Authors :
Presenting Author: Enrique Germany Morrison, PhD – Universite Catholique de Louvain
Roberto Santalucia, MD – Universite Catholique de Louvain; Vincent Joris, MD – Universite Catholique de Louvain; Venethia Danthine, MD, PhD Candidate – Universite Catholique de Louvain; Inci Cakiroglu, PhD Candidate – Universite Catholique de Louvain; Andres Torres, PhD Candidate – Universite Catholique de Louvain; Antoine Nonclerq, PhD – Universite Libre de Bruxelles; Riëm El Tahry, MD, PhD – Universite Catholique de Louvain
Rationale:
Vagus Nerve Stimulation (VNS) is a therapeutic method used for patients with drug-resistant epilepsy (DRE) for over 30 years [1], but its effectiveness varies amongst individuals. An individualized dose could potentially yield a more effective therapy than a standard dose. The primary assumed mechanism for VNS therapy is thalamocortical desynchronization [2]. Despite achieving maximum responses between three and six months, a personalized titration process is still absent. Several biomarkers have been suggested, such as Laryngeal motor evoked potentials and Pupil Dilation (PD), but still, no acute central effects were recognized as individual dosing biomarkers. This research examines the preliminary results of acute central metrics that could serve as potential central biomarkers, allowing clinicians to make more precise adjustments in stimulation intensity to achieve optimal therapeutic outcomes and minimize side effects.
Methods:
Twenty-eight patients with DRE (six generalized and twenty-two focal epilepsy) were recruited. Each patient's clinical VNS settings were used, a sequence of at least six stimulation trains of 18 seconds VNS ON state was triggered ranging from 0.25 mA until clinical setting + 0.25mA. During the entire stimulation session, a 64-channel EEG + 2 LMEP horizontal plane-oriented electrodes on the neck were recorded. Data was processed to compute each band's spectral power band estimation and scalp allocation and pairwise phase synchronization.
Results:
Spectral analysis was conducted over each epoch grouped by intensity. Responders (R)
showed higher theta power allocated in the central region compared to non-responders (NR), while NR showed more parieto-occipital theta activity. Regarding alpha power, intensity was strongly present in bilateral central-parietal regions in R, while NR showed less central activity (
Figure 1). Phase synchronization analysis showed R had a consistent desynchronization near clinical programmed intensities, whereas NR showed no change (wPLI ratio value 1) around clinical intensity values, suggesting non-responders might be over or under-stimulated (
Figure 2).
Conclusions:
Aligning clinical titration practices with reliable target dose biomarkers could significantly improve the outcomes of VNS treatment. LMEP threshold value for all patients R and NR was around 0.75 mA. By combining peripheral biomarkers of nerve activation and central biomarkers during individual dosing monitoring, the titration phase could potentially be guided in a more personalized way, instead of rushing to high clinical intensities according to average population response.
References
[1] Goggins, E. et al. 2022. Clinical perspectives on vagus nerve stimulation: present and future.
Clinical Science. 136, 9 (2022), 695–709. DOI:
[2] Sangare, A. et al. 2020. The Effectiveness of Vagus Nerve Stimulation in Drug-Resistant Epilepsy Correlates with Vagus Nerve Stimulation-Induced Electroencephalography Desynchronization. Brain Connectivity. 10, 10 (2020), 566–577. DOI:https://doi.org/10.1089/brain.2020.0798.
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Funding: This work was supported by the WELBIO department, WEL Research Institute, avenue Pasteur, 6, 1300 Wavre, Belgium.
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