Predicting efficacy of neuromodulation in epilepsy

Rationale: In patients with medically refractory epilepsy who are not eligible for surgical treatment, neuromodulation, including vagus nerve stimulation (VNS), remains as a last resort. However, a good response (> 50% seizure reduction) is achieved in only approximately 50% of patients. At present, we cannot predict who will benefit from VNS. Ultra long-term EEG measurements have recently become feasible by using minimally invasive subcutaneous electrodes. We hypothesize that the combination of this technique with network analysis of resting state fMRI and 64-channel EEG can provide insight in the brain circuits involved in the disturbed brain dynamics and can result in a significant improvement in response prediction of individual patients who are candidates for VNS.

Objective: We aim to identify biomarkers to predict the success of VNS using pre-operative ultra-long EEG recordings, restingstate 64-channel EEG, and MRI.

Main study parameters/endpoints: The primary goal of the pilot study is to test the feasibility and patients' satisfaction of the subcutaneous EEG electrode using a short questionnaire. If successful, the study will be expanded to evaluate the predictive value of the pre-operative ultra long-term EEG recordings measured with the subcutaneous electrode, the pre-operative resting state 64-channel EEG and pre-operative MRI. The primary outcome measure for this prediction model is the response rate (i.e. change in seizure frequency) to VNS assessed with the subcutaneous EEG electrode.

We will use ultra long-term EEG measurements that both serve as a reliable and objective measure for electrographic seizures and allow extraction of features that characterize the epilepsy phenotype as candidate biomarkers to assess the efficacy of neuromodulation. This will be complemented with network analysis of resting state fMRI and 64-channel EEG to provide insight in the brain circuits involved in the disturbed brain dynamics. We hypothesize that this combination of techniques can result in a significant improvement in response prediction of individual patients who are candidates for VNS.

• EEG will be recorded from 2 months pre-operative until 2 months postoperative, from 5 until 7 months postoperative and from 11 until 13 months postoperative.
• Baseline (2 months pre-operative, before insertion of the subcutaneous EEG electrode) and postoperative (13 months postoperative, after explantation of the subcutaneous EEG electrode) 64-channel EEG and MRI (anatomical, DWI and fMRI).
• Baseline (-2 months) and at the end of the study (+13 months) to fill in four questionnaires about their psychologica) well-being: the Quality of Life in Epilepsy (QOLIE-31-P), the Generalized Anxiety Disorder 7-item (GAD-7), the Patient Health Questionnaire (PHQ-9), and the Beck Depression Inventory-II (BDI-II).
• Three times (-2 months, -1.5 months and +13 months) to fill in a short questionnaire to evaluate the patient satisfaction about the subcutaneous EEG electrode.

Not applicable.