Abstract: Objective To evaluate the effect of vagal nerve stimulation（VNS） on tryptophan metabolite in plasma,and investigate whether the antiepileptic effectiveness is correlated with changes in tryptophan metabolism Methods Sixty children with intractable epilepsy were included in a randomized,doubleblind study,and were divided into highoutput stimulation group and lowoutput group,30 cases in each group After a baseline period of 12 weeks,all children underwent implantation of a vagus nerve stimulator and entered a double blind activecontrolled phase of 20 weeks Subsequently,all children received highoutput stimulation for another 19 weeks (addon phase) Tryptophan metabolites were assessed in plasma by liquid chromatographytandem mass spectrometry (LC-MS/MS) and analysed in different study stages Seizure frequency was recorded using seizure diaries Mood was assessed using Profile of Mood States(POMS) questionnaires Results Regarding tryptophan metabolites in plasma,anthranilic acid(AA) levels were significantly higher at the end of the addon phase compared with baseline(P=0002),and were correlated significantly with improvement of mood(r=0.37,P=0.042） and seizure frequency reduction(r=0.35,P<0.01) No significant differences were found between high and lowoutput groups regarding seizure frequency Conclusion Vagus nerve stimulation may induces a consistent increase in AA,a neuroprotective and anticonvulsant tryptophan metabolite Moreover,increased AA levels are probably associated with improvement in mood and reduction of seizure frequency

Key words: Intractable seizures, Vagal nerve stimulation, Tryptophan metabolism, Anthranilic acid, Profile of mood states