Electrophysiological Signatures of Treatment-Resistant Epilepsy in Adult Patients

Abstract

Roughly a third of adults with epilepsy do not achieve durable seizure freedom on medication, a population the International League Against Epilepsy formally designates as drug-resistant once two tolerated, appropriately chosen antiseizure medication schedules have failed. Electroencephalography, in its many forms, remains the primary tool for characterizing this population physiologically rather than merely pharmacologically, because it is the only routinely available modality that observes the electrical process of seizure generation directly. This article synthesizes the literature on the electrophysiological signatures that distinguish and localize treatment-resistant epilepsy in adults, moving from the definitional and epidemiological framework that makes the category meaningful, through scalp and ambulatory interictal signatures, into the intracranial and high-frequency-oscillation literature that has dominated invasive evaluation for over two decades, and on to the network-level reframing of the epileptogenic zone and the continuously recorded electrocorticographic streams now generated by chronically implanted neurostimulation devices. Read together, the evidence supports interictal spikes, high-frequency oscillations, network connectivity measures, and device-derived electrocorticography as complementary, increasingly well-evidenced signatures rather than substitutes for one another, while leaving recording standardization, the specificity of pathological versus physiological high-frequency activity, and the reconciliation of short-duration pre-surgical findings with multi-year real-world device data as open methodological challenges for the field.