Biochemical implications of ketogenic diet in children with intractable epilepsy: a metabolimics approach.

Anti-epileptic drugs are the treatment of first choice in childhood epilepsy.
In case of treatment failure, which occurs in 10-20% of the children, there is
a need for other treatment options such as the ketogenic diet. Each year, 40-50
children with intractable epilepsy start with the ketogenic diet, which is
prescribed in a limited number of centres in the Netherlands. The ketogenic
diet consists of high fat and low carbohydrate and protein concentrates. Fat
will be the most important energy source instead of carbohydrates. The aim of
the diet is to come in ketosis. Ketosis probably plays a role in the reduction
of the number of epileptic seizures, but it is still unclear in which way this
influences the brain metabolism and how it protects against seizures. At this
moment it can not be predicted in which child the ketogenic diet will be
effective. This diet has, however, a large impact on daily life of both patient
and parents/caretakers because of the radical changes in eating habits.

Because the ketogenic diet has a large impact on daily life of both patient and
parents/caretakers, it would be a great improvement if one would be able to
predict the effectiveness at a much earlier stage. We hope to be able to trace
mechanisms by which the ketogenic diet exerts its effects and to find (a)
predictive marker(s), in order to predict earlier if the diet will be effective.
The study performed in the UMCG will be a pilot study investigating metabolic
changes during the ketogenic diet. In this way, we hope to gain more insight
into the effects of the ketogenic diet on metabolic profiles and changes
therein and possibly to find (a) prediction marker(s).

During the treatment with ketogenic diet additional investigations will be
performed to better understand the effects of the ketogenic diet on metabolic
profiles and changes therein. A number of additional laboratory provisions will
be made, both in blood and in urine. Using a glucose sensor meter gives the
opportunity to continuously monitor glucose levels during 24 - 48 h. Apart from
clinical reasons to monitor glucose levels continuously, it also offers the
possibility to examine the possible relationship between glucose level, the
degree of ketonemia and the time of taking the meal.

The extra investigations will take place during regular visits, so the
additional burden is limited. For the regular treatment with ketogenic diet,
frequent examinations in blood and urine have to be performed. Our pilot study
only needs 3 extra blood drawings, which is acceptable to our opinion. The
blood necessary for the remaining investigations will be taken during the same
puncture as the regular control. Using a glucose sensor meter, information
about the glucose levels can be easily obtained every five minutes through a
subcutaneous needle, which can stay in position for 24 to 48 h. As a result,
only one puncture is necessary to obtain information over this period, which
makes the glucose sensor meter user-friendly.