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胶质瘤相关性癫痫的不明原因:理论综述与研究领域

Unexplained Causes of Glioma-Associated Epilepsies: A Review of Theories and an Area for Research.

作者信息

Saviuk Mariia, Sleptsova Ekaterina, Redkin Tikhon, Turubanova Victoria

机构信息

Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.

Cell Death Investigation and Therapy Laboratory, Anatomy and Embryology Unit, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium.

出版信息

Cancers (Basel). 2023 Nov 22;15(23):5539. doi: 10.3390/cancers15235539.

Abstract

Approximately 30% of glioma patients are able to survive beyond one year postdiagnosis. And this short time is often overshadowed by glioma-associated epilepsy. This condition severely impairs the patient's quality of life and causes great suffering. The genetic, molecular and cellular mechanisms underlying tumour development and epileptogenesis remain incompletely understood, leading to numerous unanswered questions. The various types of gliomas, namely glioblastoma, astrocytoma and oligodendroglioma, demonstrate distinct seizure susceptibility and disease progression patterns. Patterns have been identified in the presence of IDH mutations and epilepsy, with tumour location in cortical regions, particularly the frontal lobe, showing a more frequent association with seizures. Altered expression of TP53, MGMT and VIM is frequently detected in tumour cells from individuals with epilepsy associated with glioma. However, understanding the pathogenesis of these modifications poses a challenge. Moreover, hypoxic effects induced by glioma and associated with the HIF-1a factor may have a significant impact on epileptogenesis, potentially resulting in epileptiform activity within neuronal networks. We additionally hypothesise about how the tumour may affect the functioning of neuronal ion channels and contribute to disruptions in the blood-brain barrier resulting in spontaneous depolarisations.

摘要

大约30%的胶质瘤患者在确诊后能够存活超过一年。而这段短暂的时间常常被胶质瘤相关癫痫所掩盖。这种情况严重损害了患者的生活质量,给患者带来巨大痛苦。肿瘤发生和癫痫发作的遗传、分子和细胞机制仍未完全明确,导致众多问题悬而未决。不同类型的胶质瘤,即胶质母细胞瘤、星形细胞瘤和少突胶质细胞瘤,表现出不同的癫痫易感性和疾病进展模式。已发现IDH突变与癫痫的存在、肿瘤位于皮质区域(特别是额叶)与癫痫发作的关联更为频繁之间存在一定模式。在与胶质瘤相关癫痫患者的肿瘤细胞中,经常检测到TP53、MGMT和VIM的表达改变。然而,理解这些改变的发病机制具有挑战性。此外,胶质瘤诱导的、与HIF-1a因子相关的缺氧效应可能对癫痫发作产生重大影响,可能导致神经网络内的癫痫样活动。我们还推测肿瘤可能如何影响神经元离子通道的功能,并导致血脑屏障破坏,从而引起自发去极化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02b3/10705208/353b4df7c62d/cancers-15-05539-g001.jpg

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