Ketogenic Diet for Refractory Status Epilepticus in Children

  • Roberto CaraballoEmail author
Pediatrics in South America (L Landry and WB de Carvalho, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pediatrics in South America


Purpose of Review

Over the past years, the ketogenic diet (KD) has been increasingly used as emergency therapy for refractory and super-refractory status epilepticus (RSE/SRSE). The aim of this review was to evaluate the role of the KD in pediatric patients with RSE with a special focus on different types of status epilepticus.

Recent Findings

Over the past decade, several studies have been published on the use of the KD in children with RSE/SRSE. Based on our previous studies on dietary therapy in myoclonic status epilepticus and status epilepticus in epileptic encephalopathies, we consider the KD may work well in particular types of status epilepticus, especially those occurring in the epileptic encephalopathies.


When patients with RSE/SRSE do not respond to benzodiazepines, IV antiepileptic drugs, and anesthetics, the KD may be an effective and tolerable option to be considered earlier in the treatment algorithm. The development of a consensus may optimize the use of this treatment in patients with epilepsy in critical care. There is a need for randomized controlled trials to confirm what children would be the best candidates for the use of the KD as well as the time of dietary therapy initiation for the treatment of RSE/SRSE.


Refractory Superrefractory status epilepticus Convulsive Non-convulsive Ketogenic diet 


Compliance with Ethical Standards

Conflict of Interest

Roberto Caraballo declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Stafstrom CE. Dietary approaches to epilepsy treatment: old and new options on the menu. Epilepsy Curr. 2004;4(6):215–22.CrossRefGoogle Scholar
  2. 2.
    Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC, Kelly LM. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998;102(6):1358–63.CrossRefGoogle Scholar
  3. 3.
    Caraballo R. Dieta Cetogena en el tratamiento de la epilepsia. Buenos Aires: Editorial Journal; 2016.Google Scholar
  4. 4.
    Nangia S, Caraballo RH, Kang HC, Nordli DR, Scheffer IE. Is the ketogenic diet effective in specific epilepsy syndromes? Epilepsy Res. 2012 Jul;100(3):252–7. Scholar
  5. 5.
    • Caraballo RH. The use of the ketogenic diet in the treatment of epileptic encephalopathies. JICNA. 2018;18:66 This study provides an overview of the use of the ketogenic diet in epileptic encephalopathies, both those in which the diet has shown to result in a good response, such as West syndrome, Dravet syndrome, or Lennox-Gastaut syndrome, and those that are more rare or only recently identified, such as epilepsy with focal migrating seizures in infancy, febrile infection-related epilepsy syndrome, or myclonic status in non-progressive encephalopathy, about which little is known.Google Scholar
  6. 6.
    •• Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, 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(2):175–92. This update of the 2009 consensus guideline for the management of children on ketogenic diet therapy includes new concepts and recent research regarding topics of patient selection, counseling, and evaluation, diet choice and attributes, implementation, supplementation, follow-up, side events, and diet discontinuation.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Cervenka MC, Hartman AL, Venkatesan A, Geocadin RG, Kossoff EH. The ketogenic diet for medically and surgically refractory status epilepticus in the neurocritical care unit. Neurocrit Care. 2011 Dec;15(3):519–24. Scholar
  8. 8.
    Thakur KT, Probasco JC, Hocker SE, Roehl K, Henry B, Kossoff EH, et al. Ketogenic diet for adults in super-refractory status epilepticus. Neurology. 2014;82(8):665–70. Scholar
  9. 9.
    Wusthoff CJ, Kranick SM, Morley JF, Christina Bergqvist AG. The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus. Epilepsia. 2010 Jun;51(6):1083–5.
  10. 10.
    Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011;134:2802–18.CrossRefGoogle Scholar
  11. 11.
    Sahin M, Menache CC, Holmes GL, Riviello JJ. Outcome of severe refractory status epilepticus in children. Epilepsia. 2001;42(11):1461–7.CrossRefGoogle Scholar
  12. 12.
    • Sculier C, Gaínza-Lein M, Sánchez Fernández I, Loddenkemper T. Long-term outcomes of status epilepticus: a critical assessment. Epilepsia. 2018;59(Suppl Suppl 2):155–69 The findings of this study on the long-term outcomes after a status epilepticus episode in pediatric and adult patients showed that etiology is the main determinant of outcome, that the effect of age or SE duration is often difficult to distinguish from the underlying cause, and that effect of the treatment on long-term outcome after SE is still unknown.CrossRefGoogle Scholar
  13. 13.
    Bodenant M, Moreau C, Sejourné C, Auvin S, Delval A, Cuisset JM, et al. Interest of the ketogenic diet in a refractory status epilepticus in adults. Rev Neurol (Paris). 2008;164(2):194–9. Scholar
  14. 14.
    Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48–61. Scholar
  15. 15.
    • Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super-refractory status epilepticus. Seizure. 2019;68:62–71. This review summarizes the available evidence related to pediatric refractory status epilepticus and super-refractory status epilepticus focusing on epidemiology, etiologies, therapeutic approaches, and clinical outcomes.CrossRefPubMedGoogle Scholar
  16. 16.
    •• Hirsch LJ, Gaspard N, van Baalen A, Nabbout R, Demeret S, Loddenkemper T, et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018;59(4):739–44 This consensus document proposes definitions for New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions, as well as for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus to enable improved communication for investigators, physicians, families, patients, and other caregivers.CrossRefGoogle Scholar
  17. 17.
    •• Cervenka MC, Hocker S, Koenig M, Bar B, Henry-Barron B, Kossoff EH, et al. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology. 2017;88(10):938–43 This prospective multicenter study of adults patients with super-refractory status epilepticus treated with a ketogenic diet treatment algorithm provides Class IV evidence that in adults with super-refractory status epilepticus, ketogenic therapy is effective in inducing ketosisCrossRefGoogle Scholar
  18. 18.
    Kumada T, Miyajima T, Kimura N, Saito K, Shimomura H, Oda N, et al. Modified Atkins diet for the treatment of nonconvulsive status epilepticus in children. J Child Neurol. 2010;25(4):485–9. Scholar
  19. 19.
    Villeneuve N, Pinton F, Bahi-Buisson N, Dulac O, Chiron C, Nabbout R. The ketogenic diet improves recently worsened focal epilepsy. Dev Med Child Neurol. 2009 Apr;51(4):276–81. Scholar
  20. 20.
    Nabbout R, Mazzuca M, Hubert P, Peudennier S, Allaire C, Flurin V, et al. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia. 2010;51(10):2033–7. Scholar
  21. 21.
    Vaccarezza M, Silva W, Maxit C, Agosta G. Super-refractory status epilepticus: treatment with ketogenic diet in pediatrics. article in Spanish. Rev Neurol. 2012;55(1):20–5.PubMedGoogle Scholar
  22. 22.
    Caraballo RH, Flesler S, Armeno M, Fortini S, Agustinho A, Mestre G, et al. Ketogenic diet in pediatric patients with refractory focal status epilepticus. Epilepsy Res. 2014;108(10):1912–6. Scholar
  23. 23.
    O’Connor SE, Ream MA, Richardson C, Mikati MA, Trescher WH, Byler DL, et al. The ketogenic diet for the treatment of pediatric status epilepticus. Pediatr Neurol. 2014 Jan;50(1):101–3. Scholar
  24. 24.
    Cobo NH, Sankar R, Murata KK, Sewak SL, Kezele MA, Matsumoto JH. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units. J Child Neurol. 2015;30:259–66.CrossRefGoogle Scholar
  25. 25.
    Appavu B, Vanatta L, Condie J, Kerrigan JF, Jarrar R. Ketogenic diet treatment for pediatric super-refractory status epilepticus. Seizure. 2016;41:62–5. Scholar
  26. 26.
    •• Farias-Moeller R, Bartolini L, Pasupuleti A, Brittany Cines RD, Kao A, Carpenter JL. A practical approach to ketogenic diet in the pediatric intensive care unit for super-refractory status epilepticus. Neurocrit Care. 2017;26(2):267–72. This study describes the experience with a practical approach to initiation of the ketogenic diet for children with super-refractory status epilepticus in the pediatric intensive care unit through which the patients could be successfully weaned off continuous anesthetic infusions.CrossRefPubMedGoogle Scholar
  27. 27.•
    Arya R, Peariso K, Gainza-Lein M, Harvey J, Bergin A, Brenton JN, et al. Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018;144:1–6 This study provides the results of ketogenic diet therapy in patients with refractory status epilepticus treated with the ketogenic diet at institutions participating in the pediatric Status Epilepticus Research Group suggesting efficacy and safety of the treatment.CrossRefGoogle Scholar
  28. 28.
    Park EG, Lee J, Lee J. The ketogenic diet for super-refractory status epilepticus patients in intensive care units. Brain and Development. 2019;41(5):420–7. Scholar
  29. 29.
    • Peng P, Peng J, Yin F, Deng X, Chen C, He F, et al. Ketogenic diet as a treatment for super-refractory status epilepticus in febrile infection-related epilepsy syndrome. Front Neurol. 2019;10:423. The findings of this study show that in children with febrile infection-related epilepsy syndrome, a fatal epileptic encephalopathy associated with super-refractory status epilepticus, the ketogenic diet should be tried earlier in the course of the disease and that the intravenous route of administration may be an alternative for patients who cannot receive the diet enterally.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Caraballo RH, Valenzuela GR, Armeno M, Fortini S, Mestre G, Cresta A. The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus. Epileptic Disord. 2015 Dec;17(4):491–5. Scholar
  31. 31.
    Caraballo RH, Cersósimo RO, Espeche A, Arroyo HA, Fejerman N. Myoclonic status in nonprogressive encephalopathies: study of 29 cases. Epilepsia. 2007 Jan;48(1):107–13.Google Scholar
  32. 32.
    • Caraballo R, Darra F, Reyes G, Armeno M, Cresta A, Mestre G, et al. The ketogenic diet in patients with myoclonic status in non-progressive encephalopathy. Seizure. 2017;51:1–5. The findings of this study suggest that the ketogenic diet is a promising therapy for patients with myoclonic status in non-progressive encephalopathy as those who responded well to the diet cognitive performance and quality of life also improved.CrossRefPubMedGoogle Scholar
  33. 33.
    Reyes G, Flesler S, Armeno M, Fortini S, Ariela A, Cresta A, et al. Ketogenic diet in patients with epileptic encephalopathy with electrical status epilepticus during slow sleep. Epilepsy Res. 2015;113:126–31.CrossRefGoogle Scholar
  34. 34.
    • Pasca L, Caraballo RH, De Giorgis V, Reyes JG, Macasaet JA, Masnada S, et al. Ketogenic diet use in children with intractable epilepsy secondary to malformations of cortical development: a two-centre experience. Seizure. 2018;57:34–7. The findings of this study of pediatric patients with refractory epilepsy due to malformation of cortical development with ESES suggest that the ketogenic diet should be considered these patients when surgery is not a viable option.CrossRefPubMedGoogle Scholar
  35. 35.
    Caraballo RH, Cersósimo RO, Sakr D, Cresta A, Escobal N, Fejerman N. Ketogenic diet in patients with Dravet syndrome. Epilepsia. 2005;46(9):1539–44.CrossRefGoogle Scholar
  36. 36.
    Dressler A, Trimmel-Schwahofer P, Reithofer E, Mühlebner A, Gröppel G, Reiter-Fink E, et al. Efficacy and tolerability of the ketogenic diet in Dravet syndrome—comparison with various standard antiepileptic drug regimen. Epilepsy Res. 2015;109:81–9. Scholar
  37. 37.
    • Tian X, Chen J, Zhang J, Yang X, Taoyun J, Zhang Y, et al. The efficacy of ketogenic diet in 60 Chinese patients with Dravet syndrome. Front Neurol. 2019;10:625. This large study on ketogenic diet treatment in patients with Dravet syndrome indicates that the diet has many advantages for these patients, as it works rapidly, is effective in more than half of the children, and has tolerable adverse reactions.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Dutton SB, Sawyer NT, Kalume F, Jumbo-Lucioni P, Borges K, Catterall WA, et al. Protective effect of the ketogenic diet in Scn1a mutant mice. Epilepsia. 2011 Nov;52(11):2050–6. Scholar
  39. 39.
    Caraballo RH, Fortini S, Flesler S, Armeno M, Ariela A, Cresta A, et al. Ketogenic diet in patients with Lennox-Gastaut syndrome. Seizure. 2014 Oct;23(9):751–5. Scholar
  40. 40.
    Caraballo R, Noli D, Cachia P. Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet. Epileptic Disord. 2015 Jun;17(2):194–7.PubMedGoogle Scholar
  41. 41.
    Caraballo RH, Reyes G, Avaria MFL, Buompadre MC, Gonzalez M, Fortini S, et al. Febrile infection-related epilepsy syndrome: a study of 12 patients. Seizure. 2013;22:553–9. Scholar
  42. 42.
    Kossoff E, Nabbout R. Use of dietary therapy for status epilepticus. J Child Neurol. 2013;28(8):1049–51.CrossRefGoogle Scholar
  43. 43.
    Gomes D, Pimentel J, Bentes C, Aguiar de Sousa D, Antunes AP, Alvarez A, et al. Consensus protocol for the treatment of super-refractory status epilepticus. Acta Med Port. 2018;31(10):598–605. Scholar
  44. 44.
    Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007;48:43–58.CrossRefGoogle Scholar
  45. 45.
    Rho JM. How does the ketogenic diet induce anti-seizure effects? Neurosci Lett. 2017;637:4–10. Scholar
  46. 46.
    Rogawski MA, Löscher W, Rho JM. Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harb Perspect Med. 2016;6(5):a022780. Scholar
  47. 47.
    Marini C, Scheffer IE, Nabbout R, Suls A, De Jonghe P, Zara F, et al. The genetics of Dravet syndrome. Epilepsia. 2011;52(Suppl 2):24–9. Scholar
  48. 48.
    Chiusolo F, Diamanti A, Bianchi R, Fusco L, Elia M, Capriati T, et al. From intravenous to enteral ketogenic diet in PICU: a potential treatment strategy for refractory status epilepticus. Eur J Paediatr Neurol. 2016;20(6):843–7. Scholar
  49. 49.
    Armeno M, Verini A, Araujo MB, Reyes G, Caraballo RH. Ketogenic parenteral nutrition in three pediatric patients with epilepsy with migrating focal seizures. Epileptic disorders. In press.Google Scholar
  50. 50.
    •• Dressler A, Haiden N, Trimmel-Schwahofer P, Benninger F, Samueli S, Gröppel G, et al. Ketogenic parenteral nutrition in 17 pediatric patients with epilepsy. Epilepsia Open. 2017;3(1):30–9 This study provides an algorithm for ketogenic parenteral nutrition based on the guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for accurate component calculating. Although in half of the patients in this series ketosis was lower than on the oral ketogenic diet, seizures remained controlled.CrossRefGoogle Scholar
  51. 51.
    Caraballo RH, Cersósimo RO, Sakr D, Cresta A, Escobal N, Fejerman N. Ketogenic diet in patients with myoclonic-astatic epilepsy. Epileptic Disord. 2006;8(2):151–5.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurologyHospital de Pediatría Juan P. GarrahanBuenos AiresArgentina

Personalised recommendations