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. 2024 Dec;9(6):2522-2527.
doi: 10.1002/epi4.13083. Epub 2024 Oct 28.

First-in-human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation

Mikaela Patros  1 , David G S Farmer  1 , Kegan Moneghetti  2 , Matteo M Ottaviani  3 , Shobi Sivathamboo  1   4   5 , Hugh D Simpson  1   4 , Terence J O'Brien  1   4   5 , Vaughan G Macefield  1
Affiliations

First-in-human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation

Mikaela Patros et al. Epilepsia Open. 2024 Dec.

Abstract

Introduction: Vagus nerve stimulation (VNS) is an effective treatment for people with drug-resistant epilepsy. However, its mechanisms of action are poorly understood, including which nerve fibers are activated in humans during VNS in typical clinical settings and which are required for clinical efficacy. In particular, there have been no intraneural recordings of vagus nerve fiber activation in awake humans undergoing chronic VNS. In this study, for the first time, we report recordings from the vagus nerve in this setting.

Methods: The recordings were performed using a sterile tungsten microelectrode inserted percutaneously into the cervical vagus nerve under ultrasound guidance. The clinical VNS systems were used to deliver stimulation while activity in the vagus nerve was recorded.

Results: In addition to activating myelinated axons at low currents, we provide evidence that VNS can also activate unmyelinated C fibers in the vagus nerve at currents <1 mA.

Conclusions: These results add to our understanding of how VNS exerts its beneficial effects in drug-resistant epilepsy.

Plain language statement: Here we describe for the first time, electrical recordings from the vagus nerve in awake drug-resistant epilepsy patients with an implanted vagus nerve stimulation (VNS) device. We found that the VNS device was able to activate both myelinated and unmyelinated fibers within the vagus nerve, which contributes to our understanding of how VNS works in the context of drug-resistant epilepsy.

Keywords: VNS; epilepsy; microelectrode; nerve fibers; vagus nerve stimulation.

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Conflict of interest statement

MP, DGSF, KM, and MMO report no disclosures. SS is the recipient of a National Health and Medical Research Council (NHMRC) Investigator Award (2025610). She is supported by Research Program Grants from the National Institute of Health (NIH) (1U54AT012307‐01 and 1R01NS123928‐01). She reports salary support paid to her institution from Jazz Pharmaceuticals for clinical trial‐related activities; she receives no personal income for these activities. HDS has received travel support from LivaNova for educational purposes and has received competitive grant funding from the Medical Research Future Fund (MRFF) in Australia. TOB's institution has received research funding from Eisai, UCB Pharma, LivaNova, ES Therapeutics, and Kinoxis Therapeutics. He has also received competitive grant funding from the NHMRC, MRFF, NINDS, and the DoD. VGM receives funding from the NHMRC and the NIH. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

FIGURE 1
FIGURE 1
Event‐triggered averages of compound evoked potentials recorded from the cervical vagus nerve in two epilepsy patients with implanted VNS devices. The stimulus artifact was used as the trigger to generate averages of nerve activity and occurs at time 0; current intensity is displayed on the left. Pulse width was 130 μs. Each panel under P1 shows a mean ± SD of 40 stimuli, while each panel under P2 shows the mean ± SD of 30 stimuli. Arrows indicate evoked action potentials.
See this image and copyright information in PMC

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