By Eric Kossoff MD
Editor, Keto News

In the November 2008 edition of Keto News, information regarding the use of the ketogenic diet as a first-line therapy was discussed. The condition for which this novel concept was first proposed was infantile spasms. Perhaps no more frightening to a child neurologist and parent, infantile spasms, otherwise known as West Syndrome, affects 1 in 2000 infants typically aged 3-8 months. Seizures can range from subtle head nods to full-body flexion movements and can also be associated with regression in normal developmental skills. Treatments often include corticosteroids (ACTH or prednisolone) and vigabatrin, but these medications are not always effective and have potential for serious side effects.

Figure: EEG of hypsarrhythmia (the pattern seen in infantile spasms)

In 2001, Dr. Douglas Nordli and his group from Children’s Memorial Hospital in Chicago reported on their experience with 32 infants using the ketogenic diet. Of these, 17 had infantile spasms. The diet was very helpful, with 70% having a >50% spasm reduction (half of whom became spasm-free). One year later, our group at Johns Hopkins Hospital reported on the benefits of the ketogenic diet specifically for infantile spasms, with similar results in a series of 23 infants (59% having a >50% spasm reduction). In 2005, the group from South Korea also described beneficial results in 43 infants, with identical percentage improvement to Dr. Nordli’s group.

Figure: Carson Harris, an infant successful treated with the ketogenic diet for infantile spasms at our institution (www.carsonharrisfoundation.org)

The 2008 study from our group looked at results using the ketogenic diet for infantile spasms as a first-line therapy, compared to the previous three studies which predominantly described the results in infants who had failed standard therapies such as corticosteroids and vigabatrin first. Eight of 13 (62%) became spasm-free within 2 weeks of starting the diet and only one relapsed months later. As a result, the ketogenic diet is often suggested as a first-line treatment option at our hospital. As of today, 11 of 19 (58%) have been successfully treated in this way.

Last month, we presented updated information on our entire group of children since 1996 treated with the ketogenic diet at Johns Hopkins Hospital, both new-onset and those who were difficult-to-control. As a result of the previously mentioned four studies, interest in the ketogenic diet for infantile spasms is definitely at an all-time high, and I have seen a tremendous increase in the number of emails from parents and requests from neurologists to start the diet. We have since increased the children treated for infantile spasms with the diet 5-fold, to now 104 infants. Ms. Amanda Hong, a current second-year medical student at Johns Hopkins University School of Medicine, chose to research this group of patients and see if things had changed since our 2002 publication.

Ms. Amanda Hong, lead investigator

The results with this larger group of patients were generally the same, confirming prior studies. Most of the children had tough infantile spasms, with an average of 3.6 drugs tried and 7 of 10 having tried corticosteroids or vigabatrin (without success). Sixty-four percent had >50% improvement after 6 months, including those who stopped the diet before then (an “intent-to-treat” analysis). About a third of infants had prolonged periods of spasm-freedom, occasionally permanent. Side effects did occur in about a third of infants, including constipation, linear growth decline, and elevated cholesterol.

This larger number of infants allowed us to investigate factors that might predict success more accurately. In 2002, we found that trying fewer medications and being younger was tied to success on the diet. Now in 2010, the only statistically significant factor was being OLDER when the diet was started (by about one month). There was a slightly higher chance of success still for trying fewer medications before the diet (including steroids). All other factors, including cause for the infantile spasms, gender, EEG, and the ketogenic ratio did not matter.

What do these results tell us? I think first and foremost, the ketogenic diet has clearly demonstrated itself to be a very reasonable third-line treatment for infantile spasms after corticosteroids and vigabatrin, with results at least equal to any other treatment available. The 2009 expert consensus statement isted infantile spasms as one of the “indications” for the ketogenic diet and these results confirm this. There is also early evidence that the ketogenic diet could be an option first if the family is willing and the spasms started relatively recently. Future directions might include combination therapy (e.g. vigabatrin and the ketogenic diet) and results from larger series of new-onset infants. I also think the ketogenic diet would be used more widely for these infants if a set, pre-measured, simplified ketogenic diet formula could be designed (for an average 6-month-old infant) and used in situations where a dietitian was not immediately available to start the ketogenic diet.

References

• www.carsonharrisfoundation.org
• Eun SH, Kang HC, Kim DW, Kim HD. (2006) Ketogenic diet for treatment of infantile spasms. Brain Dev 28:566–571.
• Kossoff EH, Pyzik PL, McGrogan JR, Vining EPG, Freeman JM. (2002) Efficacy of the ketogenic diet for infantile spasms. Pediatrics 109:780–783.
• Kossoff EH, Hedderick EF, Turner Z, Freeman JM. (2008) A case–control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia 49:1504–1509.
• Hong AM, Hamdy RF, Turner Z, Kossoff EH. Infantile spasms treated with the ketogenic diet: Prospective single-center experience in 104 consecutive infants. Epilepsia, online early 2010.
• Mackay MT, Weiss SK, Adams-Webber T, Ashwal S, Stephens D,Ballaban-Gil K, Baram TZ, Duchowny M, Hirtz D, Pellock JM, Shields WD, Shinnar S, Wyllie E, Snead OC. (2004) Practice parameter: medical treatment of infantile spasms: report of the American Academy of neurology and the child neurology society. Neurology 62:1668–1681.
• Nordli DR, Kuroda MM, Carroll J, Koenigsberger DY, Hirsch LJ, Bruner HJ, Seidel WT, De Vivo DC. (2001) Experience with the ketogenic diet in infants. Pediatrics 108:129–133.

Topic Editor: Robert S. Fisher, M.D., Ph.D.
Last reviewed 6/17/10