Brain blood-flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: II. Prolonged effects at high and low levels of stimulation

Purpose: To measure vagus nerve stimulation (VNS)-induced cerebral blood flow (CBF) effects after prolonged VNS and to compare these effects with immediate VNS effects on CBF. Methods: Ten consenting partial epilepsy patients had positron emission tomography (PET) with intravenous [¹⁵O]H ₂O. Each had three control scans without VNS and three scans during 30 s of VNS, within 20 h after VNS began (immediate-effect study), and repeated after 3 months of VNS (prolonged study). After intrasubject subtraction of control from stimulation scans, images were anatomically transformed for intersubject averaging and superimposed on magnetic resonance imaging (MRI) for anatomic localization. Changes on t-statistical maps were considered significant at p < 0.05 (corrected for multiple comparisons). Results: During prolonged studies, CBF changes were not observed in any regions that did not have CBF changes during immediate-effect studies. During both types of studies, VNS-induced CBF increases were similarly located in the bilateral thalami, hypothalami, inferior cerebellar hemispheres, and right postcentral gyrus. During immediate-effect studies, VNS decreased bilateral hippocampal, amygdalar, and cingulate CBF and increased bilateral insular CBF; no significant CBF changes were observed in these regions during prolonged studies. Mean seizure frequency decreased by 25% over a 3-month period between immediate and prolonged PET studies, compared with 3 months before VNS began. Conclusions: Seizure control improved during a period over which some immediate VNS-induced CBF changes declined (mainly over cortical regions), whereas other VNS-induced CBF changes persisted (mainly over subcortical regions). Altered synaptic activities at sites of persisting VNS-induced CBF changes may reflect antiseizure actions.