Abstracts

Rationale: Focal brain cooling (FBC) is well established as an effective method for suppressing epileptiform discharges and is under investigation in preclinical of intractable epilepsy (IE) including status epileptics (SE). This method has been studied intensively in rodents, but more evidence from large animal and human studies is required prior to performance of clinical trials in drug-resistant epilepsy. To provide evidence that focal brain cooling is a safe and effective therapeutic intervention for intractable focal epilepsy, we investigated the placement of a titanium cooling plate over the epidural cortical surface and investigated whether focal brain cooling can prevent and/or terminate focal neocortical seizures without having a significant impact on brain functions. Methods: In this study, two cats and two macaque monkeys were chronically implanted with an epidural focal brain cooling device over the somatosensory and motor cortex, with adjacent Electrocorticography (ECoG) electrodes, a thermo sensor and a micro-injection tube. Seizures were induced by injection of penicillin G in the motor cortex. Penicillin G was diluted to 250 IU/μl, and 2000 IU was carefully applied to the brain surface using an injection cannula. Recordings were performed under the awake condition. After the end of the experiments, the animals were sacrificed for examination of the localization of the implanted subdural device. Results: In awake condition, no apparent changes in ECoG were caused by cooling of the cortex when the temperature of the cortical surface decreased to 15°C. Epileptiform discharges were also significantly suppressed at 15°C. Power spectra of low beta frequency bands, which include epileptiform discharges, were compared during the pre-cooling, cooling, and rewarming periods. A posthoc Tukey test was significant (in cat: pre-cooling vs. cooling, P < 0.01, pre-cooling vs. rewarming, P > 0.1, cooling vs. rewarming, P < 0.01; in monkey, pre-cooling vs. cooling, P < 0.05, pre-cooling vs. rewarming, P > 0.1, cooling vs. rewarming, P < 0.05). Implantation of the device for at least five months did not result in detrimental changes based on HE staining, compared with the ipsilateral hemisphere. Conclusions: The results of this study suggest that focal brain cooling has a strong effect to suppress the epileptiform seizures under the awake condition. FBC has a safe and effective potential treatment modality for IE including SE that might be suitable for clinical practice in the near future.