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Features of epileptiform activity in patients with diagnosed glioblastoma: from genetic and biochemical mechanisms to clinical aspects

https://doi.org/10.17650/2222-1468-2022-12-3-102-113

Abstract

Introduction. glioblastomas multiforme (grade Iv gliomas) are common and the most aggressive primary tumors of the brain with very unfavorable prognosis. In all previously published papers on epileptiform activity in glioblastomas, not enough information on encephalogram results is presented.

Aim. To study the features of epileptiform activity in patients with glioblastomas and development of a plan for further study of these patients.

Materials and methods. An analysis of articles from Elsevier, Embase, Scopus, The Cochrane Library, global Health, Russian Science Citation Index (RSCI) databases, Scholar, google, web of Science, pubmed search engines and scientific electronic library CyberLeninka was performed. materials were selected considering journal indexing system and citations, scientific novelty of the studies, statistical significance of the results. publications repeating data from previous articles or describing animal experiments were excluded from analysis.

Results. During the study, data on mechanisms of epileptiform activity pathogenesis, predisposing factors (tumor location in the temporal, frontal or parietal lobes, IDH-1 and / or IDH-2 gene mutations), treatment options in patients with glioblastomas were systemized. Additionally, and original plan of data accumulation for clinical studied taking into account limitations of the previous studies was developed to increase quality of results interpretation.

Conclusion. Epileptiform symptoms in glioblastomas negatively affect patients’ quality of life and lifespan. Currently, researchers actively search for an effective method of treatment of epileptic seizures in patients with glioblastomas. The most effective is combination of temozolomide with valproate and levetiracetam due to good control of seizure frequency, low toxicity, and pharmacological synergy between the drugs.

About the Authors

E. E. Tyagunova
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia
Russian Federation

Ekaterina Evgenievna Tyagunova 

 



A. S. Zakharov
Pavlov Ryazan State Medical University, Ministry of Health of Russia
Russian Federation

9 Vysokovoltnaya St., Ryazan 390026



A. I. Glukhov
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia; M.V. Lomonosov Moscow State University
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991

1 Leninskie Gory, Moscow 119991



V. Z. Dobrokhotova
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia; N. N. Blokhin National Research Institute of Oncology, Ministry of Health of Russia
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991

24 Kashirskoe Shosse, Moscow 115522



T. I. Shlapakov
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991



V. V. Kozlov
I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991



N. V. Korotkova
Pavlov Ryazan State Medical University, Ministry of Health of Russia
Russian Federation

9 Vysokovoltnaya St., Ryazan 390026



T.  E.  Tyagunova
LLC “Klassny Doctor”
Russian Federation

15 Karl Marks St., Kasimov 391000



References

1. Shlapakova T.I., Tyagunova E.E., Kostin R.K., Danilova D.A. Targeted antitumor drug delivery to glioblastoma multiforme cells. Russ J Bioorg Chem 2021;47(2):376–79. DOI: 10.1134/ S1068162021020254

2. Bogoyavlenskaya T.A., Tyagunova E.E., Kostin R.K. et al. Glioblastoma break-in; try something new. Int J Cancer Manag 2021;14(1):e109054. DOI: 10.5812/ijcm.109054

3. Shlapakova T.I., Tyagunova E.E., Kostin R.K., Danilova D.A. Targeted delivery of antitumor drugs to glioblastoma multiforme cells. Bioorganicheskaya himiya = Bioorganic Chemistry 2021;47(3):299–303. (In Russ.). DOI: 10.31857/S0132342321020251

4. Climans S.A., Brandes A.A., Cairncross J.G. 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-x

5. Avila E.K., Chamberlain M., Schiff D. et al. Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials. Neuro Oncol 2017;19(1):12–21. DOI: 10.1093/ neuonc/now190

6. Perry J.R., Laperriere N., O’Callaghan C.J. et al. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 2017;376(11):1027–37. DOI: 10.1056/NEJMoa1611977

7. Vecht C.J., Kerkhof M., Duran-Pena A. Seizure prognosis in brain tumors: new insights and evidence-based management. Oncologist 2014;19(7):751–9. DOI: 10.1634/theoncologist. 2014-0060

8. Bruna J., Miró J., Velasco R. Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment. Expert Rev Clin Pharmacol 2013;6(3):333–44. DOI: 10.1586/ecp.13.12

9. Forsgren L., Bucht G., Eriksson S., Bergmark L. Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study. Epilepsia 1996;37(3):224–9. DOI: 10.1111/j.1528-1157.1996.tb00017.x

10. Perucca P., Camfield P., Camfield C. Does gender influence susceptibility and consequences of acquired epilepsies. Neurobiol Dis 2014;72(Pt. B):125–30. DOI: 10.1016/j.nbd.2014.05.016

11. Maugeri R., Schiera G., Di Liegro C.M. et al. Aquaporins and brain tumors. Int J Mol Sci 2016; 17(7):1029. DOI: 10.3390/ ijms17071029

12. Wolburg H., Noell S., Fallier-Becker P. et al. The disturbed blood–brain barrier in human glioblastoma.Mol Asp Med 2012;33(5–6): 579–89. DOI: 10.1016/j.mam.2012.02.003

13. Vecht C., Royer-Perron L., Houillier C., Huberfeld G. Seizures and anticonvulsants in brain tumours: frequency, mechanisms and antiepileptic management. Curr Pharm Des 2017;23(42):6464–87. DOI: 10.2174/1381612823666171027130003

14. Yuen T.I., Morokoff A.P., Bjorksten A. et al. Glutamate is associated with a higher risk of seizures in patients with gliomas. Neurology 2012;79(9):883–9. DOI: 10.1212/WNL.0b013e3186fa89

15. 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(3):593–602. DOI: 10.1002/jcp. 21366

16. Buccoliero A.M., Caporalini C., Scagnet M. et al. Angiocentric glioma-associated seizures: the possible role of EATT2, pyruvate carboxylase and glutamine synthetase. Seizure 2021;86:152–4. DOI: 10.1016/j.seizure.2021.02.014

17. Lange F., Hörnschemeyer J., Kirschstein T. Glutamatergic mechanisms in glioblastoma and tumor-associated epilepsy. Cells 2021;10(5):1226. DOI: 10.3390/cells10051226

18. 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

19. Tönjes M., Barbus S., Park Y.J. et al. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat Med 2013;19(7):901–8. DOI: 10.1038/ nm.3217

20. Zhang B., Chen Y., Shi X. et al. Regulation of branchedchain amino acid metabolism by hypoxia-inducible factor in glioblastoma. Cell Mol Life Sci 2021;78(1):195–206. DOI: 10.1007/s00018-020-03483-1

21. Marcus H.J., Carpenter K.L.H., Price S.J., Hutchinson P.J. In vivo assessment of high-grade glioma biochemistry using microdialysis: a study of energy-related molecules, growth factors and cytokines. J Neurooncol 2010;97(1):11–23. DOI: 10.1007/s11060-009-9990-5

22. Venkataramani V., Tanev D.I., Strahle C. et al. Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature 2019;573(7775):532–8. DOI: 10.1038/s41586-019-1564-x

23. Venkatesh H.S., Morishita W., Geraghty A.C. et al. Electrical and synaptic integration of glioma into neural circuits. Nature 2019;573(7775):539–45. DOI: 10.1038/s41586-019-1563-y

24. Ishiuchi S., Yoshida Y., Sugawara K. et al. Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation. J Neurosci 2007;27(30):7987–8001. DOI: 10.1523/JNEUROSCI.2180-07.2007

25. Buckingham S.C., Campbell S.L., Haas B.R. et al. Glutamate release by primary brain tumors induces epileptic activity. Nat Med 2011;17(10):1269–74. DOI: 10.1038/nm.2453

26. Intlekofer A.M., Dematteo R.G., Venneti S. et al. Hypoxia induces production of L-2-Hydroxyglutarate. Cell Metab 2015;22(2): 304–11. DOI: 10.1016/j.cmet.2015.06.023

27. Madala H.R., Punganuru S.R., Arutla V. et al. Beyond brooding on oncometabolic havoc in IDH-mutant gliomas and AML: current and future therapeutic strategies. Cancers (Basel) 2018;10(2):49. DOI: 10.3390/cancers10020049

28. Toplak M., Brunner J., Schmidt J., Macheroux P. Biochemical characterization of human D-2-hydroxyglutarate dehydrogenase and two disease related variants reveals the molecular cause of D-2-hydroxyglutaric aciduria. Biochim Biophys Acta Proteins Proteom 2019;1867(11):140255. DOI: 10.1016/j.bbapap.2019.07.008

29. Flavahan W.A., Drier Y., Liau B.B. et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 2016;529(7584):110–4. DOI: 10.1038/nature16490

30. Losman J.A., Kaelin W.G. What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev 2013;27(8):836–52. DOI: 10.1101/gad.217406.113

31. Rasmussen K.D., Helin K. Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev 2016;30(7): 733–50. DOI: 10.1101/gad.276568.115

32. Xu W., Yang H, Liu Y. et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 2011;19(1):17–30. DOI: 10.1016/j. ccr.2010.12.014

33. Huberfeld G., Vecht C.J. Seizures and gliomas--towards a single therapeutic approach. Nat Rev Neurol 2016;12(4):204–16. DOI: 10.1038/nrneurol.2016.26

34. McBrayer S.K., Mayers J.R., DiNatale G.J. et al. Transaminase inhibition by 2-Hydroxyglutarate impairs glutamate biosynthesis and redox homeostasis in glioma. Cell 2018;175(1):101–16.e25. DOI: 10.1016/j.cell.2018.08.038

35. Bady P., Sciuscio D., Diserens A.C. et al. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol 2012;124(4):547–60. DOI: 10.1007/s00401-012-1016-2

36. Aldape K., Zadeh G., Mansouri S. et al. Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol 2015;129(6):829–48. DOI: 0.1007/s00401-015-1432-1

37. Berghoff A.S., Kiesel B., Widhalm G. et al. Correlation of immune phenotype with IDH mutation in diffuse glioma. Neuro Oncol 2017;19(11):1460–8. DOI: 10.1093/neuonc/nox054

38. Mu L., Long Y., Yang C. et al. The IDH1 Mutation-induced oncometabolite, 2-Hydroxyglutarate, may affect DNA methylation and expression of PD-L1 in gliomas. Front Mol Neurosci 2018;11:82. DOI: 10.3389/fnmol.2018.00082

39. Reuss D.E., Sahm F., Schrimpf D. et al. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 2015;129(1):133–46. DOI: 10.1007/s00401-014-1370-3

40. Kerkhof M., Benit C., Duran-Pena A., Vecht C.J. Seizures in oligodendroglial tumors. CNS Oncol 2015;4(5):347–56. DOI: 10.2217/cns.15.29

41. Van Meir E. G., Hadjipanayis C.G., Norden A.D. et al. Exciting new advances in neuro-oncology. CA Cancer J Clin 2010;60(3): 166–93. DOI: 10.3322/caac.20069

42. Heiland H.D., Ravi V.M., Behringer S.P. et al. Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma. Nat Commun 2019;10(1):2541. DOI: 10.1038/s41467-019-10493-6

43. Darmanis S., Sloan S.A., Croote D. et al. Single-cell RNA-Seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Rep 2017;21(5):1399–410. DOI: 10.1016/j.celrep.2017.10.030

44. Zhang Y., Chen K., Sloan S.A. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 2014;34(36):11929–47. DOI: 10.1523/JNEUROSCI.1860-14.2014

45. Zhang Y., Sloan S.A., Clarke L.E. et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 2016;89(1):37–53. DOI: 10.1016/j.neuron.2015.11.013

46. Liddelow S.A., Barres B.A. Reactive astrocytes: production, function, and therapeutic potential. Immunity 2017;46(6):957–67. DOI: 10.1016/j.immuni.2017.06.006

47. Liddelow S.A., Guttenplan K.A., Clarke L.E. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017;541(7638):481–7. DOI: 10.1038/nature21029

48. Zamanian J.L., Xu L., Foo L.C. et al. Genomic analysis of reactive astrogliosis. J Neurosci 2012;32(18):6391–410. DOI: 10.1523/JNEUROSCI.6221-11.2012

49. Yun S.P., Kam T.-I., Panicker N. et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’ s disease. Nat Med 2018;24(7):931–8. DOI: 10.1038/s41591-018-0051-5

50. Hatcher A., Yu K., Meyer J. et al. Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model. J Clin Investig 2020;130(5):2286–300. DOI: 10.1172/JCI133316

51. Lu V.M., Jue T.R., Phan K., McDonald K.L. Quantifying the prognostic significance in glioblastoma of seizure history at initial presentation: a systematic review and meta-analysis. Clin Neurol Neurosurg 2018;164:75–80. DOI: 10.1016/j.clineuro.2017.11.015

52. Sherman J.H., Moldovan K., Yeoh H. K. et al. Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. J Neurosurg 2011;114(6):1617–21. DOI: 10.3171/2010.12.JNS101602

53. Koekkoek J., Dirven L., Reijneveld J.C. et al. Epilepsy in the end of life phase of brain tumor patients: a systematic review. Neurooncol Pract 2014;1(3):134–40. DOI: 10.1093/nop/npu018

54. Rudà R., Soffietti R. What is new in the management of epilepsy in gliomas? Curr Treat Options Neurol 2015;17(6):351. DOI: 10.1007/s11940-015-0351-8

55. Haggiagi A., Avila E.K. Seizure response to temozolomide chemotherapy in patients with WHO grade II oligodendroglioma: a single-institution descriptive study. Neurooncol Pract 2019;6(3):203–8. DOI: 10.1093/nop/npy029

56. Climans S.A., Brandes A.A., Cairncross J.G. 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-x

57. Kerkhof M., Dielemans J.C., van Breemen M.S. et al. Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. Neuro Oncol 2013;15(7):961–7. DOI: 10.1093/neuonc/not057

58. Redjal N., Reinshagen C., Le A. et al. Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide. J Neurooncol 2016;127(3):505–14. DOI: 10.1007/s11060-016-2054-8

59. Bobustuc G.C., Baker C.H., Limaye A.et al. Levetiracetam enhances p53-mediated MGMT inhibition and sensitizes glioblastoma cells to temozolomide. Neuro Oncol 2010;12(9): 917–27. DOI: 10.1093/neuonc/noq044

60. Ni X.R., Guo C.C., Yu Y.J. et al. Combination of levetiracetam and IFN-α increased temozolomide efficacy in MGMT-positive glioma. Cancer Chemother Pharmacol 2020;86(6):773–82. DOI: 10.1007/s00280-020-04169-y

61. Ryu C.H., Yoon W.S., Park K.Y. et al. Valproic acid downregulates the expression of MGMT and sensitizes temozolomide-resistant glioma cells. J Biomed Biotechnol 2012;2012:987495. DOI: 10.1155/2012/987495

62. Maschio M., Albani F., Jandolo B. et al. Temozolomide treatment does not affect topiramate and oxcarbazepine plasma concentrations in chronically treated patients with brain tumor-related epilepsy. J Neurooncol 2008;90(2):217–21. DOI: 10.1007/s11060-008-9651-0

63. Cardona A.F., Rojas L., Wills B. et al. Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma. J Neurooncol 2018;136(2):363–71. DOI: 10.1007/s11060-017-2660-0

64. Krauze A.V., Mackey M., Rowe L. et al. Late toxicity in long-term survivors from a phase 2 study of concurrent radiation therapy, temozolomide and valproic acid for newly diagnosed glioblastoma. Neurooncol Pract 2018;5(4):246–50. DOI: 10.1093/nop/npy009

65. Shlapakova T.I., Kostin R.K., Tyagunova, E.E. Reactive Oxygen Species: Participation in Cellular Processes and Progression of Pathology. Russ J Bioorg Chem 2020;46(5):657–74. DOI: 10.1134/S1068162020050222

66. Nikolenko V.N., Gridin L.A., Oganesyan M.V. et al. The posterior perforated substance: a brain mystery wrapped in an enigma. Curr Top Med Chem 2019;19(32):2991–8. DOI: 10.2174/1568026619666191127122452

67. Shlapakova T.I., Kostin R.K., Tyagunova E.E. Reactive oxygen species: participation in cellular processes and the development of pathology. Bioorganicheskaya himiya = Bioorganic Chemistry 2020;46(5):466–85. (In Russ.). DOI: 10.31857/S013234232005022X

68. Berg A.T., Berkovic S.F., Brodie M.J. et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 2010;51(4):676–85. DOI: 10.1111/j.1528-1167.2010.02522.x

69. Wieser H.G., Blume W.T., Fish D. et al. ILAE Commission report. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia 2001;42(2):282–6.


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Tyagunova E.E., Zakharov A.S., Glukhov A.I., Dobrokhotova V.Z., Shlapakov T.I., Kozlov V.V., Korotkova N.V., Tyagunova T.E. Features of epileptiform activity in patients with diagnosed glioblastoma: from genetic and biochemical mechanisms to clinical aspects. Head and Neck Tumors (HNT). 2022;12(3):102-113. (In Russ.) https://doi.org/10.17650/2222-1468-2022-12-3-102-113

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