Abstracts

Rationale: Vagus Nerve Stimulation (VNS) is associated with laryngeal muscle activation and induces voice modifications, well-known side effects of the therapy that result 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 help individual titration in patients with drug-resistant epilepsy.  Methods: 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.  Results: 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. 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. Our recordings showed very good internal consistency (Cronbach's alpha >0.95 for 10 curves). Area-under-the-curve and peak-to-peak measurement proved to be complementary methods for amplitude calculation. Moreover, we determined that an optimal derivation requires only two recording electrodes, aligned on a horizontal axis around the laryngeal prominence, at half the distance between the midline and the medial edge of the sternocleidomastoid muscle.  Conclusions: We describe the optimal methodology for the recording of VNS-induced motor evoked responses from the larynx. LMEPs reflect the integrity of the lead-nerve interface, and ensure that genuine activation of vagal fibers is obtained. They could be used as a non-invasive marker of effective nerve activation, which may help the clinician to perform a more rational and individual-based titration of VNS parameters.  Funding: The research was supported by a grant from the Walloon Region-Pôle de Compétitivité Mecatech (Projet NEUROPV).