Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy

peer reviewedThe locus coeruleus–norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This system is known to prevent seizure development and induce long-term plastic changes, particularly with the release of norepinephrine in the hippocampus. However, the requisites to become responder to the therapy and the mechanisms of action are still under investigation. Using MRI, we assessed the structural and functional characteristics of the locus coeruleus and microstructural properties of locus coeruleus-hippocampus white matter tracts in patients with drug-resistant epilepsy responding or not to the therapy. Twenty-three drug-resistant epileptic patients with cervical vagus nerve stimulation were recruited for this pilot study, including 13 responders or partial responders and 10 non-responders. A dedicated structural MRI acquisition allowed in vivo localization of the locus coeruleus and computation of its contrast (an accepted marker of LC integrity). Locus coeruleus activity was estimated using functional MRI during an auditory oddball task. Finally, multi-shell diffusion MRI was used to estimate the structural properties of locus coeruleus-hippocampus tracts. These characteristics were compared between responders/partial responders and non-responders and their association with therapy duration was also explored. In patients with a better response to the therapy, trends toward a lower activity and a higher contrast were found in the left medial and right caudal portions of the locus coeruleus, respectively. An increased locus coeruleus contrast, bilaterally over its medial portions, correlated with duration of the treatment. Finally, a higher integrity of locus coeruleus-hippocampus connections was found in patients with a better response to the treatment. These new insights into the neurobiology of vagus nerve stimulation may provide novel markers of the response to the treatment and may reflect neuroplasticity effects occurring in the brain following the implantation

Translating neurophysiological research into clinical practice : the role of EEG and motor evoked potentials in optimizing vagus nerve stimulation in drug-resistant epilepsy

Epilepsy affects millions of people worldwide, with one-third of patients remaining resistant to treatment. Their daily lives are often marked by significant psychosocial burden, reduced quality of life, and stigmatisation. For these patients, vagus nerve stimulation (VNS) offers an alternative, with a clinical response observed in approximately two-thirds of cases. Yet, despite nearly thirty years of use, it remains impossible to predict who will respond or to assess the therapy’s early efficacy. Even the very definition of “response” remains debated, limiting clinical progress. This thesis aims to address these challenges by exploring: (i) how to define better and measure VNS response, (ii) how to validate clinically meaningful follow-up criteria, and (iii) how longitudinal electrophysiological data may help clarify interindividual variability in response. Throughout this work, the central focus remains on what should always guide clinical research: the patient.(MED - Sciences médicales) -- UCL, 202

Exploring graph-derived metrics from functional brain connectivity analyses from PDC and DTF connectomes as VNS outcome predictors

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A Longitudinal Vagus Nerve Stimulation Study: Effects on Laryngeal Motor Evoked Potentials and EEG Synchronization

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Synchronized P300 Event-Related Potentials with Vagus Nerve Stimulation for Predicting Responses in Epilepsy

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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

Vagus nerve stimulation-induced laryngeal motor evoked potentials for response prediction and intensity titration in drug-resistant epilepsy

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