Histopathologic Characterization of Brain Tumour Related Epilepsy and Review of Pathogenic Mechanisms

Sujata Chaturvedi; Ishita Pant; Kavita Rawat; Pragyan Sarma

doi:10.21276/apalm.3550

Authors

Sujata Chaturvedi Department of Pathology, Institute of Human Behaviour and Allied Sciences, Delhi, India
Ishita Pant Department of Pathology, Institute of Human Behaviour and Allied Sciences, Delhi, India
Kavita Rawat Department of Pathology, Institute of Human Behaviour and Allied Sciences, Delhi, India
Pragyan Sarma Department of Neurosurgery, Vardhman Mahavir Medical College and Safdarjung hospital, Delhi, India

DOI:

https://doi.org/10.21276/apalm.3550

Keywords:

Epilepsy, • Histopathology, Central Nervous System, seizures

Abstract

Background: Brain tumour related epilepsy (BTRE) may occur in 40% to 60% of brain tumours. Its incidence is highly dependent on the location and type of tumour. With the underlying molecular mechanisms getting unravelled, treatment strategies are being designed accordingly. This retrospective study was undertaken to profile the histopathology samples received in our department with the clinical diagnosis of brain tumour related epilepsy.
Methods: A retrospective study of 193 brain tumour related epilepsy cases received over a period of last 10 years (2014-24) was done. Histopathology records were revisited and the details of tumour type and grade, location and demographic details were mapped and analysed. These findings have been presented and brief review of molecular mechanisms in brain tumour related epilepsy has also been incorporated where applicable.
Results: Of the 193 seizure associated brain tumour cases, 182 (94.30%) comprised of primary central nervous system tumours and 11 (5.7%) comprised of tumours metastatic to the brain. In our series, maximum cases were found in young male adults within the age group of 21-40 yrs. Commonest location was intraparenchymal (frontal) and commonest tumour was adult type diffuse glioma.
Conclusion: Collation of clinical, demographic and histopathology findings is necessary in brain tumour related epilepsy for identifying the common patterns and developing management strategies accordingly.

References

1. Slegers RJ, Blumcke 1. Low-grade developmental and epilepsy associated brain tumors: a critical update. Acta Neuropathol Commun 2020; 8: 27

2. Seidel S, Wehner T, Miller D. Brain tumor related epilepsy: pathophysiological approaches and rational management of antiseizure medication. Neurol Res Pract 2022; 4: 45

3. Zhang J, Yao L, Peng S, Fang Y, Tang R, Liu J. Correlation between glioma location and preoperative seizures: A systematic review and meta-analysis. Neurosurgical Review 2018; 42(3):603-618

4. You G, Sha Z, Jiang T. The pathogenesis of tumour-related epilepsy and its implications for clinical treatment. Seizure 2012; 21(3):153-59

5. Wang Z, Yang W, Wang Y, Aili Y, Wang Z. Correlation of Clinicopathological Factors with Brain Tumour-Related Epilepsy in Glioma. Dis Markers. 2022 Sep 30:2022:4918294

6. Chen DY, Chen CC, Crawford JR, Wang SG. Tumor-related epilepsy: epidemiology, pathogenesis and management. J Neurooncol 2018; 139(1):13-21

7. Weller M, van DBM, Tonn JC, Stupp R. Preusser M. Cohen JME et al. European Association for Neuro-Oncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017; 18(6):315-329

8. Pallud J, McKhann GM. Diffuse Low-Grade Glioma-Related Epilepsy. Neurosurg Clin N Am. 2019;30(1):43-54

9. Van BMS, Wilms EB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms and management. Lancet Neuro. 2007; 6(5):421-430

10. Sørensen MF, Heimisdóttir SB, Sørensen MD, Mellegaard CS, Wohlleben H, Kristensen BW et al. High expression of cystine-glutamate antiporter XCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma. J Neurooncol 2018:138(1):49-53

11. Chang EF, Potts MB, Keles GE, Lamborn KR, Chang SM, Barbaro NM et al. Seizure characteristic and control following resection in 332 patients with low grade gliomas. Journal of neurosurgery 2008; 108(2):227-235

12. Wolf HK, Roos D, Blumcke I, Pietsch T, Wiestler OD. Perilesional neurochemical changes in focal epilepsies. ActaNeuropathol 1996; 91: 376-384

13. Aronica E, GorterJA, Redeker S. Distribution, characterization and clinical significance of microglia in glioneuronal tumours from patients with chronic intractable epilepsy. NeuropatholApplNeurobiol 2005; 31:280-289

14. Van Breemen MS, WilmsEB, Vecht CJ. Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management Lancet Neurol 2007; 6:421-430

15. Norden AD, Blumenfeld H. The role of subcortical structures in human epilepsy. Epilepsy Behav 2002; 3:219-231

16. Berntsson SG, Malmer B, Bondy ML, Qu Mingqi. Smits A. Tumor-associated epilepsy and glioma: are there common gentic pathways? ActaOncol 2009;48: 955-963

17. Adhikari S, Walker BC, Mittal S. Pathogenesis and management of brain tumor related epilepsy. In: Gliomas [Internet]. Brisbane (AU): Exon Publications; 2021 Apr 30. Chapter 12

18. Chernov MF, KuboO, Hayashi M, Izawa M, Maruyama T. Usukura M, et al. Proton MRS of the peritumoral brain. J NeurolSci 2005; 228:137-142

19. Douw L, van Dellen E, de Groot M. Heimans JJ, Klein M, Stam CJ, Reijneveld JC. Epilepsy is related to theta band brain connectivity and network topology in brain tumor patients. BMC Neurosci. 2010 Aug 23:11:103.

20. Beaumont A, Whittle IR. The pathogenesis of tumour associated epilepsy. Acta Neurochir Wien 2000;142: 1-15

21. McNamara JO. Emerging insights into the genesis of epilepsy. Nature 1999;399: 15-22

22. Schaller B. Influences of brain tumor-associated pH changes and hypoxia on epileptogenesis. ActaNeurolScand 2005; 111: 75-83

23. Elias AF, Lin BC, Piggott BJ. Ion Channels in Gliomas-From Molecular Basis to Treatment. Int J Mol Sci 2023 24(3):2530

24. Kraft R, Basrai D, Benndorf K, Patt S. Serum deprivation and NGF induce and modulate voltage-gated Na (+) currents in human astrocytoma cell lines. Glia 2001; 34: 59-67

25. Boyle, Y., Johns, T. G., & Fletcher, E. V. (2022, October 1). Potassium Ion Channels in Malignant Central Nervous System Cancers. Cancers. MDPI.

26. Avoli M, Louvel J, Pumain R, Kohling R. Cellular and molecular mechanisms of epilepsy in human brain. Prog Neurobiol 2005;77: 166-200

27. Sontheimer H. An unexpected role for ion channels in brain tumor metastasis. ExpBiol Med (Maywood) 2008;233: 779-791

28. Aronica E, Yankaya B, Jansen GH, Leenstra S, Veelen CW, Gorter JA et al. Ionotropic and metabotropic glutamate receptor protein expression in glio-neuronal tumours from patients with intractable epilepsy. Neuropathol ApplNeurobiol 2002; 27: 223-237

29. Haglund MM, Berger MS, Kunkel DD, Franck JE, Ghatan S, Ojemann GA. Changes in gamma-aminobutyric acid and somatostatin in epileptic cortex associated with low grade gliomas. J Neurosurg 1992;77: 209-216

30. Hwa GG, Avoli M. The involvement of excitatory amino acids in neocortical epileptogenesis: NMDA& non NMDA receptors. Exp Brain Res. 1991; 294: 691-695

31. Vezzani A, Lang B. Aronica E. Immunity and Inflammation in Epilepsy. Cold Spring Harb Perspect Med. 2015 Dec 18;6(2):a022699.

32. Youn Y, Sung K, Lee I. The role of cytokines in seizures: interleukin (IL)-18, IL-1Ra, IL-8, and IL-10.Korean J Pediatr 2013; 56 (7): 271-274

33. Li Q, Li QQ, Jia JN, Liu ZQ, Zhou HH, Mao XY. Targeting gap junction in epilepsy: perspectives and challenges. Biomedicine & Pharmacotherapy 2019; 109: 57-65

34. Glantz MJ, Cole BF, Forsyth PA, Recht LD, Wen PY, Chamberlain MC et al. Practice parameter:anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 54: 1886-1893

35. Vecht CJ, van Breemen M. Optimizing therapy of seizures in-patients with brain tumors. Neurology. 2006 Dec 26:67(12 Suppl 4):S10-3.