Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Non-Pharmacological and Non-Surgical Treatment of Refractory Childhood Epilepsy

  • 16 Accesses


Nearly 20–40% of patients with epilepsy are likely to have drug resistant epilepsy (DRE). Add-on antiseizure drugs do not produce optimal seizure control in these patients. Among the non-pharmacological options, only resective surgery is curative. However, a large majority of patients are not candidates for resective epilepsy surgery. For these children with DRE, non-pharmacological non-surgery “palliative” options should be considered early than late. These include dietary therapies and neuromodulation. While there are numerous clinical trials supporting the efficacy of dietary therapies (viz ketogenic diet, modified Atkins diet and low glycemic index therapy), the evidence for neuromodulation is still evolving. Neuromodulation techniques include vagal nerve stimulation, deep brain stimulation, and transcranial magnetic stimulation. Each of the options, whether diet or neuromodulation, has its own advantages, disadvantages and adverse events profile. These have to be considered and discussed with the family before deciding the modality being chosen.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    Yoo JY, Panov F. Identification and treatment of drug-resistant epilepsy. Continuum (Minneap Minn). 2019;25:362–80.

  2. 2.

    Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51:1069–77.

  3. 3.

    Conte F, Legros B, Van Paesschen W, Avbersek A, Muglia P, Depondt C. Long-term seizure outcomes in patients with drug resistant epilepsy. Seizure. 2018;62:74–8.

  4. 4.

    Wilder RM. The effects of ketonemia on the course of epilepsy. Mayo Clin Proc. 1921;2:307–8.

  5. 5.

    Martin-McGill KJ, Jackson CF, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2018;11:CD001903.

  6. 6.

    Kossoff EH. More fat and fewer seizures: dietary therapies for epilepsy. Lancet Neurol. 2004;3:415–20.

  7. 7.

    Neal EG, Chaffe H, Schwartz RH, et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia. 2009;50:1109–17.

  8. 8.

    Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007;48:43–58.

  9. 9.

    Bough KJ, Paquet M, Pare JF, et al. Evidence against enhanced glutamate transport in the anticonvulsant mechanism of the ketogenic diet. Epilepsy Res. 2007;74:232–6.

  10. 10.

    Danial NN, Hartman AL, Stafstrom CE, Thio LL. How does the ketogenic diet work? Four potential mechanisms. J Child Neurol. 2013;28:1027–33.

  11. 11.

    Kossoff EH, Dorward JL, Molinero MR, Holden KR. The modified Atkins diet: a potential treatment for developing countries. Epilepsia. 2008;49:1646–7.

  12. 12.

    Pfeifer HH, Thiele EA. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology. 2005;65:1810–2.

  13. 13.

    Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018;3:175–92.

  14. 14.

    van der Louw E, van den Hurk D, Neal E, et al. Ketogenic diet guidelines for infants with refractory epilepsy. Eur J Paediatr Neurol. 2016;20:798–809.

  15. 15.

    Neal EG, Chaffe H, Schwartz RH, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008;7:500–6.

  16. 16.

    Sharma S, Sankhyan N, Gulati S, Agarwala A. Use of the modified Atkins diet for treatment of refractory childhood epilepsy: a randomized controlled trial. Epilepsia. 2013;54:481–6.

  17. 17.

    Kim JA, Yoon JR, Lee EJ, et al. Efficacy of the classic ketogenic and the modified Atkins diets in refractory childhood epilepsy. Epilepsia. 2016;57:51–8.

  18. 18.

    Muzykewicz DA, Lyczkowski DA, Memon N, Conant KD, Pfeifer HH, Thiele EA. Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy. Epilepsia. 2009;50:1118–26.

  19. 19.

    Kossoff EH, Zupec-Kania BA, Amark PE, et al. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia. 2009;50:304–17.

  20. 20.

    Lin A, Turner Z, Doerrer SC, Stanfield A, Kossoff EH. Complications during ketogenic diet initiation: prevalence, treatment, and influence on seizure outcomes. Pediatr Neurol. 2017;68:35–9.

  21. 21.

    Martinez CC, Pyzik PL, Kossoff EH. Discontinuing the ketogenic diet in seizure-free children: recurrence and risk factors. Epilepsia. 2007;48:187–90.

  22. 22.

    Dalkilic EB. Neurostimulation devices used in treatment of epilepsy. Curr Treat Options Neurol. 2017;19:7.

  23. 23.

    Benbadis SR, Geller E, Ryvlin P, et al. Putting it all together: options for intractable epilepsy: an updated algorithm on the use of epilepsy surgery and neurostimulation. Epilepsy Behav. 2018;88S:33–8.

  24. 24.

    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;81:1453–9.

  25. 25.

    Nune G, DeGiorgio C, Heck C. Neuromodulation in the treatment of epilepsy. Curr Treat Options Neurol. 2015;17:375.

  26. 26.

    Chase MH, Nakamura Y, Clemente CD, Sterman MB. Afferent vagal stimulation: neurographic correlates of induced EEG synchronization and desynchronization. Brain Res. 1967;5:236–49.

  27. 27.

    Di Lazzaro V, Oliviero A, Pilato F, et al. Effects of vagus nerve stimulation on cortical excitability in epileptic patients. Neurology. 2004;62:2310–2.

  28. 28.

    The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology. 1995;45:224–30.

  29. 29.

    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.

  30. 30.

    Kostov K, Kostov H, Tauboll E. Long-term vagus nerve stimulation in the treatment of Lennox-Gastaut syndrome. Epilepsy Behav. 2009;16:321–4.

  31. 31.

    Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010;51:899–908.

  32. 32.

    Chen R, Spencer DC, Weston J, Nolan SJ. Transcranial magnetic stimulation for the treatment of epilepsy. Cochrane Database Syst Rev. 2016;8:CD011025.

  33. 33.

    DeGiorgio CM, Soss J, Cook IA, et al. Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy. Neurology. 2013;80:786–91.

  34. 34.

    Schulze-Bonhage A. Long-term outcome in neurostimulation of epilepsy. Epilepsy Behav. 2019;91:25–9.

Download references

Author information

VS and SS planned the content. VS performed the literature review and wrote the first draft which was revised by SS. Both authors approve the final draft to be submitted. SS is the guarantor for this paper.

Correspondence to Suvasini Sharma.

Ethics declarations

Conflict of Interest


Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sondhi, V., Sharma, S. Non-Pharmacological and Non-Surgical Treatment of Refractory Childhood Epilepsy. Indian J Pediatr (2020). https://doi.org/10.1007/s12098-019-03164-3

Download citation


  • Ketogenic diet
  • Modified Atkins diet
  • Vagal nerve stimulation