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. 2022 Jul 14;7(7):CD002896.
doi: 10.1002/14651858.CD002896.pub3.

Vagus nerve stimulation for focal seizures

Mariangela Panebianco  1 , Alexandra Rigby  1 , Anthony G Marson  1   2   3
Affiliations

Vagus nerve stimulation for focal seizures

Mariangela Panebianco et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator.

Objectives: To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy.

Search methods: For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform.

Selection criteria: We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery.

Data collection and analysis: We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood

Main results: We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes.

Authors' conclusions: VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.

Trial registration: ClinicalTrials.gov NCT03062514.

PubMed Disclaimer

Conflict of interest statement

MP: none known AR: none known AGM: a consortium of pharmaceutical companies (GSK, EISAI, UCB Pharma) funded the National Audit of Seizure Management in Hospitals (NASH) through grants paid to the University of Liverpool. Professor Marson is funded in part by the NIHR Applied Research Collaboration, North West Coast (NIHR ARC NWC). Professor Marson is a National Institute for Health and Care Research (NIHR) Senior Investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care. Professor Marson is the Co‐ordinating Editor of the Cochrane Epilepsy Group; however, he was not involved in the editorial process of this review update.

Figures

1
1
Study flow diagram (reflecting results of the search carried out on 3 March 2022)
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: High versus low stimulation, Outcome 1: 50% responders
1.2
1.2. Analysis
Comparison 1: High versus low stimulation, Outcome 2: 50% responders – worst‐case scenario
1.3
1.3. Analysis
Comparison 1: High versus low stimulation, Outcome 3: 50% responders – best‐case scenario
1.4
1.4. Analysis
Comparison 1: High versus low stimulation, Outcome 4: Withdrawals
1.5
1.5. Analysis
Comparison 1: High versus low stimulation, Outcome 5: Voice alteration or hoarseness
1.6
1.6. Analysis
Comparison 1: High versus low stimulation, Outcome 6: Cough
1.7
1.7. Analysis
Comparison 1: High versus low stimulation, Outcome 7: Dyspnoea
1.8
1.8. Analysis
Comparison 1: High versus low stimulation, Outcome 8: Pain
1.9
1.9. Analysis
Comparison 1: High versus low stimulation, Outcome 9: Paraesthesias
1.10
1.10. Analysis
Comparison 1: High versus low stimulation, Outcome 10: Nausea
1.11
1.11. Analysis
Comparison 1: High versus low stimulation, Outcome 11: Headache
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References

References to studies included in this review

DeGiorgio 2005 {published data only}
    1. DeGiorgio C, Heck C, Bunch S, Britton J, Green P, Lancman M, et al. Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms. Neurology 2005;65(2):317-9. [DOI: 10.1212/01.wnl.0000168899.11598.00] [PMID: ] - DOI - PubMed
Handforth 1998 {published data only}
    1. Amar AP, Heck C, Levy M, Smith T, DeGiorgio CM, Oviedo S, et al. An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique and outcome. Neurosurgery 1998;43(6):1265-76. [DOI: 10.1097/00006123-199812000-00001] [PMID: ] - DOI - PubMed
    1. Dodrill CB, Morris GL. Effects of vagal nerve stimulation on cognition and quality of life in epilepsy. Epilepsy & Behavior 2001;2(1):46-53. [DOI: 10.1006/ebeh.2000.0148] [PMID: ] - DOI - PubMed
    1. Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, et al. Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 1998;51(1):48-55. [DOI: 10.1212/wnl.51.1.48] [PMID: ] - DOI - PubMed
Klinkenberg 2012 {published data only}
    1. Aalbers MW, Klinkenberg S, Rijkers K, Verschuure P, Kessels A, Aldenkamp A, et al. The effects of vagus nerve stimulation on pro- and anti-inflammatory cytokines in children with refractory epilepsy: an exploratory study. Neuroimmunomodulation 2012;19(6):352-8. [DOI: 10.1159/000341402] [PMID: ] - DOI - PubMed
    1. Klinkenberg S, Aalbers MW, Vles JSH, Cornips EMJ, Rijkers K, Leenen L, et al. Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial. Developmental Medicine & Child Neurology 2012;54(9):855-61. [DOI: 10.1111/j.1469-8749.2012.04305.x] [PMID: ] - DOI - PubMed
    1. Klinkenberg S, Van den Borne CJ, Aalbers MW, Verschuure P, Kessels AG, Leenen L, et al. The effects of vagus nerve stimulation on tryptophan metabolities in children with intractable epilepsy. Epilepsy & Behavior 2014;37:133-8. [DOI: 10.1016/j.yebeh.2014.06.001] [PMID: ] - DOI - PubMed
Michael 1993 {published data only}
    1. Michael JE, Wegener K, Barners DW. Vagus nerve stimulation for intractable seizures: one year follow-up. Journal of Neuroscience Nursing 1993;25(6):362-6. [DOI: 10.1097/01376517-199312000-00007] [PMID: ] - DOI - PubMed
VNS Study Group 1995 {published data only}
    1. Ben-Menachem E, Hamberger A, Hedner T, Hammond EJ, Uthman BM, Slater J, et al. Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Research 1995;20(3):221-7. [DOI: 10.1016/0920-1211(94)00083-9] [PMID: ] - DOI - PubMed
    1. Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W, et al. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. Epilepsia 1994;35(3):616-26. [DOI: 10.1111/j.1528-1157.1994.tb02482.x] [PMID: ] - DOI - PubMed
    1. Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE. Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Research 2000;42(2-3):203-10. [DOI: 10.1016/s0920-1211(00)00181-9] [PMID: ] - DOI - PubMed
    1. Holder LK, Wernicke JF, Tarver WB. Treatment of refractory partial seizures: preliminary results of a controlled study. Pacing & Clinical Electrophysiology 1992;15(10 Pt 2):1557-71. [DOI: 10.1111/j.1540-8159.1992.tb02934.x] [PMID: ] - DOI - PubMed
    1. Lötvall J, Lunde H, Augustinson LE, Hedner T, Svedmyr N, Ben-Menachem E. Airway effects of direct left-sided cervical vagal stimulation in patients with complex partial seizures. Epilepsy Research 1994;18(2):149-54. [DOI: 10.1016/0920-1211(94)90007-8] [PMID: ] - DOI - PubMed

References to studies excluded from this review

Bauer 2016 {published data only}
    1. Bauer S, Baier H, Baumgartner C, Bohlmann K, Fauser S, Graf W, et al. Transcutaneous vagus nerve stimulation (tVNS) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial (cMPsE02). Brain Stimulation 2014;9(3):356-63. [DOI: 10.1016/j.brs.2015.11.003] - DOI - PubMed
Boon 2015 {published data only}
    1. Boon P, Vonck K, Van Rijckevorsel K, El Tahry R, Elger CE, Mullatti N. A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation. Seizure 2015;32:52-61. [DOI: 10.1016/j.seizure.2015.08.011] [PMID: ] - DOI - PubMed
Brodtkorb 2019 {published data only}
    1. Brodtkorb E, Samsonsen C, Jorgensen JV, Helde G. Epilepsy patients with and without perceived benefit from vagus nerve stimulation. Seizure 2019;72:28-32. - PubMed
Clarke 1997 {published data only}
    1. Clarke BM, Upton ARM, Griffin H, Fitzpatrick D, DeNardis M. Seizure control after stimulation of the vagus nerve: clinical outcome measures. Canadian Journal of Neurological Sciences 1997;24(3):222-5. [PMID: ] - PubMed
Colicchio 2010 {published data only}
    1. Colicchio G, Policicchio D, Barbati G, Cesaroni E, Fuggetta F, Meglio M, et al. Vagal nerve stimulation for drug-resistant epilepsies in different age, aetiology and duration. Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery 2010;26(6):811-9. [DOI: 10.1007/s00381-009-1069-2] [PMID: ] - DOI - PubMed
Cramer 2001 {published data only}
    1. Cramer JA. Exploration of changes in health-related quality of life after 3 months of vagus nerve stimulation. Epilepsy & Behavior 2001;2(5):460-5. [DOI: 10.1006/ebeh.2001.0248] [PMID: ] - DOI - PubMed
Cukiert 2013 {published data only}
    1. Cukiert A, Cukiert CM, Burattini JA, LIma AM, Forster CR, Baise C, et al. A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy. Neuromodulation 2013;16(6):551-6. [DOI: 10.1111/j.1525-1403.2012.00522.x] [PMID: ] - DOI - PubMed
Cukiert 2015 {published data only}
    1. Cukiert A. Vagus nerve stimulation for epilepsy: an evidence-based approach. Progress in Neurological Surgery 2015;29:39-52. [DOI: 10.1159/000434654] [PMID: ] - DOI - PubMed
DeGiorgio 2000 {published data only}
    1. DeGiorgio CM, Schachter SC, Handforth A, Salinsky M, Thompson J, Uthman B, et al. Prospective long term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 2000;41(9):1195-2000. [PMID: ] - PubMed
Dibue‐Adjei 2019 {published data only}
    1. Dibue-Adjei M, Brigo F, Yamammoto T, Vonck K, Trinka E. Vagus nerve stimulation in refractory and super-refractory status epilepticus – A systematic review. Brain Stimulation 2019;12(5):1101-10. - PubMed
Dumoulin 2018 {published data only}
    1. Dumoulin M, Liberati G, Mouraux A, El Tahry R. Optimization of vagus nerve therapy: a study of the behavioral and electrophysiological effects of transcutaneous VNS. Brain Stimulation 2019;12(2):454, Abstract no: 360. [DOI: 10.1016/j.brs.2018.12.473] - DOI
Ernst 2019 {published data only}
    1. Ernst LD, Krause KL, Kellog MA, Raslan AM, Spencer DC. Novel use of responsive neurostimulation (RNS System) in the treatment of super refractory status epilepticus. Journal of Clinical Neurophysiology 2019;36(3):242-5. - PubMed
Fisher 2016 {published data only}
    1. Fisher RS, Afra P, Macken M, Minecan DN, Bagic A, Benbadis SR, et al. Automatic vagus nerve stimulation triggered by ictal tachycardia: clinical outcomes and device performance – the U.S. E-37 trial. Neuromodulation 2016;19(2):188-95. [DOI: 10.1111/ner.12376] [PMID: ] - DOI - PMC - PubMed
Galbarriatu 2015 {published data only}
    1. Galbarriatu L, Pomposo I, Aurrecoechea J, Marinas A, Agundez M, Gomez JC, et al. Vagus nerve stimulation therapy for treatment-resistant epilepsy: a 15-year experience at a single institution. Clinical Neurology & Neurosurgery 2015;137:89-93. [DOI: 10.1016/j.clineuro.2015.06.023] [PMID: ] - DOI - PubMed
Garcia‐Navarrete 2013 {published data only}
    1. Garcia-Navarrete E, Torres CV, Gallego I, Navas M, Pastor J, Sola RG. Long-term results of vagal nerve stimulation for adults with medication-resistant epilepsy who have been on unchanged antiepileptic medication. Seizure 2013;22(1):9-13. [DOI: 10.1016/j.seizure.2012.09.008] [PMID: ] - DOI - PubMed
Geller 2017 {published data only}
    1. Geller EB, Skarpaas TL, Gross RE, Goodman RR, Barkley GL, Bazil CW, et al. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy. Epilepsia 2017;58(6):994-1004. [DOI: 10.1111/epi.13740] [PMID: ] - DOI - PubMed
George 1994 {published data only}
    1. George R, Salinsky M, Kuzniecky R, Rosenfeld W, Bergen D, Tarver WB, et al. Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. Epilepsia 1994;35(3):637-43. [DOI: 10.1111/j.1528-1157.1994.tb02484.x] [PMID: ] - DOI - PubMed
Ghani 2015 {published data only}
    1. Ghani S, Vilensky J, Turner B, Tubbs RS, Loukas M. Meta-analysis of vagus nerve stimulation treatment for epilepsy: correlation between device setting parameters and acute response. Child's Nervous System 2015;31(12):2291-304. [DOI: 10.1007/s00381-015-2921-1] [PMID: ] - DOI - PubMed
He 2015 {published data only}
    1. He W, Wang X-Y, Zhou L, Li Z-M, Jing X-H, Lv Z-L, et al. Transcutaneous auricular vagus nerve stimulation for pediatric epilepsy: study protocol for a randomized controlled trial. Trials 2015;16:371. [DOI: 10.1186/s13063-015-0906-8] [PMID: ] - DOI - PMC - PubMed
Ho 2016 {published data only}
    1. Ho B, Baker M, Lai M. Vagus nerve stimulation: effects on cholinergic neural networks? International Journal of Surgery 2016;36(Suppl 1):S40, Abstract no: 1307. [DOI: 10.1016/j.ijsu.2016.08.050] - DOI
Hornig 1997 {published data only}
    1. Hornig GW, Murphy JV, Schallert G, Tilton C. Left vagus nerve stimulation in children with refractory epilepsy: an update. Southern Medical Journal 1997;90(5):484-8. [PMID: ] - PubMed
Jobst 2017 {published data only}
    1. Jobst BC, Kapur R, Barkley GL, Bazil CW, Berg MJ, Bergey GK, et al. Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas. Epilepsia 2017;58(6):1005-14. [DOI: 10.1111/epi.13739] [PMID: ] - DOI - PubMed
Lee 2013 {published data only}
    1. Lee D, Isojarvi J, Benbadis SR. Response to clobazam in vagus nerve stimulation (VNS) vs non-VNS patients. Annals of Neurology 2013;74(Suppl 17):S74, Abstract no: M2221. [DOI: 10.1002/ana.24068] - DOI
Liu 2017 {published data only}
    1. Liu H, Yang Z, Huang L, Qu W, Hao H, Li L. Heart-rate variability indices as predictors of the response to vagus nerve stimulation in patients with drug-resistant epilepsy. Epilepsia 2017;58(6):1015-22. [DOI: 10.1111/epi.13738] [PMID: ] - DOI - PubMed
Madaan 2021 {published data only}
    1. Madaan P, Gupta A, Gulati S. Pediatric epilepsy surgery: indications and evaluation. Indian Journal of Pediatrics 2021;88(10):1000-6. - PubMed
Marras 2013 {published data only}
    1. Marras CE, Chiesa V, De Benedictis A, Franzini A, Rizzi M, Villani F, et al. Vagus nerve stimulation in refractory epilepsy: new indications and outcome assessment. Epilepsy & Behavior 2013;28(3):374-8. [DOI: 10.1016/j.yebeh.2013.05.021] [PMID: ] - DOI - PubMed
Marrosu 2003 {published data only}
    1. Marrosu F, Serra A, Maleci A, Puligheddu M, Biggio G, Piga M. Correlation between GABA-A receptor density and vagus nerve stimulation in individuals with drug-resistant partial epilepsy. Epilepsy Research 2003;55(1-2):59-70. [DOI: 10.1016/s0920-1211(03)00107-4] [PMID: ] - DOI - PubMed
Marrosu 2005 {published data only}
    1. Marrosu F, Santoni F, Puligheddu M, Barberini L, Maleci A, Ennas F, et al. Increase in 20-50 Hz (gamma frequencies) power spectrum and synchronization after chronic vagal nerve stimulation. Clinical Neurophysiology 2005;116(9):2026-36. [DOI: 10.1016/j.clinph.2005.06.015] [PMID: ] - DOI - PubMed
Morris 1999 {published data only}
    1. Morris GL 3rd, Mueller WM, Vagus Nerve Stimulation Group. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology 1999;53(8):1731-5. [DOI: 10.1212/wnl.53.8.1731] [PMID: ] - DOI - PubMed
Muller 2010 {published data only}
    1. Muller K, Fabo D, Entz L, Kelemen A, Halasz P, Rasonyi G, et al. Outcome of vagus nerve stimulation for epilepsy in Budapest. Epilepsia 2010;51(Suppl.3):98-101. [DOI: 10.1111/j.1528-1167.2010.02620.x] [PMID: ] - DOI - PubMed
NCT00215215 {published data only}
    1. NCT00215215. Effectiveness study comparing treatment with drug(s) or adjunctive VNS therapy for pharmacoresistant partial seizures. clinicaltrials.gov/show/NCT00215215 (first received 22 September 2005).
NCT01118455 {published data only}
    1. NCT01118455. Trial to assess vagus nerve stimulation therapy vs. anti-epileptic drug treatment in children with refractory seizures. clinicaltrials.gov/show/NCT01118455 (first received 6 May 2010).
NCT01178437 {published data only}
    1. NCT01178437. Transcutaneous non-invasive stimulation of the vagus nerve for the treatment of difficult-to-treat epilepsy. clinicaltrials.gov/show/NCT01178437 (first received 10 August 2010).
NCT01910129 {published data only}
    1. NCT01910129. Neurostimulation to the vagus nerve for the reduction in frequency of seizures associated with epilepsy. clinicaltrials.gov/show/NCT01910129 (first received 29 July 2013).
NCT02385526 {published data only}
    1. NCT02385526. Vagus nerve stimulation titration protocol to improve tolerance and accelerate adaptation. clinicaltrials.gov/show/NCT02385526 (first received 11 March 2015).
NCT02465970 {published data only}
    1. NCT02465970. Effects of transcranial direct current stimulation (TDCS) in drug-resistant partial epilepsy. clinicaltrials.gov/show/NCT02465970 (first received 9 June 2015).
NCT02603991 {published data only}
    1. NCT02603991. Prospective cohort study on the efficacy of vagus nerve stimulation for children and adolescents with epilepsy. clinicaltrials.gov/show/NCT02603991 (first received 13 November 2015).
Pelot 2018 {published data only}
    1. Pelot NA, Grill WM. Effects of vagal neuromodulation on feeding behaviour. Brain Research 2018;1693(Pt B):180-7. [DOI: 10.1016/j.brainres.2018.02.003] [PMID: ] - DOI - PMC - PubMed
Perez‐Carbonell 2020 {published data only}
    1. Perez-Carbonell L, Faulkner H, Higgins S, Koutroumanidis M, Leschziner G. Vagus nerve stimulation for drug-resistant epilepsy. Practical Neurology 2020;20(3):189-98. - PubMed
Robinson 2013 {published data only}
    1. Robinson R, European Paediatric VNS Study Group. Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial. Developmental Medicine and Child Neurology 2013;55(2):195. [DOI: 10.1111/dmcn.12026] [PMID: ] - DOI - PubMed
Ronkainem 2006 {published data only}
    1. Ronkainen E, Korpelainen JT, Heikkinen E, Myllyla VV, Huikuri HV, Isojarvi JIT. Cardiac autonomic control in patients with refractory epilepsy before and during vagus nerve stimulation treatment: a one-year follow-up study. Epilepsia 2006;47(3):556-62. [DOI: 10.1111/j.1528-1167.2006.00467.x] [PMID: ] - DOI - PubMed
Rossignol 2009 {published data only}
    1. Rossignol E, Lortie A, Thomas T, Bouthiller A, Scavarda D, Mercier C, et al. Vagus nerve stimulation in pediatric epileptic syndromes. Seizure 2009;18(1):34-7. [DOI: 10.1016/j.seizure.2008.06.010] [PMID: ] - DOI - PubMed
Salanova 2021 {published data only}
    1. Salanova V, Sperling MR, Gross RE, Irwin CP, Vollhaber JA, Giftakis JE. The SANTE study at 10 years of follow-up: effectiveness, safety, and sudden unexpected death in epilepsy. Epilepsia 2021;62(6):1306-17. - PubMed
Salinsky 1996 {published data only}
    1. Salinsky MC, Uthman BM, Ristanovic RK, Wernicke JF, Tarver WB, Vagus Nerve Stimulation Study Group. Vagus nerve stimulation for the treatment of medically intractable seizures: results of a 1-year open-extension trial. Archives of Neurology 1996;53(11):1176-80. [PMID: ] - PubMed
Scherrrmann 2001 {published data only}
    1. Scherrmann J, Hoppe C, Kral T, Schramm J, Elger CE. Vagus nerve stimulation: clinical experience in a large patient series. Journal of Clinical Neurophysiology 2001;18(5):408-14. [PMID: ] - PubMed
Shimizu 1995 {published data only}
    1. Shimizu H, Ishijima B, Nakamura K, Asakura T, Ohtsuki T, Yoshimoto T, et al. Effect of vagal stimulation on intractable epilepsy. Psychiatry and Clinical Neurosciences 1995;49(3):S254-5. [DOI: 10.1111/j.1440-1819.1995.tb02194.x] [PMID: ] - DOI - PubMed
Sirven 2000 {published data only}
    1. Sirven JI, Sperling M, Naritoku D, Schachter S, Labar D, Holmes M, et al. Vagus nerve stimulation therapy for epilepsy in older adults. Neurology 2000;54(3):1179-82. [PMID: ] - PubMed
Tormasiova 2014 {published data only}
    1. Tormasiova M, Kollova A, Bratsky L. Immediate post-implantation effect of baseline stimulation parameters of vagus nerve stimulation in patients with refractory epilepsy. Stereotactic and Functional Neurosurgery 2014;92(Suppl 2):216, Abstract no: 224.
Uthman 1993 {published data only}
    1. Uthman BM, Wilder BJ, Penry JK, Dean C, Ramsay RE, Reid SA, et al. Treatment of epilepsy by stimulation of the vagus nerve. Neurology 1993;43(7):1338-45. [PMID: ] - PubMed
Wang 2004 {published data only}
    1. Wang LN, Zhao LF, Wang YZ. Basic and clinical study of vagus nerve stimulation in the treatment of epilepsy. Chinese Journal of Clinical Rehabilitation 2004;8(13):2516-7.
Wang 2009 {published data only}
    1. Wang H, Chen X, Lin Z, Shao Z, Sun B, Shen H, et al. Long-term effect of vagus nerve stimulation on interictal epileptiform discharges in refractory epilepsy. Journal of the Neurological Sciences 2009;284(1-2):96-102. [DOI: 10.1016/j.jns.2009.04.012] - DOI - PubMed
Zambrelli 2016 {published data only}
    1. Zambrelli E, Saibene AM, Furia F, Chiesa V, Vignoli A, Pipolo C. Laryngeal motility alteration: a missing link between sleep apnea and vagus nerve stimulation for epilepsy. Epilepsia 2016;57(1):e24-7. [DOI: 10.1111/epi.13252] - DOI - PubMed

References to ongoing studies

EUCTR2018‐003464‐32‐HU {published data only}
    1. EUCTR2018-003464-32-HU. Effect of mirtazapine on seizure frequency in epileptic patients with vagal nerve stimulation device. www.clinicaltrialsregister.eu/ctr-search/trial/2018-003464-32/HU (first entered 11 August 2019).
Ji 2019 {published data only}
    1. Ji T, Yang Z, Liu Q, Liao J, Yin F, Chen Y, et al. Vagus nerve stimulation for pediatric patients with intractable epilepsy between 3 and 6 years of age: a study protocol for a double-blind, randomized control trial. Trials 2019;20(1):44. [DOI: 10.1186/s13063-018-3087-4] [PMID: ] - DOI - PMC - PubMed
NCT00782249 {published data only}
    1. NCT00782249. Trial comparing different stimulation paradigms in patients treated with vagus nerve stimulation for refractory epilepsy. clinicaltrials.gov/show/NCT00782249 (first received 31 October 2008).
NCT01281293 {published data only}
    1. NCT01281293. Vagus nerve stimulation Clinical Outcomes Measured prospectively in PAtients Stimulated (V-COMPAS). clinicaltrials.gov/show/NCT01281293 (first received 21 January 2011).
NCT01378611 {published data only}
    1. NCT01378611. Does VNS interact with the serotonergic and immune system in children with intractable epilepsy? clinicaltrials.gov/show/NCT01378611 (first received 14 June 2011).
NCT02089243 {published data only}
    1. NCT02089243. Controlled Randomized Vagus Nerve Stimulation (VNS) therapy versus Resection (CoRaVNStiR). clinicaltrials.gov/show/NCT02089243 (first received 13 March 2014).
NCT02378792 {published data only}
    1. NCT02378792. Clinical trial of vagus nerve stimulation for treatment of refractory epilepsy. clinicaltrials.gov/show/NCT02378792 (first received 27 February 2015).
NCT05180916 {published data only}
    1. NCT05180916. Priming the epileptic brain: tVNS to improve efficacy of add-on AED in patients with focal epilepsy. clinicaltrials.gov/show/NCT05180916 (first received 2 July 2021).

Additional references

Aalbers 2012
    1. Aalbers MW, Klinkenberg S, Rijkers K, Verschuure P, Kessels A, Aldenkamp A, et al. The effects of vagus nerve stimulation on pro- and anti-inflammatory cytokines in children with refractory epilepsy: an exploratory study. Neuroimmunomodulation 2012;19(6):352-8. - PubMed
Amar 1998
    1. Amar AP, Heck CN, Levy ML, Smith T, DeGiorgio CM, Oviedo S, et al. An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery 1998;43(6):1265-76. - PubMed
Ben‐Menachem 1994
    1. Ben-Menachem E, Manon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W, et al, First International Vagus Nerve Stimulation Study Group. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures.. Epilepsia 1994;35(3):616-26. - PubMed
Ben‐Menachem 1995
    1. Ben-Menachem E, Hamberger A, Hedner T, Hammond EJ, Uthman BM, Slater J, et al. Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Research 1995;20(3):221-7. - PubMed
Cockerell 1995
    1. Cockerell OC, Johnson AL, Sander JW, Hart YM, Shorvon SD. Remission of epilepsy: results from the National General Practice Study of Epilepsy. Lancet 1995;346(8968):140-4. [DOI: 10.1016/s0140-6736(95)91208-8] [PMID: ] - DOI - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG. Chapter 9. Analysing data and undertaking meta-analyses. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Dodrill 2000
    1. Dodrill CB, Morris GL. Effect of vagal nerve stimulation on cognition and quality of life in epilepsy. Epilepsy & Behavior 2001;2(1):46-53. [DOI: 10.1006/ebeh.2000.0148] [PMID: ] - DOI - PubMed
Elger 2000
    1. Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE. Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Research 2000;42(2-3):203-10. [DOI: 10.1016/S0920-1211(00)00181-9] [PMID: ] - DOI - PubMed
Forsgren 2005
    1. Forsgren L, Beghi E, Oun A, Sillanpaa M. The epidemiology of epilepsy in Europe – a systematic review. European Journal of Neurology 2005;12(4):245-53. [DOI: 10.1111/j.1468-1331.2004.00992.x] [PMID: ] - DOI - PubMed
Hauser 1975
    1. Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975;16(1):1-66. [DOI: 10.1111/j.1528-1157.1975.tb04721.x] [PMID: ] - DOI - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC, editor(s). Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Holder 1992
    1. Holder LK, Wernicke JF, Tarver WB. Treatment of refractory partial seizures: preliminary results of a controlled study. Pacing & Clinical Electrophysiology 1992;15(10 Pt2):1557-71. [DOI: 10.1111/j.1540-8159.1992.tb02934.x] [PMID: ] - DOI - PubMed
Kirkham 2010
    1. Kirkham JJ, Dwan KM, Altman DG, Gamble C, Dodd S, Smyth R, et al. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews. BMJ 2010;340:c365. [DOI: ] [PMID: ] - PubMed
Klinkenberg 2014
    1. Klinkenberg S, den Borne CJ, Aalbers MW, Verschuure P, Kessels AG, Leenen L, et al. The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy. Epilepsy & Behavior 2014;37:133-8. - PubMed
Krahl 2012
    1. Krahl SE, Clark KB. Vagus nerve stimulation for epilepsy: a review of central mechanisms. Surgical Neurology International 2012;3(Suppl 4):S255-9. [DOI: 10.4103/2152-7806.103015] [PMID: ] - DOI - PMC - PubMed
Kwan 2000
    1. Kwan P, Brodie MJ. Early identification of refractory epilepsy. New England Journal of Medicine 2000;342(5):314-9. [PMID: ] - PubMed
Lefebvre 2019
    1. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Technical Supplement to Chapter 4: Searching for and selecting studies. In: Higgins JPT, Thomas J, Chandler J, Cumpston MS, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6. Cochrane, 2019. Available from training.cochrane.org/handbook/archive/v6.
Lötvall 1994
    1. Lötvall J, Lunde H, Augustinson LE, Hedner T, Svedmyr N, Ben-Menachem E. Airway effects of direct left-sided cervical vagal stimulation in patients with complex partial seizures. Epilepsy Research 1994;18(2):149-54. - PubMed
Morris 2013
    1. Morris GL 3rd, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013;81(16):1453-9. [PMID: ] - PMC - PubMed
Panebianco 2016
    1. Panebianco M, Zavanone C, Dupont S, Restivo DA, Pavone A. Vagus nerve stimulation therapy in partial epilepsy: a review. Acta Neurologica Belgica 2016;116(3):241-8. [PMID: ] - PubMed
Ramsay 1994
    1. Ramsay RE, Uthman BM, Augustinsson LE, Upton AR, Naritoku D, Willis J, et al, First International Vagus Nerve Stimulation Study Group. Vagus nerve stimulation for treatment of partial seizures: 2.Safety, side effects, and tolerability. Epilepsia 1994;35(3):627-36. - PubMed
Sackeim 2001
    1. Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, et al. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects and predictors of outcome. Neuropsychopharmacology 2001;25(5):713–28. [PMID: ] - PubMed
Schachter 1998
    1. Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia 1998;39(7):677-86. [PMID: ] - PubMed
Scheffer 2017
    1. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58(4):512-21. [PMID: ] - PMC - PubMed
Selway 1987
    1. Selway R, Nashef L. Vagus nerve stimulation. In: Membranes to Mankind – A Practical Guide to Epilepsy, chapter 48. Chalfont St Peter, Bucks: Epilepsy Society, 1987.
Vonck 2014
    1. Vonck K, Raedt R, Naulaerts J, De Vogelaere F, Thiery E, Van Roost D, et al. Vagus nerve stimulation… 25 years later! What do we know about the effects on cognition? Neuroscience & Biobehavioral Reviews 2014;45:63-71. [DOI: 10.1016/j.neubiorev.2014.05.005] [PMID: ] - DOI - PubMed

References to other published versions of this review

Panebianco 2015
    1. Panebianco M, Rigby A, Weston J, Marson AG. Vagus nerve stimulation for partial seizures. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No: CD002896. [DOI: 10.1002/14651858.CD002896.pub2] - DOI - PMC - PubMed
Privitera 2002
    1. Privitera MD, Welty TTE, Ficker DDM, Welge J. Vagus nerve stimulation for partial seizures. Cochrane Database of Systematic Reviews 2002, Issue 1. Art. No: CD002896. [DOI: 10.1002/14651858.CD002896] - DOI - PubMed

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