Diffuse low-grade glioma-related epilepsy. Neurosurg Clin N Am 2019;30(1):43–54. DOI: 10.1016/j.nec.2018.09.001

9. Neal A., Kwan P., OʼBrien T.J. et al. IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy. Epilepsy Behav 2018;78:30–6. DOI: 10.1016/j.yebeh.2017.10.027

10. Rossi J., Cavallieri F., Biagini G. et al. Epileptogenesis and tumorigenesis in glioblastoma: which relationship? Medicina (Kaunas) 2022;58(10):1349. DOI: 10.3390/medicina58101349

11. Hills K.E., Kostarelos K., Wykes R.C. Converging mechanisms of epileptogenesis and their insight in glioblastoma. Front Mol Neurosci 2022;15:903115. DOI: 10.3389/fnmol.2022.903115

12. Bouckaert C., Germonpré C., Verhoeven J. et al. Development of a rat model for glioma-related epilepsy. Int J Mol Sci 2020;21(19):6999. DOI: 10.3390/ijms21196999

13. Mauritz M., Hirsch L.J., Camfield P. et al. Acute symptomatic seizures: an educational, evidence-based review. Epileptic Disord 2022;24(1):26–49. DOI: 10.1684/epd.2021.1376

14. Kerkhof M., Koekkoek J.A.F., Vos M.J. et al. Withdrawal of antiepileptic drugs in patients with low grade and anaplastic glioma after long-term seizure freedom: a prospective observational study. J Neurooncol 2019;142(3):463–70. DOI: 10.1007/s11060-019-03117-y

15. Englot D.J., Berger M.S., Barbaro N.M., Chang E.F. Predictors of seizure freedom after resection of supratentorial low-grade gliomas. A review. J Neurosurg 2011;115(2):240–4. DOI: 10.3171/2011.3.JNS1153

16. Chaichana K.L., Parker S.L., Olivi A., Quiñones-Hinojosa A. Long-term seizure outcomes in adult patients undergoing primary resection of malignant brain astrocytomas. Clinical article. J Neurosurg 2009;111(2):282–92. DOI: 10.3171/2009.2.JNS081132