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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00880

Vagus nerve stimulation-induced laryngeal motor evoked potentials: a possible biomarker of effective nerve activation.

 Simone Vespa1,  Lars Stumpp1,  Charlotte Bouckaert2,  Jean Delbeke1, Hugo Smets3, Joaquin Cury3, Susana Ferrao Santos1, 4, Antoine Nonclercq3,  Robrecht Raedt2,  Kristl Vonck2 and  Riëm El Tahry1, 4*
  • 1Institute of Neuroscience, Catholic University of Leuven, Belgium
  • 2Institute for Neuroscience, Ghent University Hospital, Belgium
  • 3Free University of Brussels, Belgium
  • 4Cliniques Universitaires Saint-Luc, Belgium

Vagus Nerve Stimulation (VNS) therapy is associated with laryngeal muscle activation and induces voice modifications, well-known side effects of the therapy resulting from co-activation of the recurrent laryngeal nerve. In this study, we describe the non-invasive transcutaneous recording of laryngeal motor evoked potentials (LMEPs), which could serve as a biomarker of effective nerve activation and individual titration in patients with drug-resistant epilepsy. We recruited drug-resistant epileptic patients treated for at least 6 months with a VNS. Trains of 600-1200 VNS pulses were delivered with increasing current outputs. We placed 6 skin electrodes on the ventral surface of the neck, in order to record LMEPs whenever the laryngeal muscular threshold was reached. We studied the internal consistency and the variability of LMEP recordings, and compared different methods for amplitude calculation. Recruitment curves were built based on the stimulus-response relationship. We also determined the electrical axis of the LMEPs dipole in order to define the optimal electrode placement for LMEPs recording in a clinical setting. LMEPs were successfully recorded in 11/11 patients. The LMEPs threshold ranged from 0.25 to 1mA (median 0.50 mA), and onset latency was between 5.37 and 8.77 ms. The signal-to-noise ratio was outstanding in 10/11 patients. In these cases, excellent reliability (Intraclass correlation coefficient, ICC > 0.90 across three different amplitude measurements) was achieved with 10 sample averages. Moreover, our recordings showed very good internal consistency (Cronbach’s alpha >0.95 for 10 epochs). Area-under-the-curve and peak-to-peak measurement proved to be complementary methods for amplitude calculation. Finally, we determined that an optimal derivation requires only 2 recording electrodes, aligned on a horizontal axis around the laryngeal prominence. In conclusion, we describe here an optimal methodology for the recording of VNS-induced motor evoked responses from the larynx. Although furter clinical validation is still necessary, LMEPsmoght be useful as a non-invasive marker of effective nerve activation, and as an aid for the clinician to perform a more rational titration of VNS parameters.

Keywords: Vagus Nerve Stimulation, VNS, Epilepsy, biomarkers, Larynx, motor evoked potential (MEP), Internal consistency, Reliabiity, Electrical axis

Received: 21 May 2019; Accepted: 05 Aug 2019.

Copyright: © 2019 Vespa, Stumpp, Bouckaert, Delbeke, Smets, Cury, Ferrao Santos, Nonclercq, Raedt, Vonck and El Tahry. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Riëm El Tahry, Institute of Neuroscience, Catholic University of Leuven, Louvain-la-Neuve, Belgium,