surgoncoКреативная хирургия и онкологияCreative surgery and oncology2076-30932307-0501Башкирский государственный медицинский университет10.24060/2076-3093-2025-15-3-287-298surgonco-1121Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSКарбамазепин в лечении эпилепсии у больных глиобластомой (обзор литературы с описанием клинического случая)Carbamazepine for Epilepsy Treatment in Glioblastoma Patients: A Review and a Clinical Casehttps://orcid.org/0000-0001-8129-9320МуфазаловаЛ. Ф.MufazalovaLyaysan F.

Муфазалова Ляйсан Фагимовна — к.м.н., кафедра  фармакологии

Республика Башкортостан, Уфа

Lyaysan F. Mufazalova — Cand. Sci. (Med.), Department of Pharmacology

Ufa

lfmufazalova@bashgmu.ruhttps://orcid.org/0000-0002-0656-3459МуфазаловаН. А.MufazalovaNatalya A.

Муфазалова Наталья Альбертовна — д.м.н., профессор, кафедра фармакологии

Республика Башкортостан, Уфа

Natalya A. Mufazalova — Dr. Sci. (Med.), Prof., Department of Pharmacology

Ufa

https://orcid.org/0009-0002-9219-9354ИмаевА. Б.ImaevAirat B.

Имаев Айрат Богданович — к.м.н., отделение противоопухолевой лекарственной терапии № 2

Республика Башкортостан, Уфа

Airat B. Imaev — Cand. Sci. (Med.), Department of Antitumor Drug Therapy No. 2

Ufa

https://orcid.org/0009-0001-9926-1950ФархутдиноваЕ. Ф.FarkhutdinovaElena F.

Фархутдинова Елена Фаузировна — поликлиническое отделение

Республика Башкортостан, Уфа

Elena F. Farkhutdinova — Outpatient department

Ufa

https://orcid.org/0009-0004-6999-8021БезруковаС. С.BezrukovaSofya S.

Безрукова Софья Сергеевна — студентка

Республика Башкортостан, Уфа

 

Sofya S. Bezrukova — student

Ufa

https://orcid.org/0009-0006-6479-8404ДушанбаевБ. Ю.DushanbaevBulat Yu.

Душанбаев Булат Юнирович — студент

Республика Башкортостан, Уфа

 

Bulat Y. Dushanbaev — student

Ufa

Башкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian FederationРеспубликанский клинический онкологический диспансерРоссияRepublican Oncology ClinicRussian Federation202517092025153287298Copyright © Муфазалова Л.Ф., Муфазалова Н.А., Имаев А.Б., Фархутдинова Е.Ф., Безрукова С.С., Душанбаев Б.Ю., 20252025Муфазалова Л.Ф., Муфазалова Н.А., Имаев А.Б., Фархутдинова Е.Ф., Безрукова С.С., Душанбаев Б.Ю.Mufazalova L.F., Mufazalova N.A., Imaev A.B., Farkhutdinova E.F., Bezrukova S.S., Dushanbaev B.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surgonco.ru/jour/article/view/1121

Глиобластома — злокачественная опухоль головного мозга, характеризующаяся агрессивным течением, устойчивостью к  химиолучевой и  иммунотерапии, рецидивированием и  высокой летальностью. Заболеваемость глиобластомой составляет от 3,2 до 5 на 100 000 человек. В последние годы отмечен рост заболеваемости среди пациентов в  возрасте до  45  лет. У  25–60% больных глиобластомой развивается эпилепсия, снижая качество жизни и ухудшая прогноз заболевания. У 35–40% пациентов эпиприступы являются первым проявлением глиобластомы, но могут появляться и в процессе лечения/рецидива глиобластомы. На риск развития и тяжесть течения эпилепсии оказывают влияние объем опухоли, характер роста, локализация, наличие предоперационных судорог, мутации IDH1–2, объем остаточной опухоли. Этиопатогенез эпилепсии, ассоциированной с глиобластомой, является многофакторным и малоизученным. Ведущая роль в эпилептогенезе отводится дисфункции ионных каналов с увеличением уровня внеклеточного K+, гиперэкспрессией SCN1A и SCN2A альфа-субъединиц Na+-каналов, а также дисрегуляторных Ca 2+-каналов. В результате в перитуморальной зоне нарушаются гомеостаз тормозных и возбуждающих нейротрансмиттеров, процессы реполяризации/деполяризации, электро‑химическое взаимодействие между нейронами и клетками опухоли. Для лечения эпилепсии, ассоциированной с глиобластомой, наиболее часто применяется карбамазепин ввиду его высокой клинической эффективности. Противоэпилептическая активность карбамазепина обусловлена инактивацией Na+-каналов, потенцированием потенциал-зависимых K+-, Cl–-каналов, ГАМК-ергической системы, торможением выброса глутамата, влиянием на  гомеостаз других нейромедиаторных систем головного мозга. Немаловажное значение имеет способность карбамазепина подавлять пролиферацию клеток в ряде клеточных линий злокачественной глиомы. Несмотря на  то что карбамазепин является индуктором микросомальных ферментов печени, он не снижает эффективность темозоламида, который не метаболизируется в печени. Возможные при применении карбамазепина нежелательные реакции не требуют отмены препарата. Учитывая высокую клиническую эффективность карбамазепина, необходимы дальнейшие исследования его плейотропных эффектов у больных эпилепсией, ассоциированной с глиобластомой и другими злокачественными опухолями головного мозга.

Glioblastoma is a malignant brain tumor characterized by an aggressive course, resistance to chemoradiation and immunotherapy, recurrence, and high mortality. The incidence of glioblastoma ranges from 3.2 to 5 per 100,000 people. In recent years, an increase in the incidence of glioblastoma among patients under 45 years of age has been observed. Epilepsy develops in 25–60% of the patients, reducing their quality of life and worsening the prognosis of the disease. In 35–40% of the patients, epileptic seizures are the first manifestation of glioblastoma, being also possible during its treatment or relapse. The risk of epilepsy development and its severity are affected by the tumor volume, growth pattern, localization, presence of preoperative seizures, IDH1-2 mutations, and residual tumor volume. The epilepsy associated with glioblastoma is characterized by a multifactorial and poorly understood etiopathogenesis. The leading role in epileptogenesis is attributed to dysfunction of ion channels with an increase in the level of extracellular K+, hyperexpression of SCN1A and SCN2A alpha subunits of Na+ channels, as well as dysregulatory Ca2+ channels. As a result, in the peritumoral zone, the homeostasis of inhibitory and excitatory neurotransmitters, repolarization/depolarization processes, and electrochemical interactions between neurons and tumor cells are disrupted. Due to its high clinical effectiveness, carbamazepine is most often used to treat glioblastoma-associated epilepsy. The antiepileptic activity of carbamazepine is related to the inactivation of Na+ channels, potentiation of potential-dependent K+, Cl–channels, the GABA-ergic system, inhibition of glutamate release, and the effect on the homeostasis of other neurotransmitter systems in the brain. The ability of carbamazepine to suppress cell proliferation in a number of malignant glioma cell lines is also of high significance. Although carbamazepine is an inducer of liver microsomal enzymes, it does not reduce the effectiveness of temozolomide, which is not metabolized in the liver. Possible adverse carbamazepine-associated reactions do not require its discontinuation. Given the high clinical effectiveness of carbamazepine, further studies of its pleiotropic effects in patients with epilepsy associated with glioblastoma and other malignant brain tumors are required.

глиобластомаэпилепсиякарбамазепиннежелательные лекарственные реакциилекарств взаимодействиятемозоламидпротивосудорожные средствановообразования головного мозгаglioblastomaepilepsycarbamazepineadverse drug reactionsdrug interactionstemozolomideanticonvulsantsbrain neoplasmsДанная работа не финансировалась.This work is not funded.ReferencesHu S., Kao H.Y., Yang T., Wang Y. Early and Bi-hemispheric seizure onset in a rat glioblastoma Multiforme model. Neurosci Lett. 2022;766:136351. DOI: 10.1016/j.neulet.2021.136351Hu S., Kao H.Y., Yang T., Wang Y. Early and Bi-hemispheric seizure onset in a rat glioblastoma Multiforme model. Neurosci Lett. 2022;766:136351. DOI: 10.1016/j.neulet.2021.136351Wang G.M., Cioffi G., Patil N., Waite K.A., Lanese R., Ostrom Q.T., et al. Importance of the intersection of age and sex to understand variation in incidence and survival for primary malignant gliomas. Neuro Oncol. 2022;24(2):302–10. DOI: 10.1093/neuonc/noab199Wang G.M., Cioffi G., Patil N., Waite K.A., Lanese R., Ostrom Q.T., et al. Importance of the intersection of age and sex to understand variation in incidence and survival for primary malignant gliomas. Neuro Oncol. 2022;24(2):302–10. DOI: 10.1093/neuonc/noab199Chehade G., Lawson T.M., Lelotte J., Daoud L., Di Perri D., Whenham N., et al. Long-term survival in patients with IDH-wildtype glioblastoma: clinical and molecular characteristics. ActaNeurochir (Wien). 2023;165(4):1075–85. DOI: 10.1007/s00701-023-05544-3Chehade G., Lawson T.M., Lelotte J., Daoud L., Di Perri D., Whenham N., et al. Long-term survival in patients with IDH-wildtype glioblastoma: clinical and molecular characteristics. ActaNeurochir (Wien). 2023;165(4):1075–85. DOI: 10.1007/s00701-023-05544-3Salvalaggio A., Pini L., Bertoldo A., Corbetta M. Glioblastoma and brain connectivity: the need for a paradigm shift. Lancet Neurol. 2024;23(7):740–8. DOI: 10.1016/S1474-4422(24)00160-1Salvalaggio A., Pini L., Bertoldo A., Corbetta M. Glioblastoma and brain connectivity: the need for a paradigm shift. Lancet Neurol. 2024;23(7):740–8. DOI: 10.1016/S1474-4422(24)00160-1Yanovich-Arad G., Ofek P., Yeini E., Mardamshina M., Danilevsky A., Shomron N., et al. Proteogenomics of glioblastoma associates molecular patterns with survival. Cell Rep. 2021;34(9):108787. DOI: 10.1016/j.celrep.2021.108787Yanovich-Arad G., Ofek P., Yeini E., Mardamshina M., Danilevsky A., Shomron N., et al. Proteogenomics of glioblastoma associates molecular patterns with survival. Cell Rep. 2021;34(9):108787. DOI: 10.1016/j.celrep.2021.108787Hamad A., Yusubalieva G.M., Baklaushev V.P., Chumakov P.M., Lipatova A.V. Recent developments in glioblastoma therapy: oncolytic viruses and emerging future strategies. Viruses. 2023;15(2):547. DOI: 10.3390/v15020547Hamad A., Yusubalieva G.M., Baklaushev V.P., Chumakov P.M., Lipatova A.V. Recent developments in glioblastoma therapy: oncolytic viruses and emerging future strategies. Viruses. 2023;15(2):547. DOI: 10.3390/v15020547Roda D., Veiga P., Melo J.B., Carreira I.M., Ribeiro I.P. Principles in the management of glioblastoma. Genes. 2024;15(4):501. DOI: 10.3390/genes15040501Roda D., Veiga P., Melo J.B., Carreira I.M., Ribeiro I.P. Principles in the management of glioblastoma. Genes. 2024;15(4):501. DOI: 10.3390/genes15040501Coppola A., Hernandez-Hernandez L., Balestrini S., Krithika S., Moran N., Hale B., et al. Cortical myoclonus and epilepsy in a family with a new SLC20A2 mutation. J Neurol. 2020;267(8):2221–7. DOI: 10.1007/s00415-020-09821-4Coppola A., Hernandez-Hernandez L., Balestrini S., Krithika S., Moran N., Hale B., et al. Cortical myoclonus and epilepsy in a family with a new SLC20A2 mutation. J Neurol. 2020;267(8):2221–7. DOI: 10.1007/s00415-020-09821-4de Bruin M.E., van der Meer P.B., Dirven L., Taphoorn M.J.B., Koekkoek J.A.F. Efficacy of antiepileptic drugs in glioma patients with epilepsy: a systematic review. NeurooncolPract. 2021;8(5):501–17. DOI: 10.1093/nop/npab030de Bruin M.E., van der Meer P.B., Dirven L., Taphoorn M.J.B., Koekkoek J.A.F. Efficacy of antiepileptic drugs in glioma patients with epilepsy: a systematic review. NeurooncolPract. 2021;8(5):501–17. DOI: 10.1093/nop/npab030Rossi J., Cavallieri F., Bassi M.C., Biagini G., Rizzi R., Russo M., et al. Efficacy and tolerability of perampanel in brain tumor-related epilepsy: a systematic review. Biomedicines. 2023;11(3):651. DOI: 10.3390/biomedicines11030651Rossi J., Cavallieri F., Bassi M.C., Biagini G., Rizzi R., Russo M., et al. Efficacy and tolerability of perampanel in brain tumor-related epilepsy: a systematic review. Biomedicines. 2023;11(3):651. DOI: 10.3390/biomedicines11030651Soeung V., Puchalski R.B., Noebels J.L. The complex molecular epileptogenesis landscape of glioblastoma. Cell Rep Med. 2024;5(8):101691. DOI: 10.1016/j.xcrm.2024.101691Soeung V., Puchalski R.B., Noebels J.L. The complex molecular epileptogenesis landscape of glioblastoma. Cell Rep Med. 2024;5(8):101691. DOI: 10.1016/j.xcrm.2024.101691Moher D., Liberati A., Tetzlaff J., Altman D.G. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;3(3):e123–30. DOI: 10.1136/bmj.b2535Moher D., Liberati A., Tetzlaff J., Altman D.G. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;3(3):e123–30. DOI: 10.1136/bmj.b2535Xu K., Zhang C., WeiGao, Shi Y., Pu S., Huang N., et al. The involvement of circRNAs in molecular processes and their potential use in therapy and diagnostics for glioblastoma. Gene. 2025;940:149214. DOI: 10.1016/j.gene.2025.149214Xu K., Zhang C., WeiGao, Shi Y., Pu S., Huang N., et al. The involvement of circRNAs in molecular processes and their potential use in therapy and diagnostics for glioblastoma. Gene. 2025;940:149214. DOI: 10.1016/j.gene.2025.149214Cruz N., Herculano-Carvalho M., Roque D., Faria C.C., Cascao R., Ferreira H.A., et al. Highlighted advances in therapies for difficultto-treat brain tumours such as glioblastoma. Pharmaceutics. 2023 15(3):928. DOI: 10.3390/pharmaceutics 15030928Cruz N., Herculano-Carvalho M., Roque D., Faria C.C., Cascao R., Ferreira H.A., et al. Highlighted advances in therapies for difficultto-treat brain tumours such as glioblastoma. Pharmaceutics. 2023 15(3):928. DOI: 10.3390/pharmaceutics 15030928An J., Freeman E., Stewart I.J., Dore M. Association of traumatic brain injury and glioblastoma multiforme: a case series. Mil Med. 2024;189(1–2):e391–5. DOI: 10.1093/milmed/usad162An J., Freeman E., Stewart I.J., Dore M. Association of traumatic brain injury and glioblastoma multiforme: a case series. Mil Med. 2024;189(1–2):e391–5. DOI: 10.1093/milmed/usad162Lange F., Hornschemeyer J., Kirschstein T. Glutamatergic mechanisms in glioblastoma and tumor-associated epilepsy. Cells. 2021;10(5):1226. DOI: 10.3390/cells10051226Lange F., Hornschemeyer J., Kirschstein T. Glutamatergic mechanisms in glioblastoma and tumor-associated epilepsy. Cells. 2021;10(5):1226. DOI: 10.3390/cells10051226Stella M., Baiardi G., Pasquariello S., Sacco F., Dellacasagrande I., Corsaro A., et al. Antitumor potential of antiepileptic drugs in human glioblastoma: pharmacological targets and clinical benefits. Biomedicines. 2023;11(2):582. DOI: 10.3390/biomedicines11020582Stella M., Baiardi G., Pasquariello S., Sacco F., Dellacasagrande I., Corsaro A., et al. Antitumor potential of antiepileptic drugs in human glioblastoma: pharmacological targets and clinical benefits. Biomedicines. 2023;11(2):582. DOI: 10.3390/biomedicines11020582Molinaro A.M., Hervey-Jumper S., Morshed R.A., Young J., Han S.J., Chunduru P., et al. Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol. 2020;6(4):495–503. DOI: 10.1001/jamaoncol.2019.6143Molinaro A.M., Hervey-Jumper S., Morshed R.A., Young J., Han S.J., Chunduru P., et al. Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma. JAMA Oncol. 2020;6(4):495–503. DOI: 10.1001/jamaoncol.2019.6143Schaff L.R., Mellinghoff I.K. Glioblastoma and other primary brain malignancies in adults: a review. JAMA. 2023;329(7):574–87. DOI: 10.1001/jama.2023.0023Schaff L.R., Mellinghoff I.K. Glioblastoma and other primary brain malignancies in adults: a review. JAMA. 2023;329(7):574–87. DOI: 10.1001/jama.2023.0023Рахматуллина И.Р., Золотухин К.Н., Самородов А.В. Реализация технологий «Point-of-care testing» в условиях интенсивной терапии. Наука и инновации в медицине. 2017;4(8):23–7.Rakhmatullina I.R., Zolotukhin K.N., Samorodov A.V. Implementation of “Point-of-care testing” technologies in intensive care. Science and innovation in medicine. 2017;4(8):23–27 (In Russ.).Золотухин К.Н., Поляков И.В., Самородов А.В. Сравнительный анализ мониторинга центральной гемодинамики монитором МПР 6-03 «Тритон» и «Picco plus». Тольяттинский медицинский консилиум. 2012;3–4:19–23.Zolotukhin K.N., Polyakov I.V., Samorodov A.V. Comparative analysis of central hemodynamic monitoring by the MPR 6-03 “Triton” and “Picco plus” monitors. Togliatti Medical Council. 2012;3–4:19–23 (In Russ.).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.2022.903115Hills 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.2022.903115Verma S., Malviya R., Uniyal P. Survival of patients with primary brain tumor: a data analysis of 10 years. Curr Pharm Des. 2024;30(15):1129– 32. DOI: 10.2174/0113816128306113240328050608Verma S., Malviya R., Uniyal P. Survival of patients with primary brain tumor: a data analysis of 10 years. Curr Pharm Des. 2024;30(15):1129– 32. DOI: 10.2174/0113816128306113240328050608Grabowski M.M., Sankey E.W., Ryan K.J., Chongsathidkiet P., Lorrey S.J., Wilkinson D.S., et al. Immune suppression in gliomas. J Neurooncol. 2021;151(1):3–12. DOI: 10.1007/s11060-020-03483-yGrabowski M.M., Sankey E.W., Ryan K.J., Chongsathidkiet P., Lorrey S.J., Wilkinson D.S., et al. Immune suppression in gliomas. J Neurooncol. 2021;151(1):3–12. DOI: 10.1007/s11060-020-03483-yDuan X., Yang B., Zhao C., Tie B., Cao L., Gao Y. Prognostic value of preoperative hematological markers in patients with glioblastoma multiforme and construction of random survival forest model. BMC Cancer. 2023;23(1):432. DOI: 10.1186/s12885-023-10889-0Duan X., Yang B., Zhao C., Tie B., Cao L., Gao Y. Prognostic value of preoperative hematological markers in patients with glioblastoma multiforme and construction of random survival forest model. BMC Cancer. 2023;23(1):432. DOI: 10.1186/s12885-023-10889-0Tong E., Horsley P., Wheeler H., Wong M., Venkatesha V., Chan J., et al. Hypofractionated re-irradiation with bevacizumab for relapsed chemorefractory glioblastoma after prior high dose radiotherapy: a feasible option for patients with large-volume relapse. J Neurooncol. 2024;168(1):69–76. DOI: 10.1007/s11060-024-04643-0Tong E., Horsley P., Wheeler H., Wong M., Venkatesha V., Chan J., et al. Hypofractionated re-irradiation with bevacizumab for relapsed chemorefractory glioblastoma after prior high dose radiotherapy: a feasible option for patients with large-volume relapse. J Neurooncol. 2024;168(1):69–76. DOI: 10.1007/s11060-024-04643-0Ванг Юи, Муфазалова Н.А., Муфазалова Л.Ф., Ильясова Н.В., Мурадова Р.Р., Киёмов И.Э. и др. Перспективы применения перампанела в лечении эпилепсии у пациентов со злокачественными глиомами головного мозга. Обзоры по клинической фармакологии и лекарственной терапии. 2024;22(3):223–36. DOI: 10.17816/RCF629243Wang Yi, Mufazalova N.A., Mufazalova L.F., Ilyasova N.V., Muradova R.R., Kiyomov I.E., et al. Potential use of perampanel in the treatment of epilepsy in patients with malignant brain gliomas. Reviews on Clinical Pharmacology and Drug Therapy. 2024;22(3):223–36 (In Russ.) DOI: 10.17816/RCF629243Ураков А.Л., Никитина И.Л., Клен Е.Э., Ванг Ю., Самородов А.В. Перспективы фармакологической валидации использования тромбоцитов в качестве «периферической модели» нейронов. Обзоры по клинической фармакологии и лекарственной терапии. 2023;21(4):307–17. DOI: 10.17816/RCF568907Urakov A.L., Nikitina I.L., Klen E.E., Wang Y., Samorodov A.V. Prospects for the pharmacological validation of the use of platelets as a “peripheral model” of neurons. Reviews on Clinical Pharmacology and Drug Therapy. 2023;21(4):307–17 (In Russ.) DOI: 10.17816/RCF568907Hertler C., Felsberg J., Gramatzki D., Le Rhun E., Clarke J., Soffietti R., et al. Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419). Eur J Cancer. 2023;189:112913. DOI: 10.1016/j.ejca.2023.05.002Hertler C., Felsberg J., Gramatzki D., Le Rhun E., Clarke J., Soffietti R., et al. Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders’ Collaborative Consortium (EORTC 1419). Eur J Cancer. 2023;189:112913. DOI: 10.1016/j.ejca.2023.05.002Climans S.A., Brandes A.A., Cairncross J.G., Ding K., Fay M., Laperriere N., et al. Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients. J. Neurooncol. 2020;149(1):65–71. DOI: 10.1007/s11060-020-03573-xClimans S.A., Brandes A.A., Cairncross J.G., Ding K., Fay M., Laperriere N., et al. Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients. J. Neurooncol. 2020;149(1):65–71. DOI: 10.1007/s11060-020-03573-xSharma P., Aaroe A., Liang J., Puduvalli V.K. Tumor microenvironment in glioblastoma: Current and emerging concepts. Neurooncol Adv. 2023;5(1):vdad009. DOI: 10.1093/noajnl/vdad009Sharma P., Aaroe A., Liang J., Puduvalli V.K. Tumor microenvironment in glioblastoma: Current and emerging concepts. Neurooncol Adv. 2023;5(1):vdad009. DOI: 10.1093/noajnl/vdad009Senhaji N., SqualliHoussaini A., Lamrabet S., Louati S., Bennis S. Molecular and circulating biomarkers in patients with glioblastoma. Int J Mol Sci. 2022;23(13):7474. DOI: 10.3390/ijms23137474Senhaji N., SqualliHoussaini A., Lamrabet S., Louati S., Bennis S. Molecular and circulating biomarkers in patients with glioblastoma. Int J Mol Sci. 2022;23(13):7474. DOI: 10.3390/ijms23137474Du Y., Li R., Fu D., Zhang B., Cui A., Shao Y., et al. Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy. CNS NeurosciTher. 2024;30(4):e14717. DOI: 10.1111/cns.14717Du Y., Li R., Fu D., Zhang B., Cui A., Shao Y., et al. Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy. CNS NeurosciTher. 2024;30(4):e14717. DOI: 10.1111/cns.14717Yagi C., Tatsuoka J., Sano E., Hanashima Y., Ozawa Y., Yoshimura S., et al. Anti-tumor effects of anti-epileptic drugs in malignant glioma cells. Oncol Rep. 2022;48(6):216. DOI: 10.3892/or.2022.8431Yagi C., Tatsuoka J., Sano E., Hanashima Y., Ozawa Y., Yoshimura S., et al. Anti-tumor effects of anti-epileptic drugs in malignant glioma cells. Oncol Rep. 2022;48(6):216. DOI: 10.3892/or.2022.8431Lopez-Anguita S., Gutierrez-Ruano B., Munoz-Gonzalez A., Valenzuela-Rojas F.J., Olmedilla-Gonzаlez M.N. Epilepsy in cancer patients: primary prevention and the importance of high-risk patient screening. Rev Neurol. 2022;75(11):349–56. DOI: 10.33588/rn.7511.2022200Lopez-Anguita S., Gutierrez-Ruano B., Munoz-Gonzalez A., Valenzuela-Rojas F.J., Olmedilla-Gonzаlez M.N. Epilepsy in cancer patients: primary prevention and the importance of high-risk patient screening. Rev Neurol. 2022;75(11):349–56. DOI: 10.33588/rn.7511.2022200Sanchez-Villalobos J.M., Aledo-Serrano A., Villegas-Martinez I., Shaikh M.F., Alcaraz M. Epilepsy treatment in neuro-oncology: A rationale for drug choice in common clinical scenarios. Front Pharmacol. 2022;13:991244. DOI: 10.3389/fphar.2022.991244Sanchez-Villalobos J.M., Aledo-Serrano A., Villegas-Martinez I., Shaikh M.F., Alcaraz M. Epilepsy treatment in neuro-oncology: A rationale for drug choice in common clinical scenarios. Front Pharmacol. 2022;13:991244. DOI: 10.3389/fphar.2022.991244Tabaee Damavandi P., Pasini F., Fanella G., Cereda G.S., Mainini G., DiFrancesco J.C., et al. Perampanel in brain tumor-related epilepsy: a systematic review. Brain Sci. 2023;13(2):326. DOI: 10.3390/brainsci13020326Tabaee Damavandi P., Pasini F., Fanella G., Cereda G.S., Mainini G., DiFrancesco J.C., et al. Perampanel in brain tumor-related epilepsy: a systematic review. Brain Sci. 2023;13(2):326. DOI: 10.3390/brainsci13020326Demetz M., Hecker C., Salim H.A., Krigers A., Steinbacher J., Machegger L., et al. Epilepsy as primary tumor manifestation correlates with patient status, age, and tumor volume but not with survival in elderly glioblastoma patients: a retrospective bicentric analysis. Neurosurg Rev. 2025;48(1):264. DOI: 10.1007/s10143-025-03397-1Demetz M., Hecker C., Salim H.A., Krigers A., Steinbacher J., Machegger L., et al. Epilepsy as primary tumor manifestation correlates with patient status, age, and tumor volume but not with survival in elderly glioblastoma patients: a retrospective bicentric analysis. Neurosurg Rev. 2025;48(1):264. DOI: 10.1007/s10143-025-03397-1Loscher W., Klein P. The pharmacology and clinical efficacy of antiseizure medications: from bromide salts to cenobamate and beyond. CNS Drugs. 2021;35(9):1033–4. DOI: 10.1007/s40263-021-00827-8Loscher W., Klein P. The pharmacology and clinical efficacy of antiseizure medications: from bromide salts to cenobamate and beyond. CNS Drugs. 2021;35(9):1033–4. DOI: 10.1007/s40263-021-00827-8Zhang Y., Duan W., Chen L., Chen J., Xu W., Fan Q., et al. Potassium ion channel modulation at cancer-neural interface enhances neuronal excitability in epileptogenic glioblastoma multiforme. Neuron. 2025;113(2):225–43. DOI: 10.1016/j.neuron.2024.10.016Zhang Y., Duan W., Chen L., Chen J., Xu W., Fan Q., et al. Potassium ion channel modulation at cancer-neural interface enhances neuronal excitability in epileptogenic glioblastoma multiforme. Neuron. 2025;113(2):225–43. DOI: 10.1016/j.neuron.2024.10.016Ruda R., Mo F., Pellerino A. Epilepsy in brain metastasis: an emerging entity. Curr Treat Options Neurol. 2020;22(2):6. DOI: 10.1007/s11940- 020-0613-yRuda R., Mo F., Pellerino A. Epilepsy in brain metastasis: an emerging entity. Curr Treat Options Neurol. 2020;22(2):6. DOI: 10.1007/s11940-020-0613-yArmstrong T.S., Grant R., Gilbert M.R., Lee J.W., Norden A.D. Epilepsy in glioma patients: Mechanisms, management, and impact of anticonvulsant therapy. Neuro-Oncology. 2016;18(6):779–89. DOI: 10.1093/neuonc/nov269Armstrong T.S., Grant R., Gilbert M.R., Lee J.W., Norden A.D. Epilepsy in glioma patients: Mechanisms, management, and impact of anticonvulsant therapy. Neuro-Oncology. 2016;18(6):779–89. DOI: 10.1093/neuonc/nov269Radin D.P., Tsirka S.E. Interactions between tumor cells, neurons, and microglia in the glioma microenvironment. Int. J. Mol. Sci. 2020;21(22):8476. DOI: 10.3390/ijms21228476Radin D.P., Tsirka S.E. Interactions between tumor cells, neurons, and microglia in the glioma microenvironment. Int. J. Mol. Sci. 2020;21(22):8476. DOI: 10.3390/ijms21228476Prager B.C., Bhargava S., Mahadev V., Hubert C.G., Rich J.N. Glioblastoma stem cells: driving resilience through chaos. Trends Cancer. 2020;6(3):223–35. DOI: 10.1016/j.trecan.2020.01.009Prager B.C., Bhargava S., Mahadev V., Hubert C.G., Rich J.N. Glioblastoma stem cells: driving resilience through chaos. Trends Cancer. 2020;6(3):223–35. DOI: 10.1016/j.trecan.2020.01.009Joghataei M.T., Bakhtiarzadeh F., Dehghan S., Ketabforoush A.H.M.E., Golab F., Zarbakhsh S., et al. The role of neurotransmitters in glioblastoma multiforme-associated seizures. Int J Dev Neurosci. 2023;83(8):677–90. DOI: 10.1002/jdn.10294Joghataei M.T., Bakhtiarzadeh F., Dehghan S., Ketabforoush A.H.M.E., Golab F., Zarbakhsh S., et al. The role of neurotransmitters in glioblastoma multiforme-associated seizures. Int J Dev Neurosci. 2023;83(8):677–90. DOI: 10.1002/jdn.10294Wang Yu., Bulatova N.R., Klen E.E., Rozit G.A., Nikitina I.L., Startseva L.V., et al. Efficacy of 4-(2-(4-nttrophenyl)-2-oxoethyl)-1- (thietane-3-yl)-1h-1,2,4-triazol-4 bromide in the rat model of inferior vena cava thrombosis. Translational medicine. 2024;11(1):19–27. DOI: 10.18705/2311-4495-2024-11-1-19-27Wang Yu., Bulatova N.R., Klen E.E., Rozit G.A., Nikitina I.L., Startseva L.V., et al. Efficacy of 4-(2-(4-nttrophenyl)-2-oxoethyl)-1- (thietane-3-yl)-1h-1,2,4-triazol-4 bromide in the rat model of inferior vena cava thrombosis. Translational medicine. 2024;11(1):19–27. DOI: 10.18705/2311-4495-2024-11-1-19-27Kamilov F.K., Timirkhanova G.A., Samorodov A.V., Khaliullin F.A. Choosing potential dissolution medium to study the influence of water-insoluble substances on aggregation of platelets within preclinical studies under conditions in vitro. Biology and Medicine. 2013; 5(1):15–9.Kamilov F.K., Timirkhanova G.A., Samorodov A.V., Khaliullin F.A. Choosing potential dissolution medium to study the influence of water-insoluble substances on aggregation of platelets within preclinical studies under conditions in vitro. Biology and Medicine. 2013; 5(1):15–9.Maschio M., Aguglia U., Avanzini G., Banfi P., Buttinelli C., Capovilla G, et al. Management of epilepsy in brain tumors. Neurol Sci. 2019;40(10):2217–34. DOI: 10.1007/s10072-019-04025-9Maschio M., Aguglia U., Avanzini G., Banfi P., Buttinelli C., Capovilla G, et al. Management of epilepsy in brain tumors. Neurol Sci. 2019;40(10):2217–34. DOI: 10.1007/s10072-019-04025-9Муфазалова Н.А., Валеева Л.А., Муфазалова Л.Ф., Батракова К.В. Нежелательные лекарственные реакции. Взаимодействие лекарственных средств. Противоэпилептические препараты. Уфа; 2021.Mufazalova N.A., Valeeva L.A., Mufazalova L.F., Batrakova K.V. Adverse drug reactions. Drug Interactions. Anticonvulsants. Ufa; 2021 (In Russ.).Wang Y., Yang H., Li N., Wang L., Guo C., Ma W., et al. A novel ubiquitin ligase adaptor PTPRN suppresses seizure susceptibility through endocytosis of NaV1.2 sodium channels. Adv Sci. 2024;11(29):e2400560. DOI: 10.1002/advs.202400560Wang Y., Yang H., Li N., Wang L., Guo C., Ma W., et al. A novel ubiquitin ligase adaptor PTPRN suppresses seizure susceptibility through endocytosis of NaV1.2 sodium channels. Adv Sci. 2024;11(29):e2400560. DOI: 10.1002/ advs.202400560Василенко А.В., Улитин А.Ю., Лебедев И.А., Аблаев Н.Р., Диконенко М.В., Мансуров А.С. и др. Эпилепсия у больных с глиобластомой: механизмы возникновения и проблемы лечения (часть 2). Медицинский алфавит. 2023;(33):13–9. DOI: 10.33667/2078-5631-2023-33-13-19Vasilenko A.V., Ulitin A.Yu., Lebedev I.A., Ablaev N.R., Dikonenko M.V., Mansurov A.S., et al. Epilepsy in patients with glioblastoma: mechanisms of occurrence and problems of treatment (part 2). Medical alphabet. 2023;(33):13–9 (In Russ.). DOI: 10.33667/2078-5631-2023-33-13-19Beydoun A., DuPont S., Zhou D., Matta M., Nagire V., Lagae L. Current role of carbamazepine and oxcarbazepine in the management of epilepsy. Seizure. 2020;83:251–63. DOI: 10.1016/j.seizure.2020.10.018Beydoun A., DuPont S., Zhou D., Matta M., Nagire V., Lagae L. Current role of carbamazepine and oxcarbazepine in the management of epilepsy. Seizure. 2020;83:251–63. DOI: 10.1016/j.seizure.2020.10.018Шнайдер Н.А., Бочанова Е.Н., Дмитренко Д.В. и др. Фармакогенетика карбамазепина. Эпилепсия и пароксизмальные состояния. 2019;11(4):364–78. DOI: 10.17749/2077-8333.2019.11.4.364-378Shnayder N.A., Bochanova E.N., Dmitrenko D.V., Nasyrova R.F. Pharmacogenetics of carbamazepine. Epilepsy and Paroxysmal Conditions. 2019;11(4):364–78 (In Russ.). DOI: 10.17749/2077-8333.2019.11.4.364-378Vaiman E., Gayduk A., Strelnik A., Smirnova D., Davydkin I., Fedyashov I., et al. Possible clinical and pharmacogenetic predictors of the efficacy and safety of carbamazepine in post-COVID-19 depression. Psychiatr Danub. 2022;34(8):31–7. PMID: 36170698Vaiman E., Gayduk A., Strelnik A., Smirnova D., Davydkin I., Fedyashov I., et al. Possible clinical and pharmacogenetic predictors of the efficacy and safety of carbamazepine in post-COVID-19 depression. Psychiatr Danub. 2022;34(8):31–7. PMID: 36170698Zhao G.X., Zhang Z., Cai W.K., Shen M.L., Wang P., He G.H. Associations between CYP3A4, CYP3A5 and SCN1A polymorphisms and carbamazepine metabolism in epilepsy: A meta-analysis. Epilepsy Res. 2021;173:106615. DOI: 10.1016/j.eplepsyres.2021.106615Zhao G.X., Zhang Z., Cai W.K., Shen M.L., Wang P., He G.H. Associations between CYP3A4, CYP3A5 and SCN1A polymorphisms and carbamazepine metabolism in epilepsy: A meta-analysis. Epilepsy Res. 2021;173:106615. DOI: 10.1016/j.eplepsyres.2021.106615Ortega-Vazquez A., Dorado P., Fricke-Galindo I., Jung-Cook H., Monroy-Jaramillo N., Martinez-Juаrez I.E., et al. CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy. Pharmacogenomics J. 2016;16(3):286–92. DOI: 10.1038/tpj.2015.45Ortega-Vazquez A., Dorado P., Fricke-Galindo I., Jung-Cook H., Monroy-Jaramillo N., Martinez-Juаrez I.E., et al. CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy. Pharmacogenomics J. 2016;16(3):286–92. DOI: 10.1038/tpj.2015.45Riffi R., Boughrara W., Chentouf A., Ilias W., Brahim N.M.T., Berrebbah A.A., et al. Pharmacogenetics of carbamazepine: a systematic review on CYP3A4 and CYP3A5 polymorphisms. CNS Neurol Disord Drug Targets. 2024;23(12):1463–73. DOI: 10.2174/0118715273298953240529100325Riffi R., Boughrara W., Chentouf A., Ilias W., Brahim N.M.T., Berrebbah A.A., et al. Pharmacogenetics of carbamazepine: a systematic review on CYP3A4 and CYP3A5 polymorphisms. CNS Neurol Disord Drug Targets. 2024;23(12):1463–73. DOI: 10.2174/0118715273298953240529100325Amos K., Garcia-Bournissen F., Zhao L., Taheri S. Carbamazepineinduced liver injury in an 11-year-old female: Case report and review of the literature. J Paediatr Child Health. 2023;59(1):165–8. DOI: 10.1111/jpc.16200Amos K., Garcia-Bournissen F., Zhao L., Taheri S. Carbamazepineinduced liver injury in an 11-year-old female: Case report and review of the literature. J Paediatr Child Health. 2023;59(1):165–8. DOI: 10.1111/jpc.16200Drokov A.P., Lipatova L.V., Shnayder N.A. Pharmacogenetic markers for metabolic impairments in treatment with valproic acid. Neuroscience and behavioral physiology. 2020;50(1):13–9. DOI: 10.1007/s11055-019-00861-6Drokov A.P., Lipatova L.V., Shnayder N.A. Pharmacogenetic markers for metabolic impairments in treatment with valproic acid. Neuroscience and behavioral physiology. 2020;50(1):13–9. DOI: 10.1007/s11055-019-00861-6Manni R., Toscano G., Terzaghi M. Epilepsy and cardiovascular function: seizures and antiepileptic drugs effects. In: Govoni S., Politi P., Vanoli (eds) Brain and Heart Dynamics. Springer; 2020. Р. 507–15. DOI: 10.1007/978-3-030-28008-6_30Manni R., Toscano G., Terzaghi M. Epilepsy and cardiovascular function: seizures and antiepileptic drugs effects. In: Govoni S., Politi P., Vanoli (eds) Brain and Heart Dynamics. Springer; 2020. Р. 507–15. DOI: 10.1007/978-3-030-28008-6_30Rissardo J.P., Caprara A.L.F.. Carbamazepine-, Oxcarbazepine-, Eslicarbazepine-associated movement disorder: a literature review. Clin Neuropharmacol. 2020;43(3):66–80. DOI: 10.1097/WNF.0000000000000387Rissardo J.P., Caprara A.L.F.. Carbamazepine-, Oxcarbazepine-, Eslicarbazepine-associated movement disorder: a literature review. Clin Neuropharmacol. 2020;43(3):66–80. DOI: 10.1097/WNF.0000000000000387Benit C.P., Vecht C.J. Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids. Neurooncol. Pract. 2016;3(4):245–60. DOI: 10.1093/nop/npv038Benit C.P., Vecht C.J. Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids. Neurooncol. Pract. 2016;3(4):245–60. DOI: 10.1093/nop/npv038Cacho-Diaz B., San-Juan D., Salmeron K., Boyzo C., Lorenzana-Mendoza N. Choice of antiepileptic drugs affects the outcome in cancer patients with seizures. Clin Transl Oncol. 2018;20(12):1571–6. DOI: 10.1007/s12094-018-1892-6Cacho-Diaz B., San-Juan D., Salmeron K., Boyzo C., Lorenzana-Mendoza N. Choice of antiepileptic drugs affects the outcome in cancer patients with seizures. Clin Transl Oncol. 2018;20(12):1571–6. DOI: 10.1007/s12094-018-1892-6Kobylarek D., Iwanowski P., Lewandowska Z., Limphaibool N., Szafranek S., Labrzycka A., et al. Advances in the potential biomarkers of epilepsy. Front Neurol. 2019;10:685. DOI: 10.3389/fneur.2019.00685Kobylarek D., Iwanowski P., Lewandowska Z., Limphaibool N., Szafranek S., Labrzycka A., et al. Advances in the potential biomarkers of epilepsy. Front Neurol. 2019;10:685. DOI: 10.3389/fneur.2019.00685Cai M., Tang X. Human archaea and associated metabolites in health and disease. Biochemistry. 2022;61(24):2835–40. DOI: 10.1021/acs.biochem.2c00232Cai M., Tang X. Human archaea and associated metabolites in health and disease. Biochemistry. 2022;61(24):2835–40. DOI: 10.1021/acs.biochem.2c00232Zhou T., Wang N., Xu L., Huang H., Yu C., Zhou H. Effects of carbamazepine combined with vitamin B12 on levels of plasma homocysteine, hs-CRP and TNF-α in patients with epilepsy. Exp Ther Med. 2018;15(3):2327–32. DOI: 10.3892/etm.2018.5698Zhou T., Wang N., Xu L., Huang H., Yu C., Zhou H. Effects of carbamazepine combined with vitamin B12 on levels of plasma homocysteine, hs-CRP and TNF-α in patients with epilepsy. Exp Ther Med. 2018;15(3):2327–32. DOI: 10.3892/etm.2018.5698

The authors declare that there are no conflicts of interest present.