Quantitative electroencephalography (qEEG) Brain symmetry index (BSI) Vagus nerve stimulation (VNS) A B S T R A C TPurpose: Vagus nerve stimulation (VNS) has shown to be an effective treatment for drug resistant epilepsy, with achieving more than 50% seizure reduction in one third of the treated patients. In order to predict which patients will profit from VNS, we previously found that a low pairwise derived Brain Symmetry Index (pdBSI) could potentially predict good responders to VNS treatment. These findings however have to be validated before they can be generalized. Methods: 39 patients (age 18-68 years) with medically intractable epilepsy who were referred for an implanted VNS system were included. Routine EEG registrations, recorded before implantation, were analyzed. Artefact-free epochs with eyes open and eyes closed were quantitatively analyzed. The pdBSI was tested for relation with VNS outcome one year after surgery. Results: Twenty-three patients (59%) obtained a reduction in seizure frequency, of whom ten (26%) had a reduction of at least 50% (good responders) and thirteen (33%) a reduction of less than 50% (moderate responders). Sixteen patients without seizure reduction are defined as non-responders. No significant differences were found in the pdBSI of good responders (mean 0.27), moderate responders (mean 0.26) and non-responders (mean 0.25) (p > 0.05). Besides seizure reduction, many patients (56%) reported additional positive effects of VNS in terms of seizure duration, seizure intensity and/or postictal recovery. Conclusion: EEG features that correlate with VNS therapy outcome may enable better patient selection and prevent unnecessary VNS surgery. Contrary to earlier findings, this validation study suggests that pdBSI might not be helpful to predict VNS therapy outcome.