Abstracts

Rationale: There is a growing recognition of the need to consider epilepsy as a disease involving neuronal networks. Delineating functional networks as part of the planning for epilepsy surgery is also crucial to avoid iatrogenic deficits. Cortico-cortical evoked potentials (CCEPs) use low-frequency stimulation of intracranial electrodes to probe the effective connectivity between cortical areas and have also been suggested as an approach to map the epileptogenic zone. The potential risks of performing CCEPs systematically in patients undergoing intracranial EEG monitoring are poorly understood. They include afterdischarges (ADs) or epileptic seizures triggered by electrical stimulation, and arrhythmias upon stimulation of cortical areas involved in the control of heart rate.Methods: We performed CCEPs in 13 consecutive patients with drug-resistant focal epilepsy undergoing intracranial EEG monitoring (subdural grids and strips as well as depth electrodes and stereo-electrodes). We systematically delivered bipolar stimulation to all pairs of neighboring electrodes (20 pulses, 10 mA for subdural electrodes, 4-10 mA for stereo-electrodes, 1 Hz) while recording intracranial EEG. We looked for ADs or epileptic seizures, as well as changes in beat-to-beat heart rate in the 9 patients in whom the ECG trace was of sufficient quality to measure it.Results: 1192 stimulation sites were probed in 13 patients (average 92 per patient, standard deviation 39.4). Afterdischarges: we observed ADs upon stimulation of 9 sites in 4 patients (0.8% of all stimulated sites, 31% of all patients). In all 9 cases, the stimulated sites were part of the seizure onset zone. On one occasion, the AD evolved into a clinical seizure. ADs arose upon stimulation of 3/828 subdural electrodes, 2/89 depth electrodes, and 4/275 stereo-electrodes. They were significantly more frequent upon depth or stereo-electrode stimulation than upon subdural electrode stimulation (Fisher s exact test, p=0.0277). There were no differences in the frequency of ADs between depth and stereo-electrodes (p=0.6372). Heart rate: during low-frequency stimulation, the beat-to-beat heart rate was below 50/min on stimulation of 64 sites in 4 patients (5.4%), the majority of which were observed in one patient with a slow baseline heart rate; it never decreased below 40/min. The heart rate was above 100/min on stimulation of 114 sites in 5 patients (9.6%), above 110/min on stimulation of 40 sites in one patient (3.4%), and above 120/min on stimulation of 2 sites in the same patient (0.2%), who had a fast baseline heart rate. It never rose above 130/min.Conclusions: Recording CCEPs through systematic low-frequency bipolar stimulation of intracranial electrodes is a safe procedure. The overall risk of triggering ADs is low. Triggering ADs is more common upon stimulation of depth and stereo-electrodes than subdural electrodes. It may represent a specific, if insensitive, test for localizing the seizure onset zone. Low-frequency stimulation appears to carry no risk of clinically significant bradycardia or tachycardia.