The therapeutic effects of ketogenic diet, lacosamide, and combination therapy in children with refractory epilepsy.

BACKGROUND: Intractable epilepsy in children poses significant clinical challenges due to limited efficacy of conventional anti-epileptic drugs (AEDs), leading to persistent neurodevelopmental impairments. This study investigated the therapeutic effects of ketogenic diet (KD), lacosamide (LCM), and their combination on refractory epilepsy, with comprehensive assessment of seizure control, EEG dynamics (including epileptiform patterns and spectral characteristics), cognitive function, lipid metabolism, and endothelial health. METHODS: Ninety children with refractory epilepsy were divided into three treatment groups: KD (n = 30), LCM (n = 30), and KD + LCM (n = 30). Assessments included detailed EEG characterization (seizure types, interictal discharges, spectral bands), cognitive testing (attention/memory), lipid profiles, and endothelial markers at baseline, 3-, and 6-months post-treatment. RESULTS: The KD + LCM group showed superior seizure reduction at 3/6 months (t = 2.171, P = 0.035; t = 3.177, P = 0.003), with 76.7% achieving ≥ 50% interictal discharge reduction (P = 0.008) and 63.3% seizure type simplification (P = 0.003) at 6 months. Cognitive performance significantly improved (attention: Δ=-10.8 ± 2.0; memory: Δ=-9.4 ± 1.8; both P < 0.001), strongly correlating with frontal θ-band modulation (|r|>0.68). Combination therapy also enhanced α/β/δ/θ spectral power (P ≤ 0.019), improved lipid profiles, and restored endothelial function versus monotherapies (all P < 0.05). CONCLUSIONS: KD and LCM combination therapy provides comprehensive benefits-superior seizure control, EEG normalization, cognitive enhancement, metabolic optimization, and vascular protection-making it a promising multimodal approach for refractory epilepsy management.