Characterization of Vagus Nerve Stimulation (VNS) Dose-Dependent Effects on EEG Power Spectrum and Synchronization.

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities. Notably, responders exhibited distinct EEG changes compared to non-responders. Our study has found that VNS intensity significantly influences EEG power topographic allocation and brain desynchronization, suggesting the potential use of acute dose-dependent effects to personalized VNS therapy in the treatment of epilepsy. The findings underscore the importance of individualized VNS dosing for optimizing therapeutic outcomes and highlight the use of EEG metrics as an effective tool for monitoring and adjusting VNS parameters. These insights offer a new avenue for developing individualized VNS therapy strategies, enhancing treatment efficacy in epilepsy.

Functional brain connectivity indexes derived from low-density EEG of pre-implanted patients as VNS outcome predictors.

Objective. In 1/3 of patients, anti-seizure medications may be insufficient, and resective surgery may be offered whenever the seizure onset is localized and situated in a non-eloquent brain region. When surgery is not feasible or fails, vagus nerve stimulation (VNS) therapy can be used as an add-on treatment to reduce seizure frequency and/or severity. However, screening tools or methods for predicting patient response to VNS and avoiding unnecessary implantation are unavailable, and confident biomarkers of clinical efficacy are unclear.Approach. To predict the response of patients to VNS, functional brain connectivity measures in combination with graph measures have been primarily used with respect to imaging techniques such as functional magnetic resonance imaging, but connectivity graph-based analysis based on electrophysiological signals such as electroencephalogram, have been barely explored. Although the study of the influence of VNS on functional connectivity is not new, this work is distinguished by using preimplantation low-density EEG data to analyze discriminative measures between responders and non-responder patients using functional connectivity and graph theory metrics.Main results. By calculating five functional brain connectivity indexes per frequency band upon partial directed coherence and direct transform function connectivity matrices in a population of 37 refractory epilepsy patients, we found significant differences (p< 0.05) between the global efficiency, average clustering coefficient, and modularity of responders and non-responders using the Mann-Whitney U test with Benjamini-Hochberg correction procedure and use of a false discovery rate of 5%.Significance. Our results indicate that these measures may potentially be used as biomarkers to predict responsiveness to VNS therapy.

Clinical added value of interictal automated electrical source imaging in the presurgical evaluation of MRI-negative epilepsy: A real-life experience in 29 consecutive patients.

OBJECTIVE: During the presurgical evaluation, manual electrical source imaging (ESI) provides clinically useful information in one-third of the patients but it is time-consuming and requires specific expertise. This prospective study aims to assess the clinical added value of a fully automated ESI analysis in a cohort of patients with MRI-negative epilepsy and describe its diagnostic performance, by evaluating sublobar concordance with stereo-electroencephalography (SEEG) results and surgical resection and outcome. METHODS: All consecutive patients referred to the Center for Refractory Epilepsy (CRE) of St-Luc University Hospital (Brussels, Belgium) for presurgical evaluation between 15/01/2019 and 31/12/2020 meeting the inclusion criteria, were recruited to the study. Interictal ESI was realized on low-density long-term EEG monitoring (LD-ESI) and, whenever available, high-density EEG (HD-ESI), using a fully automated analysis (Epilog PreOp, Epilog NV, Ghent, Belgium). The multidisciplinary team (MDT) was asked to formulate hypotheses about the epileptogenic zone (EZ) location at sublobar level and make a decision on further management for each patient at two distinct moments: i) blinded to ESI and ii) after the presentation and clinical interpretation of ESI. Results leading to a change in clinical management were considered contributive. Patients were followed up to assess whether these changes lead to concordant results on stereo-EEG (SEEG) or successful epilepsy surgery. RESULTS: Data from all included 29 patients were analyzed. ESI led to a change in the management plan in 12/29 patients (41%). In 9/12 (75%), modifications were related to a change in the plan of the invasive recording. In 8/9 patients, invasive recording was performed. In 6/8 (75%), the intracranial EEG recording confirmed the localization of the ESI at a sublobar level. So far, 5/12 patients, for whom the management plan was changed after ESI, were operated on and have at least one-year postoperative follow-up. In all cases, the EZ identified by ESI was included in the resection zone. Among these patients, 4/5 (80%) are seizure-free (ILAE 1) and one patient experienced a seizure reduction of more than 50% (ILAE 4). CONCLUSIONS: In this single-center prospective study, we demonstrated the added value of automated ESI in the presurgical evaluation of MRI-negative cases, especially in helping to plan the implantation of depth electrodes for SEEG, provided that ESI results are integrated into the whole multimodal evaluation and clinically interpreted.

Carbamazepine efficacy in a severe electro-clinical presentation of SLC13A5-epilepsy.

Recessive mutations in the SLC13A5 gene encoding the sodium-dependent citrate transporter are a recently identified cause of developmental and epileptic encephalopathy. Here, we describe a child harboring a novel homozygous loss-of-function mutation in the SLC13A5 gene (c.1496C>T-p.Ser499Phe) and exhibiting an unusual extremely severe neonatal presentation with drug-resistant seizures and burst-suppression EEG pattern. Early carbamazepine use resulted in dramatic improvement both clinically and on EEG features. Follow-up from the neonatal period to the age of 4 years is documented. This case expands the electro-clinical phenotype associated with SLC13A5-related disease and confirms the efficacy and safety of carbamazepine in nonstructural early-onset epilepsies.

A qualitative awake EEG score for the diagnosis of continuous spike and waves during sleep (CSWS) syndrome in self-limited focal epilepsy (SFE): A case-control study.

PURPOSE: To determine whether awake EEG criteria can differentiate epileptic encephalopathy with continuous spike and waves during sleep (EE-CSWS) at the time of cognitive regression from typical, self-limited focal epilepsy (SFE). METHODS: This retrospective case-control study was based on the analysis of awake EEGs and included 15 patients with EE-CSWS and 15 age-matched and sex-matched patients with typical SFE. The EEGs were anonymised and scored by four independent readers. The following qualitative and quantitative EEG indices were analysed: slow-wave index (SLWI), spike-wave index (SWI), spike-wave frequency (SWF), long spike-wave clusters (CLSW) and EEG score (between grades 0 and 4). Sensitivity and specificity were assessed using receiver operating characteristic (ROC) curves and their reproducibility with a kappa test. RESULTS: Based on a highly sensitive cut-off, EE-CSWS patients were 8.4 times more likely than those with SFE to have an SLWI > 6%, 15 times more likely to have an SWI > 10 % and six times more likely to have a CLSW of ≥ 1 s. There was substantial agreement between readers (with kappa values of 0.64, 0.69 and 0.67). EE-CSWS patients were 13 times more likely to have an SWF of > 11 % and 149 times more likely to have an EEG score of ≥ 3 than typical SFE patients. Agreement about these ratings was almost perfect (kappa 0.91 and 0.86). CONCLUSION: An EEG score of ≥ 3 on a 20-min awake EEG differentiates typical SFE from EE-CSWS at the time of cognitive regression, with good reliability across readers with different levels of expertise.

Vomiting and retching as presenting signs of focal epilepsy in children.

Ictal vomiting is a rare condition easily misdiagnosed as a common disease. We report two children presenting with retching and vomiting as the main ictal manifestation. Patient 1 was a four-year-old girl with a history of daily nocturnal vomiting for two months, first interpreted as a functional disorder, then as a viral infection. She presented with vomiting accompanied by focal right-sided hemifacial clonic jerking, occurring multiple times per day. Video-EEG demonstrated ictal discharges associated with the retching and vomiting, over a normal background, and occasional interictal focal spikes. MRI was normal. PET demonstrated left-sided opercular hypometabolism. Patient 2 was a girl with a history of focal epilepsy, secondary to a right central dysembryoplastic tumour, first resected with subsequent seizure freedom at the age of three years. At five years of age, she presented with recurrent episodes of retching and vomiting initially diagnosed as migraine. Video-EEG showed ictal discharges, clinically correlating with retching, vomiting and clonic facial jerking, with normal interictal activity. Brain MRI showed a progression of the tumour. A second resection resulted in seizure freedom. Ictal vomiting often goes undiagnosed, especially in children, causing treatment delays. An ictal origin should be considered, particularly when the episodes are recurrent and stereotyped. [Published with video sequences].