Vagus Nerve Stimulation for Epilepsy


Epilepsy refractory to medical management with antiepileptic drugs continues to pose a problem to clinicians as well as to patients struggling with the limitations imposed on them by their condition. Vagus nerve stimulation (VNS) is a safe and effective surgical treatment for patients with refractory epilepsy who are not candidates for surgery involving resection of temporal lobe structures or epileptogenic foci. Even in those with failed surgical resection, VNS may still provide some benefit, though this must be elucidated. Although the mechanism is still poorly understood, several theories exist as to how VNS exerts its antiepileptic effects and several clinical trials have demonstrated its efficacy and safety. VNS has become the most widely used nonpharmacological therapy for the treatment of drug‐resistant epilepsy.

Key Concepts:

  • VNS is a safe and effective treatment for patients with refractory epilepsy who are not candidates for surgery involving resection of temporal lobe structures or epileptogenic foci and possibly those that have failed to respond to surgical correction.

  • Increased reduction of seizure frequency with VNS occurs over time resulting in decreased need for antiepileptic drugs with increased duration of stimulation.

  • In addition to the benefit of seizure reduction, data exists to support improved subjective quality of life scores with use of VNS.

  • Although the insertion of the VNS unit is a surgical procedure, it can often be performed as an outpatient surgery and thus does not require inpatient hospitalization as resection‐based epilepsy surgery does.

  • VNS is generally well tolerated with side effects including mild and including voice alteration and throat pain.

Keywords: vagus nerve stimulation; refractory epilepsy; epilepsy surgery; epilepsy

Figure 1.

Comparison of the newer implant model (103) compared to prior models. Average battery life is 6 years. Used with permission from Cyberonics, Inc. © 2006 Cyberonics, Inc. All rights reserved.



Agostini E, Chinnock JE, Daly MS and Murray JG (1957) Functional and histological studies of the vagus nerve and its branches to the heart, lungs, and abdominal viscera in the cat. Journal of Physiology 135: 182–205.

Amar AP, Apuzzo ML and Liu LY (2008) Vagus nerve stimulation therapy after failed cranial surgery for intractable epilepsy; results from the vagus nerve stimulation therapy patient outcome registry. Neurosurgery 62 (suppl. 2): 506–513.

Amar AP, Heck CN, Levy ML et al. (1998) An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery 43: 1265–1280.

Bailey P and Bremer FA (1938) A sensory cortical representation of the vagus nerve with a note on the effects of low pressure on the cortical electrogram. Journal of Neurophysiology 1: 405–412.

Benbadis SR (2005a) Practical management issues for idiopathic generalized epilepsies. Epilepsia 46(suppl. 9): 125–132.

Benbadis SR (2005b) Psychogenic non‐epileptic seizures. In: Wyllie E (ed.) The Treatment of Epilepsy: Principles and Practice, 4th edn, pp. 623–630. Philadelphia, Lippincott: Williams and Wilkins.

Benbadis SR, Nyhenhuis J, Tatum WO 4th et al. (2001) MRI of the brain is safe in patients implanted with the vagus nerve stimulator. Seizure 10(7): 512–515.

Benbadis SR, O'Neill E, Tatum WO and Heriaud L (2004) Outcome of prolonged EEG‐video monitoring at a typical referral epilepsy center. Epilepsia 45: 1150–1153.

Benbadis SR, Tatum WO and Vale FL (2000) When drugs don't work: an algorithmic approach to medically intractable epilepsy. Neurology 5: 1780–1784.

Ben‐Menachem E, Manon‐Espaillat R, Ristanovic R et al. (1994) Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia 35(3): 616–626.

DeGiorgio C, Heck C, Bunch S et al. (2005) Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms. Neurology 65(2): 317–319.

DeGiorgio CM, Schachter SC, Handforth A et al. (2000) Prospective long‐term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 41(9): 1195–1200.

DeGiorgio CM, Thompson J, Lewis P et al. (2001) Vagus nerve stimulation: analysis of device parameters in 154 patients during the long‐term XE5 study. Epilepsia 42: 1017–1020.

Dell P and Olson R (1951) Thalamic, cortical and cerebellar projections of vagal visceral afferences. Comptes rendus des séances de la Société de biologie et de ses filiales 145(13–14): 1084–1088.

Elliott RE, Rodgers SD, Bassani L et al. (2011) Vagus nerve stimulation for children with treatment‐resistant epilepsy: a consecutive series of 141 cases. Journal of Neurosurgery: Pediatrics 7(5): 491–500.

Fernandez‐Guardiola A, Martinez A, Valdes‐Cruz A et al. (2001) Vagus nerve prolonged stimulation in cats: effects on epileptogenesis (amygdala electrical kindling): behavioral and electrographic changes. Epilepsia 42: 822–829.

Foley JO and Dubois F (1937) Quantitative studies of the vagus nerve in the cat. I. The ratio of sensory and motor fibers. Journal of Comparative Neurology 67: 49–97.

Handforth A, DeGiorgio CM, Schachter SC et al. (1998) Vagus nerve stimulation therapy for partial‐onset seizures: a randomized active‐control trial. Neurology 51(1): 48–55.

Henry TR (2003) Vagus nerve stimulation for epilepsy: anatomical, experimental and mechanistic investigations. In: Schachter SC and Schmidt D (eds) Vagus Nerve Stimulation, 2nd edn. London: Martin Dunitz Group.

Hosain S, Nikalov B, Harden C et al. (2000) Vagus nerve stimulation treatment for Lennox‐Gastaut syndrome. Journal of Child Neurology 15: 509–512.

Hsieh T, Chen M, McAfee A and Kifle Y (2008) Sleep‐related breathing disorder in children with vagal nerve stimulators. Pediatric Neurology 38(2): 99–103.

Kemeny AA (2003) Surgical technique in vagus nerve stimulation. In: Schachter SC and Schmidt D (eds) Vagus Nerve Stimulation, 2nd edn, pp. 36–48. London: Martin Dunitz.

Lockard JS, Congdon WC and DuCharme LL (1990) Feasibility and safety of vagal stimulation in the monkey model. Epilepsia 31(suppl. 2): S20–S26.

Majoie HJ, Rijkers K, Berfelo MW et al. (2011) Vagus nerve stimulation in refractory epilepsy: effects on pro‐ and anti‐inflammatory cytokines in peripheral blood. Neuroimmunomodulation 18(1): 52–56

McLachlan RS (1993) Suppression of interictal spikes and seizures by stimulation of the vagus nerve. Epilepsia 34(5): 918–923.

Morris GL 3rd, Gloss D, Buchhalter J et al. (2013) Evidence‐based guideline update: vagus nerve stimulation for the treatment of epilepsy. Neurology 81: 1453–1459.

Morris GL and Mueller WM (1999) Long‐term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01‐E05. Neurology 53(8): 1731–1735.

Murphy JV (1999) Left vagal nerve stimulation in children with medically refractory epilepsy. The Pedriatic VNS Study Group. Journal of Pediatrics 134: 563–566.

Naritoku DK, Terry WJ and Helfert RH (1995) Regional induction of fos immunoreactivity in the brain by anticonvulsant stimulation of the vagus nerve. Epilepsy Research 22: 53–62.

Ng M and Devinsky O (2004) Vagus nerve stimulation for refractory idiopathic generalised epilepsy. Seizure 13: 176–178.

Peijing R, Aihua L, Jianguo Z et al. (2014) An alternative therapy for drug‐resistant epilepsy: transcutaneous auricular vagus nerve stimulation. Chinese Medical Journal 127(2): 300–304.

Penry JK and Dean JC (1990) Prevention of intractable partial seizures by intermittent vagal stimulation in humans: preliminary results. Epilepsia 31(suppl. 2): S40–S43.

Rafael H and Moromizato P (1998) Vagus nerve stimulation (VNS) may be useful in treating patients with symptomatic generalized epilepsy. Epilepsia 39: 1018.

Reid SA (1990) Surgical technique for implantation of the neurocybernetic prosthesis. Epilepsia 31(suppl. 2): S38–S39.

Saneto RP, Sotero de Menezes MA, Ojemann JG et al. (2006) Vagus nerve stimulation for intractable seizures in children. Pediatric Neurology 35(5): 323–326.

Shen H, Fuchino Y, Miyamoto D, Nomura H and Matsuki D (2012) Vagus nerve stimulation enhances perforant path‐CA3 synaptic transmission via the activation of β‐adrenergic receptors and the locus coeruleus. International Journal of Neuropsychopharmacology 15(4): 523–530

Tatum WO, Johnson KD, Goff S, Ferreira JA and Vale FL (2001) Vagus nerve stimulation and drug reduction. Neurology 56(4): 561–563.

Tatum WO, Moore DB, Stecker MM et al. (1999) Ventricular asystole during vagus nerve stimulation for epilepsy in humans. Neurology 52: 1267–1269.

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.

Uthman BM, Reichl AM, Dean JC et al. (2004) Effectiveness of vagus nerve stimulation in epilepsy patients: a 12‐year observation. Neurology 63(6): 1124–1126.

Vale FL, Ahmadian A, Youssef AS, Tatum WO and Benbadis SR (2011) Long‐term outcome of vagus nerve stmulation therapy after failed epilepsy surgery. Seizure 20: 244–248.

Zabara J (1985a) Peripheral control of hypersynchronous discharge in epilepsy. Electroencephalography and Clinical Neurophysiology 61: S162.

Zabara J (1985b) Time course of seizure control to brief repetitive stimuli. Epilepsia 26: 518.

Further Reading

Rielo D and Benbadis SR (2007) Vagus nerve stimulation. eMedicine Journal [serial online].

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Haas, Alexander M, Benbadis, Selim R, and Vale, Fernando(Oct 2014) Vagus Nerve Stimulation for Epilepsy. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020285.pub2]