Abstracts

Rationale: The purpose of this study was to investigate the acute effect of transcutaneous Vagus Nerve Stimulation (t-VNS) on the occurrence of epileptiform activity during intracranial EEG monitoring. Methods: The study is an investigator initiated, single-blinded, clinical trial. Acute effects of t-VNS on interictal epileptiform activity were investigated in adult patients with drug resistant epilepsy while undergoing intracranial EEG recording as part of a pre-surgery program. Patients were stimulated with t-VNS (Nemos®) by the end of their intracranial monitoring, when antiepileptic drugs (AEDs) had been tapered (Table). During a study time of 4 x 60 minutes, first hour was baseline, 2nd or 3rd hour was stimulation, and 4th hour no stimulation. Standard stimulation parameters with a pulse duration of 250 µsec were used and the current output was individually adjusted within the first 2 minutes of stimulation to the level of tolerance (0.5 mA – 3.5 mA; mean 0.9 mA).  Vigilance of the patients was sought to be kept stable during the four hours of the study. To automatically detect and quantify spike activity for each electrode contact, we used the open-source software, AnyWave (Colombet et al, 2015). Spikes were automatically detected in AnyWave using Delphos (Detector of ElectroPhysiological Oscillations and Spikes) (Roehri et al, 2016). The primary endpoint was a change in interictal epileptiform activity during 60 min of t-VNS stimulation and during the following 60 min, as compared to baseline. Results: Responses to nine t-VNS stimulations were evaluated in eight patients (two with cortical dysplasia, two with hippocampal sclerosis, one with multiple nodular heterotopias, and three had unknown causes). One patient was studied twice during two separate implantations. None of the patients had seizures during the stimulation. The table shows demographic data as well as spike-activity for the generally most active depth EEG electrode contact during the hour of stimulation and the subsequent hour as % of the hour preceding stimulation (baseline). The mean spike activity for all patients was 96% and 97% for the two periods respectively, i.e. no change at all. In general, fluctuations in activity between 10 minutes periods during baseline was substantial ranging from 70 to 130 percent of the mean baseline. In the figure we have plotted the deviations from 100% for the four patients who showed any decrease during the stimulation period.  The fluctuations may very well be random, but if real, it shows that the expected effect of the actual stimulation protocol in future studies on a larger cohort might be very modest, and only occur in a subset of patients. Conclusions: This pilot study was not able to demonstrate any significant acute effect of t-VNS. Only a few patients might be responders, but even so, the reduction of spike-activity was unimpressive. The fluctuation of spike-activity during the four hours was substantial in many patients. In future studies longer stimulation periods and/or repeated trials in the same patient might be needed. Funding: The project has been funded by the Lundbeck Foundation