Abstracts

Rationale: Traditional inpatient initiation of ketogenic diet (KD) allows the rapid titration of diet ratios, but it can also result in acute metabolic fluctuations. Slow outpatient titration of the diet provides an opportunity to achieve good seizure control at lower ratios. The aim of this study was to analyze the seizure outcome at 2 years following outpatient slow initiation of classic KD, and the effective ratios. Methods: Patients were eligible if they were aged 17 or under at baseline and initiated on the classic KD through an outpatient protocol between January 2010 and April 2016 for the treatment of medically refractory epilepsy. KD was initiated at a low ratio, 0.6-1:1. Depending on tolerability and desired seizure control, the ratio was increased in increments of 0.15:1 to 0.67:1 every 1 to 3 weeks. Prior to July 2015, data was collected through retrospective chart review whereas from July 2015 onwards, data was collected prospectively. The processes of diet initiation, caregiver education, and monitoring of clinical measures related to KD had been standardized since 2010. Outcome variables were first assessed at baseline before diet initiation, and then at 2 years after diet initiation. We used the last known seizure frequency for patients who discontinued the KD before 2 years. Analysis was conducted on an intention to treat basis. Results: 37 patients (M:F 19:18, age 5 mo - 16 yr 5 mo, median age of 4 yr 4 mo) satisfied the inclusion criteria. 7 (18.9%) patients were seizure free at last follow up, 8 (21.6%) had 91 - <100% decrease in seizure frequency, 5 (13.5%) had 51-90% decrease in seizure frequency, and 17 (45.9%) had 50% or less decrease. Overall, seizure frequency decreased from a mean of 539.2 (SD 1292.0) at baseline to 102.2 (SD 169.4) at 2 years (p=0.025). At 2-years, 18 patients remained on KD while 19 discontinued. Of these 18 patients, 14 patients had >50% reduction in seizure frequency, including 6 who were seizure-free and 7 with a 91- <100% reduction in seizure frequency. The mean effective ratios for patients on KD at 2 years were 1.66 (SD 0.42), 2.48 (SD 0.66), and 2.09 those with 100%, 91-99% and 51-90% seizure frequency reduction, respectively. The median age at initiation was lower for patients who became seizure free (5 years 6 months) than other responders (6 years 3 months). The patients who discontinued during the 2 years were followed up for a median of 6 months (range: 1 month to 21 months). Primary reasons for KD discontinuation were ineffectiveness of therapy in achieving adequate seizure control (15 patients), food refusal (3 patients, this includes one patients who was seizure free on diet for 1 year and one who had >90% reduction in seizure frequency at 18 months), and poor compliance (1 patient). Conclusions: Many patients were able to achieve good seizure control through slow outpatient initiation of classic KD. Efficacy was maintained at 2 years. This study demonstrated that many patients who are arbitrarily put on higher ratios by rapid inpatient or outpatient titration method, might have had good seizure control even at lower ratios had there been a slower titration of ratio. Funding: Ontario Brain Insitute