Introduction: Although focal brain cooling has been a candidate for epilepsy treatment, the therapeutic feasibility remains to be elucidated. Of particular importance in this regard is to clarify cooling-induced neurovascular and metabolic changes. To address this issue, cerebral blood flow (CBF) and microdialysis measurements were performed during focal brain cooling of epileptogenic zone in epileptic patients.
Methods: A PID-controlled, thermoelectrically-driven cooling device (cooling area: 40x40 mm for cortex, 10x10mm for hippocampus) was intraoperatively applied on the cortical or hippocampal epileptogenic foci in intractably epileptic patients, and CBF measurement (n=6) and microdialysis (n=9) were performed.
Findings: Although CBF in the epileptic foci was transiently reduced during 15°C cooling, it was reversible and immediately recovered following rewarming. Cooling-induced metabolic changes were qualitatively similar across patients. Of glycolytic metabolism, lactate levels were significantly reduced (p<0.01) during cooling and rewarming period, while glucose and pyruvate levels remained relatively unaffected. Extracellular levels of glutamate, gamma-aminobtyric acid (GABA) and grycerol were significantly decreased during cooling (p<0.05) with the effect remained even after rewarming (p<0.05).
Interpretation: It has been reported that autoregulation and metabolic coupling in epilepsy are impaired. This study showed, for the first time, coupling of CBF and metabolism with cooling of the epileptogenic zone to 15°C. Decreased lactate, grycerol and glutamate levels suggested neuroprotective effects of cooling. Together with the previous our investigations in animals, the results suggested a feasibility of hypothermal device-based therapy.