The effectiveness of VNS in drug-resistant epilepsy correlates with VNS induced EEG desynchronization.

Aim To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractoryepilepsy treated by vagus nerve stimulation (VNS), between VNS stimulated "ON" and non-stimulated "OFF" periods. Introduction VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiepileptic effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Methods Scalp-EEG were performed for 35 patients treated by VNS, using 21 channels and two additional electrodes on the neck in order to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of at least 50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and non-responder patients. Results Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were responders (R) and 15 were non-responders (NR). For responder patients, PLI during ON periods was significantly lower than during OFF periods in delta (p=0.009), theta (p=0.02) and beta (p=0.04) frequency bands. For non-responder patients, there were no significant differences between ON and OFF periods.Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p=0.02),theta (p=0.04) and beta (p=0.03) frequency bands. Our results were confirmed using PLV in theta band No significant differences in MST were observed between R and NR patients. Conclusion The correlation between VNS induced interictal EEG time series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal function.