Project description:ImportanceEpilepsy affects at least 1.2% of the population, with one-third of cases considered to be drug-resistant epilepsy (DRE). For these cases, focal cooling therapy may be a potential avenue for treatment, offering hope to people with DRE for freedom from seizure. The therapy leverages neuroscience and engineering principles to deliver a reversible treatment unhindered by pharmacology.ObservationsAnalogous to (but safer than) the use of global cooling in postcardiac arrest and neonatal ischemic injury, extensive research supports the premise that focal cooling as a long-term treatment for epilepsy could be effective. The potential advantages of focal cooling are trifold: stopping epileptiform discharges, seizures, and status epilepticus safely across species (including humans).Conclusions and relevanceThis Review presents the most current evidence supporting focal cooling in epilepsy. Cooling has been demonstrated as a potentially safe and effective treatment modality for DRE, although it is not yet ready for use in humans outside of randomized clinical trials. The Review will also offer a brief overview of the technical challenges related to focal cooling in humans, including the optimal device design and cooling parameters.