Five percent CO2 is a potent, fast-acting inhalation anticonvulsant

Abstract

SUMMARYPurpose: CO 2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO 2 can be used to suppress seizures in epilepsy patients. The effect of CO 2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and nonhuman primates, and based on these data, preliminary tests were carried out in humans. Methods: In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. Five percent CO 2 was applied for 5 min, 3 min before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drugresistant partial epilepsy were examined with video-EEG (electroencephalography) and received 5% CO 2 in medical carbogen shortly after electrographic seizure onset.Results: In rats, 5% CO 2 strongly suppressed cortical afterdischarges, by approximately 75%, whereas responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO 2 from 37 to 44-45 mm Hg (corresponding to inhalation of 5% CO 2 or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicucullineinduced epileptiform spikes by approximately 25%. In a pilot trial carried out in seven patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO 2 was started after seizure generalization. Conclusions: Five percent CO 2 has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO 2 can be used for acute treatment to suppress seizures in epilepsy patients.

Emerging roles of Na+/H+ exchangers in epilepsy and developmental brain disorders

“…This can be achieved by asking patients to hold their breath or through inhalation of CO 2 . Self-acidification by the inhalation of 5% CO 2 was shown to reduce seizure duration in both animal seizure models and human epilepsy patients (Tolner et al, 2011; Yang et al, 2014). Interestingly, neonatal asphyxia is associated with seizure development during the hypoxia recovery period.…”

Seizures and Brain Regulatory Systems

“…Both may influence cardiac conduction, thus certain cardiac impairments may be secondary effects of ictal respiratory dysfunction (Seyal et al, 2011). However, the administration of exogenous carbon dioxide reduces seizure duration (Tolner et al, 2011), thus hypercapnia may contribute to seizure termination processes and serve a protective function.…”

Combined electrophysiological and biosensor approaches to study purinergic regulation of epileptiform activity in cortical tissue

“…The fact that hyperventilation-induced hypocapnia is used to provoke seizures as a diagnostic test (Mendez and Brenner, 2006) and enhance electroconvulsive seizures, as are A1 receptor antagonists such as caffeine, theophylline and aminophylline (Loo et al, 2010), strongly suggests an important tonic inhibitory role for endogenous adenosine in the regulation of human seizures. Moreover, successful attempts to terminate human epileptic seizures, even after their initiation, have been made using 5 % CO2 inhalation (Tolner et al, 2011). Indeed, we have shown in hippocampal slices that hypercapnia is a powerful stimulus for adenosine release and adenosine A1 receptordependent suppression of seizure activity (Dulla et al, 2005).…”