Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions

SUMMARY Purpose: Focal brain cooling is effective for suppression of epileptic seizures, but it is unclear if seizures can be suppressed without a substantial influence on normal neurologic function. To address the issue, a thermoelectrically driven cooling system was developed and applied in freemoving rat models of focal seizure and epilepsy. Methods: Focal seizures limited to the unilateral forelimb were induced by local application of a penicillin G solution or cobalt powder to the unilateral sensorimotor cortex. A proportional integration and differentiation (PID)‐controlled, thermoelectrically driven cooling device (weight of11 g)and bipolarelectrodeswere chronically implanted ontheeloquentarea(ontheepilepticfocus)andtheeffects of cooling (20, 15, and 10� C) on electrocorticography, seizurefrequency,andneurologicchangeswereinvestigated. Key Findings: Cooling was associated with a distinct reduction of the epileptic discharges. In both models, cooling of epileptic foci significantly improved both seizure frequency and neurologic functions from 20� C down to 15� C. Cooling to 10� C also suppressed seizures, but with no further improvement in neurologic function. Subsequent investigation of sensorimotor function revealed significant deterioration in foot-fault tests and the receptive field size at 15� C. Significance: Despite the beneficial effects in ictal rats, sensorimotor functions deteriorated at 15� C, thereby suggesting a lower limit for the therapeutic temperature. These results provide important evidence of atherapeutic effect of temperatures from 20 to 15� C using an implantable, hypothermal device for focal epilepsy.