Abstract
Background: Chronic vagal nerve stimulation (VNS) is a well-established non-pharmacological treatment option for drug-resistant epilepsy. This study sought to develop a statistical model for prediction of VNS efficacy. We hypothesized that reactivity of the electroencephalogram (EEG) to external stimuli measured during routine preoperative evaluation differs between VNS responders and non-responders.Materials and Methods: Power spectral analyses were computed retrospectively on pre-operative EEG recordings from 60 epileptic patients with VNS. Thirty five responders and 25 non-responders were compared on the relative power values in four standard frequency bands and eight conditions of clinical assessment—eyes opening/closing, photic stimulation, and hyperventilation. Using logistic regression, groups of electrodes within anatomical areas identified as maximally discriminative by n leave-one-out iterations were used to classify patients. The reliability of the predictive model was verified with an independent data-set from 22 additional patients.Results: Power spectral analyses revealed significant differences in EEG reactivity between responders and non-responders; specifically, the dynamics of alpha and gamma activity strongly reflected VNS efficacy. Using individual EEG reactivity to develop and validate a predictive model, we discriminated between responders and non-responders with 86% accuracy, 83% sensitivity, and 90% specificity.Conclusion: We present a new statistical model with which EEG reactivity to external stimuli during routine presurgical evaluation can be seen as a promising avenue for the identification of patients with favorable VNS outcome. This novel method for the prediction of VNS efficacy might represent a breakthrough in the management of drug-resistant epilepsy, with wide-reaching medical and economic implications.
Highlights
Resective surgery is currently the best therapeutic option for treatment of patients with drug-resistant epilepsy, but a substantial number of intractable patients remains who are ineligible for such treatment or for whom resective surgery fails to abolish seizures
Cohort 1 The vagal nerve stimulation (VNS) device was implanted in 110 patients in our center between 2005 and 2012
EEG, 13 (12%) due to attrition, and 20 (18%) who switched between VNS outcomes during the follow-up period
Summary
Resective surgery is currently the best therapeutic option for treatment of patients with drug-resistant epilepsy, but a substantial number of intractable patients remains who are ineligible for such treatment or for whom resective surgery fails to abolish seizures. It is presumed that VNS increases seizure threshold by activating neuronal networks in the thalamus and other limbic structures [3, 4], but the precise mechanism of VNS action is not yet understood fully Both synchronization and desynchronization of the electroencephalogram (EEG) has been proposed as a possible mechanism behind the antiepileptic effect of VNS [5, 6], and recent neurophysiological studies focusing on EEG parameters lend support to this: Fraschini et al report a significant correlation between VNS-induced global desynchronization in gamma bands and positive clinical outcome in temporal lobe epilepsy patients [7]. Differential alterations in brain rhythms from VNS therapy between responders and non-responders might reflect inter-individual variability in the (non-specific) susceptibility of EEG to be synchronized or desynchronized by external stimulation. It follows that differences in this susceptibility might underlie individual VNS efficacy. We hypothesized that reactivity of the electroencephalogram (EEG) to external stimuli measured during routine preoperative evaluation differs between VNS responders and non-responders
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