Dr Peter Brukner OAM

4 mins read

While the benefit of the ketogenic diet in children with drug-resistant epilepsy (DRE) has been known for over a century, only recently have studies been published looking at its use in adolescents and adults with DRE

The latest study, published in January 2023 in the journal Neurology, investigated if a Modified Atkins Diet (ketogenic diet) along with standard drug therapy (SDT) was more effective than SDT alone in reducing seizure frequency and improving psychological outcomes at 6 months in adolescents and adults with DRE.
 
A prospective randomized controlled trial was conducted at a tertiary care referral centre, in India. Persons with DRE aged 10-55 years attending outpatient epilepsy clinics between August 2015 and April 2019, who had more than two seizures/month despite using at least three appropriate anti-seizure medications (ASMs) at their maximum tolerated doses and had not been on any form of diet therapy for the past one year, were enrolled. Patients were assessed for the eligibility and randomly assigned to receive SDT plus MAD (intervention arm) or SDT alone (control arm).The primary outcome was >50% reduction in seizure- frequency, and the secondary outcomes were quality of life (QOL), behaviour, adverse events and rate of withdrawal at six months.
 
160 patients (80 adults and 80 adolescents) were randomized to either intervention or control arm. At six months > 50% seizure reduction was seen in 26.2% in the intervention group versus 2.5 % in the control group. Improvement in QOL was 52.1 in the intervention group versus 42.5 in the control group. Behaviour scores could be performed in 49 patients and improvement was seen in intervention versus control group (65.6 versus 71.4) at the end of the study. 
 
This study is consistent with a number of previous studies which show that a ketogenic diet is effective in reducing seizures in those with drug-resistant epilepsy. The results seem consistent among children, adolescents and adults. 

Low carb and childhood epilepsy

The ketogenic diet (KD) has been used to treat epilepsy in children since 1921. The original protocol using a high fat, low carbohydrate diet was created at the Mayo Clinic in Rochester, USA (Wilder, 1921), and popularized by the Johns Hopkins Hospital in Baltimore, MD (Freeman et al.,1998). It is now used in the management of drug-resistant childhood epilepsy in all the leading childrens’ hospitals throughout the world.

In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation.

This study was subsequently updated in 2018.

Goswami and Sharma wrote in 2019 “Ketogenic diet (KD) is a time-tested therapeutic modality for refractory epilepsy, which has re-emerged as a robust alternative to anti-epileptic pharmacotherapy. There is a growing body of evidence which supports the anti-seizure efficacy, safety profile and feasibility of KD use in childhood epilepsy.”

Two meta-analyses were published in 2020. Soubron et al concluded that “Despite the heterogeneity between all studies, the beneficial results underline that dietary interventions should be considered for children and adolescents with refractory epilepsy who are not eligible for epilepsy surgery.” Lyons et al concluded that “Ketogenic diet therapy is an effective treatment option for infants with drug-resistant epilepsy.”

Further references
  1. Liu XY, Chen J, Zhu M, et al. Three and Six Months of Ketogenic Diet for Intractable Childhood Epilepsy: A Systematic Review and Meta-Analysis. Front Neurol. 2019;10:244. doi:10.3389/fneur.2019.00244
  2. Cai Q-Y, Zhou Z-J, Luo R, et al. Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World J Pediatr. 2017;13(6):528-536. doi:10.1007/s12519-017-0053-2
  3. Kim SH, Shaw A, Blackford R, et al. The ketogenic diet in children 3 years of age or younger: A 10-year single-center experience. Scientific Reports. 2019;9(1):8736. doi:10.1038/s41598-019-45147-6
  4. Luz IR, Pereira C, Garcia P, et al. Ketogenic Diet for Refractory Childhood Epilepsy: Beyond Seizures Control, the Experience of a Portuguese Pediatric Centre. Acta Médica Portuguesa. 2019;32(12):760-766. doi:10.20344/amp.12184 PDF
  5. Le Pichon JB, Thompson L, Gustafson M, Abdelmoity A. Initiating the ketogenic diet in infants with treatment refractory epilepsy while maintaining a breast milk diet. Seizure. 2019;69:41-43. doi:10.1016/j.seizure.2019.03.017
  6. Dressler A, Trimmel-Schwahofer P. The ketogenic diet for infants: How long can you go? Epilepsy Res. 2020;164:106339. doi:10.1016/j.eplepsyres.2020.106339 ABSTRACT
  7. Wirrell E, Eckert S, Wong-Kisiel L, Payne E, Nickels K. Ketogenic Diet Therapy in Infants: Efficacy and Tolerability. Pediatr Neurol. 2018;82:13-18. doi:10.1016/j.pediatrneurol.2017.10.018
  8. Sharma S, Goel S, Kapoor D, et al. Evaluation of the Modified Atkins Diet for the Treatment of Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial. J Child Neurol. Published online April 9, 2021:8830738211004747. doi:10.1177/08830738211004747
  9. Zhang J, Chen G, Wang J, et al. Efficacy of the ketogenic diet on ACTH- or corticosteroid-resistant infantile spasm: a multicentre prospective control study. Epileptic Disord. Published online March 26, 2021. doi:10.1684/epd.2021.1256
  10. Lin K-L, Lin J-J, Wang H-S. Application of ketogenic diets for pediatric neurocritical care. Biomedical Journal. Published online July 5, 2020. doi:10.1016/j.bj.2020.02.002
  11. 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;134(5):e1431-1435. doi:10.1542/peds.2013-3106
  12. García-Peñas JJ. S.L.U 2021 Viguera Editores. Epilepsy, cognition, and the ketogenic diet: Neurología.com. doi:10.33588/rn.66S01.2017529

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