6th Edition of Neurology World Conference 2026

Abstract

Drug-resistant epilepsy affects approximately one-third of patients with epilepsy and remains a major clinical challenge despite advances in antiseizure medications. Increasing evidence suggests that epigenetic mechanisms—heritable changes in gene expression without alterations in DNA sequence—play a key role in pharmacoresistance and represent promising therapeutic targets. A narrative literature review was conducted following PRISMA guidance and the PCC framework. Searches were performed in PubMed, LILACS, SciELO, and Connected Papers, including studies published in English, Portuguese, or Spanish. The review focused on epigenetic mechanisms associated with drug resistance in refractory epilepsy, emphasizing emerging therapeutic strategies targeting DNA methylation, histone modifications, and microRNA regulation. Current evidence indicates that aberrant DNA methylation is associated with altered expression of genes involved in drug transport and metabolism, particularly ABCB1, contributing to reduced intracerebral concentrations of antiseizure medications. Histone deacetylase overexpression, notably HDAC2 and HDAC4, has been linked to repression of neuroprotective and synaptic plasticity–related genes, impairing therapeutic response. Preclinical studies demonstrate that histone deacetylase inhibitors exert neuroprotective and seizure-modulating effects. In parallel, dysregulated microRNAs, including miR-134 and miR-335-5p, have been implicated in synaptic dysfunction and reduced drug sensitivity. Experimental use of antagomiRs targeting these microRNAs has shown seizure-suppressive effects, highlighting their therapeutic potential. Epigenetic therapies represent a promising and innovative approach for the management of drug-resistant epilepsy. Targeting epigenetic mechanisms may complement conventional antiseizure medications by addressing underlying molecular contributors to pharmacoresistance. Although current evidence is largely preclinical, advances in epigenetic-based interventions may enable more personalized and effective treatment strategies for patients with refractory epilepsy. Biography of Presenter about 100 words: Andressa Palomino dos Santos is a medical student at Centro Universitário do Planalto Central Apparecido dos Santos (UNICEPLAC), Brazil. Her academic interests focus on neurology, epilepsy, and translational neuroscience, with particular emphasis on mechanisms underlying drug-resistant epilepsy. She has participated in scientific research exploring the role of epigenetic regulation in pharmacoresistance and emerging therapeutic strategies. Andressa is interested in pursuing an international academic career in neurology and values research as a foundation for evidence-based and personalized medical care.