By Marcello Cherchi, MD PhD
For patients
Transcutaneous vagal nerve stimulation (tVNS) is a treatment in which a machine placed on the neck or ear uses a magnet to stimulate part of the nervous system called the vagus nerve. Some researchers believe this may help several disorders that cause disequilibrium.
For clinicians
Overview
Transcutaneous vagal nerve stimulation (tVNS) has been studied for numerous medical conditions, including a few otoneurological conditions such as migraine associated vertigo and persistent postural perceptual dizziness. Its mechanism of action remains unclear. The particular protocols and parameters are not well established. This treatment modality appears safe and well-tolerated, though evidence supporting its efficacy is weak.
Introduction
Vagal nerve stimulation (VNS) has been studied for a variety of medical conditions. The original methodology was invasive (implanting a stimulator), but eventually non-invasive methods (transcutaneous) were also explored, such as transcutaneous vagal nerve stimulation (tVNS). Some of its potential applications were discovered accidentally, such as when a patient whose epilepsy was being treated with vagal nerve stimulation reported that migraines were aborted by the procedure (Sadler et al. 2002).
Neurological conditions for which vagal nerve stimulation have been studied include epilepsy, headaches (usually migraine and cluster), Parkinson’s disease, Alzheimer’s disease, rehabilitation from stroke and traumatic brain injury (Wang et al. 2021).
Mechanism
The mechanisms by which vagal nerve stimulation exerts its effects are incompletely understood (Groves and Brown 2005; Hilz 2022; Hu et al. 2021; Wang et al. 2021). Candidate mechanisms include central and peripheral anti-inflammatory effects, modulation of blood-brain barrier permeability, modulation of vasomotor activity, influencing neural plasticity and others (Wang et al. 2021).
There is debate regarding the specific protocol of stimulation parameters is optimal (Cao et al. 2021), and it is possible that this may vary from one condition to another. Most protocols study cervical tVNS, but auricular stimulation of the vagus nerve (Butt et al. 2020; Huang et al. 2023; Zhang et al. 2019) has also been explored.
Adverse effects
Transcutaneous vagal nerve stimulation appears to be safe and well-tolerated (Grazzi et al. 2017; Mwamburi et al. 2018; Redgrave et al. 2018).
Relevance in otoneurology
There are several otoneurological conditions for which tVNS may be applicable.
Transcutaneous VNS has been studied as a treatment for migraine (Hord et al. 2003; Huang et al. 2023; Lenaerts et al. 2008; Luo et al. 2020; Mwamburi et al. 2020; Schoenen and Ambrosini 2020), both as a prophylactic (Barbanti et al. 2015; Cecchini et al. 2009; Diener et al. 2019; Grazzi et al. 2017; Kinfe et al. 2015; Mauskop 2005; Najib et al. 2022; Silberstein et al. 2016) and abortive (Barbanti et al. 2015) therapy. As of this writing the only vagal nerve stimulation device that has received FDA approval is the GammaCore®. A few studies have specifically studied tVNS for migraine associated vertigo (Beh 2020, 2021; Beh and Friedman 2019).
One study has explored tVNS for persistent postural perceptual dizziness (PPPD) (Eren et al. 2018).
Most meta-analyses and systematic review of the literature on tVNS report that the evidence supporting its efficacy is weak (Lai et al. 2020; Moisset et al. 2020; Reuter et al. 2019; Song et al. 2023).
Other notes
Transcutaneous vagal nerve stimulation sems be well-tolerated and safe. Evidence of its efficacy for otoneurological conditions appears weak.
References
Barbanti P, Grazzi L, Egeo G, Padovan AM, Liebler E, Bussone G (2015) Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: an open-label study. J Headache Pain 16: 61. doi: 10.1186/s10194-015-0542-4
Beh SC (2020) Emerging evidence for noninvasive vagus nerve stimulation for the treatment of vestibular migraine. Expert Rev Neurother 20: 991-993. doi: 10.1080/14737175.2020.1806060
Beh SC (2021) Nystagmus and Vertigo in Acute Vestibular Migraine Attacks: Response to Non-Invasive Vagus Nerve Stimulation. Otol Neurotol 42: e233-e236. doi: 10.1097/MAO.0000000000002892
Beh SC, Friedman DI (2019) Acute vestibular migraine treatment with noninvasive vagus nerve stimulation. Neurology 93: e1715-e1719. doi: 10.1212/WNL.0000000000008388
Butt MF, Albusoda A, Farmer AD, Aziz Q (2020) The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat 236: 588-611. doi: 10.1111/joa.13122
Cao J, Zhang Y, Li H, Yan Z, Liu X, Hou X, Chen W, Hodges S, Kong J, Liu B (2021) Different modulation effects of 1 Hz and 20 Hz transcutaneous auricular vagus nerve stimulation on the functional connectivity of the periaqueductal gray in patients with migraine. J Transl Med 19: 354. doi: 10.1186/s12967-021-03024-9
Cecchini AP, Mea E, Tullo V, Curone M, Franzini A, Broggi G, Savino M, Bussone G, Leone M (2009) Vagus nerve stimulation in drug-resistant daily chronic migraine with depression: preliminary data. Neurol Sci 30 Suppl 1: S101-4. doi: 10.1007/s10072-009-0073-3
Diener HC, Goadsby PJ, Ashina M, Al-Karagholi MA, Sinclair A, Mitsikostas D, Magis D, Pozo-Rosich P, Irimia Sieira P, Lainez MJ, Gaul C, Silver N, Hoffmann J, Marin J, Liebler E, Ferrari MD (2019) Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial. Cephalalgia 39: 1475-1487. doi: 10.1177/0333102419876920
Eren OE, Filippopulos F, Sonmez K, Mohwald K, Straube A, Schoberl F (2018) Non-invasive vagus nerve stimulation significantly improves quality of life in patients with persistent postural-perceptual dizziness. J Neurol 265: 63-69. doi: 10.1007/s00415-018-8894-8
Grazzi L, Egeo G, Liebler E, Padovan AM, Barbanti P (2017) Non-invasive vagus nerve stimulation (nVNS) as symptomatic treatment of migraine in young patients: a preliminary safety study. Neurol Sci 38: 197-199. doi: 10.1007/s10072-017-2942-5
Groves DA, Brown VJ (2005) Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev 29: 493-500. doi: 10.1016/j.neubiorev.2005.01.004
Hilz MJ (2022) Transcutaneous vagus nerve stimulation – A brief introduction and overview. Auton Neurosci 243: 103038. doi: 10.1016/j.autneu.2022.103038
Hord ED, Evans MS, Mueed S, Adamolekun B, Naritoku DK (2003) The effect of vagus nerve stimulation on migraines. J Pain 4: 530-4. doi: 10.1016/j.jpain.2003.08.001
Hu B, Akerman S, Goadsby PJ (2021) Characterization of opioidergic mechanisms related to the anti-migraine effect of vagus nerve stimulation. Neuropharmacology 195: 108375. doi: 10.1016/j.neuropharm.2020.108375
Huang Y, Zhang Y, Hodges S, Li H, Yan Z, Liu X, Hou X, Chen W, Chai-Zhang T, Kong J, Liu B (2023) The modulation effects of repeated transcutaneous auricular vagus nerve stimulation on the functional connectivity of key brainstem regions along the vagus nerve pathway in migraine patients. Front Mol Neurosci 16: 1160006. doi: 10.3389/fnmol.2023.1160006
Kinfe TM, Pintea B, Muhammad S, Zaremba S, Roeske S, Simon BJ, Vatter H (2015) Cervical non-invasive vagus nerve stimulation (nVNS) for preventive and acute treatment of episodic and chronic migraine and migraine-associated sleep disturbance: a prospective observational cohort study. J Headache Pain 16: 101. doi: 10.1186/s10194-015-0582-9
Lai YH, Huang YC, Huang LT, Chen RM, Chen C (2020) Cervical Noninvasive Vagus Nerve Stimulation for Migraine and Cluster Headache: A Systematic Review and Meta-Analysis. Neuromodulation 23: 721-731. doi: 10.1111/ner.13122
Lenaerts ME, Oommen KJ, Couch JR, Skaggs V (2008) Can vagus nerve stimulation help migraine? Cephalalgia 28: 392-5. doi: 10.1111/j.1468-2982.2008.01538.x
Luo W, Zhang Y, Yan Z, Liu X, Hou X, Chen W, Ye Y, Li H, Liu B (2020) The Instant Effects of Continuous Transcutaneous Auricular Vagus Nerve Stimulation at Acupoints on the Functional Connectivity of Amygdala in Migraine without Aura: A Preliminary Study. Neural Plast 2020: 8870589. doi: 10.1155/2020/8870589
Mauskop A (2005) Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia 25: 82-6. doi: 10.1111/j.1468-2982.2005.00611.x
Moisset X, Pereira B, Ciampi de Andrade D, Fontaine D, Lanteri-Minet M, Mawet J (2020) Neuromodulation techniques for acute and preventive migraine treatment: a systematic review and meta-analysis of randomized controlled trials. J Headache Pain 21: 142. doi: 10.1186/s10194-020-01204-4
Mwamburi M, Liebler EJ, Staats PS (2020) Patient experience with non-invasive vagus nerve stimulator: gammaCore patient registry. Am J Manag Care 26: S15-S19. doi: 10.37765/ajmc.2020.42545
Mwamburi M, Tenaglia AT, Leibler EJ, Staats PS (2018) Review of evidence on noninvasive vagus nerve stimulation for treatment of migraine: efficacy, safety, and implications. Am J Manag Care 24: S507-S516.
Najib U, Smith T, Hindiyeh N, Saper J, Nye B, Ashina S, McClure CK, Marmura MJ, Chase S, Liebler E, Lipton RB (2022) Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial. Cephalalgia 42: 560-569. doi: 10.1177/03331024211068813
Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A (2018) Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul 11: 1225-1238. doi: 10.1016/j.brs.2018.08.010
Reuter U, McClure C, Liebler E, Pozo-Rosich P (2019) Non-invasive neuromodulation for migraine and cluster headache: a systematic review of clinical trials. J Neurol Neurosurg Psychiatry 90: 796-804. doi: 10.1136/jnnp-2018-320113
Sadler RM, Purdy RA, Rahey S (2002) Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalalgia 22: 482-4. doi: 10.1046/j.1468-2982.2002.00387.x
Schoenen J, Ambrosini A (2020) Update on noninvasive neuromodulation for migraine treatment-Vagus nerve stimulation. Prog Brain Res 255: 249-274. doi: 10.1016/bs.pbr.2020.06.009
Silberstein SD, Calhoun AH, Lipton RB, Grosberg BM, Cady RK, Dorlas S, Simmons KA, Mullin C, Liebler EJ, Goadsby PJ, Saper JR, Group ES (2016) Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. Neurology 87: 529-38. doi: 10.1212/WNL.0000000000002918
Song D, Li P, Wang Y, Cao J (2023) Noninvasive vagus nerve stimulation for migraine: a systematic review and meta-analysis of randomized controlled trials. Front Neurol 14: 1190062. doi: 10.3389/fneur.2023.1190062
Wang Y, Zhan G, Cai Z, Jiao B, Zhao Y, Li S, Luo A (2021) Vagus nerve stimulation in brain diseases: Therapeutic applications and biological mechanisms. Neurosci Biobehav Rev 127: 37-53. doi: 10.1016/j.neubiorev.2021.04.018
Zhang Y, Liu J, Li H, Yan Z, Liu X, Cao J, Park J, Wilson G, Liu B, Kong J (2019) Transcutaneous auricular vagus nerve stimulation at 1 Hz modulates locus coeruleus activity and resting state functional connectivity in patients with migraine: An fMRI study. Neuroimage Clin 24: 101971. doi: 10.1016/j.nicl.2019.101971
