Abstracts

Rationale: Vagus nerve stimulation (VNS) is an effective adjunctive treatment for refractory epilepsy, but it remains still unclear which factors determine the patient s responsiveness and which are the most optimal stimulation parameters to use. Several studies in rodents show that the locus coeruleus (LC) norepinephrine (NE) system plays an important role in the anti-epileptic effect of VNS. This study investigates the effects of two VNS paradigms on the CSF dopamine (DA), serotonin (5HT) and NE levels in normal dogs.Methods: Ten Beagle dogs were implanted with a Cyberonics pulse generator and helical electrodes around the left vagosympathetic trunk. A blinded cross-over study started 1 month after implantation. Cisternal CSF was taken immediately after 3 different conditions (1 hour of sham, rapid cycling and microburst VNS) and a minimum washout period of 1 week between different conditions was respected. The concentration of monoamines in the CSF was measured by liquid chromatography assay. Statistical analysis was performed using a multiple comparison method (Dunnett s test) to compare the concentrations of DA, 5HT and NE after the 3 different acute VNS paradigms within each dog.Results: One dog developed a left-sided Horner syndrome after implantation and was excluded from the study. Acute rapid cycling VNS did not cause significant changes in DA, 5HT and NE levels in the CSF of the dogs compared to sham VNS. Acute microburst VNS caused a significant increase in the NE levels (p=0.05), but did not cause significant alterations in 5HT nor DA concentrations.Conclusions: Acute microburst VNS results in increased CSF NE levels in the normal dog. Given the important role of the LC-NE system in the effects of VNS on experimental seizures, these results encourage further investigations into the potential and anticonvulsive effects of microburst VNS.