The relation of etiology based on the 2017 ILAE classification to the effectiveness of the ketogenic diet in drug-resistant epilepsy in childhood.

OBJECTIVE: To investigate the effectiveness and safety of the ketogenic diet (KD) in drug-resistant epilepsy in childhood in relation to the new 2017 International League Against Epilepsy (ILAE) classification of etiology. METHODS: A consecutive cohort of patients treated with the KD were categorized according to the ILAE classification into known (structural, genetic, metabolic, infectious, and immune-mediated) and unknown etiology. Primary outcome was the frequency of patients achieving seizure freedom with the KD at 3 months, secondary outcomes were seizure reduction >50% at 3 months, and both seizure freedom and seizure reduction >50% at 6, 12 months, and at last follow-up (LFU), and adverse effects. Outcomes were compared between etiology groups. RESULTS: Etiology was known in 70% (129/183). Outcomes did not differ at 3 months (known vs unknown: seizure freedom 28% vs 33%, seizure reduction 62 vs 67%), but seizure freedom was significantly less frequent in known etiology at 6 months (26% vs 43%) and beyond (22% vs 37%). Logistic regression identified duration of epilepsy, number of previous antiseizure medications (ASMs), and age-appropriate psychomotor development as positive determinants of outcome. Among individual etiology groups, the effectiveness of KD was relatively best for genetic (33% at LFU) and poorest for metabolic etiology (8% at LFU). The small number of patients with infectious and immune-mediated etiology requires larger numbers in each etiology group to corroborate our results. No differences in type and frequency of adverse effects (in 71%) between etiology groups were observed, requiring medical intervention in 21%. SIGNIFICANCE: The KD was most effective in genetic and unknown etiology, many unknowns probably represent yet unidentified genetic causes. We recommend consequent diagnostic and genetic work-up to identify etiologies that respond best to the KD. The KD should be offered early to infants with genetic epilepsy before deterioration of epileptic symptoms and of psychomotor development.

Ketogenic Diet in the Treatment of Super-Refractory Status Epilepticus at a Pediatric Intensive Care Unit: A Single-Center Experience.

Background: To evaluate the use of the ketogenic diet (KD) for treatment of super-refractory status epilepticus (SRSE) at a pediatric intensive care unit (PICU). Design: A retrospective analysis of all pediatric patients treated for SRSE with the KD at our center was performed using patient data from our prospective longitudinal KD database. Setting: SRSE is defined as refractory SE that continues or recurs 24 h or more after initiation of anesthetic drugs. We describe the clinical and electroencephalographic (EEG) findings of all children treated with KD at our PICU. The KD was administered as add-on after failure of standard treatment. Response was defined as EEG seizure resolution (absence of seizures and suppression-burst ratio ≥50%). Patients: Eight consecutive SRSE patients (four females) treated with KD were included. Median age at onset of SRSE was 13.6 months (IQR 0.9-105), and median age at KD initiation was 13.7 months (IQR 1.9 months to 8.9 years). Etiology was known in 6/8 (75%): genetic in 4 (50%), structural in 1 (12.5%), and autoimmune/inflammatory in 1 (12.5%). Main Results: Time from onset of SRSE to initiation of KD was median 6 days (IQR 1.3-9). Time until clinically relevant ketosis (beta-hydroxybutyrate (BHB) >2 mmol/L in serum) was median 68.0 h (IQR 27.3-220.5). Higher ketosis was achieved when a higher proportion of enteral feeds was possible. Four (50%) patients responded to KD treatment within 7 days. During follow-up (median 4.2 months, IQR 1.6-12.3), 5/8 patients-three of them responders-died within 3-12 months after SRSE. Conclusions: In eight patients with SRSE due to severe etiologies including Alpers syndrome, we report an initial 50% response to KD. KD was used early in SRSE and sufficient levels of ketosis were reached early in most patients. Higher ketosis was achieved with combined enteral and parenteral feedings.

The Ketogenic Diet Including Breast Milk for Treatment of Infants with Severe Childhood Epilepsy: Feasibility, Safety, and Effectiveness.

Objective: The ketogenic diet (KD) is a high-fat and restricted carbohydrate diet for treating severe childhood epilepsy. In infants, breast milk is usually fully replaced by a ketogenic formula. At our center, mothers are encouraged to include breastfeeding into the KD if still breastfeeding. This retrospective study describes achievement and maintenance of ketosis with or without inclusion of breast milk. Methods: Data were retrieved from a prospective longitudinal database of children treated with KD for epilepsy analyzing infants <1 year of age. The time to achieve clinically relevant ketosis (≥2 mmol/L beta-hydroxybutyrate) was compared with and without inclusion of breast milk into standard KD. Ketosis, nutritional intakes, effectiveness, adverse effects, and successful continuation of breastfeeding were evaluated. Results: A total of 79 infants were eligible for analysis. In 20% (16), breast milk was included. Infants with breast milk included into the KD achieved relevant ketosis in 47 hours (interquartile range [IQR] 24-95) compared with 41 hours (IQR 22-70; p = 0.779) in infants with standard KD. Beta-hydroxybutyrate at day 2 was 3.1 mmol/L (IQR 0.5-4.9) and 3.8 mmol/L (IQR 2.2-4.9). Infants with breast milk included received higher amounts of carbohydrates at baseline and calories at 3 months. Seizure freedom and adverse effects showed no relevant differences. No infections occurred in infants receiving breast milk. In two infants, KD was initiated with breast-feds after bottle-feeding KD formula. In 31%, breastfeeding was continued after the KD, and in 25%, inclusion of breast milk and breastfeeding was maintained until complete weaning. Before discharge from hospital, the amount of breast milk included was median 90 mL/day (IQR 53-203) equivalent to median 9% (IQR 6-15). Conclusions: Appropriate ketosis was achieved in most infants and maintained within 48 hours. Incorporation of breast milk into KD is feasible, safe, and effective.