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=0002),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