Ketogenic Diet Effective and Tolerable to Reduce Seizures in Infants

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Although a small-scale study, most infants had a positive response to ketogenic diet, with even greater effects seen in those with Ohtahara syndrome.

Findings from a single-center, retrospective chart study of infants less than 3 months of age showed that a ketogenic diet can be effectively and tolerably administered in this patient population as a therapeutic approach to lowering seizures. The data, presented at the 2023 American Epilepsy Society (AES) annual meeting, held December 1-5, in Orlando, Florida, warrants further research.1

Led by Joo Hi Kim, MD, a professor of pediatric neurology at the Severance Children’s Hospital, Yonsei University College of Medicine, the analysis featured 26 infants who started the ketogenic diet before the age of 3 months between 2009 and 2020. After 3 months, 22 patients comprised the efficacy analysis, with a response rate of 72.7%. Patients who experienced at least a 50% reduction in seizures were considered responders, while non-responders included those who discontinued the diet because of poor compliance, adverse events (AEs), or the need for epilepsy surgery.

After 6 months of observation, 18 patients were assessed, and the response rate was 72.2%. When comparing clinical characteristics, patients with Ohtahara syndrome showed a significant difference in response to the ketogenic diet (P = .010), although this difference was not statistically significant when controlled for etiology. Within the 6-month time frame, 3 patients discontinued their diet because of AEs which included hypoglycemia, aspiration pneumonia, and significant weight loss because of recurrent diarrhea.

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Medical treatment for epilepsy typically includes antiepileptic medications, epilepsy surgery, and vagal stimulation; although, a proportion of children remain with uncontrolled seizures. For many decades, the idea of using a ketogenic diet for infants with epilepsy was discouraged, mainly over concerns about additional complications and the inability to achieve ketosis. Over the years, research has shown that not only can infants become ketotic, but they respond to dietary therapy.

Infantile spasms, a seizure state observed in early infants, is one of the established “indications” for ketogenic diet treatment. In 2019, a single-center, parallel-cohort randomized controlled trial compared the efficacy and safety of the ketogenic diet with standard adrenocorticotropic hormone (ACTH) treatment in infants with West syndrome, the most common infantile onset epileptic encephalopathy. The trial, although underpowered, showed that ketogenic diet is as effective as ACTH in the long term but is better tolerated.2

In total, 151 infants were included, 32 in the randomized controlled portion and 69 in the parallel-cohort. At the conclusion of the 28-day period, electroclinical remission was similar between the ketogenic group and those on ACTH (RCT: 62% vs 69%; PC: 41% vs 38%; combined cohort: 47% vs 48%). In the combined cohort, time to electroclinical remission was similar between both treatments (14 days for ketogenic diet; 16 days for ACTH); however, relapse rates were 16% for the ketogenic diet group and 43% for those on ACTH (P = .09).

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REFERENCES
1. Kim JH, Ko A, Lee Ej, et al. Efficacy and safety of the ketogenic diet in young infants less than 3 months of age. Presented at: 2023 AES annual meeting; December 1-5; Orlando, FL. POSTER 3.328
2. 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. doi:10.1111/epi.14679
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