Publication Date
1-9-2024
Journal
JCI Insight
DOI
10.1172/jci.insight.174753
PMID
38193532
PMCID
PMC10906461
PubMedCentral® Posted Date
1-9-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Humans, Quality of Life, Epilepsy, Glioma, Drug Resistant Epilepsy, Immune System, Tumor Microenvironment
Abstract
Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. Metabolic modulation of the IDH1-mutant pathway provides a dual pathway for reversing immune suppression and dampening seizure activity. Elucidating the relationship between neurons and immunoreactivity is an area for the prioritization and development of the next era of ASMs.