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Ketogenic Diet for Refractory Status Epilepticus in Children

  • Pediatrics in South America (L Landry and WB de Carvalho, Section Editor)
  • Published:
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Abstract

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.

Summary

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.

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References and Recommended Reading

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  1. Stafstrom CE. Dietary approaches to epilepsy treatment: old and new options on the menu. Epilepsy Curr. 2004;4(6):215–22.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  3. Caraballo R. Dieta Cetogena en el tratamiento de la epilepsia. Buenos Aires: Editorial Journal; 2016.

    Google Scholar 

  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. https://doi.org/10.1016/j.eplepsyres.2012.01.015.

    Article  CAS  Google Scholar 

  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. •• 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. https://doi.org/10.1002/epi4.12225 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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1007/s12028-011-9546-3.

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1212/WNL.0000000000000151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1111/j.1528-1167.2009.02388.

  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.

    Article  Google Scholar 

  11. Sahin M, Menache CC, Holmes GL, Riviello JJ. Outcome of severe refractory status epilepticus in children. Epilepsia. 2001;42(11):1461–7.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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. https://doi.org/10.1016/j.neurol.2007.08.009.

    Article  CAS  Google Scholar 

  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. https://doi.org/10.5698/1535-7597-16.1.48.

    Article  PubMed  PubMed Central  Google Scholar 

  15. • Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super-refractory status epilepticus. Seizure. 2019;68:62–71. https://doi.org/10.1016/j.seizure.2018.05.012 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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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 ketosis

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1177/0883073809347597.

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1111/j.1469-8749.2008.03216.x.

    Article  Google Scholar 

  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. https://doi.org/10.1111/j.1528-1167.2010.02703.x.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.eplepsyres.2014.09.033.

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.pediatrneurol.2013.07.020.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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. https://doi.org/10.1016/j.seizure.2016.07.006.

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s12028-016-0312-4 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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. https://doi.org/10.1016/j.braindev.2018.12.007.

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.3389/fneur.2019.00423 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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1684/epd.2015.0781.

    PubMed  Google Scholar 

  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.

  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. https://doi.org/10.1016/j.seizure.2017.07.002 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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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. https://doi.org/10.1016/j.seizure.2018.03.005 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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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. https://doi.org/10.1016/j.eplepsyres.2014.10.014.

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.3389/fneur.2019.00625 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.

    Article  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1111/j.1528-1167.2011.03211.x.

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1016/j.seizure.2014.06.005.

    Article  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.seizure.2013.04.005.

    Article  PubMed  Google Scholar 

  42. Kossoff E, Nabbout R. Use of dietary therapy for status epilepticus. J Child Neurol. 2013;28(8):1049–51.

    Article  Google Scholar 

  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. https://doi.org/10.20344/amp.9679.

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  45. Rho JM. How does the ketogenic diet induce anti-seizure effects? Neurosci Lett. 2017;637:4–10. https://doi.org/10.1016/j.neulet.2015.07.034.

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1101/cshperspect.a022780.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1111/j.1528-1167.2011.02997.x.

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.ejpn.2016.08.004.

    Article  CAS  PubMed  Google Scholar 

  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.

  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.

    Article  Google Scholar 

  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.

    PubMed  Google Scholar 

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  1. Department of Neurology, Hospital de Pediatría Juan P. Garrahan, Combate de los Pozos 1881, C1245AAM, Buenos Aires, Argentina

    Roberto Caraballo MD

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Caraballo, R. Ketogenic Diet for Refractory Status Epilepticus in Children. Curr Treat Options Peds 5, 417–430 (2019). https://doi.org/10.1007/s40746-019-00185-0

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