Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

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Abstract

Epilepsy occurs in 35–95% of patients with low-grade malignant cerebral gliomas and in 29–71% of patients with high-grade gliomas. Seizures can be the first manifestation of a malignant cerebral glioma or may develop in the postoperative period and during chemoradiation therapy. This necessitates the use of antiepileptic drugs that can control seizures, ensure seizure prevention, and provide secondary seizure prophylaxis without reducing the effectiveness of anticancer therapy or the patient’s quality of life. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms, with glutamate playing a key role. Increased glutamate secretion is accompanied by elevated expression and activation of its receptors, which raises seizure susceptibility. This is associated with increased levels of brain-derived neurotrophic factor, the number of synapses between peritumoral neurons and glioma cells, and the expression of various growth factors, all of which contribute to tumor progression. In this context, special attention is given to perampanel, a glutamate receptor antagonist and third-generation antiepileptic drug, in the treatment of epilepsy in patients with malignant cerebral gliomas. It has been shown that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas but also suppresses tumor progression. Perampanel can dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. A synergistic effect of perampanel in combination with temozolamide has been identified. During chemoradiation therapy, perampanel exerts a protective effect on healthy peritumoral tissues. Adverse drug reactions associated with perampanel use are infrequent and mild. Further research is needed to investigate the anticonvulsant and antitumor efficacy of perampanel for the treatment of epilepsy in patients with malignant brain tumors.

About the authors

Yi Wang

Hangzhou Normal University

Email: makval81@rambler.ru
ORCID iD: 0000-0001-9048-0092
Scopus Author ID: 55969091300

MD, Professor

China, Hangzhou

Natalia A. Mufazalova

Bashkir State Medical University

Email: mufazalovanatalya@yandex.ru
ORCID iD: 0000-0002-0656-3459
SPIN-code: 4053-2051

Dr. Sci. (Medicine), Professor

Russian Federation, Ufa

Lyaysan F. Mufazalova

Bashkir State Medical University

Email: lya-mufazalova@yandex.ru
ORCID iD: 0000-0001-8129-9320
SPIN-code: 1542-2210

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Ufa

Nailya V. Ilyasova

Bashkir State Medical University

Email: Na1lyasova@yandex.ru
ORCID iD: 0009-0008-1774-9831
SPIN-code: 4459-6602
Russian Federation, Ufa

Raila R. Muradova

Samarkand State Medical University

Email: ismagilovaln@rambler.ru
ORCID iD: 0000-0001-9202-0479
Uzbekistan, Samarkand

Ikhtiyor E. Kiyomov

Samarkand State Medical University

Email: lukmanova.gulnur@mail.ru
ORCID iD: 0009-0004-7387-7740
Uzbekistan, Samarkand

Laylo Sh. Davurova

Samarkand State Medical University

Email: anikolaev1957@rambler.ru
ORCID iD: 0009-0009-1396-1744
Uzbekistan, Samarkand

Aleksandr V. Samorodov

Bashkir State Medical University

Author for correspondence.
Email: avsamorodov@gmail.com
ORCID iD: 0000-0001-9302-499X

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Ufa

References

  1. Ostrom QT, Patil N, Cioffi G, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro Oncol. 2020;22(12 Suppl 2):iv1–iv96. doi: 10.1093/neuonc/noaa200.
  2. Shabanov P.D., Fisher E.L., Urakov A.L. Hydrogen peroxide formulations and methods of their use for blood oxygen saturation. JMPAS. 2022;11:5489-5493. doi: 10.55522/jmpas.V11I6.4604.
  3. Hey G, Rao R, Carter A, et al. Ligand-Gated Ion Channels: Prognostic and Therapeutic Implications for Gliomas. J Pers Med. 2023;13(5):853. doi: 10.3390/jpm13050853.
  4. Gretskikh KV, Tokarev AS. Gliomas of high malignancy: a review of the literature. Part 1. Epidemiology, classification and approaches to combined treatment. Neurosurgery. 2021; 23(1):124–34. (In Russ) doi: 10.17650 / 1683-3295-2021-23-1-124-134
  5. Jahangir M, Nicholas GA, Mohtashem S. Epidemiology of Brain and Spinal Tumors. 1st ed. Editors: Jahangir M, Nicholas GA, Mohtashem S. Academic Press, 2021. P. 129-145, ISBN 9780128217368
  6. Heugenhauser J, Iglseder S, Muigg A, et al. Perampanel in brain tumor and SMART-syndrome related epilepsy - A single institutional experience. J Neurol Sci. 2021;423:117386. doi: 10.1016/j.jns.2021.117386.
  7. Ius T, Pauletto G, Tomasino B, et al. Predictors of Postoperative Seizure Outcome in Low Grade Glioma: From Volumetric Analysis to Molecular Stratification. Cancers (Basel). 2020;12(2):397. doi: 10.3390/cancers12020397.
  8. Ruda 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-y.
  9. Urakov A.L., Shabanov P.D. Opioid, cannabinoid, cocaine and methamphetamine epidemics. History, risk factors associated with them, and features of the action of drugs // Psychopharmacology and biological narcology. 2023;14(4):251-262. doi: 10.17816/phbn568586.
  10. Sanchez-Villalobos JM, Aledo-Serrano A, Villegas-Martínez I, Shaikh MF, 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.2022.991244.
  11. Vecht C, Duran-Peña A, Houillier C, et al. Seizure response to perampanel in drug-resistant epilepsy with gliomas: Early observations. J. Neurooncol. 2017;133:603–607. doi: 10.1007/s11060-017-2473-1.
  12. Wirsching HG, Weller M. Does Neuronal Activity Promote Glioma Progression? Trends Cancer. 2020;6(1):1-3. doi: 10.1016/j.trecan.2019.11.002.
  13. Tabaee Damavandi P, Pasini F, Fanella G, et al. Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review. Brain Sci. 2023;13(2):326. doi: 10.3390/brainsci13020326.
  14. Cacho-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):1571-1576. doi: 10.1007/s12094-018-1892-6.
  15. Coppola A., Zarabla A., Maialetti A., et al. Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients with Brain Tumor-Related Epilepsy (PERADET Study) Front. Neurol. 2020;11:592. doi: 10.3389/fneur.2020.00592.
  16. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. doi: 10.1136/bmj.b2535.
  17. Alifieris C, Trafalis DT. Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther. 2015;152:63-82. doi: 10.1016/j.pharmthera.2015.05.005.
  18. Hu S, Kao HY, 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.2021.136351. Epub 2021 Nov 15.
  19. Kal'yango K, Dyachenko AA, Bogdanov DV, et al. The increase in the incidence of glioblastoma against the background of a decrease in the frequency of brain tumors in 2000-2020: a population-based registry study. Journal of Neurosurgery named after N.N. Burdenko. 2022;86(5):28 36. (In Russ) doi: 10.17116/neiro20228605128
  20. Laghari AA, Ahmed SI, Qadeer N, Shamim MS. Choice of therapeutic anti-seizure medication in patients with brain tumour. J. Pak. Med. Assoc. 2019;69:442–444.
  21. Lange F, Hörnschemeyer J, Kirschstein T. Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy. Cells. 2021;10(5):1226. doi: 10.3390/cells10051226.
  22. Shabanov P.D., Nozdrachev A.D., Lebedev A.A., Lebedev V.A. Neurochemical organization of the brain reinforcing systems // Russian Journal of Physiology. 2000;86(8):935-945.
  23. Schaff LR, Mellinghoff IK. Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. JAMA. 2023;329(7):574-587. doi: 10.1001/jama.2023.0023.
  24. Solomons MR, Jaunmuktane Z, Weil RS, et al. Seizure outcomes and survival in adult low-grade glioma over 11 years: living longer and better. Neurooncol Pract. 2020;7(2):196-201. doi: 10.1093/nop/npz056. Epub 2019 Nov 21.
  25. van der Meer PB, Taphoorn MJB, Koekkoek JAF. Management of epilepsy in brain tumor patients. Curr Opin Oncol. 2022;34(6):685-690. doi: 10.1097/CCO.0000000000000876.
  26. Seidel S, Wehner T, Miller D, et al. Brain tumor related epilepsy: pathophysiological approaches and rational management of antiseizure medication. Neurol Res Pract. 2022;4(1):45. doi: 10.1186/s42466-022-00205-9
  27. Englot DJ, Berger MS, Chang EF, Garcia PA. Characteristics and treatment of seizures in patients with high-grade glioma: a review. Neurosurg Clin N Am. 2012;23(2):227-35, vii-viii. doi: 10.1016/j.nec.2012.01.009.
  28. Youngerman BE, Joiner EF, Wang X, et al. Patterns of seizure prophylaxis after oncologic neurosurgery. J Neurooncol. 2020;146(1):171-180. doi: 10.1007/s11060-019-03362-1.
  29. Maialetti A, Maschio M, Zarabla A, et al. Multimodal pathway for brain tumor-related epilepsy patients: Observational study. Acta Neurol Scand. 2020;141(6):450-462. doi: 10.1111/ane.13228.
  30. Hills KE, Kostarelos K, Wykes RC. Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma. Front. Mol. Neurosci. 2022;15:903115. doi: 10.3389/fnmol.2022.903115.
  31. Airapetov M.I., Eresko S.O., Lebedev A.A. Expression of the growth hormone secretagogue receptor 1a (GHS-R1a) in the brain // Physiological Reports. 2021. 9(21): e15113. doi: 10.14814/phy2.15113.
  32. Stella M, Baiardi G, Pasquariello S, et al. Antitumor Potential of Antiepileptic Drugs in Human Glioblastoma: Pharmacological Targets and Clinical Benefits. Biomedicines. 2023;16;11(2):582. doi: 10.3390/biomedicines11020582.
  33. Liang S, Fan X, Zhao M, et al. Clinical practice guidelines for the diagnosis and treatment of adult diffuse glioma-related epilepsy. Cancer Med. 2019;8(10):4527-4535. doi: 10.1002/cam4.2362.
  34. Ryu JY, Min KL, Chang MJ. Effect of anti-epileptic drugs on the survival of patients with glioblastoma multiforme: A retrospective, single-center study. PLoS ONE. 2019;14:e0225599. doi: 10.1371/journal.pone.0225599.
  35. Chen DY, Chen CC, Crawford JR, Wang SG. Tumor-Related Epilepsy: Epidemiology, Pathogenesis and Management. J.Neurooncol. 2018;139:13–21.doi: 10.1007/s11060-018-2862-0.
  36. Dührsen L, Sauvigny T, Ricklefs FL, et al. Seizures as presenting symptom in patients with glioblastoma. Epilepsia. 2019;60:149–154. doi: 10.1111/epi.14615.
  37. Yagi C, Tatsuoka J, Sano E, et al. Anti tumor effects of anti epileptic drugs in malignant glioma cells. Oncol Rep. 2022;48(6):216. doi: 10.3892/or.2022.8431.
  38. Ahmadipour Y, Rauschenbach L, Santos A, et al. Preoperative and early postoperative seizures in patients with glioblastoma-two sides of the same coin? Neurooncol Adv. 2020;3(1):vdaa158. doi: 10.1093/noajnl/vdaa158.
  39. de Bruin ME, van der Meer PB, Dirven L, et al. Efficacy of antiepileptic drugs in glioma patients with epilepsy: a systematic review. Neurooncol Pract. 2021;8(5):501-517. doi: 10.1093/nop/npab030.
  40. Wach J, Güresir Á, Hamed M, et al. Impact of Levetiracetam Treatment on 5-Aminolevulinic Acid Fluorescence Expression in IDH1 Wild-Type Glioblastoma. Cancers (Basel). 2022;14(9):2134. doi: 10.3390/cancers14092134.
  41. Sachdev B, Rees J. Incidentalomas to glioblastoma multiforme. Oxf Med Case Reports. 2014;2014(5):96-7. doi: 10.1093/omcr/omu036.
  42. Zheng Y, Yang Y, Ng MH, et al. Effect of perioperative seizures on mortality and recurrence in patients with brain metastases. Front Oncol. 2022;12:1048304. doi: 10.3389/fonc.2022.1048304.
  43. Armstrong TS, Grant R, Gilbert MR, Lee JW, Norden AD. Epilepsy in glioma patients: Mechanisms, management, and impact of anticonvulsant therapy. Neuro-Oncology. 2016;18:779–789. doi: 10.1093/neuonc/nov269.
  44. Cucchiara F, Ferraro S, Luci G, Bocci G. Relevant pharmacological interactions between alkylating agents and antiepileptic drugs: Preclinical and clinical data. Pharmacol Res. 2022;175:105976. doi: 10.1016/j.phrs.2021.105976.
  45. Lebedeva AV, Burd SG, Vlasov PN, et al. Treatment of epilepsy associated with primary and metastatic brain tumors. Epilepsy and paroxysmal conditions. 2021; 13 (3): 286–304. (In Russ) doi: 10.17749/2077-8333/epi.par.con.2021.099
  46. Chonan M, Saito R, Kanamori M, et al. Experience of Low Dose Perampanel to Add-on in Glioma Patients with Levetiracetam-uncontrollable Epilepsy. Neurol. Med. Chir. 2020;60:37–44. doi: 10.2176/nmc.oa.2018-0245.
  47. Mufazalova NA, Valeeva LA, Mufazalova LF, Batrakova KV. Undesirable drug reactions. Drug interactions. Antiepileptic drugs. Ufa: LLC "Print +", 2021. (In Russ)
  48. Tatsuoka J, Sano E, Hanashima Y, et al. Anti-tumor effects of perampanel in malignant glioma cells. Oncol Lett. 2022;24(6):421. doi: 10.3892/ol.2022.13541.
  49. Ogunsakin O., Tumenta T., Louis-Jean S., et al. Levetiracetam induced behavioral abnormalities in a patient with seizure disorder: a diagnostic challenge. Case Rep. Psychiatry. 2020;2020:8883802. doi: 10.1155/2020/8883802.
  50. Chen JS, Clarke R, Haddad AF, et al. The effect of levetiracetam treatment on survival in patients with glioblastoma: a systematic review and meta-analysis. J Neurooncol. 2022;156(2):257-267. doi: 10.1007/s11060-021-03940-2.
  51. Kanner AM, Bicchi MM. Antiseizure Medications for Adults With Epilepsy: A Review. JAMA. 2022;327(13):1269-1281. doi: 10.1001/jama.2022.3880.
  52. Mayer J, Kirschstein T, Resch T, et al. Perampanel attenuates epileptiform phenotype in C6 glioma. Neurosci Lett. 2020;715:134629. doi: 10.1016/j.neulet.2019.134629.
  53. Pina-Garza JE, Rosenfeld W, Saeki K, et al. Efficacy and safety of adjunctive perampanel in adolescent patients with epilepsy: Post hoc analysis of six randomized studies. Epilepsy Behav. 2020;104:106876. doi: 10.1016/j.yebeh.2019.106876.
  54. Lavu A, Aboulatta L, Abou-Setta AM, et al. Efficacy and safety of perampanel in epilepsy: A systematic review and meta-analysis of randomised controlled trials. Seizure. 2022;102:54-60. doi: 10.1016/j.seizure.2022.09.020.
  55. Rossi J, Cavallieri F, Bassi MC, et al. Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review. Biomedicines. 2023;11(3):651. doi: 10.3390/biomedicines11030651. PMID: 36979629; PMCID: PMC10045654.
  56. Steinhoff BJ, Klein P, Klitgaard H, et al. Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review. Epilepsy Behav. 2021;118:107939. doi: 10.1016/j.yebeh.2021.107939.
  57. Sagar P, Wawryk O, Vogrin S, et al. Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes. Epilepsy Behav. 2021;119:107935. doi: 10.1016/j.yebeh.2021.107935.
  58. French JA, Krauss GL, Steinhoff BJ, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013;54(1):117-25. doi: 10.1111/j.1528-1167.2012.03638.x.
  59. Krauss GL, Serratosa JM, Villanueva V, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012;78(18):1408-15. doi: 10.1212/WNL.0b013e318254473a.
  60. Kwan P, Brodie MJ, Laurenza A, FitzGibbon H, Gidal BE. Analysis of pooled phase III trials of adjunctive perampanel for epilepsy: Impact of mechanism of action and pharmacokinetics on clinical outcomes. Epilepsy Res. 2015;117:117-24. doi: 10.1016/j.eplepsyres.2015.09.002.
  61. Gidal BE, Ferry J, Majid O, Hussein Z. Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures. Epilepsia. 2013;54(8):1490-7. doi: 10.1111/epi.12240. Epub 2013 Jun 17. PMID: 23772853.
  62. Lattanzi S, Cagnetti C, Foschi N, et al. Adjunctive Perampanel in Older Patients With Epilepsy: A Multicenter Study of Clinical Practice. Drugs Aging. 2021;38(7):603-610. doi: 10.1007/s40266-021-00865-3.
  63. Witt JA, Helmstaedter C. The impact of perampanel on cognition: A systematic review of studies employing standardized tests in patients with epilepsy. Seizure. 2022;94:107-111. doi: 10.1016/j.seizure.2021.12.001.
  64. Akyuz E, Köklü B, Ozenen C, Arulsamy A, Shaikh MF. Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy. Curr Neuropharmacol. 2021;19(11):1865-1883. doi: 10.2174/1570159X19666210826125341.
  65. Cunningham M. Targeting Elevated Glutamate in Brain Tumour Related Epilepsy. Epilepsia. 2016;57((Suppl. S2)):226. doi: 10.1111/epi.13610.
  66. Lai MC, Tzeng RC, Huang CW, Wu SN. The Novel Direct Modulatory Effects of Perampanel, an Antagonist of AMPA Receptors, on Voltage-Gated Sodium and M-type Potassium Currents. Biomolecules. 2019;9(10):638. doi: 10.3390/biom9100638.
  67. Lange F., Weßlau K., Porath K., et al. AMPA receptor antagonist perampanel affects glioblastoma cell growth and glutamate release in vitro. PLoS ONE. 2019;14:e0211644. doi: 10.1371/journal.pone.0211644.
  68. Salmaggi A, Corno C, Maschio M, et al. Synergistic Effect of Perampanel and Temozolomide in Human Glioma Cell Lines. J. Pers. Med. 2021;11:390. doi: 10.3390/jpm11050390.
  69. Lange F, Hartung J, Liebelt C, et al. Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model. Front Neurosci. 2020;14:598266. doi: 10.3389/fnins.2020.598266.
  70. Rosche J, Piek J, Hildebrandt G, et al. Perampanel in the treatment of a patient with glioblastoma multiforme without IDH1 mutation and without MGMT promotor methylation. Fortschr. Neurol. Psychiatr. 2015;83:286–289. doi: 10.1055/s-0034-1399459.
  71. Izumoto S, Miyauchi M, Tasaki T, et al. Seizures and Tumor Progression in Glioma Patients with Uncontrollable Epilepsy Treated with Perampanel. Anticancer Res. 2018;38:4361–4366. doi: 10.21873/anticanres.12737.
  72. Dunn-Pirio AM, Woodring S, Lipp E, et al. Adjunctive perampanel for glioma-associated epilepsy. Epilepsy Behav. Case Rep. 2018;10:114–117. doi: 10.1016/j.ebcr.2018.09.003.
  73. Maschio M, Pauletto G, Zarabla A, et al. Perampanel in patients with brain tumor-related epilepsy in real-life clinical practice: A retrospective analysis. Int. J. Neurosci. 2019;129:593–597. doi: 10.1080/00207454.2018.1555160.
  74. Maschio M, Zarabla A, Maialetti A, et al. Perampanel in brain tumor-related epilepsy: Observational pilot study. Brain Behav. 2020;10(6):e01612. doi: 10.1002/brb3.1612. Epub 2020 Apr 14.
  75. Prokudin MYu, Martynov BV, Yakovenko AI, et al. The role of glutamine synthetase expression and the cystine/glutamate transporter (SLC7A11, xCT) in the pathogenesis of epilepsy in patients with supratentorial gliomas of the brain. Epilepsy and paroxysmal states. 2022; 14 (2): 204–213. doi: 10.17749/2077-8333/epi.par.con.2022.118.
  76. Muller-Langle A, Lutz H, Hehlgans S, et al. NMDA Receptor-Mediated Signaling Pathways Enhance Radiation Resistance, Survival and Migration in Glioblastoma Cells-A Potential Target for Adjuvant Radiotherapy. Cancers. 2019;11:503. doi: 10.3390/cancers11040503.
  77. Brocke KS, Staufner C, Luksch H, et al. Glutamate receptors in pediatric tumors of the central nervous system. Cancer Biol. Ther. 2010;9:455–468. doi: 10.4161/cbt.9.6.10898.
  78. Venkataramani V, Tanev DI, Strahle C, et al. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature. 2019;573(7775):532-538. doi: 10.1038/s41586-019-1564-x.
  79. Venkatesh HS, Morishita W, Geraghty AC, et al. Electrical and synaptic integration of glioma into neural circuits. Nature. 2019;573(7775):539-545. doi: 10.1038/s41586-019-1563-y.
  80. Radin DP, Tsirka SE. Interactions between tumor cells, neurons, and microglia in the glioma microenvironment. Int. J. Mol. Sci. 2020;21:8476. doi: 10.3390/ijms21228476
  81. Lo M., Wang Y.-Z., Gout P.W. The x(c)- cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases. J. Cell. Physiol. 2008;215:593–602. doi: 10.1002/jcp.21366.
  82. Takeuchi S, Wada K, Toyooka T, et al. Increased xCT expression correlates with tumor invasion and outcome in patients with glioblastomas. Neurosurgery. 2013 Jan;72(1):33-41; discussion 41. doi: 10.1227/NEU.0b013e318276b2de.
  83. Long Y, Tao H, Karachi A, et al. Dysregulation of Glutamate Transport Enhances Treg Function That Promotes VEGF Blockade Resistance in Glioblastoma. Cancer Res. 2020 Feb 1;80(3):499-509. doi: 10.1158/0008-5472.CAN-19-1577.
  84. Xuan DTM, Wu CC, Wang WJ, et al. Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway. Int J Med Sci. 2023;20(1):35-49. doi: 10.7150/ijms.75625.
  85. Rosati A, Poliani PL, Todeschini A, et al. Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme. Neuro Oncol. 2013;15(5):618-25. doi: 10.1093/neuonc/nos338.
  86. Pallud J, Le Van Quyen M, Bielle F, et al. Cortical GABAergic excitation contributes to epileptic activities around human glioma. Sci Transl Med. 2014;6(244):244ra89. doi: 10.1126/scitranslmed.3008065.
  87. Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75:279–286. doi: 10.1001/jamaneurol.2017.3949.
  88. Loscher W, Klein P. The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond. CNS Drugs. 2021;35(9):935-963. doi: 10.1007/s40263-021-00827-8
  89. Lee SA, Jeon JY, Kim HW. Effect of perampanel on aggression in patients with refractory focal epilepsy: A 6-month longitudinal study. Epilepsy Behav. 2020;102:106658. doi: 10.1016/j.yebeh.2019.106658.

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3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».