Abstracts

Rationale: The modified Atkins diet (MAD) is prescribed for adults with drug-resistant epilepsy. MAD stimulates fat metabolism, producing ketone bodies that can be measured in the blood, breath, and urine. The Johns Hopkins Adult Epilepsy Diet Center (AEDC) uses urine ketones as a biomarker of compliance with MAD. Urine ketone values may decrease over time despite compliance with MAD in a phenomenon called ketoadaption. It is unknown at what time point ketoadaptation occurs in adults on MAD and whether or not this varies from patient to patient. The aims of this study were to: 1) determine if urine ketone values are a reliable biomarker for seizure reduction (higher ketones correlate with fewer seizures) in the first 1 and 3 months on MAD and 2) determine if urine ketones remain elevated throughout treatment (at 6 and 12 months). Methods: Adults (= 18 years) from the AEDC database with quantifiable seizures and treated with MAD for 3 months or more were included. This was a retrospective review of medical records, lab results, and monthly calendars containing self-reported seizure frequency (daily) and urine ketones (biweekly) at baseline, and month 1, 3, 6, and 12. Ketones were coded on a 1 to 5 scale (1=negative, 5=large) and the change from baseline was calculated. The percent change from baseline in seizure rate and response rate (= 50% reduction from baseline) were calculated at each time point. Descriptive statistics and Spearman Correlation were used. Results: Of 176 patients included, 116 were female (65.9%), median age 31 years (range 4 to 86). The average ketone value at month 1 was 2.89 (small, n=151). The average at month 3 was 2.79 (small, n=120). At month 6, the ketone value increased to 2.91 (small, n=69). Ketone values trended down to 2.51 (trace to small, n=62) at month 12. Median seizure reductions at each time point are as follows: 66.8% (n=130) at month 1, 64.3% (n=93) at month 3, 81.6% (n=66) at month 6, and 82.5% (n=49) at month 12. Changes from baseline in urine ketones and seizure rate were negatively correlated (n=120, r=-0.19, p=0.03) at month 1, indicating that as ketone values increased, the percent seizure reduction decreased. Changes in ketones and seizure frequency were not significantly correlated at 3, 6, and 12 months (n=85, r=0.03, p=0.79; n=49, r=0.12, p=0.04; n=43, r=0.01, p=0.94, respectively). Conclusions: Unexpectedly, urine ketone values did not positively correlate with seizure reduction in adults on a modified Atkins diet, even at 1 month of treatment. In fact, a negative correlation was seen. As seen previously, the attrition rate was high (nearly 50% at 12 months) which could account for some findings. Further studies are needed to better understand the process of ketoadaptation and the role of ketone bodies in seizure cessation. Funding: Johns Hopkins University Summer Training and Research Program; Nutricia North America; Johns Hopkins Institute for Clinical and Translational Research