Association of IDH1 Mutations with Epilepsies in Patients with Diffuse Adult Glioma according to the WHO 2021 Classification

Authors

  • Almir Džurlić Clinic of Neurosurgery, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0002-6786-9267
  • Ibrahim Omerhodžić Clinic of Neurosurgery, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0001-5143-8801
  • Bekir Rovčanin Clinic of Neurosurgery, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0002-7298-3240
  • Faruk Alagić Department of Neurosurgery, Cantonal Hospital Dr. Irfan Ljubijankić, Bihać, Bosnia and Herzegovina https://orcid.org/0000-0001-5126-3933
  • Adi Ahmetspahić Clinic of Neurosurgery, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0003-1599-1807
  • Salko Zahirović Clinic of Neurosurgery, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Enra Mehmedika-Suljic Clinic of Neurology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina

DOI:

https://doi.org/10.3889/oamjms.2022.10925

Keywords:

Epilepsy, Diffuse Adult Glioma, WHO 2021 CNS classification, IDH mutation

Abstract

BACKGROUND: Tumors of the central nervous system comprise a wide range of over 100 histological distinct subtypes with different descriptive epidemiology, clinical features, treatments, and outcomes. The presence of isocitrate dehydrogenase gene mutation 1 (IDH1) has become one of the most critical biomarkers for molecular classification and prognosis in adult diffuse gliomas. About 65–90% of patients with adult diffuse gliomas have seizures as their initial symptoms.

AIM: The objective of this study was to determine the association between IDH1 mutations in adult diffuse gliomas with an incidence of symptomatic epilepsy.

METHODS: The study was conducted as an observational, cross-sectional, and prospective clinically controlled study at the Clinic of Neurosurgery of the Clinical Center of the University of Sarajevo. The research included a total of 100 patients treated at the Clinic of Neurosurgery, with pathohistological confirmation of glioma Grades II–IV who were stratified by groups according to tumor grade. Data were collected on tumor localization and grade, the presence of IDH mutations, and the presence of epileptic seizures as the first symptom of the glioma.

RESULTS: Out of a total of 100 patients, 39 had IDH 1 mutations, while 61 patients were without them: Of these, diffuse astrocytoma Grade II 30 cases (30%), Grade III 5 (5%), and Grade IV 7 (7%), and the number of patients with glioblastoma was 58 (58%). In the group of patients with IDH 1 mutations, epileptic seizures were present in 87.2% compared to the group of patients without IDH 1 mutations (wild type) in which epileptic seizures were present in 16.4% of cases. Statistical analysis showed that the positive mutated IDH-type carries an almost 70% increase in the likelihood of epileptic seizures (χ2 = 8.378; p = 0.0001). If we separate the group of diffuse astrocytomas in the IDH 1-positive subgroup, 34 patients (85.81%) had epileptic seizures, while in the IDH 1-negative subgroup, there were no patients with epileptic seizures, which carries a statistically significant difference in frequency in favor of IDH 1-positive tumors (p ≤ 0.001).

CONCLUSION: There is a clear connection between the presence of IDH1 mutations and the occurrence of epileptic seizures in the clinical picture of patients with diffuse adult glioma.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, et al. CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol. 2017;19 Suppl 5:v1-88. https://doi.org/10.1093/neuonc/nox158 PMid:29117289 DOI: https://doi.org/10.1093/neuonc/nox158

Lapointe S, Perry A, Butowski NA. Primary brain tumours in adults. Lancet. 2018;392(10145):432-46. https://doi.org/10.1016/S0140-6736(18)30990-5 PMid:30060998 DOI: https://doi.org/10.1016/S0140-6736(18)30990-5

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33. https://doi.org/10.3322/caac.21654 PMid:33433946 DOI: https://doi.org/10.3322/caac.21654

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella- Branger D, et al. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro Oncol. 2021;23(8):1231-51. https://doi.org/10.1093/neuonc/noab106 PMid:34185076 DOI: https://doi.org/10.1093/neuonc/noab106

Duan WC, Wang L, Li K, Wang WW, Zhan YB, Zhang FJ, et al. IDH mutations but not TERTp mutations are associated with seizures in lower-grade gliomas. Medicine (Baltimore). 2018;97(50):e13675. https://doi.org/10.1097/MD.0000000000013675 PMid:30558073 DOI: https://doi.org/10.1097/MD.0000000000013675

Pitkänen A, Ekolle Ndode-Ekane X, Lapinlampi N, Puhakka N. Epilepsy biomarkers – Toward etiology and pathology specificity. Neurobiol Dis. 2019;123:42-58. https://doi.org/10.1016/j.nbd.2018.05.007 PMid:29782966 DOI: https://doi.org/10.1016/j.nbd.2018.05.007

Chen H, Judkins J, Thomas C, Wu M, Khoury L, Benjamin CG, et al. Mutant IDH1 and seizures in patients with glioma. Neurology. 2017;88(19):1805-13. https://doi.org/10.1212/WNL.0000000000003911 PMid:28404805 DOI: https://doi.org/10.1212/WNL.0000000000003911

Zou Y, Bai HX, Wang Z, Jiang Y, Yang L. Association of IDH1/2 mutation with preoperative seizure in low-grade gliomas: How strong is the evidence? Epilepsy Res. 2015;112:154-5. https://doi.org/10.1016/j.eplepsyres.2015.02.012 PMid:25769499 DOI: https://doi.org/10.1016/j.eplepsyres.2015.02.012

Skardelly M, Brendle E, Noell S, Behling F, Wuttke TV, Schittenhelm J, et al. Predictors of preoperative and early postoperative seizures in patients with intra-axial primary and metastatic brain tumors: A retrospective observational single center study. Ann Neurol. 2015;78(6):917-28. https://doi.org/10.1002/ana.24522 PMid:26385488 DOI: https://doi.org/10.1002/ana.24522

Li Y, Shan X, Wu Z, Wang Y, Ling M, Fan X. IDH1 mutation is associated with a higher preoperative seizure incidence in low-grade glioma: A systematic review and meta-analysis. Seizure. 2018;55:76-82. https://doi.org/10.1016/j.seizure.2018.01.011 PMid:29414139 DOI: https://doi.org/10.1016/j.seizure.2018.01.011

Feyissa AM, Worrell GA, Tatum WO, Chaichana KL, Jentoft ME, Guerrero Cazares H, et al. Potential influence of IDH1 mutation and MGMT gene promoter methylation on glioma-related preoperative seizures and postoperative seizure control. Seizure. 2019;69:283-9. https://doi.org/10.1016/j.seizure.2019.05.018 PMid:31141785 DOI: https://doi.org/10.1016/j.seizure.2019.05.018

Song L, Quan X, Chen C, Chen L, Zhou J. Correlation between tumor molecular markers and perioperative epilepsy in patients with glioma: A systematic review and meta-analysis. Front Neurol. 2021;12:692751. https://doi.org/10.3389/fneur.2021.692751 PMid:34539550 DOI: https://doi.org/10.3389/fneur.2021.692751

Yang Y, Mao Q, Wang X, Liu Y, Mao Y, Zhou Q, et al. An analysis of 170 glioma patients and systematic review to investigate the association between IDH-1 mutations and preoperative glioma-related epilepsy. J Clin Neurosci. 2016;31:56-62. https://doi.org/10.1016/j.jocn.2015.11.030 PMid:27406953 DOI: https://doi.org/10.1016/j.jocn.2015.11.030

Murugan AK, Alzahrani AS. Isocitrate dehydrogenase IDH1 and IDH2 mutations in human cancer: Prognostic implications for gliomas. Br J Biomed Sci. 2022;79:10208. https://doi.org/10.3389/bjbs.2021.10208 PMid:35996504 DOI: https://doi.org/10.3389/bjbs.2021.10208

Sporikova Z, Slavkovsky R, Tuckova L, Kalita O, Megova Houdova M, Ehrmann J, et al. IDH1/2 mutations in patients with diffuse gliomas: A Single Centre Retrospective Massively Parallel Sequencing Analysis. Appl Immunohistochem Mol Morphol. 2022;30(3):178-83. https://doi.org/10.1097/PAI.0000000000000997 PMid:35262523 DOI: https://doi.org/10.1097/PAI.0000000000000997

Xia L, Wu B, Fu Z, Feng F, Qiao E, Li Q, et al. Prognostic role of IDH mutations in gliomas: A meta-analysis of 55 observational studies. Oncotarget. 2015;6(19):17354-65. https://doi.org/10.18632/oncotarget.4008 PMid:26220714 DOI: https://doi.org/10.18632/oncotarget.4008

Mellinghoff IK, Ellingson BM, Touat M, Maher E, De La Fuente MI, Holdhoff M, et al. Ivosidenib in isocitrate dehydrogenase 1-mutated advanced glioma. J Clin Oncol. 2020;38(29):3398-406. https://doi.org/10.1200/JCO.19.03327 PMid:32530764 DOI: https://doi.org/10.1200/JCO.19.03327

Vo AH, Ambady P, Spencer D. The IDH1 inhibitor ivosidenib improved seizures in a patient with drug-resistant epilepsy from IDH1 mutant oligodendroglioma. Epilepsy Behav Rep. 2022;18:100526. https://doi.org/10.1016/j.ebr.2022.100526 PMid:35198955 DOI: https://doi.org/10.1016/j.ebr.2022.100526

Downloads

Published

2022-10-13

How to Cite

1.
Džurlić A, Omerhodžić I, Rovčanin B, Alagić F, Ahmetspahić A, Zahirović S, Mehmedika-Suljic E. Association of IDH1 Mutations with Epilepsies in Patients with Diffuse Adult Glioma according to the WHO 2021 Classification. Open Access Maced J Med Sci [Internet]. 2022 Oct. 13 [cited 2024 Nov. 12];10(B):2465-9. Available from: https://oamjms.eu/index.php/mjms/article/view/10925