脑肿瘤相关癫痫的诊治研究进展
A Review on Advances in the Diagnosis and Treatment of Brain Tumor-Related Epilepsy
DOI: 10.12677/acm.2025.153802, PDF,   
作者: 董新宇, 翟 瑄*:重庆医科大学附属儿童医院神经外科,重庆
关键词: 脑肿瘤癫痫抗癫痫药物Brain Tumors Epilepsy Antiepileptic Drugs
摘要: 脑肿瘤相关癫痫(BTRE)是脑肿瘤患者常见的并发症,影响生活质量和预后。BTRE的机制涉及神经递质失衡、肿瘤微环境改变和离子通道异常。目前的治疗包括药物、手术、放疗和化疗,但耐药性癫痫和复发仍是挑战。本文总结了BTRE的病理生理机制、诊断评估方法和现有治疗策略。
Abstract: Brain tumor-associated epilepsy (BTRE) is a common complication in patients with brain tumors, affecting their quality of life and prognosis. The mechanism of BTRE involves neurotransmitter imbalance, changes in tumor microenvironment, and abnormal ion channels. The current treatments include medication, surgery, radiation therapy, and chemotherapy, but drug-resistant epilepsy and recurrence remain challenges. This article summarizes the pathophysiological mechanisms, diagnostic evaluation methods, and existing treatment strategies of BTRE.
文章引用:董新宇, 翟瑄. 脑肿瘤相关癫痫的诊治研究进展[J]. 临床医学进展, 2025, 15(3): 1760-1767. https://doi.org/10.12677/acm.2025.153802

参考文献

[1] Avila, E.K., Tobochnik, S., Inati, S.K., Koekkoek, J.A.F., McKhann, G.M., Riviello, J.J., et al. (2023) Brain Tumor-Related Epilepsy Management: A Society for Neuro-Oncology (SNO) Consensus Review on Current Management. Neuro-Oncology, 26, 7-24. [Google Scholar] [CrossRef] [PubMed]
[2] Villemure, J. and de Tribolet, N. (1996) Epilepsy in Patients with Central Nervous System Tumors. Current Opinion in Neurology, 9, 424-428. [Google Scholar] [CrossRef] [PubMed]
[3] Venkatesh, H.S., Morishita, W., Geraghty, A.C., Silverbush, D., Gillespie, S.M., Arzt, M., et al. (2019) Electrical and Synaptic Integration of Glioma into Neural Circuits. Nature, 573, 539-545. [Google Scholar] [CrossRef] [PubMed]
[4] Yang, Y., Mao, Q., Wang, X., Liu, Y., Mao, Y., Zhou, Q., et al. (2016) An Analysis of 170 Glioma Patients and Systematic Review to Investigate the Association between IDH-1 Mutations and Preoperative Glioma-Related Epilepsy. Journal of Clinical Neuroscience, 31, 56-62. [Google Scholar] [CrossRef] [PubMed]
[5] Venkataramani, V., Tanev, D.I., Strahle, C., Studier-Fischer, A., Fankhauser, L., Kessler, T., et al. (2019) Glutamatergic Synaptic Input to Glioma Cells Drives Brain Tumour Progression. Nature, 573, 532-538. [Google Scholar] [CrossRef] [PubMed]
[6] Glantz, M.J., Cole, B.F., Forsyth, P.A., Recht, L.D., Wen, P.Y., Chamberlain, M.C., et al. (2000) Practice Parameter: Anticonvulsant Prophylaxis in Patients with Newly Diagnosed Brain Tumors. Neurology, 54, 1886-1893. [Google Scholar] [CrossRef] [PubMed]
[7] Su, X., Chen, H., Wang, Z. and Lan, Q. (2015) Relationship between Tumour Location and Preoperative Seizure Incidence in Patients with Gliomas: A Systematic Review and Meta-Analysis. Epileptic Disorders, 17, 397-408. [Google Scholar] [CrossRef] [PubMed]
[8] Pelliccia, V., Deleo, F., Gozzo, F., Sartori, I., Mai, R., Cossu, M., et al. (2017) Early and Late Epilepsy Surgery in Focal Epilepsies Associated with Long-Term Epilepsy-Associated Tumors. Journal of Neurosurgery, 127, 1147-1152. [Google Scholar] [CrossRef] [PubMed]
[9] Kwon, C., Wagner, R.G., Carpio, A., Jetté, N., Newton, C.R. and Thurman, D.J. (2022) The Worldwide Epilepsy Treatment Gap: A Systematic Review and Recommendations for Revised Definitions—A Report from the ILAE Epidemiology Commission. Epilepsia, 63, 551-564. [Google Scholar] [CrossRef] [PubMed]
[10] Scheffer, I.E., Berkovic, S., Capovilla, G., Connolly, M.B., French, J., Guilhoto, L., et al. (2017) ILAE Classification of the Epilepsies: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia, 58, 512-521. [Google Scholar] [CrossRef] [PubMed]
[11] Fiest, K.M., Sauro, K.M., et al. (2017) Prevalence and Incidence of Epilepsy: A Systematic Review and Meta-Analysis of International Studies. Neurology, 88, 296-303.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5272794/
[12] Chiang, S., Moss, R., Stern, J.M., Hughes, I., Josephson, S.A., Pearce, J.R., et al. (2022) Development of a Core Outcome Set for Quality of Life for Adults with Drug-Resistant Epilepsy: A Multistakeholder Delphi Consensus Study. Epilepsia, 64, 170-183. [Google Scholar] [CrossRef] [PubMed]
[13] Ostrom, Q.T., Price, M., Neff, C., Cioffi, G., Waite, K.A., Kruchko, C., et al. (2022) CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro-Oncology, 24, v1-v95. [Google Scholar] [CrossRef] [PubMed]
[14] Blumcke, I., Spreafico, R., Haaker, G., Coras, R., Kobow, K., Bien, C.G., et al. (2017) Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery. New England Journal of Medicine, 377, 1648-1656. [Google Scholar] [CrossRef] [PubMed]
[15] Lote, K., Stenwig, A.E., et al. (1998) Prevalence and Prognostic Significance of Epilepsy in Patients with Gliomas. European Journal of Cancer, 34, 98-102.
https://pubmed.ncbi.nlm.nih.gov/9624245/
[16] Breemen, M.S.M., Rijsman, R.M., Taphoorn, M.J.B., Walchenbach, R., Zwinkels, H. and Vecht, C.J. (2009) Efficacy of Anti-Epileptic Drugs in Patients with Gliomas and Seizures. Journal of Neurology, 256, 1519-1526. [Google Scholar] [CrossRef] [PubMed]
[17] Malbari, F., Zhu, H., Riviello, J.J. and Clarke, D. (2021) Antiepileptic Drug Management in Pediatric Patients with Brain Tumor-Related Epilepsy. Epilepsy & Behavior, 125, Article 108359. [Google Scholar] [CrossRef] [PubMed]
[18] Lin, A.L. and Avila, E.K. (2016) Neurologic Emergencies in the Patients with Cancer. Journal of Intensive Care Medicine, 32, 99-115. [Google Scholar] [CrossRef] [PubMed]
[19] Armstrong, T.S., Grant, R., Gilbert, M.R., Lee, J.W. and Norden, A.D. (2015) Epilepsy in Glioma Patients: Mechanisms, Management, and Impact of Anticonvulsant Therapy: Table 1. Neuro-Oncology, 18, 779-789. [Google Scholar] [CrossRef] [PubMed]
[20] Marcus, H.J., Carpenter, K.L.H., Price, S.J. and Hutchinson, P.J. (2009) In Vivo Assessment of High-Grade Glioma Biochemistry Using Microdialysis: A Study of Energy-Related Molecules, Growth Factors and Cytokines. Journal of Neuro-Oncology, 97, 11-23. [Google Scholar] [CrossRef] [PubMed]
[21] Yuen, T.I., Morokoff, A.P., Bjorksten, A., D’Abaco, G., Paradiso, L., Finch, S., et al. (2012) Glutamate Is Associated with a Higher Risk of Seizures in Patients with Gliomas. Neurology, 79, 883-889. [Google Scholar] [CrossRef] [PubMed]
[22] MacKenzie, G., O’Toole, K.K., Moss, S.J. and Maguire, J. (2016) Compromised Gabaergic Inhibition Contributes to Tumor-Associated Epilepsy. Epilepsy Research, 126, 185-196. [Google Scholar] [CrossRef] [PubMed]
[23] Pallud, J., Le Van Quyen, M., Bielle, F., Pellegrino, C., Varlet, P., Labussiere, M., et al. (2014) Cortical Gabaergic Excitation Contributes to Epileptic Activities around Human Glioma. Science Translational Medicine, 6, 244ra89. [Google Scholar] [CrossRef] [PubMed]
[24] Aronica, E., Boer, K., Becker, A., et al. (2008) Gene Expression Profile Analysis of Epilepsy-Associated Gangliogliomas. Neuroscience, 151, 272-292.
https://pubmed.ncbi.nlm.nih.gov/18093740/
[25] Aronica, E., Boer, K., Redeker, S., et al. (2007) Differential Expression Patterns of Chloride Transporters, Na+-K+-2Cl-Cotransporter and K+-Cl-Cotransporter, in Epilepsy-Associated Malformations of Cortical Development. Neuroscience, 145, 185-196.
https://pubmed.ncbi.nlm.nih.gov/17207578/
[26] Eftekhari, S., Mehvari Habibabadi, J., Najafi Ziarani, M., Hashemi Fesharaki, S.S., Gharakhani, M., Mostafavi, H., et al. (2012) Bumetanide Reduces Seizure Frequency in Patients with Temporal Lobe Epilepsy. Epilepsia, 54, e9-e12. [Google Scholar] [CrossRef] [PubMed]
[27] Hormigo, A., Liberato, B., et al. (2004) Nonconvulsive Status Epilepticus in Patients with Cancer: Imaging Abnormalities. Archives of Neurology, 61, 362-365.
https://pubmed.ncbi.nlm.nih.gov/15023812/
[28] Riela, A.R., Sires, B.P. and Kiffin Penry, J. (1991) Transient Magnetic Resonance Imaging Abnormalities during Partial Status Epilepticus. Journal of Child Neurology, 6, 143-145. [Google Scholar] [CrossRef] [PubMed]
[29] Kramer, R.E., Dinner, D.S., et al. (1987) Transient Focal Abnormalities of Neuroimaging Studies during Focal Status Epilepticus. Epilepsia, 28, 528-532.
https://pubmed.ncbi.nlm.nih.gov/3653056/
[30] Schaul, N., Green, L., Peyster, R. and Gotman, J. (1986) Structural Determinants of Electroencephalographic Findings in Acute Hemispheric Lesions. Annals of Neurology, 20, 703-711. [Google Scholar] [CrossRef] [PubMed]
[31] Preu, M., Preiss, S., Syrbe, S., et al. (2015) Signs and Symptoms of Pediatric Brain Tumors and Diagnostic Value of Preoperative EEG. Child’s Nervous System, 31, 2051-2054.
https://pubmed.ncbi.nlm.nih.gov/26248670/
[32] van der Meer, P.B., Driven, L., et al. (2021) Prescription Preferences of Antiepileptic Drugs in Brain Tumor Patients: An International Survey among EANO Members. Neuro-Oncology Practice, 9, 105-113.
https://pubmed.ncbi.nlm.nih.gov/35371521/
[33] van der Meer, P.B., Driven, L., et al. (2022) Effectiveness of Antiseizure Medication Duotherapies in Patients with Glioma: A Multicenter Observational Cohort Study. Neurology, 99, e999-e1008.
https://pubmed.ncbi.nlm.nih.gov/36219797/
[34] van Opijnen, M.P., van der Meer, P.B., Dirven, L., Fiocco, M., Kouwenhoven, M.C.M., van den Bent, M.J., et al. (2021) The Effectiveness of Antiepileptic Drug Treatment in Glioma Patients: Lamotrigine versus Lacosamide. Journal of Neuro-Oncology, 154, 73-81. [Google Scholar] [CrossRef] [PubMed]
[35] Rudà, R., Houillier, C., Maschio, M., Reijneveld, J.C., Hellot, S., De Backer, M., et al. (2020) Effectiveness and Tolerability of Lacosamide as Add-On Therapy in Patients with Brain Tumor-Related Epilepsy: Results from a Prospective, Noninterventional Study in European Clinical Practice (Vibes). Epilepsia, 61, 647-656. [Google Scholar] [CrossRef] [PubMed]
[36] Coppola, A., Zarabla, A., et al. (2020) Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients with Brain Tumor-Related Epilepsy (PERADET Study). Frontiers in Neurology, 11, Article 592.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7336340/
[37] Maschio, M., Maialetti, A., Mocellini, C., Domina, E., Pauletto, G., Costa, C., et al. (2020) Effect of Brivaracetam on Efficacy and Tolerability in Patients with Brain Tumor-Related Epilepsy: A Retrospective Multicenter Study. Frontiers in Neurology, 11, Article 813. [Google Scholar] [CrossRef] [PubMed]
[38] Kwan, P., Arzimanoglou, A., Berg, A.T., Brodie, M.J., Allen Hauser, W., Mathern, G., et al. (2010) Definition of Drug Resistant Epilepsy: Consensus Proposal by the Ad Hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia, 51, 1069-1077. [Google Scholar] [CrossRef] [PubMed]
[39] Jo, J., Nevel, K., Sutyla, R., et al. (2020) Predictors of Early, Recurrent, and Intractable Seizures in Low-Grade Glioma. Neuro-Oncology Practice, 8, 40-47.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7906271/
[40] van Breemen, M.S., Wilms, E.B. and Vecht, C.J. (2007) Epilepsy in Patients with Brain Tumours: Epidemiology, Mechanisms, and Management. The Lancet Neurology, 6, 421-430. [Google Scholar] [CrossRef] [PubMed]
[41] Robertson, F.C., Ullrich, N.J., Manley, P.E., Al-Sayegh, H., Ma, C. and Goumnerova, L.C. (2018) The Impact of Intraoperative Electrocorticography on Seizure Outcome after Resection of Pediatric Brain Tumors: A Cohort Study. Neurosurgery, 85, 375-383. [Google Scholar] [CrossRef] [PubMed]
[42] Lamberink, H.J., Otte, W.M., Blümcke, I., Braun, K.P.J., Aichholzer, M., Amorim, I., et al. (2020) Seizure Outcome and Use of Antiepileptic Drugs after Epilepsy Surgery According to Histopathological Diagnosis: A Retrospective Multicentre Cohort Study. The Lancet Neurology, 19, 748-757. [Google Scholar] [CrossRef] [PubMed]
[43] Zhu, Q., Liang, Y., Fan, Z., Liu, Y., Zhou, C., Zhang, H., et al. (2022) The Utility of Intraoperative ECoG in Tumor-Related Epilepsy: Systematic Review. Clinical Neurology and Neurosurgery, 212, Article 107054. [Google Scholar] [CrossRef] [PubMed]
[44] Warsi, N.M., Mohammad, A.H., et al. (2023) Electrocorticography-Guided Resection Enhances Postoperative Seizure Freedom in Low-Grade Tumor-Associated Epilepsy: A Systematic Review and Meta-Analysis. Neurosurgery, 92, 18-26.
https://pubmed.ncbi.nlm.nih.gov/36519857/
[45] Goel, K., Pek, V., Shlobin, N.A., Chen, J., Wang, A., Ibrahim, G.M., et al. (2022) Clinical Utility of Intraoperative Electrocorticography for Epilepsy Surgery: A Systematic Review and Meta-Analysis. Epilepsia, 64, 253-265. [Google Scholar] [CrossRef] [PubMed]
[46] Koekkoek, J.A.F., Kerkhof, M., Dirven, L., Heimans, J.J., Reijneveld, J.C. and Taphoorn, M.J.B. (2015) Seizure Outcome after Radiotherapy and Chemotherapy in Low-Grade Glioma Patients: A Systematic Review. Neuro-Oncology, 17, 924-934. [Google Scholar] [CrossRef] [PubMed]
[47] Ruda, R., Magliola, U., Bertero, L., Trevisan, E., Bosa, C., Mantovani, C., et al. (2013) Seizure Control Following Radiotherapy in Patients with Diffuse Gliomas: A Retrospective Study. Neuro-Oncology, 15, 1739-1749. [Google Scholar] [CrossRef] [PubMed]
[48] Rogers, L.R., Morris, H.H. and Lupica, K. (1993) Effect of Cranial Irradiation on Seizure Frequency in Adults with Low-Grade Astrocytoma and Medically Intractable Epilepsy. Neurology, 43, 1599-1599. [Google Scholar] [CrossRef] [PubMed]
[49] Castellano, A., Donativi, M., Rudà, R., De Nunzio, G., Riva, M., Iadanza, A., et al. (2015) Evaluation of Low-Grade Glioma Structural Changes after Chemotherapy Using DTI-Based Histogram Analysis and Functional Diffusion Maps. European Radiology, 26, 1263-1273. [Google Scholar] [CrossRef] [PubMed]
[50] van der Meer, P.B., Taphoorn, M.J.B. and Koekkoek, J.A.F. (2022) Management of Epilepsy in Brain Tumor Patients. Current Opinion in Oncology, 34, 685-690. [Google Scholar] [CrossRef] [PubMed]