| High fat ketogenic diets are used clinically in the treatment of intractable seizures. Although ketosis is a salient feature of the ketogenic diet, the importance of ketosis to seizure control has been difficult to define, primarily because a reliable, noninvasive measure of systemic ketosis is currently unavailable. In this thesis, the usefulness of breath acetone as a measure of systemic ketosis was explored, and the overall objective was to determine if there was a relationship between breath acetone and seizure frequency in children with epilepsy on a ketogenic diet. Children with refractory seizures on a ketogenic diet had significantly elevated breath acetone levels compared to epilepsy and healthy control children (2530 ± 600 nmol/L vs. 19 ± 9 nmol/L and 21 ± 4 nmol/L, respectively; Chapter 6). Breath acetone was a significant predictor of the plasma ketones in mildly ketotic adults (Chapter 5) and in children with epilepsy on a ketogenic diet (Chapter 7). A hand-held breath acetone analyzer (Alcohol Countermeasure Systems Co., Mississauga, Ontario, Canada) was developed to assess breath acetone levels in the home setting. This device reliably measured breath acetone levels >500 nmol/L (Chapter 8). In a two-week study assessing the relationship between daily mean breath acetone and seizure frequency in 6 children on a ketogenic diet, no within or between-subject relationships were found, but there was a trend for children with lower breath acetone levels (<3000 nmol/L) to be seizure-free, while children with higher breath acetone levels (>5000 nmol/L) experienced 0–10 seizures per day (Chapter 9). Ketone body metabolism, as opposed to ketone body concentration, may be important to examine, as this knowledge may explain individual variability in ketone levels, as well as enhance our understanding of the anticonvulsant mechanism of the diet. |
