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Vagus nerve stimulation: a 20-year Australian experience

  • Original Article - Functional Neurosurgery - Epilepsy
  • Published:
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Abstract

Background

Vagus nerve stimulation (VNS) therapy was first approved in the mid-1990s in the USA, Europe and Australia, with demonstrable efficacy in paediatric populations. Benefit in seizure frequency reduction can be observed up to 2 years post-intervention; however, few studies assess outcomes beyond this period. Furthermore, paediatric cohort sizes are small, limiting generalisability of outcome assessments. We evaluate VNS insertion outcomes and complications or side-effects in a large paediatric cohort, over a 20-year period from Queensland’s first VNS insertion.

Methods

A retrospective review was conducted of all paediatric VNS insertions at the Queensland Children’s Hospital (QCH) and the Mater Children’s Hospital/Mater Children’s Private Hospital (MCH/MCPH) Brisbane. A minimum of 1-year follow-up from 1999 to 2020 was required for inclusion. Patients were assessed on demographics, epilepsy details, seizure outcomes and complications or side-effects.

Results

In this extended follow-up cohort (76 patients, 7.2 ± 5.3 years), 51.3% of patients had ≥ 50% seizure frequency reduction, while 73.7% experienced an Engel III outcome (worthwhile benefit) or better. Eleven patients (14.9%) were seizure-free at follow-up, and 81.6% retained long-term therapy. Stimulation-related side-effects are common (17.1%) but rarely result in stimulation cessation (3.9%). Cessation occurred in 14 patients (18.4%) and most commonly related to minimal benefit (13.2%). Demographics, aetiology, seizure nature and surgical factors did not influence outcomes.

Conclusion

Over extended treatment periods, a large proportion of patients will benefit significantly from VNS therapy. Approximately 4 of 5 patients will retain VNS therapy, and in cases of cessation, this is most commonly related to minimal benefit. Underlying demographics, aetiology or seizure nature do not influence outcomes. This 20-year Queensland assessment of VNS therapy outcomes informs long-term expectation of VNS therapy.

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References

  1. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. The Vagus Nerve Stimulation Study Group (1995). Neurology 45:224–230

  2. Amar AP, Heck CN, Levy ML, Smith T, DeGiorgio CM, Oviedo S, Apuzzo ML (1998) An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome. Neurosurgery 43:1265–1276; discussion 1276–1280. doi:https://doi.org/10.1097/00006123-199812000-00001

  3. 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. https://doi.org/10.1016/j.seizure.2007.04.005

    Article  CAS  PubMed  Google Scholar 

  4. Ben-Menachem E, Manon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W, Tarver WB, Wernicke JF (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 35:616–626. https://doi.org/10.1111/j.1528-1157.1994.tb02482.x

    Article  CAS  PubMed  Google Scholar 

  5. Bulacio JC, Jehi L, Wong C, Gonzalez-Martinez J, Kotagal P, Nair D, Najm I, Bingaman W (2012) Long-term seizure outcome after resective surgery in patients evaluated with intracranial electrodes. Epilepsia 53:1722–1730. https://doi.org/10.1111/j.1528-1167.2012.03633.x

    Article  PubMed  Google Scholar 

  6. DeGiorgio CM, Schachter SC, Handforth A, Salinsky M, Thompson J, Uthman B, Reed R, Collins S, Tecoma E, Morris GL, 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, Heck C (2000) Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 41:1195–1200

    Article  CAS  Google Scholar 

  7. 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. https://doi.org/10.1212/01.wnl.0000168899.11598.00

    Article  CAS  PubMed  Google Scholar 

  8. Dwivedi R, Ramanujam B, Chandra PS, Sapra S, Gulati S, Kalaivani M, Garg A, Bal CS, Tripathi M, Dwivedi SN, Sagar R, Sarkar C, Tripathi M (2017) Surgery for drug-resistant epilepsy in children. N Engl J Med 377:1639–1647. https://doi.org/10.1056/NEJMoa1615335

    Article  PubMed  Google Scholar 

  9. Elliott RE, Morsi A, Geller EB, Carlson CC, Devinsky O, Doyle WK (2011) Impact of failed intracranial epilepsy surgery on the effectiveness of subsequent vagus nerve stimulation. Neurosurgery 69:1210–1217. https://doi.org/10.1227/NEU.0b013e3182230ae3

    Article  PubMed  Google Scholar 

  10. Elliott RE, Rodgers SD, Bassani L, Morsi A, Geller EB, Carlson C, Devinsky O, Doyle WK (2011) Vagus nerve stimulation for children with treatment-resistant epilepsy: a consecutive series of 141 cases. J Neurosurg Pediatr 7:491–500. https://doi.org/10.3171/2011.2.PEDS10505

    Article  PubMed  Google Scholar 

  11. Engel J Jr (1993) Surgical treatment of the epilepsies, 2nd edn. Raven Press, New York

    Google Scholar 

  12. Englot DJ, Chang EF, Auguste KI (2011) Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg 115:1248–1255. https://doi.org/10.3171/2011.7.JNS11977

    Article  PubMed  Google Scholar 

  13. Englot DJ, Rolston JD, Wright CW, Hassnain KH, Chang EF (2016) Rates and predictors of seizure freedom with vagus nerve stimulation for intractable epilepsy. Neurosurgery 79:345–353. https://doi.org/10.1227/NEU.0000000000001165

    Article  PubMed  Google Scholar 

  14. Galbarriatu L, Pomposo I, Aurrecoechea J, Marinas A, Agundez M, Gomez JC, Acera MA, Martinez MJ, Valle E, Maestro I, Mateos B, Cabrera A, Fernandez 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. https://doi.org/10.1016/j.clineuro.2015.06.023

    Article  CAS  PubMed  Google Scholar 

  15. Geerts A, Arts WF, Stroink H, Peeters E, Brouwer O, Peters B, Laan L, van Donselaar C (2010) Course and outcome of childhood epilepsy: a 15-year follow-up of the Dutch Study of Epilepsy in Childhood. Epilepsia 51:1189–1197. https://doi.org/10.1111/j.1528-1167.2010.02546.x

    Article  PubMed  Google Scholar 

  16. Hamilton P, Soryal I, Dhahri P, Wimalachandra W, Leat A, Hughes D, Toghill N, Hodson J, Sawlani V, Hayton T, Samarasekera S, Bagary M, McCorry D, Chelvarajah R (2018) Clinical outcomes of VNS therapy with AspireSR((R)) (including cardiac-based seizure detection) at a large complex epilepsy and surgery centre. Seizure 58:120–126. https://doi.org/10.1016/j.seizure.2018.03.022

    Article  PubMed  Google Scholar 

  17. Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, Henry TR, Collins SD, Vaughn BV, Gilmartin RC, Labar DR, Morris GL 3rd, Salinsky MC, Osorio I, Ristanovic RK, Labiner DM, Jones JC, Murphy JV, Ney GC, Wheless JW (1998) Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51:48–55

    Article  CAS  Google Scholar 

  18. Healy S, Lang J, Te Water Naude J, Gibbon F, Leach P (2013) Vagal nerve stimulation in children under 12 years old with medically intractable epilepsy. Childs Nerv Syst 29:2095–2099. https://doi.org/10.1007/s00381-013-2143-3

    Article  PubMed  Google Scholar 

  19. Klinkenberg S, Aalbers M, Vles J, Cornips E, Rijkers K, Leened L, Kessels F, Aldenkamp A, Majoie M (2013) Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial. Dev Med Child Neurol 55:195. https://doi.org/10.1111/dmcn.12026

    Article  PubMed  Google Scholar 

  20. Knorr C, Greuter L, Constantini S, Fried I, Kremer U, Datta AN, Guzman R, Soleman J (2020) Subgroup analysis of seizure and cognitive outcome after vagal nerve stimulator implantation in children. Childs Nerv Syst. https://doi.org/10.1007/s00381-020-04628-0

    Article  PubMed  Google Scholar 

  21. Kulju T, Haapasalo J, Rainesalo S, Lehtimaki K, Peltola J (2019) Autostimulation in vagus nerve stimulator treatment: modulating neuromodulation. Neuromodulation 22:630–637. https://doi.org/10.1111/ner.12897

    Article  PubMed  Google Scholar 

  22. Kulju T, Haapasalo J, Verner R, Dibue-Adjei M, Lehtimaki K, Rainesalo S, Peltola J (2020) Frequency of automatic stimulations in responsive vagal nerve stimulation in patients with refractory epilepsy. Neuromodulation 23:852–858. https://doi.org/10.1111/ner.13238

    Article  PubMed  Google Scholar 

  23. Kwan P, Brodie MJ (2000) Early identification of refractory epilepsy. N Engl J Med 342:314–319. https://doi.org/10.1056/NEJM200002033420503

    Article  CAS  PubMed  Google Scholar 

  24. Lagae L, Verstrepen A, Nada A, Van Loon J, Theys T, Ceulemans B, Jansen K (2015) Vagus nerve stimulation in children with drug-resistant epilepsy: age at implantation and shorter duration of epilepsy as predictors of better efficacy? Epileptic Disord 17:308–314. https://doi.org/10.1684/epd.2015.0768

    Article  PubMed  Google Scholar 

  25. Morris GL 3rd, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C (2013) 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 81:1453–1459. https://doi.org/10.1212/WNL.0b013e3182a393d1

    Article  PubMed  PubMed Central  Google Scholar 

  26. Murphy JV, Torkelson R, Dowler I, Simon S, Hudson S (2003) Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center. Arch Pediatr Adolesc Med 157:560–564. https://doi.org/10.1001/archpedi.157.6.560

    Article  PubMed  Google Scholar 

  27. Orosz I, McCormick D, Zamponi N, Varadkar S, Feucht M, Parain D, Griens R, Vallee L, Boon P, Rittey C, Jayewardene AK, Bunker M, Arzimanoglou A, Lagae L (2014) Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia 55:1576–1584. https://doi.org/10.1111/epi.12762

    Article  PubMed  Google Scholar 

  28. Revesz D, Frojd V, Rydenhag B, Ben-Menachem E (2018) Estimating long-term vagus nerve stimulation effectiveness: accounting for antiepileptic drug treatment changes. Neuromodulation 21:797–804. https://doi.org/10.1111/ner.12775

    Article  PubMed  Google Scholar 

  29. Scherrmann J, Hoppe C, Kral T, Schramm J, Elger CE (2001) Vagus nerve stimulation: clinical experience in a large patient series. J Clin Neurophysiol 18:408–414. https://doi.org/10.1097/00004691-200109000-00004

    Article  CAS  PubMed  Google Scholar 

  30. Serdaroglu A, Arhan E, Kurt G, Erdem A, Hirfanoglu T, Aydin K, Bilir E (2016) Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up. Childs Nerv Syst 32:641–646. https://doi.org/10.1007/s00381-015-3004-z

    Article  PubMed  Google Scholar 

  31. Soleman J, Stein M, Knorr C, Datta AN, Constantini S, Fried I, Guzman R, Kramer U (2018) Improved quality of life and cognition after early vagal nerve stimulator implantation in children. Epilepsy Behav 88:139–145. https://doi.org/10.1016/j.yebeh.2018.09.014

    Article  PubMed  Google Scholar 

  32. Terra VC, Furlanetti LL, Nunes AA, Thome U, Nisyiama MA, Sakamoto AC, Machado HR (2014) Vagus nerve stimulation in pediatric patients: is it really worthwhile? Epilepsy Behav 31:329–333. https://doi.org/10.1016/j.yebeh.2013.10.011

    Article  PubMed  Google Scholar 

  33. Thompson EM, Wozniak SE, Roberts CM, Kao A, Anderson VC, Selden NR (2012) Vagus nerve stimulation for partial and generalized epilepsy from infancy to adolescence. J Neurosurg Pediatr 10:200–205. https://doi.org/10.3171/2012.5.PEDS11489

    Article  PubMed  Google Scholar 

  34. Wang HJ, Tan G, Zhu LN, Chen D, Xu D, Chu SS, Liu L (2019) Predictors of seizure reduction outcome after vagus nerve stimulation in drug-resistant epilepsy. Seizure 66:53–60. https://doi.org/10.1016/j.seizure.2019.02.010

    Article  PubMed  Google Scholar 

  35. Wheless JW, Gienapp AJ, Ryvlin P (2018) Vagus nerve stimulation (VNS) therapy update. Epilepsy Behav 88S:2–10. https://doi.org/10.1016/j.yebeh.2018.06.032

    Article  PubMed  Google Scholar 

  36. Yalnizoglu D, Ardicli D, Bilginer B, Konuskan B, Karli Oguz K, Akalan N, Turanli G, Saygi S, Topcu M (2020) Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: a single-center experience. Epilepsy Behav 110:107147. https://doi.org/10.1016/j.yebeh.2020.107147

    Article  PubMed  Google Scholar 

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Correspondence to Charles F. Yates.

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This article is part of the Topical Collection on Functional Neurosurgery - Epilepsy

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Yates, C.F., Riney, K., Malone, S. et al. Vagus nerve stimulation: a 20-year Australian experience. Acta Neurochir 164, 219–227 (2022). https://doi.org/10.1007/s00701-021-05046-0

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