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Genes Involved in Pharmacoresistant Epilepsy

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Pharmacoresistance in Epilepsy

Abstract

This chapter is devoted to resistance to antiepileptic drugs (AEDs) and its genetic mechanisms. There are three general hypothesis proposed for pharmacoresistant epilepsy: (1) Target hypothesis, (2) Drug transporter hypothesis, and the (3) Intrinsic Severity Hypothesis (Gorter and Potschka, Jasper’s basic mechanisms of the epilepsies, 4th ed. National Center for Biotechnology Information (USA), Bethesda, MD, 2012).

In diagnosing poor response to treatment, it is also important to separate drug resistance from incorrect diagnosis of epilepsy syndrome for example: (a) Epilepsy caused by mutations in Glucose transporter gene 1 (GLUT1) being treated with valproate (VPA) worsens the seizures in this disease whereas replacement of glucose with ketogenic diet alleviates seizures and the glucose deficit in the central nervous system. (Klepper, Epilepsia 49(Suppl 8):46–49, 2008; Klepper et al., Neuropediatrics 40(5):207–210, 2009) (b) Genetic or idiopathic epilepsies such as Childhood Absence Epilepsy (CAE), Juvenile Myoclonic Epilepsy (JME) and Dravet’s Syndrome can be aggravated when treated with Na+ channel blockers (Genton, Brain Dev 22(2):75–80, 2000; Guerrini et al., Epilepsia 39(5):508–512, 1998; Thomas et al., Brain 129(Pt 5):1281–1292, 2006; Martínez-Juárez et al., Brain 129(Pt 5):1269–1280, 2006) and (c) Mitochondrial disorders can also be aggravated by VPA (Finsterer and Zarrouk Mahjoub, Expert Opin Drug Metab Toxicol 8(1):71–79, 2012).

Herein, we describe the three general hypothesis; we also summarize the “difficult to treat” genetic epilepsies.

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Authors and Affiliations

  1. Epilepsy Clinic, National Institute of Neurology and Neurosurgery, Insurgentes sur 3877, Col. La Fama, Del. Tlalpan, Mexico City, Distrito Federal, 14269, Mexico

    Iris E. Martínez-Juárez M.D. M.Sc., Laura Elena Hernández-Vanegas M.D. & Nayelli Rodríguez y Rodríguez

  2. Clinical Epileptology Fellowship, National Autonomous University of Mexico, Mexico City, Mexico

    Iris E. Martínez-Juárez M.D. M.Sc. & Laura Elena Hernández-Vanegas M.D.

  3. Epilepsy Clinic, Hospital General San Juan de Dios, Guatemala city, Guatemala

    Jorge Alfredo León-Aldana M.D.

  4. West Los Angeles VA Medical Center, 11301 Wilshire Blvd, Los Angeles, CA, 90073, USA

    Antonio V. Delgado-Escueta M.D.

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  1. Iris E. Martínez-Juárez M.D. M.Sc.
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  2. Laura Elena Hernández-Vanegas M.D.
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  3. Nayelli Rodríguez y Rodríguez
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  4. Jorge Alfredo León-Aldana M.D.
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Correspondence to Iris E. Martínez-Juárez M.D. M.Sc. .

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Editors and Affiliations

  1. , Pharmacobiology Department, Center for Research and Advanced Studies, Av. Instituto Politécnico Nacional 2508, Mexico City, 07360, Mexico

    Luisa Rocha

  2. , Disciplina de Neurologia Experimental, UNIFESP/EPM, Rua Botucatu 740, São Paulo, 04023-900, Brazil

    Esper A. Cavalheiro

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Martínez-Juárez, I.E., Hernández-Vanegas, L.E., Rodríguez y Rodríguez, N., León-Aldana, J.A., Delgado-Escueta, A.V. (2013). Genes Involved in Pharmacoresistant Epilepsy. In: Rocha, L., Cavalheiro, E. (eds) Pharmacoresistance in Epilepsy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6464-8_2

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