Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy

Objective: To determine possible sites of therapeutic action of vagus nerve stimulation (VNS), by correlating acute VNS-induced regional cerebral bloo d flow (rCBF) alterations and chronic therapeutic responses. Background.- S ire previously found that VNS acutely induces rCBF alterations at sites tha t receive vagal afferents and higher-order projections, including dorsal me dulla, somatosensory cortex (contralateral to stimulation), thalamus and ce rebellum bilaterally, and several limbic structures (including hippocampus and amygdala bilaterally), Methods: VNS-induced rCBF changes were measured by subtracting resting rCBF from rCBF during VNS, using [0-15]water and PET , immediately before ongoing VNS began, in II partial epilepsy patients. T- statistical mapping established relative rCBF increases and decreases for e ach patient. Percent changes in frequency of complex partial seizures (with or without secondary generalization) during three months of VNS compared w ith pre-VNS baseline, and T-thresholded rCBF changes (for each of the 25 re gions of previously observed significant CBF change), were rank ordered acr oss patients. Spearman rank correlation coefficients assessed associations of seizure-frequency change and t-thresholded rCBF change. Results: Seizure -frequency changes ranged from 71% decrease to 12% increase during VNS. Onl y the right and left thalami showed significant associations of rCBF change with seizure-frequency change. Increased right and left thalamic CBF corre lated with decreased seizures (p < 0.001). Conclusions: Increased thalamic synaptic activities probably mediate some antiseizure effects of VNS. Futur e studies should examine neurotransmitter-receptor alterations in reticular and specific thalamic nuclei during VNS.