Research progress on the characteristics of glioma related epilepsy under WHO classification_Journal of Epilepsy

Authors：

QIU Hao , XUE Jishan ,  DU Peng

Department of Neurosurgery, the Second Affiliated Hospital of Xinjiang Medical University, Urumqi830000, China;

Corresponding author：

DU Peng, Email: 13699994376@163.com

Keywords：

Glioma related epilepsy; Clinical features; World Health Organization; Local metabolism

DOI：

10.7507/2096-0247.202411012

Video：

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Glioma related epilepsy (GRE) is a complication that seriously affects the quality of life and treatment process of glioma patients. The genes and biomolecules in the tumor microenvironment may contribute to the mechanisms and pathways of epilepsy. In addition, it has been found that epileptic seizures can promote the growth of brain tumors, making controlling epilepsy a key factor in treating brain tumors., However, in current understanding, not all genetic molecular features carried by gliomas themselves are involved in the pathogenesis of GRE. With the deepening understanding of GRE, it has been discovered that some molecular features of gliomas are involved in the pathogenesis of GRE, mainly through the Ras/Raf/MAPK (MEK)/ERK and PI3K/AKT/mTOR pathways, which are also involved in the pathogenesis of gliomas. In 2021, the World Health Organization (WHO) classified diffuse gliomas into two categories: adult and pediatric, and further subdivided them into types such as astrocytoma, oligodendroglioma, and glioblastoma. This classification helps to more accurately understand and apply the molecular characteristics of gliomas, promote the standardization of tumor pathological diagnosis, and may have an impact on the treatment and prognosis evaluation of GRE. This review links genes and biomolecules in the tumor microenvironment through the latest WHO classification, summarizes previous research and recent findings, and provides a deeper understanding of the molecular characteristics of gliomas and their relationship with epilepsy related molecular pathways. It explores more effective treatment methods to suppress epilepsy symptoms and tumor growth, which is of great significance for improving the diagnosis and treatment of GRE.

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2.	Chipaux M, Szurhaj W, Vercueil L J, et al. Epilepsy diagnostic and treatment needs identified with a collaborative database involv-ing tertiary centers in France. Epilepsia, 2016, 57: 757-769.
3.	Oushy S, Sillauu SH, Ney DE, et al. New-onset seizure during and after brain tumor excision: a risk assessment analysis. J Neu-rosurg, 2018, 128: 1713-1718.
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7.	Delev D, Daka K, Heynckes S, et al. Long-term epilepsy-associated tumors: transcriptional signatures reﬂect clinical course. Scientific reports, 2020, 10(1): 96.
8.	Koh HY, Kim SH, Jang J, et al. BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors. Nat Med, 2018, 24(11): 1662-1668.
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10.	Prabowo AS, Iyer AM, Veersema TJ, et al. BRAFV600E mutation is associated with mTOR signaling activation in Glioneuronaltumors. Brain Pathol, 2014, 24: 52-66.
11.	Liu Q, Cai L, Sun Y, et al. Epilepsy outcome and pathology analysis for ganglioglioma: a series of 51 pediatric patients. Pediatr Neurol. 2023, 149: 127-133.
12.	Qaddoumi I, Orisme W, Wen J, et al. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology. Neuropathol, 2016, 131: 833-845.
13.	Xie M, Wang X, Duan Z, et al. Low-grade epilepsy-associated neuroepithelial tumors: Tumor spectrum and diagnosis based on genetic alterations. Frontiers in Neuroscience, 2023, 16: 107-314.
14.	Suh YY, Lee K, Shim YM, et al. MYB/MYBL1: QKI fusion-positive diffuse glioma. Journal of Neuropathology and Experimental Neurology, 2023, 82(3): 250-260.
15.	Kurokawa R, Baba A, Emile P, et al. Neuroimaging features of angiocentric glioma: a case series and systematic review. Journal of neuroimaging, 2022, 32(3): 389-399.
16.	Wang H, Zhu J, Zhu P, et al. Angiocentric glioma: a case report and review of the literature. Journal of Clinical Neuroscience, 2021, 94: 179-185.
17.	Wefers AK, Stichel D, Schrimpf D, et al. Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course. Acta Neuropathol, 2020, 139: 193-209.
18.	Huse JT, Snuderl M, Jones DT, et al. Polymorphous low-grade neuroepithelial tumor of the young PLNTY: an epileptogenic neoplasm with oligodendroglioma-like components, aberrant CD34 expression, and genetic alterations involving the MAP kinase pathway. Acta Neuropathol, 2017, 133(3): 417-429.
19.	Hinojosa J, Victoria Becerra V, Candela-Cantó S, et al. Extra-temporal pediatric low-grade gliomas and epilepsy. Childs Nerv Syst, 2024, 40(10): 3309-3327.
20.	Rosemberg S, Fujiwara D. Epidemiology ofpediatric tumors of the nervous system according to the WHO 2000 classiﬁcation: a report of 1195 cases from a single institution. Childs Nerv Syst, 2005, 21(11): 940-944.
21.	Collins VP, Jones DT, Giannini C. Pilocytic astrocytoma: pathology, molecular mechanisms and markers. Acta Neuropathol, 2015, 129(6): 775-788.
22.	Ryall, Scott, Zapotocky, et al. Michal integrated molecular and clinical analysis of 1, 000 pediatric low-grade gliomas. Cancer cell, 2020, 37(4): 569-583.
23.	Xing H, Song Y, Zhang Z, et al. Clinical characteristics of BRAF V600E gene mutation in patients of epilepsy-associated brain tumor: a meta-analysis. J Mol Neurosci, 2021, 71: 1815-1824.

1. van Breemen MS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management. Lancet Neurol, 2007, 6(5): 421-430.
2. Chipaux M, Szurhaj W, Vercueil L J, et al. Epilepsy diagnostic and treatment needs identified with a collaborative database involv-ing tertiary centers in France. Epilepsia, 2016, 57: 757-769.
3. Oushy S, Sillauu SH, Ney DE, et al. New-onset seizure during and after brain tumor excision: a risk assessment analysis. J Neu-rosurg, 2018, 128: 1713-1718.
4. Bech KT, Seyedi JF, Schulz M, et al. The risk of developing seizures before and after primary brain surgery of low- and high-grade gliomas. Clin Neurol Neurosurg, 2018, 169: 185-191.
5. Bale, Tejus A, Marc K, et al. The 2021 WHO classification of tumors of the central nervous system: an update on pediatric low-grade gliomas and glioneuronal tumors. Brain Pathology, 2022 : e13060.
6. Blümcke I, Coras R, Wefers AK, et al. Challenges in the histopathological classiﬁcation of ganglioglioma and DNT: mi-croscopic agreement studies and a preliminary genotype phenotype analysis. Neuropathol Appl Neurobiol, 2019, 45(2): 95-107.
7. Delev D, Daka K, Heynckes S, et al. Long-term epilepsy-associated tumors: transcriptional signatures reﬂect clinical course. Scientific reports, 2020, 10(1): 96.
8. Koh HY, Kim SH, Jang J, et al. BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors. Nat Med, 2018, 24(11): 1662-1668.
9. Koelsche C, Wohrer A, Jeibmann A, et al. Mutant BRAF V600E protein in ganglioglioma is predominantly expressed by neuronal tumor cells. Neuropathol, 2013, 125: 891-900.
10. Prabowo AS, Iyer AM, Veersema TJ, et al. BRAFV600E mutation is associated with mTOR signaling activation in Glioneuronaltumors. Brain Pathol, 2014, 24: 52-66.
11. Liu Q, Cai L, Sun Y, et al. Epilepsy outcome and pathology analysis for ganglioglioma: a series of 51 pediatric patients. Pediatr Neurol. 2023, 149: 127-133.
12. Qaddoumi I, Orisme W, Wen J, et al. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology. Neuropathol, 2016, 131: 833-845.
13. Xie M, Wang X, Duan Z, et al. Low-grade epilepsy-associated neuroepithelial tumors: Tumor spectrum and diagnosis based on genetic alterations. Frontiers in Neuroscience, 2023, 16: 107-314.
14. Suh YY, Lee K, Shim YM, et al. MYB/MYBL1: QKI fusion-positive diffuse glioma. Journal of Neuropathology and Experimental Neurology, 2023, 82(3): 250-260.
15. Kurokawa R, Baba A, Emile P, et al. Neuroimaging features of angiocentric glioma: a case series and systematic review. Journal of neuroimaging, 2022, 32(3): 389-399.
16. Wang H, Zhu J, Zhu P, et al. Angiocentric glioma: a case report and review of the literature. Journal of Clinical Neuroscience, 2021, 94: 179-185.
17. Wefers AK, Stichel D, Schrimpf D, et al. Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course. Acta Neuropathol, 2020, 139: 193-209.
18. Huse JT, Snuderl M, Jones DT, et al. Polymorphous low-grade neuroepithelial tumor of the young PLNTY: an epileptogenic neoplasm with oligodendroglioma-like components, aberrant CD34 expression, and genetic alterations involving the MAP kinase pathway. Acta Neuropathol, 2017, 133(3): 417-429.
19. Hinojosa J, Victoria Becerra V, Candela-Cantó S, et al. Extra-temporal pediatric low-grade gliomas and epilepsy. Childs Nerv Syst, 2024, 40(10): 3309-3327.
20. Rosemberg S, Fujiwara D. Epidemiology ofpediatric tumors of the nervous system according to the WHO 2000 classiﬁcation: a report of 1195 cases from a single institution. Childs Nerv Syst, 2005, 21(11): 940-944.
21. Collins VP, Jones DT, Giannini C. Pilocytic astrocytoma: pathology, molecular mechanisms and markers. Acta Neuropathol, 2015, 129(6): 775-788.
22. Ryall, Scott, Zapotocky, et al. Michal integrated molecular and clinical analysis of 1, 000 pediatric low-grade gliomas. Cancer cell, 2020, 37(4): 569-583.
23. Xing H, Song Y, Zhang Z, et al. Clinical characteristics of BRAF V600E gene mutation in patients of epilepsy-associated brain tumor: a meta-analysis. J Mol Neurosci, 2021, 71: 1815-1824.

Journal of Epilepsy

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