RECENT ADVANCEMENTS IN THE DIAGNOSIS AND TREATMENT OF EPILEPSY

Abstract

Epilepsy represents one of the most prevalent neurological disorders globally, affecting over fifty million individuals with significant morbidity, mortality, and socioeconomic burden. The past three years have witnessed transformative advances across the epilepsy care continuum, fundamentally reshaping diagnostic paradigms and therapeutic possibilities. This comprehensive scientific review synthesizes breakthrough developments in epilepsy diagnosis and treatment from 2024 through early 2026. In diagnostic innovation, the validation of blood-based DNA methylation biomarkers capable of distinguishing focal cortical dysplasia subtypes IIa and IIb with exceptional accuracy represents a seminal advance, offering noninvasive presurgical diagnosis for previously MRI-negative cases. Concurrently, neuroimaging has evolved from lesion-centric localization toward sophisticated network-based connectomic approaches integrating ultra-high-field magnetic resonance, functional connectivity analyses, and quantitative positron emission tomography. Therapeutic advancements span multiple domains: precision sodium channel modulators including relutrigine and vormatrigine have demonstrated unprecedented efficacy in developmental and epileptic encephalopathies and focal epilepsy respectively, with regulatory filings underway; antisense oligonucleotide therapy targeting SCN2A gene expression offers the first disease-modifying strategy for genetic epilepsies; interleukin blockade with anakinra and tocilizumab has achieved consensus recommendation status for new onset refractory status epilepticus and febrile infection-related epilepsy syndrome; and electromagnetic neuromodulation technologies encompassing responsive neurostimulation, deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and emerging transcranial ultrasound stimulation provide expanding options for pharmacoresistant populations. Computational neuroscience contributions include neural mass modeling demonstrating that sleep electroencephalography can reveal synaptic hyperexcitability parameters predictive of imminent seizure risk. This review concludes that epilepsy care is undergoing fundamental paradigm shifts from symptomatic seizure control toward etiologic, precision therapeutics and from invasive intracranial evaluation toward minimally invasive and noninvasive diagnostic methodologies.