and investigate the usefulness of the EEC as a predictor of the subjectsresponse to the KD, In Phase 1, the current practices for initiation of the ketogenic diet and its efficacy (defined as >50% reduction ofseizure frequency at the 3-month interval compared to baseline) will be investigated. We propose that a gradualintroduction of the KD, without a 24 to 48 hour preceding fast (Grad-KD), is as safe and efficacious as the currentlyrecommended initiation of the KD (CR-KD) with fast. Safety of the two protocols will be evaluated during a six-dayinpatient admission and the first three months of exposure. Efficacy will be determined at three months. Baseline and 1-month changes in the routine electroencephalogram (EEG) will be examined simultaneously. The predictive power of thechanges between the baseline and 1-month EEG for the 3-month response (defined above) will be shown in those EEGrecords that have diminished background slowing or reduction of potentially epileptogenic discharges. In a pilot studywe will investigate the mechanistic hypothesis that the antiepileptic properties of the KD is dueto anincrease inCNS-Gamma Amino Butyric Acid (GABA), asmeasured by MRI Spectroscopy at baseline, 0.5-month and3-month in the CR-KD therapy. We will also examine the association between changes in CNS-GABA at 0.5-month andresponse to KD therapy (defined above). In Phase 2, subjects who have demonstrated a positive response at 3 months will be followed. The maintenance KDin responders on two caloric intakes will be evaluated. The currently recommended KD is hypocaloric, providing only 75%of subject's caloric needs, and does not allow any weight gain for the 12 months duration of treatment. The necessity ofsemi-starvation to maintain a positive clinical response has not been evaluated scientifically. We will examine if aEucaloric KD (Eu-KD), with adequate calories for the subject allowing for normal weight gain, is as effective as thecurrently recommended Hypocaloric KD (Hypo-KD) with no weight gain or loss over 12 months. As part of this evaluation,comparisons of two methods used to estimate caloric needs, Recommended Daily Allowance (RDA) tables and RestingEnergy Expenditure (by indirect calorimetry), will be made. In addition, the effect of the KD on several nutritionalDarameters including anthropometry, body composition and bone mineral status, will be evaluated, allowing the 12-monthimpact of the Eu-KD versus Hypo-KD diets on nutritional status to be compared.
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