Epilepsy Currents最新文献

This article reflects key themes and discussions from the American Epilepsy Society Annual Meeting 2025, Epilepsy and Aging Special Interest Group (SIG) session entitled "Multimodal Biomarkers of Epilepsy in Older Adults." The perspectives presented here are intended to highlight emerging priorities for the field. Epilepsy in older adults is the fastest-growing segment of the epilepsy population worldwide. Despite rising incidence, prevalence, and substantial morbidity, care for late-onset epilepsy (LOE) remains anchored to a seizure-centric framework that inadequately addresses the broader consequences of seizures in later life. Older adults with LOE face markedly increased risks of dementia, mortality, and stroke, yet are frequently excluded from epilepsy and Alzheimer's disease (AD) clinical trials. Patient-centered outcomes, including cognition, sleep, function, and quality of life, remain underprioritized. In this article, we argue that LOE requires multimodal biomarkers and multidisciplinary care. We contend that LOE should be reframed as a biologically meaningful warning signal of network vulnerability and overlapping brain pathology, rather than a late-life complication to be managed pragmatically. Cognitive dysfunction is common, heterogeneous, and often precedes overt neurodegenerative diagnoses, positioning cognition as an early clinical signal. Neuroimaging and electrophysiological evidence further place LOE along a continuum intersecting cardiovascular risk factors, sleep disruption, and AD biology, challenging traditional silos between epilepsy and dementia care. We argue for greater inclusion of older adults in antiseizure medication trials and for the inclusion of individuals with epilepsy in AD clinical trials. We propose a brain-health-centered framework for LOE that integrates longitudinal electroencephalography, particularly sleep-inclusive strategies, routine cognitive screening with targeted neuropsychological assessment, neuroimaging, vascular and sleep risk evaluation, and selective use of neurodegenerative biomarkers when clinically actionable. Together, these shifts move care beyond seizure counting toward a comprehensive brain-health model aligned with the realities of aging epilepsy.

Biomolecular condensates are membrane-less compartments that are found in all different types of cells, including neurons. They form by a process called "liquid-liquid phase separation" which happens when it becomes more energetically favorable for macromolecules to cluster, rather than diffuse freely while surrounded by their water-shells. Most research on biomolecular condensates has focused on their role in cellular stress and regulating protein expression, but we are now recognizing their importance in neuronal processes such as synaptic transmission and neurodegeneration. To date, however, little consideration has been given to any role in epileptic pathology. Here we outline what is known about biomolecular condensates, how they form, how they might influence cellular physiology, and how these processes might relate to various open questions in epilepsy research. In particular, we draw attention to their possible role in the cellular regulatory effects of mTOR and how this impacts the control of ionic distribution. We explain how this affects circadian modulation of cortical function, including the susceptibility to seizures.

Thalamic neuromodulation for drug-resistant epilepsy has evolved from ablative thalamotomy to network-guided deep-brain stimulation (DBS) and responsive neurostimulation (RNS). Currently, the only Food and Drug Administration-approved DBS target is the anterior thalamic nucleus, which provides substantial and durable seizure reduction, particularly in limbic and temporal epilepsies. There is growing evidence that the centromedian and pulvinar nuclei are implicated in generalized, multifocal, and posterior neocortical epilepsies. Advanced imaging, probabilistic atlases, and connectomics can be used to refine targeting; however, they are limited by patient specificity, acquisition burden, and interatlas variability. Thalamic stereoelectroencephalography may clarify potential neuromodulation target selection by characterizing ictal recruitment, network dynamics, and biomarkers. Although DBS and RNS each have unique benefits, no modality has demonstrated superior. Pediatric data are heterogeneous and scarcer, but seizure reduction and safety profiles are similar to adults. Further studies are needed to optimize neuromodulation target selection and programming paradigms.