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

Abstract

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.

Keywords: ILAE classification; drug-resistant epilepsy; epilepsy syndromes; etiology; ketogenic diet; seizure freedom.