Elaine Wirrell, Susan Eckert, Lily Wong-Kisiel, Eric Payne and
Katherine Nickels. Ketogenic Diet Therapy in Infants: Efficacy and Tolerability. Pediatric Neurology. In press.
Abstract
Purpose
The aim of this study was to evaluate tolerability and
efficacy of the ketogenic diet in infants less than 12 months of age.
Methods
Infants less than 12 months of age, commencing the ketogenic
diet between 09/2007 and 07/2016 were identified. Records were reviewed for
epilepsy details, diet initiation details, efficacy and tolerability.
Results
27 infants commenced the ketogenic diet (56% male, median
age 7 months). Median age at seizure onset was 1.9 months and 92% had daily
seizures. An epilepsy syndrome was noted in 19 (West-11, Epilepsy in Infancy
with Migrating Focal Seizures-5, Early Myoclonic Encephalopathy-1, Ohtahara-1,
Dravet-1). Infants were on a median of 2 and had failed a median of 1
antiepileptic drugs for lack of efficacy. All initiated a traditional ketogenic
diet at full calories without fasting, and all but one started the diet in
hospital.
Significant hypoglycemia during initiation was seen in two -
both had emesis +/- decreased oral intake. 88% developed urinary ketosis by 48
hours and all were successfully discharged on the diet (median ratio 3:1).
Of those continuing the ketogenic diet, responder rates at
1, 6 and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving
seizure freedom. By 12 months, 2 stopped the diet for serious adverse effects
(1-markedly increased triglycerides, 1-dehydration and severe ketoacidosis), 5
discontinued for lack of efficacy, 6 were lost to follow-up and 2 died of
unrelated causes.
Conclusions
The ketogenic diet is an effective and well-tolerated
treatment for infants with intractable epilepsy. In-hospital initiation is
strongly recommended due to risk of hypoglycemia with emesis or reduced intake.
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From the article
One 10 month old with known acquired structural etiology had
outpatient dietary teaching and then initiated the ketogenic at home, starting
at a 1:1 ratio, and increasing by a ratio of 0.5 per day, with close telephone
follow-up with an experienced ketogenic dietician. This child achieved moderate
to large ketosis within 6 days and had no adverse effects with dietary initiation…
The majority of infants in our study had very severe
epilepsy with daily seizures and etiologies and syndromes highly correlated
with medical intractability. In addition, most also had significant
developmental delay, a common comorbidity of early-life epilepsy. Seizure types
predominantly included both spasms and focal seizures, which are typical of
what are seen in refractory infantile epilepsies. Despite the young age at
which dietary therapy was started (median of 7 months), these children were
clearly medically refractory.
With the exception of one case, all infants were initiated
on the diet in hospital, consistent with the consensus statement recently
published on ketogenic diet initiation in infants. All patients in our study
were started on a traditional ketogenic diet. A recent Korean study found that
a traditional ketogenic diet was significantly more likely to result in seizure
freedom in children younger than two years of age than a modified Atkins diet.
Infants were commenced on a 2:1 ratio, which is higher than the 1:1 ratio
recently recommended in the consensus statement.
No infant was fasted, and all started the diet on full
calories, to minimize the risk of hypoglycemia. Younger children are
potentially at greater risk of hypoglycemia due to more limited glycogen
stores, and the consensus statement also recommended dietary initiation without
fasting in infants. Most, but not all
infants in our study underwent routine glucose checks every 6-12 hours until
ketosis was well-established. However, only two infants developed hypoglycemia
during dietary initiation, and both of these were associated with reduced oral
intake and/or emesis. In both cases, additional glucose checks were performed
based on our protocol, which mandates glucose testing if infants take less than
two thirds of their allotted meal, or with any emesis…
Despite lack of fasting, the majority of infants rapidly
attained ketosis, with nearly all showing urine ketones by 24-48 hours. The
infant brain may be uniquely programmed to utilize ketones. Work in animal
models has shown that as a consequence of high fat content in maternal milk,
the brain metabolism of suckling animals represents a model of naturally
occurring ketosis with an increased rate of uptake and metabolism of ketone
bodies. This unique ability to metabolize ketones may also explain the high
efficacy rates in our study, as well as that of Dressler et al…
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