Abstract
The vagus nerve is responsible for the parasympathetic innervation of the major thoracic and abdominal organs. It also carries sensory afferent fibres from these viscera and reaches different brain structures. These connections have proven useful in the treatment of different diseases. Afferent stimulation of the left vagus nerve is used to treat epilepsy and major depression, and stimulation of the right vagus nerve is being tried for the treatment of heart failure. The device used for the therapy delivers intermittent stimuli. It is indicated worldwide for the treatment of drug-resistant epilepsy in patients who are not appropriate candidates for respective surgery. It has also received approval for the treatment of major depression, obesity and episodic cluster headache by the Food and Drug Administration. Randomised controlled trials and prospective studies have confirmed the efficacy and safety of this therapy in epilepsy. Nevertheless, sporadic cases of ventricular asystole have been reported. To evaluate the effect of vagus nerve stimulation therapy on the autonomic nervous system, different studies that assess heart function and blood pressure changes have been conducted, although the methods employed were not homogeneous. These studies have found subtle or no significant changes in heart rate variability and blood pressure in epileptic patients. Moreover, this therapy may reduce the risk of one of the most lethal conditions in epilepsy—sudden unexpected death.
Similar content being viewed by others
References
Krahl SE (2012) Vagus nerve stimulation for epilepsy: a review of the peripheral mechanisms. Surg Neurol Int 3:S47–S52. doi:10.4103/2152-7806.103015
Foley JO, DuBois F (1937) Quantitative studies of the vagus nerve in the cat. I. The ratio of sensory and motor fibers. J Comp Neurol 67:49–97. doi:10.1002/cne.900670104
Krahl SE, Clark KB (2012) Vagus nerve stimulation for epilepsy: a review of the central mechanisms. Surg Neurol Int 3:255–259. doi:10.4103/2152-7806.103015
Agostini E, Chinnock JE, Daly MD, Murray JG (1957) Functional and histological studies of the vagus nerve and its branches to the heart, lungs, and abdominal viscera in the cat. J Physiol 135:182–205
Verlinden TJM, Rijkers K (2016) Morphology of the human cervical vagus nerve: implications for vagus nerve stimulation treatment. Acta Neurol Scand 133:173–182. doi:10.1111/ane.12462
Randall WC, Milosavljevic M, Wurster RD, Geis GS, Ardell JL (1986) Selective vagal innervation of the heart. Ann Clin Lab Sci 1986:198–208
Ben-Menachem E, Revesz D, Simon BJ, Silberstein S (2015) Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur J Neurol 22:1260–1268. doi:10.1111/ene.12629
Harden C, Tomson T, Gloss D, Buchhalter J, Cross JH, Donner E, French JA, Gil-Nagel A, Hesdorffer DC, Smithson WH, Spitz MC, Walczak TS, Sander JW, Ryvlin P (2017) Practice guideline summary: sudden unexpected death in epilepsy incidence rates and risk factors: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 88:1674–1680. doi:10.1212/WNL.0000000000003685
Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51:1069–1077. doi:10.1111/j.1528-1167.2009.02397
Ben-Menachem E (2002) Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol 1:477–478. doi:10.1016/S1474-4422(02)00220-X
Giordano F, Zicca A, Barba C, Guerrini R, Genitori L (2017) Vagus nerve stimulation: surgical technique of implantation and revision and related morbidity. Epilepsia 58:S85–S90. doi:10.1111/epi.13678
Tarver WB, George RE, Maschino SE (1992) Clinical experience with a helical bipolar stimulating lead. Pacing Clin Electrophysiol 15:1545–1556. doi:10.1111/j.1540-8159.1992.tb02933.x
Labiner DM, Ahern GL (2007) Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings. Acta Neurol Scand 115:23–33. doi:10.1111/j.1600-0404.2006.00732.x
DeGiorgio C, Heck C, Bunch S, Britton J, Green P, Lancman M, Murphy J, Olejniczak P, Shih J, Arrambide S, Soss J (2005) Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms. Neurology 65:317–319. doi:10.1212/01.wnl.0000168899.11598.00
Liporace J, Hucko D, Morrow R, Barolat G, Nei M, Schnur J, Sperling M (2001) Vagal nerve stimulation: adjustments to reduce painful side effects. Neurology 57:885–886. doi:10.1212/WNL.57.5.885
Boon P, Vonck K, van Rijckevorsel K, El Tahry R, Elger CE, Mullatti M, Schulze-Bonhage A, Wagner L, Diehl B, Hamer H, Reuber M, Kostov H, Legros B, Noachtar S, Weber YG, Coenen VA, Rooijakkers V, Schijns OEMG, Selway R, Van Roost D, Eggleston KS, Van Grunderbeek W, Jayewardene AK, McGuire RM (2015) A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation. Seizure 32:52–61. doi:10.1016/j.seizure.2015.08.011
McGregor A, Wheless J, Baumgartner J, Bettis D (2005) Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans. Epilepsia 46:91–96. doi:10.1111/j.0013-9580.2005.16404.x
Navas M, García Navarrete A, Pascual JM, Carrasco R, Núñez JA, Shakur SF, Pastor J, Sola RG (2010) Treatment of refractory epilepsy in adult patients with right-sided vagus nerve stimulation. Epilepsy Res 90:1–7. doi:10.1016/j.eplepsyres.2010.04.007
Bauer S, Baier H, Baumgartner C, Bohlmann K, Fauser S, Graf W, Hillenbrand B, Hirsch M, Last C, Lerche H, Mayer T, Schulze-Bonhage A, Steinhoff BJ, Weber Y, Hartlep A, Rosenow F, Hamer HM (2016) Transcutaneous vagus nerve stimulation (tVNS) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial (cMPsE02). Brain Stimul 9:356–363. doi:10.1016/j.brs.2015.11.003
He W, Jing X, Wang X, Rong P, Li L, Shi H, Shang H, Wang Y, Zhang J, Zhu B (2013) Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial. Epilepsy Behav 28:343–346. doi:10.1016/j.yebeh.2013.02.001
Stefan H, Kreiselmeyer G, Kerling F, Kurzbuch K, Rauch C, Heers M, Kasper BS, Hammen T, Rzonsa M, Pauli E, Ellrich J, Graf W, Hopfengärtner R (2012) Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia 53:e115–e118. doi:10.1111/j.1528-1167.2012.03492.x
Vonck K, Van Laere K, Dedeurwaerdere S, Caemaert J, De Reuck J, Boon P (2001) The mechanism of action of vagus nerve stimulation for refractory epilepsy. J Clin Neurophysiol 18:394–401
Krahl SE, Senanayake SS, Handforth A (2001) Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression in rats. Epilepsia 42:586–589. doi:10.1046/j.1528-1157.2001.09700.x
Krahl SF, Clark KB, Smith DC et al (1998) Locus coeruleus lesions suppress the seizure attenuating effects of vagus nerve stimulation. Epilepsia 39:709–714. doi:10.1111/j.1528-1157.1998.tb01155.x
Henry TR (2002) Therapeutic mechanisms of vagus nerve stimulation. Neurology 59(Suppl 4):S3–S14. doi:10.1212/WNL.59.6_suppl_4.S3
Jaseja H (2010) EEG-desynchronization as the major mechanism of anti-epileptic action of vagal nerve stimulation in patients with intractable seizures: clinical neurophysiological evidence. Med Hypotheses 74:855–856. doi:10.1016/j.mehy.2009.11.031
The Vagus Nerve Stimulation Study Group (1995) A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 45:224–230. doi:10.1212/WNL.45.2.224
Handforth A, DeGiorgio CM, Schachter SC, Uthman BM et al (1998) Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51:48–55. doi:10.1212/WNL.51.1.48
Morris GL, Mueller WM, Vagus Nerve Stimulation Study Group EO1–EO5 (1999) Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology 53:1731–1735. doi:10.1212/WNL.53.8.1731
DeGiorgio CM, Schachter SC, Handforth A, Salinsky M, Thompson J, Uthman YB, Reed R, Collins S, Tecoma E, Morris LG, Vaughn B, Naritoku DK, Henry T, Labar D, Gilmartin R, Labiner D, Osorio I, Ristanovic R, Jones J, Murphy J, Ney G, Wheless J, Lewis P, Hecket C (2000) Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 41:1195–1200. doi:10.1111/j.1528-1157.2000.tb00325.x
De Herdt V, Boon P, Ceulemans B, Hauman H, Lagae L, Legros B, Sadzot B, Van Bogaert P, van Rijckevorsel K, Verhelst H, Vonck K (2007) Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol 11:261–269. doi:10.1016/j.ejpn.2007.01.008
Elliott RE, Morsi A, Kalhorn SP, Marcus J, Sellin J, Kang M, Silverberg A, Rivera E, Geller E, Carlson C, Devinsky O, Doyle WK (2011) Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response. Epilepsy Behav 20:57–63. doi:10.1016/j.yebeh.2010.10.017
Galbarriatu L, Pomposo I, Aurrecoechea J, Marinas A, Agúndez M, Gómez JC, Acera MA, Martínez MJ, Valle E, Maestro I, Mateos B, Cabrera A, Fernández J, Iturri F, Garamendi I (2015) Vagus nerve stimulation therapy for treatment-resistant epilepsy: a 15-year experience at a single institution. Clin Neurol Neurosurg 137:89–93. doi:10.1016/j.clineuro.2015.06.023
McHugh JC, Singh HW, Phillips J, Murphy K, Doherty CP, Delanty N (2007) Outcome measurement after vagal nerve stimulation therapy: proposal of a new classification. Epilepsia 48:375–378. doi:10.1111/j.1528-1167.2006.00931.x
Helmers SL, Wheless JW, Frost M et al (2001) Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study. J Child Neurol 16:843–848. doi:10.1177/08830738010160111101
Vonck K, Thadani V, Gilbert K, Dedeurwaerdere S, De Groote L, De Herdt V, Goossens L, Gossiaux F, Achten E, Thiery E, Vingerhoets G, Van Roost D, Caemaert J, De Reuck J, Roberts D, Williamson P, Boon P (2004) Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. J Clin Neurophysiol 21:283–289
Fernandez L, Gedela S, Tamber M, Sogawa Y (2015) Vagus nerve stimulation in children less than 3 years with medically intractable epilepsy. Epilepsy Res 112:37–42. doi:10.1016/j.eplepsyres.2015.02.009
Ryvlin P, Gilliam G, Nguyen DK, Colicchio G, Iudice A, Tinuper P, Zamponi N, Aguglia U, Wagner L, Minotti L, Stefan H, Boon P, Sadler M, Benna P, Raman P, Perucca E (2014) The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia 55:893–900. doi:10.1111/epi.12611
Elliott RE, Morsi A, Tanweer O, Grobelny B, Geller E, Carlson C, Devinsky O, Doyle WK (2011) Efficacy of vagus nerve stimulation over time: review of 65 consecutive patients with treatment-resistant epilepsy treated with VNS N10 years. Epilepsy Behav 20:478–483. doi:10.1016/j.yebeh.2010.12.042
Ardesch JJ, Buschman HP, Wagener-Schimmel LJ, van der Aa HE, Hageman G (2007) Vagus nerve stimulation for medically refractory epilepsy: a long-term follow-up study. Seizure 16:579–585. doi:10.1016/j.seizure.2007.04.005
Winston KR, Levisohn P, Miller BR, Freeman J (2001) Vagal nerve stimulation for status epilepticus. Pediatr Neurosurg 34:190–192. doi:10.1159/000056018
Patwardhan RV, Dellabadia J Jr, Rashidi M, Grier L, Nanda A (2005) Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report. Surg Neurol 64:170–173. doi:10.1016/j.surneu.2004.11.026
Sierra-Marcos A, Maestro I, Rodríguez-Osorio X, Miró J, Donaire A, Aparicio J, Rumiá J, Forcadas M, Garamendi I, Pardo J, López J, Prieto Á, Plans G, Falip M, Carreño M (2012) Successful outcome of episodes of status epilepticus after vagus nerve stimulation: a multicenter study. Eur J Neurol 19:1219–1223. doi:10.1111/j.1468-1331.2012.03707.x
Annegers JF, Coan SP, Hauser WA, Leestma J (2000) Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death. Epilepsia 41:549–553. doi:10.1111/j.1528-1157.2000.tb00208.x
Tatum WO IV, Moore DB, Stecker MM, Baltuch GH, French JA, Ferreira JA, Carney PM, Labar DR, Vale FL (1999) Ventricular asystole during vagus nerve stimulation for epilepsy in humans. Neurology 52:1267–1269. doi:10.1212/WNL.52.6.1271
Ardesch JJ, Buschman HP, van der Burgh PH, Wagener-Schimmel LJ, van der Aa HE, Hageman G (2007) Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Clin Neurol Neurosurg 109:849–852. doi:10.1016/j.clineuro.2007.07.024
Schuurman PR, Beukers RJ (2009) Ventricular asystole during vagal nerve stimulation. Epilepsia 50:967–968. doi:10.1111/j.1528-1167.2008.01907.x
Amark P, Stodberg T, Wallstedt L (2007) Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia 48:1023–1024. doi:10.1111/j.1528-1167.2007.01023.x
Borusiak P, Zilbauer M, Cagnoli S, Heldmann M, Jenke A (2009) Late-onset cardiac arrhythmia associated with vagus nerve stimulation. J Neurol 256:1578–1580. doi:10.1007/s00415-009-5162-y
Iriarte J, Urrestarazu E, Alegre M et al (2009) Late-onset periodic asystolia during vagus nerve stimulation. Epilepsia 50:928–932. doi:10.1111/j.1528-1167.2008.01918.x
Shankar R, Olotu VO, Cole N, Sullivan H, Joryet C (2013) Case report: vagal nerve stimulation and late onset asystole. Seizure 22:312–314. doi:10.1016/j.seizure.2012.12.011
Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE (2000) Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res 42:203–210. doi:10.1016/S0920-1211(00)00181-9
Harden CL, Pulver MC, Ravdin LD, Nikolov B, Halper JP, Labar DR (2000) A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy Behav 1:93–99. doi:10.1006/ebeh.2000.0046
Grimonprez A, Raedt A, Portelli J, Dauwe I, Larsen LE, Bouckaert C, Delbeke J, Carrette E, Meurs A, De Herdt V, Boon P, Vonck K (2015) The antidepressant-like effect of vagus nerve stimulation is mediated through the locus coeruleus. J Psychiatr Res 68:1–7. doi:10.1016/j.jpsychires.2015.05.002
Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG (2005) Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry 58:347–354. doi:10.1016/j.biopsych.2005.05.025
Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM et al (2005) Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry 58:355–363. doi:10.1016/j.biopsych.2005.05.024
Ikramuddin S, Blackstone RP, Brancatisano A, Toouli J, Shah SN, Wolfe BM, Fujioka K, Maher JW, Swain J, Que FG, Morton JM, Leslie DB, Brancatisano R, Kow L, O’Rourke RW, Deveney C, Takata M, Miller CJ, Knudson MB, Tweden KS, Shikora SA, Sarr MG, Billington CJ (2014) Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial. JAMA 312:915–922. doi:10.1001/jama.2014.10540
Apovian CM, Shah SN, Wolfe BM, Ikramuddin S, Miller CJ, Tweden KS, Billington CJ, Shikora SA (2017) Two-year outcomes of vagal nerve blocking (vBloc) for the treatment of obesity in the recharge trial. Obes Surg 27:169–176. doi:10.1007/s11695-016-2325-7
Gaul C, Diener HC, Silver N, Magis D, Reuter U, Andersson A, Liebler EJ, Straube A, on behalf of PREVA Study Group (2016) Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia 36:534–546. doi:10.1177/0333102415607070
Silberstein SD, Mechtler LL, Kudrow DB, Calhoun AH, McClure C, Saper JR, Liebler EJ, Rubenstein Engel E, Tepper SJ, on behalf of ACT1 Study Group (2016) Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache 56:1317–1332. doi:10.1111/head.12896
Klein HU, De Ferrari GM (2010) Vagus nerve stimulation: a new approach to reduce heart failure. Cardiol J 17:638–643
De Ferrari GM, Crijns HJGM, Borggrefe M, Milasinovic G, Smid J, Zabel M, Gavazzi A, Sanzo A, Dennert R, Kuschyk J, Raspopovic S, Klein H, Swedberg K, Schwartz PJ, for the CardioFit Multicenter Trial Investigators (2011) Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J 32:847–855. doi:10.1093/eurheartj/ehq424
Zannad F, De Ferrari GM, Tuinenburg AE, Wright D, Brugada J, Butter C, Klein H, Stolen C, Meyer S, Stein KM, Ramuzat A, Schubert B, Daum D, Neuzil P, Botman C, Castel MA, D’Onofrio A, Solomon SD, Wold N, Ruble SB (2015) Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial. Eur Heart J 36:425–433. doi:10.1093/eurheartj/ehu345
Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS (2014) Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Cardiac Fail 20:808–816. doi:10.1016/j.cardfail.2014.08.009
Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS (2016) Extended follow-up of patients with heart failure receiving autonomic regulation therapy in the ANTHEM-HF study. J Cardiac Fail 22:639–642. doi:10.1016/j.cardfail.2015.11.002
Libbus I, Nearing BD, Amurthur B, KenKnight BH, Verrier RL (2016) Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study. Heart Rhythm 13:721–728. doi:10.1016/j.hrthm.2015.11.030
Gold MR, Van Veldhuisen DJ, Hauptman PJ, Borggrefe M, Kubo SH, Lieberman RA, Milasinovic G, Berman BJ, Djordjevic S, Neelagaru S, Schwartz PJ, Starling RC, Mann DL (2016) Vagus nerve stimulation for the treatment of heart failure: the INOVATE-HF trial. J Am Coll Cardiol 68:149–158. doi:10.1016/j.jacc.2016.03.525
Beaumont E, Southerland EM, Hardwick JC, Wright GL, Ryan S, Li Y, KenKnight BH, Armour JA, Ardell JL (2015) Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction. Am J Physiol Heart Circ Physiol 309:H1198–H1206. doi:10.1152/ajpheart.00393.2015
Tomson T, Ericson M, Ihrman C, Lindblad LE (1998) Heart rate variability in patients with epilepsy. Epilepsy Res 30:77–83. doi:10.1016/S0920-1211(97)00094-6
Strzelczyk A, Adjei P, Scott CA, Bauer S, Rosenow F, Walker MC, Surges R (2012) Postictal increase in T-wave alternans after generalized tonic–clonic seizures. Epilepsia 52:2112–2117. doi:10.1111/j.1528-1167.2011.03266.x
Kamath MV, Upton ARM, Talalla A, Fallen EL (1992) Neurocardiac responses to vagoafferent electrostimulation in humans. Pacing Clin Electrophysiol 15:1581–1587. doi:10.1111/j.1540-8159.1992.tb02937.x
Setty AB, Vaughn BV, Quint SR, Robertson KR, Messenheimer JA (1998) Heart period variability during vagal nerve stimulation. Seizure 7:213–217. doi:10.1016/S1059-1311(98)80038-1
Frei MG, Osorio I (2001) Left vagus nerve stimulation with the neurocybernetic prosthesis has complex effects on heart rate and on its variability in humans. Epilepsia 42:1007–1016. doi:10.1046/j.1528-1157.2001.0420081007.x
Galli R, Limbruno U, Pizzanelli C, Giorgi FS, Lutzemberger L, Strata G, Pataleo L, Mariani M, Iudice A, Murri L (2003) Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation. Auton Neurosci 107:52–59. doi:10.1016/S1566-0702(03)00081-X
Ronkainen E, Korpelainen JT, Heikkinen E, Myllylä VV, Huikuri HV, Isojärvi JIT (2006) Cardiac autonomic control in patients with refractory epilepsy before and during vagus nerve stimulation treatment: a one-year follow-up study. Epilepsia 47:556–562. doi:10.1111/j.1528-1167.2006.00467.x
Stemper B, Devinsky O, Haendl T, Welsch G, Hilz MJ (2008) Effects of vagus nerve stimulation on cardiovascular regulation in patients with epilepsy. Acta Neurol Scand 117:231–236. doi:10.1111/j.1600-0404.2007.00944.x
Zaaimi B, Grebe R, Berquin P, Wallois F (2007) Vagus nerve stimulation therapy induces changes in heart rate of children during sleep. Epilepsia 48:923–930. doi:10.1111/j.1528-1167.2006.01019.x
Zaaimi B, Grebe R, Berquin P, Wallois F (2009) Vagus nerve stimulation induces changes in respiratory sinus arrhythmia of epileptic children during sleep. Epilepsia 50(11):2473–2480. doi:10.1111/j.1528-1167.2009.02190.x
Cadeddu C, Deidda M, Mercuro G, Tuveri A, Muroni A, Nocco S, Puligheddu M, Maleci A, Marrosu F (2010) Cardiovascular modulation during vagus nerve stimulation therapy in patients with refractory epilepsy. Epilepsy Res 92:145–152. doi:10.1016/j.eplepsyres.2010.08.012
Jansen K, Vandeput S, Milosevic M, Ceulemans B, Van Huffel S, Brown L, Penders J, Lagae L (2011) Autonomic effects of refractory epilepsy on heart rate variability in children: influence of intermittent vagus nerve stimulation. Dev Med Child Neurol 53:1143–1149. doi:10.1111/j.1469-8749.2011.04103.x
Mulders DM, de Vos CC, Vosman I, van Putten MJ (2015) The effect of vagus nerve stimulation on cardiorespiratory parameters during rest and exercise. Seizure 33:24–28. doi:10.1016/j.seizure.2015.10.004
Garamendi I, Acera M, Agundez M, Galbarriatu L, Marinas A, Pomposo I, Valle E, Palma JA, Gomez-Esteban JC (2017) Cardiovascular autonomic and hemodynamic responses to vagus nerve stimulation in drug-resistant epilepsy. Seizure 45:56–60. doi:10.1016/j.seizure.2016.11.018
Schomer AC, Nearing BD, Schachter SC, Verrier RL (2014) Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy. Epilepsia 55:1996–2002. doi:10.1111/epi.12855
Verrier RL, Nearing BD, Olin B, Boon P (2016) Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial. Epilepsy Behav 62:85–89. doi:10.1016/j.yebeh.2016.06.016
Acknowledgements
We would like to acknowledge the contributions of Dr Iñigo Gabilondo (PhD) of the Biocruces Health Research Institute and Dr Lara Galbarriatu of the Neurosurgery Department of the Cruces University Hospital.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
This study did not receive specific grants from any funding agencies in the public, commercial or non-profit sectors. None of the authors have any conflict of interest to disclose.
Rights and permissions
About this article
Cite this article
Garamendi-Ruiz, I., Gómez-Esteban, J.C. Cardiovascular autonomic effects of vagus nerve stimulation. Clin Auton Res 29, 183–194 (2019). https://doi.org/10.1007/s10286-017-0477-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10286-017-0477-8