Abstracts

RATIONALE: The ketogenic diet (KD) has been used to treat pharmacoresistant epilepsy, both idiopathic and symptomatic, especially in children. The efficacy of the KD has been evaluated in myoclonic, atonic, simple partial and complex partial, generalized tonic, tonic-clonic, typical and atypical absence seizures, with an overall efficacy range of 33-100%. However, the mechanisms underlying the efficacy of the KD in the treatment of seizure disorders is still not clarified. In this experiment, we studied the effects of KD and starving which also increases the circulating levels of ketone bodies on the expression of spike-and-wave discharges (SWD) in our genetic model of absence seizures, the GAERS.
METHODS: Sixteen adult GAERS with fully developed expression of SWD were used for this study. The baseline measurement of number and duration of SWD was performed on rats receiving their normal carbohydrate-rich diet. Eight rats were then exposed to the KD (provided by Harlan) for 2 weeks while 8 GAERS were fasted over 3 days. The number and duration of SWD were recorded on days 1, 2, 3, 4, 7, 10 and 14. The concentration of glucose and beta-hydroxybutyrate (BHB) was measured in the plasma during the period of treatment.
RESULTS: In animals receiving a normal carbohydrate-rich diet, glucose concentration reached 1.25 mg/ml. It was reduced by 2-fold after 3 days of fasting; blood glucose level decreased by 30% after 24 h of KD, normalized at 48 h and remained in the normal range for the remaining duration of the treatment by the KD. BHB levels increased from very low values in GAERS with a control diet to 7.3-11.4 [mu]M in rats under KD and 5.6 mM in fasting rats. However, there was no change in either the number or duration of SWD over the 3 days of fasting or the 14 days of KD treatment.
CONCLUSIONS: Thus, although the KD is able to improve seizure occurrence in children with typical absence epilepsy, we did not record any effect of fasting or of the diet in our genetic model of absence seizures. Neither the time that the animals spend in expressing the seizures nor the total number of seizures reflecting excitability are affected. These data show that, at least in GAERS, the KD does not seem to critically affect the specific balance between GABA and glutamate that we hypothesized to underlie the occurrence of absence seizures.
Support: INSERM U 398