Levetiracetam (LEV) and oxcarbazepine (OXC) are commonly used in the treatment of epilepsy, but their efficacy and safety have seldom been compared for the treatment of children with benign epilepsy with centrotemporal spikes (BECTS). We thus assessed the efficacy of LEV and OXC monotherapy in the treatment of children with BECTS, and the effect of this treatment on children’s intelligence and cognitive development. This was a randomized, single-center trial. Children with BECTS were randomized (1:1) into LEV and OXC groups, and were assessed at 1, 3 and 6 months after treatment. The primary outcomes were the frequency of seizures and changes in intelligence and cognitive function. Secondary outcomes were electroencephalogram (EEG) results and safety. Seventy children were enrolled and randomized to the LEV group or the OXC group, and 32 of the 35 children in each group completed the study. After 6 months, the effective treatment rate of the OXC group was significantly higher than that of the LEV group (78.12 vs. 53.12%, p = 0.035). However, no significant inter-group difference was observed in EEG improvement (p = 0.211). In terms of intelligence and cognitive development, children in the OXC group exhibited significantly improved choice reaction time, mental rotation, and Wisconsin Card Sorting Test results (all p < 0.05). Both LEV and OXC were well tolerated, with 18.75 and 21.88% of children reporting mild adverse events (p = 0.756). OXC monotherapy was more effective than LEV for children with BECTS. In addition, children with OXC monotherapy had higher improvements in children’s intelligence and cognitive function than those with LEV monotherapy.

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The ketogenic diet (KD) demonstrates antiepileptogenic and neuroprotective efficacy, but the precise mechanisms are unclear. Here we explored the mechanism through systematic proteomics analysis of the lithium chloride-pilocarpine rat model. Sprague-Dawley rats (postnatal day 21, P21) were randomly divided into control (Ctr), seizure (SE), and KD treatment after seizure (SE + KD) groups. Tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectroscopy (LC-MS/MS) were utilized to assess changes in protein abundance in the hippocampus. A total of 5,564 proteins were identified, of which 110 showed a significant change in abundance between the SE and Ctr groups (18 upregulated and 92 downregulated), 278 between SE + KD and SE groups (218 upregulated and 60 downregulated), and 180 between Ctr and SE + KD groups (121 upregulated and 59 downregulated) (all p < 0.05). Seventy-nine proteins showing a significant change in abundance between SE and Ctr groups were reciprocally regulated in the SD + KD group compared to the SE group (i.e., the seizure-induced change was reversed by KD). Of these, five (dystrobrevin, centromere protein V, oxysterol-binding protein, tetraspanin-2, and progesterone receptor membrane component 2) were verified by parallel reaction monitoring. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that proteins of the synaptic vesicle cycle pathway were enriched both among proteins differing in abundance between SE and Ctr groups as well as between SE + KD and SE groups. This comprehensive proteomics analyze of KD-treated epilepsy by quantitative proteomics revealed novel molecular mechanisms of KD antiepileptogenic efficacy and potential treatment targets.