Pharmacological inhibition of ictal and interictal epileptiform discharges


Submitted: 5 June 2023
Accepted: 12 June 2023
Published: 31 August 2023
Abstract Views: 1038
pdf: 115
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Background: epilepsy is a brain disorder characterized by an enduring predisposition to generate epileptic seizures. Seizures are a transient occurrence of signs and/or symptoms due to abnormal excessive and synchronous neuronal activity in the brain. Electroencephalogram (EEG), a non-invasive instrumental test, has an important role in the diagnosis of epilepsy, as well as in monitoring the results and long-term treatment because it can detect interictal and ictal discharges that are crucial for confirmation and classification of seizures. Antiepileptic drugs are the first treatment option in patients with epilepsy, although the effectiveness of such drugs is limited only to symptom control and requires a regular intaking by the patient. These drugs exploit the cell membrane channels, modifying their permeability, allowing either an increase in the inhibitory neurotransmission or the reduction in the excitatory one, by hyperpolarizing neurons and avoiding the recurrence of the epileptic seizures without reversing or stopping the underlying mechanism of epileptogenesis. Materials and Methods: the internship took place in the Neurophysiopathology department of the Antonio, Biagio and Cesare Arrigo’s hospital in Alessandria, from October 2022 to March 2023. During this period, it was possible to attend the emergency treatment of prolonged and recurrent epileptic seizures during EEGrafic recording and the consequential amendments of the ictal discharges induced by the administration of antiepileptic drugs. Follow up EEG was also performed to investigate the modifications of interictal activity after a period of treatment with antiepileptic drugs. The patient who has been analyzed in this paper, underwent EEG recordings obtained by using bridge electrodes placed on the scalp according to the international 10-20 system. Objectives: the aim of this study is to analyze the mechanisms of action of the main antiepileptic drugs, in relation to the physiological cellular mechanisms regulating the neuronal excitability and their effect on the ictal and interictal epileptiform discharges in the EEG recordings.


RS Fischer. A practical clinical definition of epilepsy. Epilepsia. 2014;55:475-82. DOI: https://doi.org/10.1111/epi.12550

Benbadis SR, Beniczky S, Bertram E, et al. The role of EEG in patients with suspected epilepsy. Epileptic Disord. 2020;22:143-55. DOI: https://doi.org/10.1684/epd.2020.1151

HF Lodish. Molecular Cell Biology. De Gruyter, Berlin, Germany. 1996. 1084 pp.

Yogeeswari P, Sriram D, Vaigundaragavendran J. The GABA shunt: an attractive and potential therapeutic target in the treatment of epileptic disorders. Curr Drug Metab. 2005;6:127-39. DOI: https://doi.org/10.2174/1389200053586073

«Bak LK, Schousboe A, Waagepetersen HS. (2006), The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. Journal of Neurochemistry. 2006;98:641-53. DOI: https://doi.org/10.1111/j.1471-4159.2006.03913.x

EE Benarroch. NMDA receptors: recent insights and clinical correlations. Neurology. 2011,76:1750-7. DOI: https://doi.org/10.1212/WNL.0b013e31821b7cc9

Sieghart W, Ramerstorfer J, Sarto-Jackson I, et al. A novel GABA(A) receptor pharmacology: drugs interacting with the α(+) β(-) interface. Br J Pharmacol. 2012;166:476-85. DOI: https://doi.org/10.1111/j.1476-5381.2011.01779.x

A Ghit, D Assal, AS Al-Shami, DEE Hussein. GABAA receptors: structure, function, pharmacology, and related disorders. Journal of Genetic Engineering and Biotechnology. 2021;19:1-15. DOI: https://doi.org/10.1186/s43141-021-00224-0

Wang X, Lambert NA. GABA(B) receptors couple to potassium and calcium channels on identified lateral perforant pathway projection neurons. J Neurophysiol. 2000;83:1073-8. DOI: https://doi.org/10.1152/jn.2000.83.2.1073

Zhang D, Pan ZH, Awobuluyi M, Lipton SA. Structure and function of GABA(C) receptors: a comparison of native versus recombinant receptors. Trends Pharmacol Sci. 2001;22:121-32. DOI: https://doi.org/10.1016/S0165-6147(00)01625-4

AL Hodgkin, AF Huxley. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 1952;117:500-44. DOI: https://doi.org/10.1113/jphysiol.1952.sp004764

Treiman DM. GABAergic mechanisms in epilepsy. Epilepsia. 2001;42:8-12. DOI: https://doi.org/10.1046/j.1528-1157.2001.042suppl.3008.x

Riss J, Cloyd J, Gates J, Collins S. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008;118:69-86. DOI: https://doi.org/10.1111/j.1600-0404.2008.01004.x

Löscher W, Rogawski MA. How theories evolved concerning the mechanism of action of barbiturates. Epilepsia. 2012;53:12-25.

Löscher, W. and Rogawski, M.A. How theories evolved concerning the mechanism of action of barbiturates. Epilepsia. 2012.53:12-25. DOI: https://doi.org/10.1111/epi.12025

Ben-Menachem E. Mechanism of action of vigabatrin: correcting misperceptions. Acta Neurol Scand Suppl. 2011;192:5-15. DOI: https://doi.org/10.1111/j.1600-0404.2011.01596.x

Macdonald RL, Kelly KM. Antiepileptic drug mechanisms of action. Epilepsia. 1995;36:S2-12. DOI: https://doi.org/10.1111/j.1528-1157.1995.tb05996.x

Schachter, S.C. Tiagabine. Epilepsia. 1999;40:S17-22. DOI: https://doi.org/10.1111/j.1528-1157.1999.tb00915.x

Patocka J, Wu Q, Nepovimova E, Kuca K. Phenytoin - An anti-seizure drug: Overview of its chemistry, pharmacology and toxicology. Food Chem Toxicol. 2020;142:111393. DOI: https://doi.org/10.1016/j.fct.2020.111393

Goa KL, Sorkin EM. Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. Drugs. 1993;46:409-27. DOI: https://doi.org/10.2165/00003495-199346030-00007

Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurol Scand. 2016;133:160-72. DOI: https://doi.org/10.1111/ane.12529

Ohno Y, Tokudome K. Therapeutic Role of Synaptic Vesicle Glycoprotein 2A (SV2A) in Modulating Epileptogenesis. CNS Neurol Disord Drug Targets. 2017;16:463-71. DOI: https://doi.org/10.2174/1871527316666170404115027

Deshpande LS, Delorenzo RJ. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy. Front Neurol. 2014;5:11. DOI: https://doi.org/10.3389/fneur.2014.00011

L Talevi. Sviluppo e test di un sistema BCI SSVEP-based. Available from: https://www.researchgate.net/publication/340717588_Sviluppo_e_test_di_un_sistema_BCI_SSVEP-based

LICE. Libro Bianco dell’Epilessia. 2019. Available from: https://www.fondazionelice.it/pdf/Libro_bianco.pdf

Sardo, S., & Piras, B. (2023). Pharmacological inhibition of ictal and interictal epileptiform discharges. Working Paper of Public Health, 11(1). https://doi.org/10.4081/wpph.2023.9764

Downloads

Download data is not yet available.

Citations