Studies Show Benefit of Ketogenic Diet for Steroid-refractory Infantile Spasms

Keto News (1).png

Epilepsy News From:

Wednesday, April 28, 2021

Over the past 14 years, we have periodically profiled articles that have demonstrated the value of ketogenic diets, often in formula/liquid form, to babies with infantile spasms. For this particularly troubling form of epilepsy, the gold-standard first-line therapies historically used are steroids (e.g. prednisolone or ACTH) or vigabatrin. However, these drugs can have significant side effects and for decades doctors have looked for alternative choices.

Keto News back in July 2010 highlighted a large series from our hospital of 104 infants treated with the ketogenic diet. Just recently, in May 2019, Keto News reported on a study from Austria of a group of 50 babies who had NOT been treated with steroids or vigabatrin had excellent outcomes when the ketogenic diet was used as a first-line therapy.   

Over the past few weeks, the results from 2 large studies were published.

Results from China

The first study I had become aware of back in 2018 at the biannual ketogenic diet conference in Jeju, South Korea, where early results were shown to the audience. Dr. Yuwu Jiang, a Professor and Director of the Department of Pediatrics at Peking University First Hospital in Beijing, presented the information and was the fourth author of this paper, which was just published online in the journal Epileptic Disorders

ketonews.jpg
Dr. Jiang lecturing in Beijing in 2019

What were the results?

In this study, 227 children were divided into two groups: 135 went on the ketogenic diet and 92 were treated with the same anti-seizure medications (control).  All of the children had tried steroids for infantile spasms unsuccessfully. This is perhaps the largest randomized, controlled trial ever performed of the ketogenic diet to my knowledge.

  • Children treated with the ketogenic diet were significantly more likely to have >50% spasm reduction and/or EEG normalization (41% vs. 21%).
  • Children on the ketogenic diet were also more likely to be spasm-free for at least a week with normal EEG, but it wasn’t statistically significant (13% vs. 11%).
  • It didn’t matter what the etiology was (prior studies have shown that infantile spasms that was “idiopathic” (no cause found) did better)…and also younger age didn’t influence outcomes.
  • Ketone levels also didn’t correlate with spasm improvement.
  • Surprisingly, a LOWER ketogenic ratio (<3:1) did seem to matter for spasm-freedom. The reasons for this aren’t clear.

Second study from India

In early April, results were published in Journal of Child Neurology using a slightly different diet (the modified Atkins diet) but with a similar idea – randomizing infants who had failed steroids (and often up to 4 other antiseizure medications) to either diet or continued medications (4 weeks of waiting to start the diet).  In this study done at Lady Hardinge Medical College in New Delhi, India, 46 infants received the modified Atkins diet immediately with 45 in the control group (waiting 4 weeks).

ketonews2.png
First author, Dr. Suvasini Sharma, who was the prestigious Sheila Wallace Awardee at the Child Neurology Society Annual Meeting this past year.

What were the results?

  • 11/46 on the diet were spasm-free compared to 0/45 controls.
  • Similarly, 30/46 on the diet had >50% spasm reduction compared to 0/45 controls.  
  • Side effects with the Modified Atkins Diet were mild and mostly constipation, sedation, and occasionally poor appetite.

What does all of this mean?

The results of these two large studies continue to demonstrate to neurologists that the ketogenic diet is a very valuable treatment for infantile spasms.  In both studies, babies were treated with steroids first, as is often done worldwide. When it didn’t work, the neurologists then were also faced with a similar decision – try other drugs (e.g. vigabatrin, topiramate) if not used before OR ketogenic diet therapy. The ketogenic (or Modified Atkins) diet were better. I suspect this research will continue to convince neurologists that the ketogenic diet should absolutely be used earlier: perhaps (as in the study from China) second-line, and maybe even first-line (if spasms have only been going on a couple of weeks) based on 2 studies from our center and Austria. Certainly more research is needed before the ketogenic diet is placed in guidelines before steroids and/or vigabatrin, but the growing research is absolutely intriguing!

REFERENCES

Zhang J, Chen G, Wang J, Jiang Y, Yang Z, Xu K, Peng J, Zhou S, Jiang L, Li B, Zhang D, Liu Z, Huang L, Chen C, Fang F, Chen Y, Wu Y, Zhong J, Zha J, Yin F, Yu L, Wu Y.   Efficacy of the ketogenic diet on ACTH- or corticosteroid-resistant infantile spasm: a multicentre prospective control study.  Epileptic Disorders. 2021 Mar 26. doi: 10.1684/epd.2021.1256. Online ahead of print.

Sharma S, Goel S, Kapoor D, Garg D, Panda I, Elwadhi A, Patra B, Mukherjee SB, Pemde H.  Evaluation of the Modified Atkins Diet for the treatment of epileptic spasms refractory to hormonal therapy: A randomized controlled trial.  J Child Neurology 2021 April 9.  doi: 10.1177/08830738211004747.  Online ahead of print.

Authored by: Eric Kossoff MD on 4/2021

Our Mission

The mission of the Epilepsy Foundation is to lead the fight to overcome the challenges of living with epilepsy and to accelerate therapies to stop seizures, find cures, and save lives.

 
24/7 helpline
P