Drug resistance epilepsy: definition and mechanisms
Main Article Content
Keywords
epilepsy, Drug-resistant epilepsy, treatment
Abstract
Epilepsy is a chronic disease characterized by recurrent unprovoked seizures due to aberrant enlargement or synchronization of a group of neurons. Drug-resistant epilepsy is when despite using two or more drugs at their therapeutic dose, the person continues to have recurrent seizures, affecting approximately one third of patients. There are multiple hypotheses of resistance mechanisms, usually variable and multifactorial. They can be divided into three groups: disease-related mechanisms, drug-related mechanisms and genetic mechanisms. There are still many studies to be done to better understand these mechanisms and to generate different treatment proposals.
References
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24. Dahlin M, Singleton S, David JA, Basuchoudhary A, Wickström R, Mazumder R, et al. Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet. eBioMedicinet. 2022;80:104061.
25. Kobow K, Baulac S, Von Deimling A, Lee JH. Molecular diagnostics in drug-resistant focal epilepsy define new disease entities. Brain Pathology. 2021;31:e12963.
26. Isolan GR, Marth V, Frizon L, Dini L, Dini S, Yamaki VN, et al. Surgical treatment of drug-resistant epilepsy caused by gliomas in eloquent areas: experience report. Arq Neuropsiquiatr. 2019;77(11):797-805.
27. Shih YC, Chou CC, Peng SJ, Yu HY, Hsu SP, Lin CF, et al. Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy. Epilepsia. 2022;00:1-12.
28. Fu M, Tao J, Wang D, Zhang Z, Wang X, Ji Y, et al. Downregulation of MicroRNA-34c-5p facilitated neuroinflammation in drug-resistant epilepsy. Brain Research. 2020;1749:147130.
29. Yamanaka G, Takamatsu T, Morichi S, Yamazaki T, Mizoguchi I, Ohno K, et al. Interleukin-1β in peripheral monocytes is associated with seizure frequency in pediatric drug-resistant epilepsy. Journal of Neuroimmunology. 2021;352:577475.
30. Jo HJ, Kenny DL, Balzekas I, Benarroch EE, Jones DT, Brinkmann BH, et al. Nuclei-specific thalamic connectivity predicts seizure frequency in drug-resistant medial temporal lobe epilepsy. NeuroImage: Clinical. 2019;10167.
2. Peng J, Pang N, Wang Y, Wang XL, Chen J, Xiong J, et al. Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy. CNS Neurosci Ther. 2019;25:14-20.
3. Xue-Ping W, Hai-Jiao W, Li-Na Z, Xu D, Ling L. Risk factors for drug-resistant epilepsy: a systematic review and meta-analysis. Medicine. 2019;98:30.
4. Holmes M, Flaminio Z, Vardhan M, Xu F, Li X, Devinsky O, et al. Cross talk between drug-resistant epilepsy and the gut microbiome. Epilepsia. 2020;00:1-10.
5. Leal A, Pinto MF, Lopes F, Bianchi AM, Henriques J, Ruano MG, et al. Heart rate variability analysis for the identification of the preictal interval in patients with drug-resistant epilepsy. Scientific Reports. 2021;11:5987.
6. Miranda DM, Rosa DV, Costa BS, Nicolau NF, Magno LA, De Paula JJ, et al. Telomere shortening in patients with drug-resistant epilepsy. Epilepsy Research. 2020;166:106427.
7. Proost R, Lagae L, Van Paesschen W, Jansen K. Sleep in children with refractory epilepsy and epileptic encephalopathies: A systemic review of literature. European Journal of Paediatric Neurology. 2022;38:53-61.
8. Morales L, Galan L, Bosch-Bayard J, Batista K, Báez MM, Alfonso M, et al. Relation of Brain Perfusion Patterns to Sudden Unexpected Death Risk Stratification: A Study in Drug Resistant Focal Epilepsy. Behav Sci. 2022;12:207.
9. Chari A, Seunarine KK, He X, Tisdall MM, Clark CA, Bassett DS, et al. Drug-resistant focal epilepsy in children is associated with increased modal controllability of the whole brain and epileptogenic regions. Communications Biology. 2022;5:394.
10. Wesselingh R, Broadley J, Buzzard K, Tarlinton D, Seneviratne U, Kyndt C, et al. Prevalence, risk factors, and prognosis of drug-resistant epilepsy in autoimmune encephalitis. Epilepsy & Behavior. 2022;132:108729.
11. Gomez A, McLachlan RS, Mirsattari SM, Diosy DC, Burneo JG. Prognostic factors in patients with refractory idiopathic generalized epilepsy. Epilepsy Research. 2017;140:69-73.
12. Caraballo RH. Manejo práctico de las epilepsias farmacorresistentes en pediatría. Medicina. 2022;82:7-12.
13. Bartolini E, Ferrari AR, Lattanzi S, Pradella S, Zaccara G. Drug-resistant epilepsy at the age extremes: Disentangling the underlying etiology. Epilepsy & Behavior. 2022;132:108739.
14. Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020;72:606-638.
15. Gesche J, Dyremose C, Delcomyn L, Rubboli G, Beier CP. Pseudoresistance in idiopathic/genetic generalized epilepsies - Definitions, risk factors, and outcome. Epilepsy & Behavior. 2022;130:108633.
16. Brodtkorb E, Samsonsen C, Kutschera J, Bråthen G, Helde G, Reimers A. Treatment non-adherence in pseudo-refractory epilepsy. 2016;122:1-6.
17. Negri M, Camporeze B, Silva J, Borsari L, Alves G, De Souza L, et al. The single nucleotide variant n.60G > C in the microRNA-146a associated with susceptability to drug-resistant epilepsy. Epilepsy Research. 202;162:106305.
18. Farnaz S, Hasanpour K, Nazarzadeh M, Adli A, Sadat M, Asadi A, et al. ABCG2, SCN1A and CYP3A5 genes polymorphism and drug-resistant epilepsy in children: HA case-control study. Seizure: European Journal of Epilepsy.2022;97:58-62.
19. Mehvari J, Badihian S, Tabrizi N, Manouchehri N, Zare M, Basiratnia R. Evaluation of dual pathology among drug-resistant epileptic patients with hippocampal sclerosis. Neurol Sci. 2018.
20. Wolking S, Moreau C, McCormack M, Krause R, Krenn M, Consortium E, et al. Assessing the role of rare genetic variants in drug-resistant, no-lesional focal epilepsy. Annals of Clinical and Translational Neurology. 2021;8(7):1376-1387.
21. Margari L, Legrottaglie AR, Vincenti A, Coppola G, Operto FF, Buttiglione M, et al. Association between SCN1A gene polymorphisms and drug resistant epilepsy in pediatric patients. Seizure. 2018;55:30-35.
22. Krami AM, Ratib C, Charoute H, Rouba H, Roky R, Barakat A, et al. Association between G2677T/A polymorphism in ABCB1 gene and the risk of drug resistance epilepsy: An updated systematic review and meta-analysis. Epilepsy Research. 2022;185:106977.
23. Wu CC, Tsai MH, Chu YJ, Weng WC, Fan PC, Lee WT. The role of targeted gene panel in pediatric drug-resistant epilepsy. Epilepsy & Behavior. 2020;106:107003.
24. Dahlin M, Singleton S, David JA, Basuchoudhary A, Wickström R, Mazumder R, et al. Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet. eBioMedicinet. 2022;80:104061.
25. Kobow K, Baulac S, Von Deimling A, Lee JH. Molecular diagnostics in drug-resistant focal epilepsy define new disease entities. Brain Pathology. 2021;31:e12963.
26. Isolan GR, Marth V, Frizon L, Dini L, Dini S, Yamaki VN, et al. Surgical treatment of drug-resistant epilepsy caused by gliomas in eloquent areas: experience report. Arq Neuropsiquiatr. 2019;77(11):797-805.
27. Shih YC, Chou CC, Peng SJ, Yu HY, Hsu SP, Lin CF, et al. Clinical characteristics and long-term outcome of cerebral cavernous malformations-related epilepsy. Epilepsia. 2022;00:1-12.
28. Fu M, Tao J, Wang D, Zhang Z, Wang X, Ji Y, et al. Downregulation of MicroRNA-34c-5p facilitated neuroinflammation in drug-resistant epilepsy. Brain Research. 2020;1749:147130.
29. Yamanaka G, Takamatsu T, Morichi S, Yamazaki T, Mizoguchi I, Ohno K, et al. Interleukin-1β in peripheral monocytes is associated with seizure frequency in pediatric drug-resistant epilepsy. Journal of Neuroimmunology. 2021;352:577475.
30. Jo HJ, Kenny DL, Balzekas I, Benarroch EE, Jones DT, Brinkmann BH, et al. Nuclei-specific thalamic connectivity predicts seizure frequency in drug-resistant medial temporal lobe epilepsy. NeuroImage: Clinical. 2019;10167.
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Published
Jan 27, 2023
Article Details
How to Cite
Sequeira-Quesada, C., Céspedes-Valverde, M., Delgado-Gómez, D., & Chaves-Jiménez, M. (2023). Drug resistance epilepsy: definition and mechanisms. Hispano-American Journal of Health Sciences, 8(4), 141–147. https://doi.org/10.56239/rhcs.2022.84.579
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Author Biography
Carlos Sequeira-Quesada, Escuela de Medicina y Cirugía, Universidad de Costa Rica. San José, Costa Rica
Médico Residente del Postgrado de Neurología