Abstracts

Rationale: Many epilepsies presenting in infancy are poorly responsive to anti-seizure medicines (ASMs) with poor prognosis for neurodevelopmental outcome. Ketogenic diets (KD) are high-fat, low-carbohydrate diets, which have been shown to reduce seizures in randomised controlled trials in older children and adults. No high-quality evidence is available for infants.

Methods: Infants (1-24 months of age) with epilepsy, average ≥4 seizures/week and previous trial of two ASMs, were randomised after a baseline period to receive a classical KD or further ASM. The primary outcome was number of seizures during weeks 6-8 accounting for the number of seizures at baseline. Secondary outcomes included the number seizure free, with ≥50% seizure reduction, and tolerance to KD assessed by questionnaire and laboratory results.

Results: A total of 78 children were randomised to KD and 58 to ASM (randomisation accounting for dietitian effect). The median number of daily seizures was similar in both groups at 8 weeks (IRR 1.33 95% CI 0.84, 2.11). The odds ratio of achieving ≥50% seizure reduction was 1.21 (95% CI 0.55, 2.65), and 0.88 (95% CI 0.27, 2.80) for seizure freedom. In the KD group, 28/63 (44%) had ≥50% seizure reduction compared with 19/47 (40%) in the ASM group; 7/63 infants (11%) on KD were seizure-free, compared with 6/48 (13%) in the ASM group. A higher proportion of infants in the ASM group changed the number or dose of concurrent ASMs during the intervention period (24/48 [50%]) compared to the KD group (9/66 [14%]). Side effect score was similar in both groups (KD median 40 IQR 38,42; ASM median 41 IQR 39,44). There were no clinically significant differences other than those expected in clinical or laboratory parameters between groups. Forty-four of 78 (56%) infants randomised to KD and 32/58 (55%) randomised to ASM provided data at 12 months. Overall health and global behaviour were numerically improved in the KD group compared to the ASM group at 12 months (coefficient 1.23 95% CI -12.70, 15.17 for health; 12.72 95% CI -1.56, 27.00 for behaviour). Physical abilities, parental satisfaction with child's overall growth and development, pain, temperament and mood, overall behaviour, getting along with others, general health perceptions, parental emotional impact, parental time impact, and family cohesion all numerically favoured the ASM group. A similar proportion of infants reported at least one serious adverse event at any time in both groups (43% ASM, and 51% KD). The most common serious adverse events were seizures (MedDRA class "Nervous system disorders") in both groups. Three infants died in the KD arm, all considered unrelated to treatment.

Conclusions: The KD appears similar in effectiveness and tolerance to further ASM in infants with drug-resistant epilepsy. More infants in the ASM group had changes in ASMs during the intervention period compared to the KD group. The odds ratio of achieving seizure freedom at 8 weeks numerically favoured KD compared to further ASM.

Funding: Funded by National Institute for Health and Care Research EME Programme, EudraCT 2013-002195-40