Epilepsia resistente a fármacos: definición y mecanismos
Contenido principal del artículo
Keywords
epilepsia, epilepsia resistente a los medicamentos, tratamiento
Resumen
La epilepsia es una enfermedad crónica que se caracteriza por crisis epilépticas recurrentes no provocadas debido a un aumento aberrante o a la sincronización de un grupo de neuronas. La epilepsia resistente a fármacos es cuando a pesar de utilizar dos o más fármacos en su dosis terapéutica, la persona sigue teniendo crisis recurrentes, esto afecta aproximadamente a un tercio de los pacientes. Existen múltiples hipótesis de mecanismos de resistencia, usualmente son variables y multifactoriales. Se puede dividir en tres grupos: mecanismos relacionados con la enfermedad, mecanismos relacionados a los fármacos y mecanismos genéticos. Aún faltan muchos estudios por realizar para comprender de una mejor manera estos mecanismos y generar diferentes propuestas de tratamiento.
Citas
1. Ouédraogo O, Rébillard RM, Jamann H, Mamane VH, Clénet ML, Daigneault A, et al. Increased frequency of proinflammatory CD4 T cells and pathological levels of serum neurofilament light chain in adult drug-resistant epilepsy. Epilepsia. 2020;00:1-14.
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.
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.
Barra lateral del artículo
Publicado
ene 27, 2023
Detalles del artículo
Cómo citar
Sequeira-Quesada, C., Céspedes-Valverde, M., Delgado-Gómez, D., & Chaves-Jiménez, M. (2023). Epilepsia resistente a fármacos: definición y mecanismos . Revista Hispanoamericana De Ciencias De La Salud, 8(4), 141–147. https://doi.org/10.56239/rhcs.2022.84.579
Sección
Artículos de Revisión
Esta obra está bajo una licencia internacional Creative Commons Atribución-CompartirIgual 4.0.
La RHCS usa la licencia Creative Commons 4.0 Internacional (CC BY 4.0). Para obtener más información, visite https://creativecommons.org/licenses/by/4.0/
Biografía del autor/a
MD Carlos Sequeira-Quesada, Escuela de Medicina y Cirugía, Universidad de Costa Rica. San José, Costa Rica
Médico Residente del Postgrado de Neurología