Skip to main content
PMC home page
Neurotherapeutics logoLink to Neurotherapeutics
. 2009 Apr;6(2):228–237. doi: 10.1016/j.nurt.2009.01.010

Vagus nerve stimulation in the treatment of refractory epilepsy

Andrew H Milby 1, Casey H Halpern 1, Gordon H Baltuch 1,2,✉
PMCID: PMC5084198  PMID: 19332314

Summary

Many patients with epilepsy suffer from persistent seizures despite maximal anti-epileptic drug therapy. Chronic, intermittent vagus nerve stimulation has been proven to be an effective option for many patients suffering from refractory seizures who are not candidates for surgical resection. Although only a small minority of patients will be entirely seizure-free, vagus nerve stimulation, as an adjunct to medical therapy, may result in significant improvements in quality of life. Vagus nerve stimulation is generally well-tolerated, as device implantation is associated with a low rate of perioperative complications, and the majority of side effects are stimulation-dependent and thus reversible.

Key Words: Vagus nerve stimulation, vagal, epilepsy, seizure

References

  • 1.A global survey on epilepsy surgery, 1980–1990: a report by the Commission on Neurosurgery of Epilepsy, the International League Against Epilepsy. Epilepsia 1997;38:249–255. [DOI] [PubMed]
  • 2.Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–319. doi: 10.1056/NEJM200002033420503. [DOI] [PubMed] [Google Scholar]
  • 3.Terry R, Tarver WB, Zabara J. An implantable neurocybernetic prosthesis system. Epilepsia. 1990;31(suppl 2):S33–37. doi: 10.1111/j.1528-1157.1990.tb05846.x. [DOI] [PubMed] [Google Scholar]
  • 4.Terry RS, Tarver WB, Zabara J. The implantable neurocybernetic prosthesis system. Pacing Clin Electrophysiol. 1991;14:86–93. doi: 10.1111/j.1540-8159.1991.tb04052.x. [DOI] [PubMed] [Google Scholar]
  • 5.Reid SA. Surgical technique for implantation of the neurocybernetic prosthesis. Epilepsia. 1990;31(suppl 2):S38–S39. doi: 10.1111/j.1528-1157.1990.tb05847.x. [DOI] [PubMed] [Google Scholar]
  • 6.Uthman BM, Wilder BJ, Penry JK, et al. Treatment of epilepsy by stimulation of the vagus nerve. Neurology. 1993;43:1338–1345. doi: 10.1212/wnl.43.7.1338. [DOI] [PubMed] [Google Scholar]
  • 7.Penry JK, Dean JC. Prevention of intractable partial seizures by intermittent vagal stimulation in humans: preliminary results. Epilepsia. 1990;31(suppl 2):S40–S43. doi: 10.1111/j.1528-1157.1990.tb05848.x. [DOI] [PubMed] [Google Scholar]
  • 8.Landy HJ, Ramsay RE, Slater J, et al. Vagus nerve stimulation for complex partial seizures: surgical technique, safety, and efficacy. J Neurosurg. 1993;78:26–31. doi: 10.3171/jns.1993.78.1.0026. [DOI] [PubMed] [Google Scholar]
  • 9.Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol. 2002;1:477–482. doi: 10.1016/S1474-4422(02)00220-X. [DOI] [PubMed] [Google Scholar]
  • 10.Shafique S, Dalsing MC. Vagus nerve stimulation therapy for treatment of drug-resistant epilepsy and depression. Perspect Vasc Surg Endovasc Ther. 2006;18:323–327. doi: 10.1177/1531003506297200. [DOI] [PubMed] [Google Scholar]
  • 11.Milby AH, Halpern CH, Baltuch GH. Vagus nerve stimulation for epilepsy and depression. Neurotherapeutics. 2008;5:75–85. doi: 10.1016/j.nurt.2007.10.071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Hancock JC, Hoover DB, Hougland MW. Distribution of muscarinic receptors and acetylcholinesterase in the rat heart. J Auton Nerv Syst. 1987;19:59–66. doi: 10.1016/0165-1838(87)90145-7. [DOI] [PubMed] [Google Scholar]
  • 13.Saper CB, Kibbe MR, Hurley KM, et al. Brain natriuretic peptide-like immunoreactive innervation of the cardiovascular and cerebrovascular systems in the rat. Circ Res. 1990;67:1345–1354. doi: 10.1161/01.res.67.6.1345. [DOI] [PubMed] [Google Scholar]
  • 14.McGregor A, Wheless J, Baumgartner J, et al. Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans. Epilepsia. 2005;46:91–96. doi: 10.1111/j.0013-9580.2005.16404.x. [DOI] [PubMed] [Google Scholar]
  • 15.Tarver WB, George RE, Maschino SE, et al. Clinical experience with a helical bipolar stimulating lead. Pacing Clin Electrophysiol. 1992;15:1545–1556. doi: 10.1111/j.1540-8159.1992.tb02933.x. [DOI] [PubMed] [Google Scholar]
  • 16.Ali II, Pirzada NA, Kanjwal Y, et al. Complete heart block with ventricular asystole during left vagus nerve stimulation for epilepsy. Epilepsy Behav. 2004;5:768–771. doi: 10.1016/j.yebeh.2004.05.008. [DOI] [PubMed] [Google Scholar]
  • 17.Ardesch JJ, Buschman HP, van der Burgh PH, et al. Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Clin Neurol Neurosurg. 2007;109:849–852. doi: 10.1016/j.clineuro.2007.07.024. [DOI] [PubMed] [Google Scholar]
  • 18.Tatum WOT, Moore DB, Stecker MM, et al. Ventricular asystole during vagus nerve stimulation for epilepsy in humans. Neurology. 1999;52:1267–1269. doi: 10.1212/wnl.52.6.1267. [DOI] [PubMed] [Google Scholar]
  • 19.Asconape JJ, Moore DD, Zipes DP, et al. Bradycardia and asystole with the use of vagus nerve stimulation for the treatment of epilepsy: a rare complication of intraoperative device testing. Epilepsia. 1999;40:1452–1454. doi: 10.1111/j.1528-1157.1999.tb02019.x. [DOI] [PubMed] [Google Scholar]
  • 20.George R, Salinsky M, Kuzniecky R, et al. Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994;35:637–643. doi: 10.1111/j.1528-1157.1994.tb02484.x. [DOI] [PubMed] [Google Scholar]
  • 21.Ben-Menachem E, Manon-Espaillat R, Ristanovic R, et al. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994;35:616–626. doi: 10.1111/j.1528-1157.1994.tb02482.x. [DOI] [PubMed] [Google Scholar]
  • 22.Labiner DM, Ahem GL. Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings. Acta Neurol Scand. 2007;115:23–33. doi: 10.1111/j.1600-0404.2006.00732.x. [DOI] [PubMed] [Google Scholar]
  • 23.Henry TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology. 2002;59:S3–S14. doi: 10.1212/wnl.59.6_suppl_4.s3. [DOI] [PubMed] [Google Scholar]
  • 24.Vonck K, Boon P, Van Roost D. Anatomical and physiological basis and mechanism of action of neurostimulation for epilepsy. Acta Neurochir Suppl. 2007;97:321–328. doi: 10.1007/978-3-211-33081-4_35. [DOI] [PubMed] [Google Scholar]
  • 25.Woodbury DM, Woodbury JW. Effects of vagal stimulation on experimentally induced seizures in rats. Epilepsia. 1990;31(suppl 2):S7–S19. doi: 10.1111/j.1528-1157.1990.tb05852.x. [DOI] [PubMed] [Google Scholar]
  • 26.Labiner DM, Schwirtz D, Ahem GL, et al. Shorter pulse width of vagus nerve stimulation is as effective in reducing seizure frequency as standard stimulation and is better tolerated. Epilepsia. 1999;40(suppl 7):141–141. [Google Scholar]
  • 27.Krahl SE, Senanayake SS, Handforth A. Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression in rats. Epilepsia. 2001;42:586–589. doi: 10.1046/j.1528-1157.2001.09700.x. [DOI] [PubMed] [Google Scholar]
  • 28.Carpenter MB. Core text of neuroanatomy. 4th ed. Baltimore: Williams & Wilkins; 1991. [Google Scholar]
  • 29.Steriade M, Contreras D. Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity. J Neurosci. 1995;15:623–642. doi: 10.1523/JNEUROSCI.15-01-00623.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Henry TR, Votaw JR, Pennell PB, et al. Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. Neurology. 1999;52:1166–1173. doi: 10.1212/wnl.52.6.1166. [DOI] [PubMed] [Google Scholar]
  • 31.Vonck K, De Herdt V, Bosman T, et al. Thalamic and limbic involvement in the mechanism of action of vagus nerve stimulation, a SPECT study. Seizure. 2008;17:699–706. doi: 10.1016/j.seizure.2008.05.001. [DOI] [PubMed] [Google Scholar]
  • 32.Zanchetti A, Wang SC, Moruzzi G. The effect of vagal afferent stimulation on the EEG pattern of the cat. Electroencephalogr Clin Neurophysiol. 1952;4:357–361. doi: 10.1016/0013-4694(52)90064-3. [DOI] [PubMed] [Google Scholar]
  • 33.Chase MH, Nakamura Y, Clemente CD, et al. Afferent vagal stimulation: neurographic correlates of induced EEG synchronization and desynchronization. Brain Res. 1967;5:236–249. doi: 10.1016/0006-8993(67)90089-3. [DOI] [PubMed] [Google Scholar]
  • 34.Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia. 1998;39:677–686. doi: 10.1111/j.1528-1157.1998.tb01151.x. [DOI] [PubMed] [Google Scholar]
  • 35.Valdes-Cruz A, Magdaleno-Madrigal VM, Martinez-Vargas D, et al. Long-term changes in sleep and electroencephalographic activity by chronic vagus nerve stimulation in cats. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:828–834. doi: 10.1016/j.pnpbp.2007.12.020. [DOI] [PubMed] [Google Scholar]
  • 36.Koo B. EEG changes with vagus nerve stimulation. J Clin Neurophysiol. 2001;18:434–441. doi: 10.1097/00004691-200109000-00008. [DOI] [PubMed] [Google Scholar]
  • 37.Murphy JV. Left vagal nerve stimulation in children with medically refractory epilepsy. The Pediatric VNS Study Group. J Pediatr. 1999;134:563–566. doi: 10.1016/S0022-3476(99)70241-6. [DOI] [PubMed] [Google Scholar]
  • 38.Lundgren J, Amark P, Blennow G, et al. Vagus nerve stimulation in 16 children with refractory epilepsy. Epilepsia. 1998;39:809–813. doi: 10.1111/j.1528-1157.1998.tb01173.x. [DOI] [PubMed] [Google Scholar]
  • 39.Vonck K, Boon P, D’Have M, et al. Long-term results of vagus nerve stimulation in refractory epilepsy. Seizure. 1999;8:328–334. doi: 10.1053/seiz.1999.0299. [DOI] [PubMed] [Google Scholar]
  • 40.Hamberger A, Haglid K, Nystrom B, et al. Co-variation of free amino acids in human epileptogenic cortex. Neurochem Res. 1993;18:519–25. doi: 10.1007/BF00967256. [DOI] [PubMed] [Google Scholar]
  • 41.Ben-Menachem E, Hamberger A, Hedner T, et al. Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Res. 1995;20:221–227. doi: 10.1016/0920-1211(94)00083-9. [DOI] [PubMed] [Google Scholar]
  • 42.Naritoku DK, Terry WJ, Helfert RH. Regional induction of fos immunoreactivity in the brain by anticonvulsant stimulation of the vagus nerve. Epilepsy Res. 1995;22:53–62. doi: 10.1016/0920-1211(95)00035-9. [DOI] [PubMed] [Google Scholar]
  • 43.Krahl SE, Clark KB, Smith DC, et al. Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia. 1998;39:709–714. doi: 10.1111/j.1528-1157.1998.tb01155.x. [DOI] [PubMed] [Google Scholar]
  • 44.Cunningham JT, Mifflin SW, Gould GG, et al. Induction of c-Fos and DeltaFosB immunoreactivity in rat brain by vagal nerve stimulation. Neuropsychopharmacology. 2008;33:1884–1895. doi: 10.1038/sj.npp.1301570. [DOI] [PubMed] [Google Scholar]
  • 45.Meldrum B. Amino acid neurotransmitters and new approaches to anticonvulsant drug action. Epilepsia. 1984;25(suppl 2):S140–S149. doi: 10.1111/j.1528-1157.1984.tb05646.x. [DOI] [PubMed] [Google Scholar]
  • 46.Uthman BM, Wilder BJ, Hammond EJ, et al. Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures. Epilepsia. 1990;31(suppl 2):S44–S50. doi: 10.1111/j.1528-1157.1990.tb05849.x. [DOI] [PubMed] [Google Scholar]
  • 47.Wilder BJ, Uthman BM, Hammond EJ. Vagal stimulation for control of complex partial seizures in medically refractory epileptic patients. Pacing Clin Electrophysiol. 1991;14:108–115. doi: 10.1111/j.1540-8159.1991.tb04054.x. [DOI] [PubMed] [Google Scholar]
  • 48.Murphy JV, Hornig G, Schallert G. Left vagal nerve stimulation in children with refractory epilepsy. Preliminary observations. Arch Neurol. 1995;52:886–889. doi: 10.1001/archneur.1995.00540330064016. [DOI] [PubMed] [Google Scholar]
  • 49.Labar D, Nikolov B, Tarver B, et al. Vagus nerve stimulation for symptomatic generalized epilepsy: a pilot study. Epilepsia. 1998;39:201–205. doi: 10.1111/j.1528-1157.1998.tb01359.x. [DOI] [PubMed] [Google Scholar]
  • 50.A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. The Vagus Nerve Stimulation Study Group. Neurology 1995;45:224–230. [DOI] [PubMed]
  • 51.Handforth A, DeGiorgio CM, Schachter SC, et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology. 1998;51:48–55. doi: 10.1212/wnl.51.1.48. [DOI] [PubMed] [Google Scholar]
  • 52.Amar AP, DeGiorgio CM, Tarver WB, et al. Long-term multi-center experience with vagus nerve stimulation for intractable partial seizures: results of the XE5 trial. Stereotact Funct Neurosurg. 1999;73:104–108. doi: 10.1159/000029764. [DOI] [PubMed] [Google Scholar]
  • 53.Salinsky MC, Uthman BM, Ristanovic RK, et al. Vagus nerve stimulation for the treatment of medically intractable seizures. Results of a 1-year open-extension trial. Vagus Nerve Stimulation Study Group. Arch Neurol. 1996;53:1176–1180. doi: 10.1001/archneur.1996.00550110128021. [DOI] [PubMed] [Google Scholar]
  • 54.Morris GL, Mueller WM. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology. 1999;53:1731–1735. doi: 10.1212/wnl.53.8.1731. [DOI] [PubMed] [Google Scholar]
  • 55.Kawai K, Shimizu H, Maehara T, et al. Outcome of long-term vagus nerve stimulation for intractable epilepsy. Neurol Med Chir (Tokyo) 2002;42:481–489. doi: 10.2176/nmc.42.481. [DOI] [PubMed] [Google Scholar]
  • 56.Scherrmann J, Hoppe C, Kral T, et al. Vagus nerve stimulation: clinical experience in a large patient series. J Clin Neurophysiol. 2001;18:408–414. doi: 10.1097/00004691-200109000-00004. [DOI] [PubMed] [Google Scholar]
  • 57.Spanaki MV, Allen LS, Mueller WM, et al. Vagus nerve stimulation therapy: 5-year or greater outcome at a university-based epilepsy center. Seizure. 2004;13:587–590. doi: 10.1016/j.seizure.2004.01.009. [DOI] [PubMed] [Google Scholar]
  • 58.Labar D. Vagus nerve stimulation for 1 year in 269 patients on unchanged antiepileptic drugs. Seizure. 2004;13:392–398. doi: 10.1016/j.seizure.2003.09.009. [DOI] [PubMed] [Google Scholar]
  • 59.Tatum WO, Johnson KD, Goff S, et al. Vagus nerve stimulation and drug reduction. Neurology. 2001;56:561–563. doi: 10.1212/wnl.56.4.561. [DOI] [PubMed] [Google Scholar]
  • 60.Boon P, Vonck K, Vandekerckhove T, et al. Vagus nerve stimulation for medically refractory epilepsy; efficacy and cost-benefit analysis. Acta Neurochir (Wien) 1999;141:447–452. doi: 10.1007/s007010050324. [DOI] [PubMed] [Google Scholar]
  • 61.McLachlan RS, Sadler M, Pillay N, et al. Quality of life after vagus nerve stimulation for intractable epilepsy: is seizure control the only contributing factor? Eur Neurol. 2003;50:16–19. doi: 10.1159/000070853. [DOI] [PubMed] [Google Scholar]
  • 62.McGlone J, Valdivia I, Penner M, et al. Quality of life and memory after vagus nerve stimulator implantation for epilepsy. Can J Neurol Sci. 2008;35:287–296. doi: 10.1017/s0317167100008854. [DOI] [PubMed] [Google Scholar]
  • 63.Homig GW, Murphy JV, Schallert G, et al. Left vagus nerve stimulation in children with refractory epilepsy: an update. South Med J. 1997;90:484–488. doi: 10.1097/00007611-199705000-00003. [DOI] [PubMed] [Google Scholar]
  • 64.Alexopoulos AV, Kotagal P, Loddenkemper T, et al. Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy. Seizure. 2006;15:491–503. doi: 10.1016/j.seizure.2006.06.002. [DOI] [PubMed] [Google Scholar]
  • 65.Patwardhan RV, Stong B, Bebin EM, et al. Efficacy of vagal nerve stimulation in children with medically refractory epilepsy. Neurosurgery. 2000;47:1353–1357. doi: 10.1097/00006123-200012000-00016. [DOI] [PubMed] [Google Scholar]
  • 66.Hosain S, Nikalov B, Harden C, et al. Vagus nerve stimulation treatment for Lennox-Gastaut syndrome. J Child Neurol. 2000;15:509–512. doi: 10.1177/088307380001500803. [DOI] [PubMed] [Google Scholar]
  • 67.Frost M, Gates J, Helmers SL, et al. Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia. 2001;42:1148–1152. doi: 10.1046/j.1528-1157.2001.23900.x. [DOI] [PubMed] [Google Scholar]
  • 68.You SJ, Kang HC, Ko TS, et al. Comparison of corpus callosotomy and vagus nerve stimulation in children with Lennox-Gastaut syndrome. Brain Dev. 2008;30:195–199. doi: 10.1016/j.braindev.2007.07.013. [DOI] [PubMed] [Google Scholar]
  • 69.Major P, Thiele EA. Vagus nerve stimulation for intractable epilepsy in tuberous sclerosis complex. Epilepsy Behav. 2008;13:357–360. doi: 10.1016/j.yebeh.2008.04.001. [DOI] [PubMed] [Google Scholar]
  • 70.De Herdt V, Waterschoot L, Vonck K, et al. Vagus nerve stimulation for refractory status epilepticus. Eur J Paediatr Neurol 2008 Jun 26. [Epub ahead of print]. [DOI] [PubMed]
  • 71.Zamponi N, Rychlicki F, Corpaci L, et al. Vagus nerve stimulation (VNS) is effective in treating catastrophic 1 epilepsy in very young children. Neurosurg Rev. 2008;31:291–297. doi: 10.1007/s10143-008-0134-8. [DOI] [PubMed] [Google Scholar]
  • 72.Danielsson S, Viggedal G, Gillberg C, et al. Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight pediatric patients with autism spectrum disorders: a prospective 2-year follow-up study. Epilepsy Behav. 2008;12:298–304. doi: 10.1016/j.yebeh.2007.10.007. [DOI] [PubMed] [Google Scholar]
  • 73.Hallböök T, Lundgren J, Stjemqvist K, et al. Vagus nerve stimulation in 15 children with therapy resistant epilepsy; its impact on cognition, quality of life, behavior and mood. Seizure. 2005;14:504–513. doi: 10.1016/j.seizure.2005.08.007. [DOI] [PubMed] [Google Scholar]
  • 74.Sherman EM, Connolly MB, Slick DJ, et al. Quality of life and seizure outcome after vagus nerve stimulation in children with intractable epilepsy. J Child Neurol. 2008;23:991–998. doi: 10.1177/0883073808315417. [DOI] [PubMed] [Google Scholar]
  • 75.Smyth MD, Tubbs RS, Bebin EM, et al. Complications of chronic vagus nerve stimulation for epilepsy in children. J Neurosurg. 2003;99:500–503. doi: 10.3171/jns.2003.99.3.0500. [DOI] [PubMed] [Google Scholar]
  • 76.MacDonald J, Couldwell WT. Revision of vagal nerve stimulator electrodes: technical approach. Acta Neurochir (Wien) 2004;146:567–570. doi: 10.1007/s00701-004-0246-z. [DOI] [PubMed] [Google Scholar]
  • 77.Ramsay RE, Uthman BM, Augustinsson LE, et al. Vagus nerve stimulation for treatment of partial seizures: 2. Safety, side effects, and tolerability. First International Vagus Nerve Stimulation Study Group. Epilepsia. 1994;35:627–636. doi: 10.1111/j.1528-1157.1994.tb02483.x. [DOI] [PubMed] [Google Scholar]
  • 78.Hatton KW, McLarney JT, Pittman T, et al. Vagal nerve stimulation: overview and implications for anesthesiologists. Anesth Analg. 2006;103:1241–1249. doi: 10.1213/01.ane.0000244532.71743.c6. [DOI] [PubMed] [Google Scholar]
  • 79.Kim W, Clancy RR, Liu GT. Horner syndrome associated with implantation of a vagus nerve stimulator. Am J Ophthalmol. 2001;131:383–384. doi: 10.1016/S0002-9394(00)00782-0. [DOI] [PubMed] [Google Scholar]
  • 80.Lundy DS, Casiano RR, Landy HJ, et al. Effects of vagal nerve stimulation on laryngeal function. J Voice. 1993;7:359–364. doi: 10.1016/S0892-1997(05)80259-0. [DOI] [PubMed] [Google Scholar]
  • 81.Zumsteg D, Jenny D, Wieser HG. Vocal cord adduction during vagus nerve stimulation for treatment of epilepsy. Neurology. 2000;54:1388–1389. doi: 10.1212/wnl.54.6.1388. [DOI] [PubMed] [Google Scholar]
  • 82.Shaffer MJ, Jackson CE, Szabo CA, et al. Vagal nerve stimulation: clinical and electrophysiological effects on vocal fold function. Ann Otol Rhinol Laryngol. 2005;114:7–14. doi: 10.1177/000348940511400103. [DOI] [PubMed] [Google Scholar]
  • 83.Shaw GY, Sechtem P, Searl J, et al. Predictors of laryngeal complications in patients implanted with the Cyberonics vagal nerve stimulator. Ann Otol Rhinol Laryngol. 2006;115:260–267. doi: 10.1177/000348940611500403. [DOI] [PubMed] [Google Scholar]
  • 84.Ebben MR, Sethi NK, Conte M, et al. Vagus nerve stimulation, sleep apnea, and CPAP titration. J Clin Sleep Med. 2008;4:471–473. [PMC free article] [PubMed] [Google Scholar]
  • 85.Hsieh T, Chen M, McAfee A, et al. Sleep-related breathing disorder in children with vagal nerve stimulators. Pediatr Neurol. 2008;38:99–103. doi: 10.1016/j.pediatrneurol.2007.09.014. [DOI] [PubMed] [Google Scholar]
  • 86.Papathanasion ES, Papacostas SS. Sleep-related breathing disorders in children with vagal nerve stimulators. Pediatr Neurol. 2008;39:142–142. doi: 10.1016/j.pediatrneurol.2008.04.009. [DOI] [PubMed] [Google Scholar]
  • 87.Banzett RB, Guz A, Paydarfar D, et al. Cardiorespiratory variables and sensation during stimulation of the left vagus in patients with epilepsy. Epilepsy Res. 1999;35:1–11. doi: 10.1016/S0920-1211(98)00126-0. [DOI] [PubMed] [Google Scholar]
  • 88.Stemper B, Devinsky O, Haendl T, et al. Effects of vagus nerve stimulation on cardiovascular regulation in patients with epilepsy. Acta Neurol Scand. 2008;117:231–236. doi: 10.1111/j.1600-0404.2007.00944.x. [DOI] [PubMed] [Google Scholar]
  • 89.DeGiorgio CM, Schachter SC, Handforth A, et al. Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia. 2000;41:1195–1200. doi: 10.1111/j.1528-1157.2000.tb00325.x. [DOI] [PubMed] [Google Scholar]
  • 90.Amark P, Stodberg T, Wallstedt L. Late onset bradyarrhythmia during vagus nerve stimulation. Epilepsia. 2007;48:1023–1024. doi: 10.1111/j.1528-1167.2007.01023.x. [DOI] [PubMed] [Google Scholar]
  • 91.Annegers JF, Coan SP, Hauser WA, et al. Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death. Epilepsia. 2000;41:549–553. doi: 10.1111/j.1528-1157.2000.tb00208.x. [DOI] [PubMed] [Google Scholar]
  • 92.Wakai S, Kotagal P. Vagus nerve stimulation for children and adolescents with intractable epilepsies. Pediatr Int. 2001;43:61–65. doi: 10.1046/j.1442-200x.2001.01326.x. [DOI] [PubMed] [Google Scholar]
  • 93.Farooqui S, Boswell W, Hemphill JM, et al. Vagus nerve stimulation in pediatric patients with intractable epilepsy: case series and operative technique. Am Surg. 2001;67:119–121. [PubMed] [Google Scholar]
  • 94.Majoie HJ, Berfelo MW, Aldenkamp AP, et al. Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study. Seizure. 2005;14:10–18. doi: 10.1016/j.seizure.2004.02.003. [DOI] [PubMed] [Google Scholar]
  • 95.Helmers SL, Wheless JW, Frost M, et al. Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study. J Child Neurol. 2001;16:843–848. doi: 10.1177/08830738010160111101. [DOI] [PubMed] [Google Scholar]
  • 96.Aldenkamp AP, Majoie HJ, Berfelo MW, et al. Long-term effects of 24-month treatment with vagus nerve stimulation on behaviour in children with Lennox-Gastaut syndrome. Epilepsy Behav. 2002;3:475–479. doi: 10.1016/S1525-5050(02)00517-6. [DOI] [PubMed] [Google Scholar]
  • 97.Chavel SM, Westerveld M, Spencer S. Long-term outcome of vagus nerve stimulation for refractory partial epilepsy. Epilepsy Behav. 2003;4:302–309. doi: 10.1016/S1525-5050(03)00109-4. [DOI] [PubMed] [Google Scholar]
  • 98.Hui AC, Lam JM, Wong KS, et al. Vagus nerve stimulation for refractory epilepsy: long term efficacy and side-effects. Chin Med J (Engl) 2004;117:58–61. [PubMed] [Google Scholar]
  • 99.Holmes MD, Silbergeld DL, Drouhard D, et al. Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes. Seizure. 2004;13:340–345. doi: 10.1016/j.seizure.2003.09.002. [DOI] [PubMed] [Google Scholar]
  • 100.Huf RL, Mamelak A, Kneedy-Cayem K. Vagus nerve stimulation therapy: 2-year prospective open-label study of 40 subjects with refractory epilepsy and low IQ who are living in long-term care facilities. Epilepsy Behav. 2005;6:417–423. doi: 10.1016/j.yebeh.2005.01.009. [DOI] [PubMed] [Google Scholar]
  • 101.Rychlicki F, Zamponi N, Trignani R, et al. Vagus nerve stimulation: clinical experience in drug-resistant pediatric epileptic patients. Seizure. 2006;15:483–490. doi: 10.1016/j.seizure.2006.06.001. [DOI] [PubMed] [Google Scholar]
  • 102.Saneto RP, Sotero de Menezes MA, Ojemann JG, et al. Vagus nerve stimulation for intractable seizures in children. Pediatr Neurol. 2006;35:323–326. doi: 10.1016/j.pediatrneurol.2006.06.005. [DOI] [PubMed] [Google Scholar]
  • 103.Ardesch JJ, Buschman HP, Wagener-Schimmel LJ, et al. Vagus nerve stimulation for medically refractory epilepsy: a long-term follow-up study. Seizure. 2007;16:579–585. doi: 10.1016/j.seizure.2007.04.005. [DOI] [PubMed] [Google Scholar]
  • 104.De Herdt V, Boon P, Ceulemans B, et al. Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol. 2007;11:261–269. doi: 10.1016/j.ejpn.2007.01.008. [DOI] [PubMed] [Google Scholar]
  • 105.Kostov H, Larsson PG, Roste GK. Is vagus nerve stimulation a treatment option for patients with drug-resistant idiopathic generalized epilepsy? Acta Neurol Scand Suppl. 2007;187:55–58. doi: 10.1111/j.1600-0404.2007.00848.x. [DOI] [PubMed] [Google Scholar]
  • 106.Amar AP, Apuzzo ML, Liu CY. Vagus nerve stimulation therapy after failed cranial surgery for intractable epilepsy: results from the vagus nerve stimulation therapy patient outcome registry. Neurosurgery. 2008;62(suppl 2):506–513. doi: 10.1227/01.neu.0000316253.54651.5e. [DOI] [PubMed] [Google Scholar]
  • 107.Rossignol E, Lortie A, Thomas T, et al. Vagus nerve stimulation in pediatric epileptic syndromes. Seizure. 2009;18:34–37. doi: 10.1016/j.seizure.2008.06.010. [DOI] [PubMed] [Google Scholar]

Articles from Neurotherapeutics are provided here courtesy of Elsevier

RESOURCES