KD Treatment for Super-refractory Status Epilepticus

Summary

The purpose of the study is to investigate to evaluate the efficacy and safety of ketogenic diet (KD) as an adjunctive therapy in patients with Super Refractory Status Epilepticus (SRSE) in the intensive care unit (ICU).

Timeline

Start

2025-10-20

Primary completion

2027-02-01

Completion

2027-03-01

Publications

• Background Singh RK, Joshi SM, Potter DM, Leber SM, Carlson MD, Shellhaas RA. Cognitive outcomes in febrile infection-related epilepsy syndrome treated with the ketogenic diet. Pediatrics. 2014 Nov;134(5):e1431-5. doi: 10.1542/peds.2013-3106.
• Background Li Y, Yang X, Zhang J, Jiang T, Zhang Z, Wang Z, Gong M, Zhao L, Zhang C. Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites. mBio. 2021 Mar 30;12(2):e03601-20. doi: 10.1128/mBio.03601-20.
• Background Nabbout R, Mazzuca M, Hubert P, Peudennier S, Allaire C, Flurin V, Aberastury M, Silva W, Dulac O. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia. 2010 Oct;51(10):2033-7. doi: 10.1111/j.1528-1167.2010.02703.x. Epub 2010 Aug 31.
• Background 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. doi: 10.1111/j.1528-1167.2009.02388.x. Epub 2009 Oct 20.
• Background Mahmoud SH, Ho-Huang E, Buhler J. Systematic review of ketogenic diet use in adult patients with status epilepticus. Epilepsia Open. 2019 Nov 24;5(1):10-21. doi: 10.1002/epi4.12370. eCollection 2020 Mar.
• Background Yudkoff M, Daikhin Y, Horyn O, Nissim I, Nissim I. Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia. 2008 Nov;49 Suppl 8(Suppl 8):73-5. doi: 10.1111/j.1528-1167.2008.01841.x.
• Background Lowe H, Keller AE, Tanzini E, Aimola S, Liu YMC, Zak M, Chan V, Kobayashi J, Donner EJ. Ketonuria and Seizure Control in the Medium Chain Triglyceride and Classic Ketogenic Diets. Can J Neurol Sci. 2022 May;49(3):433-436. doi: 10.1017/cjn.2021.122. Epub 2021 Jun 2.
• Background Kaul N, Nation J, Laing J, Nicolo JP, Deane AM, Udy AA, Kwan P, O'Brien TJ. Modified low ratio ketogenic therapy in the treatment of adults with super-refractory status epilepticus. JPEN J Parenter Enteral Nutr. 2022 Nov;46(8):1819-1827. doi: 10.1002/jpen.2373. Epub 2022 Apr 7.
• Background van der Louw E, Aldaz V, Harvey J, Roan M, van den Hurk D, Cross JH, Auvin S; Review Group. Optimal clinical management of children receiving ketogenic parenteral nutrition: a clinical practice guide. Dev Med Child Neurol. 2020 Jan;62(1):48-56. doi: 10.1111/dmcn.14306. Epub 2019 Jul 16.
• Background Kaul N, Laing J, Nicolo JP, Nation J, Kwan P, O'Brien TJ. Practical Considerations for Ketogenic Diet in Adults With Super-Refractory Status Epilepticus. Neurol Clin Pract. 2021 Oct;11(5):438-444. doi: 10.1212/CPJ.0000000000001009.
• Background Martin-McGill KJ, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020 Jun 24;6(6):CD001903. doi: 10.1002/14651858.CD001903.pub5.
• Background Buchhalter JR, D'Alfonso S, Connolly M, Fung E, Michoulas A, Sinasac D, Singer R, Smith J, Singh N, Rho JM. The relationship between d-beta-hydroxybutyrate blood concentrations and seizure control in children treated with the ketogenic diet for medically intractable epilepsy. Epilepsia Open. 2017 May 19;2(3):317-321. doi: 10.1002/epi4.12058. eCollection 2017 Sep.
• Background Gilbert DL, Pyzik PL, Freeman JM. The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones. J Child Neurol. 2000 Dec;15(12):787-90. doi: 10.1177/088307380001501203.
• Background van Delft R, Lambrechts D, Verschuure P, Hulsman J, Majoie M. Blood beta-hydroxybutyrate correlates better with seizure reduction due to ketogenic diet than do ketones in the urine. Seizure. 2010 Jan;19(1):36-9. doi: 10.1016/j.seizure.2009.10.009. Epub 2009 Dec 3.
• Background Breu M, Hafele C, Glatter S, Trimmel-Schwahofer P, Golej J, Male C, Feucht M, Dressler A. Ketogenic Diet in the Treatment of Super-Refractory Status Epilepticus at a Pediatric Intensive Care Unit: A Single-Center Experience. Front Neurol. 2021 Jun 3;12:669296. doi: 10.3389/fneur.2021.669296. eCollection 2021.
• Background Cervenka MC, Hocker S, Koenig M, Bar B, Henry-Barron B, Kossoff EH, Hartman AL, Probasco JC, Benavides DR, Venkatesan A, Hagen EC, Dittrich D, Stern T, Radzik B, Depew M, Caserta FM, Nyquist P, Kaplan PW, Geocadin RG. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology. 2017 Mar 7;88(10):938-943. doi: 10.1212/WNL.0000000000003690. Epub 2017 Feb 8.
• Background Francis BA, Fillenworth J, Gorelick P, Karanec K, Tanner A. The Feasibility, Safety and Effectiveness of a Ketogenic Diet for Refractory Status Epilepticus in Adults in the Intensive Care Unit. Neurocrit Care. 2019 Jun;30(3):652-657. doi: 10.1007/s12028-018-0653-2.
• Background Park EG, Lee J, Lee J. The ketogenic diet for super-refractory status epilepticus patients in intensive care units. Brain Dev. 2019 May;41(5):420-427. doi: 10.1016/j.braindev.2018.12.007. Epub 2019 Jan 9.
• Background Caraballo RH, Flesler S, Armeno M, Fortini S, Agustinho A, Mestre G, Cresta A, Buompadre MC, Escobal N. Ketogenic diet in pediatric patients with refractory focal status epilepticus. Epilepsy Res. 2014 Dec;108(10):1912-6. doi: 10.1016/j.eplepsyres.2014.09.033. Epub 2014 Oct 13.
• Background Appavu B, Vanatta L, Condie J, Kerrigan JF, Jarrar R. Ketogenic diet treatment for pediatric super-refractory status epilepticus. Seizure. 2016 Oct;41:62-5. doi: 10.1016/j.seizure.2016.07.006. Epub 2016 Jul 21.
• Background Arya R, Peariso K, Gainza-Lein M, Harvey J, Bergin A, Brenton JN, Burrows BT, Glauser T, Goodkin HP, Lai YC, Mikati MA, Fernandez IS, Tchapyjnikov D, Wilfong AA, Williams K, Loddenkemper T; pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018 Aug;144:1-6. doi: 10.1016/j.eplepsyres.2018.04.012. Epub 2018 Apr 27.
• Background Thakur KT, Probasco JC, Hocker SE, Roehl K, Henry B, Kossoff EH, Kaplan PW, Geocadin RG, Hartman AL, Venkatesan A, Cervenka MC. Ketogenic diet for adults in super-refractory status epilepticus. Neurology. 2014 Feb 25;82(8):665-70. doi: 10.1212/WNL.0000000000000151. Epub 2014 Jan 22.
• Background Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2012 Mar 14;(3):CD001903. doi: 10.1002/14651858.CD001903.pub2.
• Background Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008 Jun;7(6):500-6. doi: 10.1016/S1474-4422(08)70092-9. Epub 2008 May 2.
• Background Goswami JN, Sharma S. Current Perspectives On The Role Of The Ketogenic Diet In Epilepsy Management. Neuropsychiatr Dis Treat. 2019 Nov 25;15:3273-3285. doi: 10.2147/NDT.S201862. eCollection 2019.
• Background Dahlin M, Hjelte L, Nilsson S, Amark P. Plasma phospholipid fatty acids are influenced by a ketogenic diet enriched with n-3 fatty acids in children with epilepsy. Epilepsy Res. 2007 Feb;73(2):199-207. doi: 10.1016/j.eplepsyres.2006.10.005. Epub 2006 Dec 5.
• Background Lindefeldt M, Eng A, Darban H, Bjerkner A, Zetterstrom CK, Allander T, Andersson B, Borenstein E, Dahlin M, Prast-Nielsen S. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes. 2019 Jan 23;5(1):5. doi: 10.1038/s41522-018-0073-2. eCollection 2019.
• Background Masino SA, Rho JM. Mechanisms of Ketogenic Diet Action. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012. Available from http://www.ncbi.nlm.nih.gov/books/NBK98219/
• Background Tagliabue A, Ferraris C, Uggeri F, Trentani C, Bertoli S, de Giorgis V, Veggiotti P, Elli M. Short-term impact of a classical ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month prospective observational study. Clin Nutr ESPEN. 2017 Feb;17:33-37. doi: 10.1016/j.clnesp.2016.11.003. Epub 2016 Dec 18.
• Background Zhang Y, Zhou S, Zhou Y, Yu L, Zhang L, Wang Y. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res. 2018 Sep;145:163-168. doi: 10.1016/j.eplepsyres.2018.06.015. Epub 2018 Jun 28.
• Background Bromfield E, Dworetzky B, Hurwitz S, Eluri Z, Lane L, Replansky S, Mostofsky D. A randomized trial of polyunsaturated fatty acids for refractory epilepsy. Epilepsy Behav. 2008 Jan;12(1):187-90. doi: 10.1016/j.yebeh.2007.09.011.
• Background Abdallah DM. Anticonvulsant potential of the peroxisome proliferator-activated receptor gamma agonist pioglitazone in pentylenetetrazole-induced acute seizures and kindling in mice. Brain Res. 2010 Sep 10;1351:246-253. doi: 10.1016/j.brainres.2010.06.034. Epub 2010 Jun 21.
• Background Trinka E, Kalviainen R. 25 years of advances in the definition, classification and treatment of status epilepticus. Seizure. 2017 Jan;44:65-73. doi: 10.1016/j.seizure.2016.11.001. Epub 2016 Nov 14.
• Background Kantanen AM, Reinikainen M, Parviainen I, Ruokonen E, Ala-Peijari M, Backlund T, Koskenkari J, Laitio R, Kalviainen R. Incidence and mortality of super-refractory status epilepticus in adults. Epilepsy Behav. 2015 Aug;49:131-4. doi: 10.1016/j.yebeh.2015.04.065. Epub 2015 Jul 2.
• Background Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011 Oct;134(Pt 10):2802-18. doi: 10.1093/brain/awr215. Epub 2011 Sep 13.

Drugs

Indications