Abstracts

Vagus nerve stimulation (VNS) is effective in pharmacoresistant epilepsy, but mechanisms of action are still unknown. Negative slow cortical potentials (SCP) reflect synchronized depolarization of neurons which can occur before seizure onset. Positive SCP indicate reduction of cortical excitation which lead to seizure inhibition. SCP changes during chronic VNS should be investigated. The direct current (DC)-EEGs of patients with pharmacoresistant epilepsy treated by chronic VNS were examined using a DC-coupled amplifier ([italic]eldith[/italic] GmbH, Germany), DC-stable electrodes and gels. Co-registration of ECG enabled the exact correlation of VNS on- and off-time. Additionally, polygraphic recording of etCO2, heart rate, respiration were undertaken for a better understanding of the mechanism generating the DC-shift. Artifact free cortical DC-shift were averaged over five to fourteen VNS-cycles and presented topographically. Different references of the EEG were investigated. Experiments in healthy subjetcs were undertaken to show the effect of hyperventilation on cortical DC-shift and on polygraphic parameters. Eighteen patients with pharmacoresistant epilepsy treated with VNS (absence epilepsy N=2, complex partial seizures N=16) were evaluated. VNS ouput current was between 0.5 and 2.25 mA, on-time: 30 seconds, off-time: 3 or 5 min. In seven of nine patients with more than 50% seizure reduction after VNS a repeated positive shift (+150 to +1.500[micro]V) was found during VNS off-time, lasting up to the next on-time period. Positive deflection was localized in regions with focal epileptic activity. Nine patients without significant seizure reduction did not show any positive shift. Three VNS nonresponders had negative DC-shift at -600 to -1.000[micro]V.
Only patients with VNS side effects showed symptoms of vegetative irritation icluding increased respiration frequency and heart rate as well as a reduced etCO2 concentration during VNS on-time, which may be a cause of the negative cortical DC-shift a seen in the hyperventilation experiments. Development of continuous positive DC-shifts during off-time induced by VNS were found in those patients, who responded to VNS therapy with at least 50% seizure reduction. Some nonresponders presented negative DC-shifts during off-time. These results may help to understand the VNS mechanism of action using systematic investigation of VNS cycle related changes in DC-EEG. Polygraphic recordings of heart rate, etCO2 and respiration were useful to differentiate neuronal and humoral factors of the DC-shift. Further evaluation of VNS responders and nonresponders is necessary to improve the clinical outcome of patients with pharmacoresistant epilepsy. (Supported by [italic]eldith[/italic] GmbH.)