Abstracts

Rationale: Ketogenic diet (KGD) is effective treatment of refractory epilepsy in children. There is little experience of its use in adults. Atkins diet, which resembles KGD, is used for weight loss. In this pilot study, we evaluated the effect of KGD on seizures and weight in patients with refractory epilepsy +/- co-morbid obesity. Methods: 6 patients with refractory epilepsy (5 women, age range 24-53) were treated with KGD. 5 had morbid obesity. Seizure frequency and weight/body mass index (BMI) were evaluated prospectively for 6 months baseline and after 3 (n=3) and 6 (n=3) months of KGD with 3:1 [fat]:[protein+carbohydrate] ratio and 1600 kcal/day caloric restriction. KGD was initiated with a 24-48 hour fast. Patients checked urine for ketones with Ketostix 1-2/day. Evaluations were 1, 3 and 5 weeks after KGD initiation, then monthly for seizure frequency using a seizure diary, weight, BMI, adverse events, quality of life using questionnaire (QOLIE-31-P) and somnolence using Epworth Sleepiness Score (ESS). Blood lipids, metabolic profiles and AED levels were checked monthly. Results: 3 patients had primary generalized epilepsy (PGE, including 1 man) with generalized tonic clonic (GTC) seizures (n=3) and absence and myoclonic seizures (n=2). 3 had cryptogenic localization-related epilepsy (LRE). Seizure duration ranged from 9-51 years, prior AEDs from 2-8, and current AEDs from 1-4, including topiramate in 5/6 cases (dose range: 200-1000 mg/d), and VNS in 1. AEDs were held constant in 5/6 subjects, and changed from dual to monotherapy in one patient during KGD initiation. Average monthly seizure frequency declined from baseline 36 to 1.3 on KGD for all subjects, 68.6 to 1.2 for PGE (both p=<0.01) and 3.8 to 1.3 for LRE. 2/3 PGE patients had ≥96% seizure reduction, starting on KGD day 3. 1 PGE patient had seizure increase from 1 to 2 GTC/month; he had intermittent KGD non-compliance (EtOH use). 1/3 LRE patient had 87% seizure reduction; two had 15-30% improvement, including one patient with incomplete KGD compliance. All 5 obese patients lost weight, range 22-58 lb. Mean weight declined from 222 lb (range 193-276) to 187 lb (range 141-216), mean BMI from 36.8 kg/m2 (range 33.3-44.2) to 31.2 (range 25.9-35.9), with mean BMI reduction of -15% (range [-10%]-[-24%])(all p =<0.01). Most weight loss occurred in the first 4 months of treatment. 1 non-obese patient lost 4 lb. AEs were mild and included nausea (n=1), diarrhea (n=1), constipation (n=2) and hyperlipidemia (n=1).4/6 patients were compliant, with urine ketones of 40-160 mg/dl. 2 patients were partially compliant.5/6 subjects felt better on KGD. Mean QOLIE-31-P scores improved from baseline 4.7 to 7 on KGD. Mean ESS score dropped from baseline 8.8 (range: 5-12) to 6.8 on KGD (range: 3-9).