Abstracts

Rationale: Focal brain cooling (FBC) has a potential to terminate epileptic discharges. Brain cooling was first proposed approximately 50 years ago and it has again come into the spotlight in recent years owing to numerous technical advances. Our group has also investigated the effect of focal cooling on epileptic seizures over the past 12 years. Therefore, in this presentation, we review our past experimental studies and discuss the future perspectives of brain cooling as a potential therapy for patients with intractable epilepsy. Methods: Focal cooling devices with "Peltier" chips or water circulation systems were employed in animal and human studies. The cooling device was placed on the cortical surfaces in rats, cats and non-human primates. Kainic acid (KA) or penicillin G was then injected into the cortex to provoke epileptiform discharges (EDs) and seizures. The cortices of the animals were cooled to varying degrees and the influences of FBC on EDs and seizures were investigated. Focal cooling was also applied in 9 patients with intractable epilepsy. During surgery, cooling was performed on the epileptogenic cortices or hippocampi which had to be resected. Changes in the EDs, cerebral blood flow (CBF) and metabolites during FBC were investigated. Results: The EDs and seizures were suppressed during cooling (15-20C) in animals. The neurophysiological functions were preserved during cooling above 15C in rats and non-human primates. Histologically, no apparent damage was observed in the cortices of rats after cooling above 0C for 1 hour. Intraoperative cooling to 15C invariably showed the suppression of EDs, which was associated with a coupling of the CBF and the metabolism, with a significant reduction in the glutamate level in humans. Conclusions: The FBC has a strong inhibitory effect on epileptic seizures and plays a neuroprotective role for the brain. The present results support the physiochemical and technical feasibility of a cooling device-based therapy for epilepsy. Funding: This work was supported by a Grant-in-Aid for Specially Promoted Research (No.20001008) granted by MEXT of Japan. Acknowledgment: I express my thanks to colleagues who belong to the Department of Neurosurgery, Yamaguchi University School of Medicine for their contribution to these hypothermia researches.