Abstracts

Rationale: We recently showed that experimental febrile seizures in neonatal rats are triggered by a respiratory alkalosis, and blocked by 5% CO₂ applied in the ambient air (Schuchmann et al., Nat Med 2006; 12: 817-823). Since changes in acid-base balance are known to have significant effects on neuronal excitability also in the mature brain, we set out to study the effects of CO₂ on cortical epileptic activity both in adult rats and humans. Methods: A rat model for myoclonic seizures was used in which electrical stimulation of the sensorimotor cortex elicits bilateral epileptiform afterdischarges in the EEG that are paralleled by clonic seizures of face and forelimb muscles. Studies in humans were performed on epileptic patients undergoing video-EEG monitoring for prospective epilepsy surgery. Gas mixtures consisted of 5% or 10% CO₂ in air in rats, and 5% CO₂ in oxygen in humans (medical carbogen). They were applied for 3 minutes before stimulation in rats, and in humans for a period of 20-30 seconds shortly after the start of generalized seizure activity. Results: In rats, 10% CO₂ application dramatically reduced or completely blocked the stimulation-evoked epileptiform afterdischarges. In the epileptic patients, 5% CO₂ application significantly reduced the duration of generalized seizures. Conclusions: Our data suggest that application of CO₂ may be effective in the acute treatment of epileptic seizures not only in neonates but also in adults.