Ketogenic Diet for Infantile Spasms: Is it a viable option instead of steroids?

Since 2001, there has been a significant amount of research showing the ketogenic diet can be a very helpful treatment for infantile spasms. Approximately 20 articles have focused on the use of the diet for infantile spasms that typically have failed to respond to the two standard, “first-line” agents of steroids (either ACTH or oral prednisolone) or vigabatrin.

An excellent recent review article by Prezioso et al. highlighted 13 papers and found that altogether a median of 65% of children had greater than 50% spasm reduction by 6 months and 35% were spasm-free. In this review, it appeared that infants without a clear cause for their infantile spasms were more likely to respond. We have highlighted this research in a Keto News article from July 2010, "Infantile Spasms and the Diet: The Evidence Grows."

So if the ketogenic diet works so well as a third agent (after steroids and vigabatrin), why not try it first?

We have done this. Back now just over a decade ago, we published our results using the ketogenic diet as a first-line therapy for infantile spasms.

• These infants were brought to medical attention within 2 weeks, so other “alternative” options could be considered for a short trial period before moving on to steroids or vigabatrin.
• In the 13 babies we published about, 8 (62%) became spasm-free.
• These results were compared to an ACTH cohort retrospectively (it was not a randomized, prospective trial). Although the results were higher with ACTH (90%), it did not reach statistical significance as a difference.
• You can read more about this in a 2008 Keto News article, "Using the Diet for Epilepsy First?," and from the Carson Harris Foundation website (a support group started by one of these families).

We have continued to treat infants with new onset infantile spasms for the past decade with continued good results. However, there were no other papers using the ketogenic diet in this way until just now.

New Research from Viennese Team

An article was just published in March in the journal Epilepsia by Dressler and her colleagues from Vienna, Austria. They designed a randomized controlled trial comparing the ketogenic diet to high-dose ACTH for infants who had not received either before. They could have been treated with vigabatrin (and therefore technically were not “new onset” infantile spasms patients). In addition, they also included infants who did not enter the trial (for various reasons), but still fit the criteria for the study and had not been treated with either ACTH or ketogenic diet therapy.

What were the results?

• In the combined group of 101 infants, there was no difference in spasm freedom by 28 days (47% for the ketogenic diet versus 48% for ACTH).
• The time to respond with a normal EEG (electroencephalogram) was also the same (14 vs. 16 days respectively).
• Relapse of spasm rates were higher for ACTH (43% vs. 16%), but this was not statistically significant.
• Side effects were much higher with ACTH (94% vs. 30%).

What about for those “new-onset” infants (the ones who had not been treated before with vigabatrin (or steroids or ACTH)?

• In this group of 50 babies, the results were better at 28 days with ACTH (80% vs. 47%).
• However, results at the last time these babies were seen in clinic (which represents long-term outcome to some degree), they saw the opposite trend: 48% spasm-free with the ketogenic diet vs. 21% with ACTH.
• It was thought that maybe this represents the higher relapse rate seen with ACTH, and therefore those babies treated with the ketogenic diet became and stayed spasm-free for longer.

What does this mean?

This was a small study, but now adds a second paper to ours with similar results. The ketogenic diet may be a feasible and successful treatment for infantile spasms before using steroids or vigabatrin.

Obviously every infant is different. Some centers may not be comfortable with this approach, and we need more studies to truly prove these treatments are equivalent. However, this paper continues to show that for some epilepsy conditions, the ketogenic diet can be thought of as worth considering before medications.

References

• Dressler A, Benninger F, Trimmel-Schwahofer P, et al. Efficacy and tolerability of the ketogenic diet versus high-dose adrenocorticotropic hormone for infantile spasms: A single-center parallel-cohort randomized controlled trial. Epilepsia 2019;60 (3), 441-451. https://www.ncbi.nlm.nih.gov/pubmed/30801699
• Kossoff EH, Hedderick EF, Turner Z, Freeman JM. A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia 2008;49:1504-1509. https://www.ncbi.nlm.nih.gov/pubmed/18410363
• Hong AM, Turner Z, Hamdy RF, Kossoff EH. Infantile spasms treated with the ketogenic diet: prospective single-center experience in 104 consecutive infants. Epilepsia, 2010; 51 (8),1403‐1407. https://www.ncbi.nlm.nih.gov/pubmed/20477843
• Prezioso G, Carlone G, Zaccara G, Verrotti A. Efficacy of ketogenic diet for infantile spasms: A systematic review. Acta Neurol Scand. 2017;37 (1), 4-11. https://www.ncbi.nlm.nih.gov/pubmed/28875525