Abstracts

Emission tomographic and functional magnetic resonance imaging studies detected increased and decreased blood flow in multiple brainstem and hemispheric sites during vagus nerve stimulation (VNS). We previously reported that acute activation of thalamic blood flow is significantly associated with seizure reduction during the first 3 months of VNS. We now compare sites of VNS-induced blood flow alteration, studied after acute and chronic VNS, with anti-seizure efficacy over 5 years.
Seizures were counted for 3 months before VNS (baseline) and the first 3 months of VNS with unchanging antiepileptic drugs, and for the remainder of 5 years of VNS with drug changes. Intravenous [oxygen-15]water and positron emission tomography (PET) measured brain blood flow in 11 consenting partial epilepsy patients. Each had 3 control scans without VNS and 3 scans during 30 seconds of VNS, within 20 hours after VNS began (acute study), and repeated after 3 months of VNS (chronic study). After intrasubject subtraction of control from stimulation scans, images were superimposed on MRI for anatomical localization. T-statistical mapping established relative blood flow increases and decreases. Percent changes from baseline in frequency of complex partial seizures (with or without secondary generalization) during 3 months of VNS, and T-thresholded blood flow changes, were rank ordered across patients; the same comparisons were made for seizure frequencies over 5 years of VNS. Spearman rank correlation coefficients assessed associations of seizure-frequency change and blood flow change, with Bonferroni correction of multiple comparisons.
Individual seizure frequency changes ranged from 12% increase to 71% decrease over 3 months, and from 6% increase to 94% decrease over 5 years. Acute PET studies showed that patients with greatest VNS-induced right and left thalamic activations had greatest seizure reductions at 3 months (p [lt] 0.001) and 5 years (p [lt] 0.05). Chronic PET studies showed that patients with greatest VNS-induced right and left thalamic activations had greatest reductions in seizures at 3 months (p [lt] 0.001) and at 5 years (p [lt] 0.005). Multiple other brain regions of acute and chronic VNS-induced blood flow changes had non-significant associations with seizure reduction at 3 months and 5 years.
Acute and chronic VNS-induced activations of polysynaptic vago-thalamic pathways are associated with long-term anti-seizure effects. Experimental studies must elucidate mechanisms of these effects.
[Supported by: Cyberonics, Inc.]