The effectiveness and tolerability of clobazam in the pediatric population: Adjunctive therapy and monotherapy in a large-cohort multicenter study.

OBJECTIVE: To evaluate the effectiveness and tolerability of clobazam therapy in the pediatric population in terms of seizure semiology, epileptic syndromes, and etiological subgroups. METHODS: A retrospective cohort study was conducted consisting of 1710 epileptic children from eight centers in seven geographic regions of Turkey. The initial efficacy of clobazam therapy was evaluated after three months of treatment. The long-term effectiveness of the drug, overall seizure outcomes, and overall therapeutic outcomes were evaluated during 12 months of therapy. RESULTS: Analysis of initial efficacy after the first three months of clobazam therapy showed that 320 (18.7 %) patients were seizure-free, 683 (39.9 %) had > 50 % seizure reductions, and 297 (17.4 %) had < 50 % seizure reductions. A positive response (seizure-free and >50 % seizure reduction) was determined for focal-onset (62.3 %) seizures, epileptic spasms (61.5 %), and generalized onset seisures (57.4). The highest positive response rate among the epileptic syndromes was for self-limited epilepsy with centrotemporal spikes (SeLECTS). The highest negative response rate was for developmental and/or epileptic encephalopathies (DEEs). Magnetic resonance imaging (MRI) revealed a structural etiological diagnosis in 25.8 % of the cohort. A higher positive response rate was observed at MRI in patients with sequelae lesions than in those with congenital lesions. The seizure recurrence rate was higher in the patient group with epilepsy with genetic and metabolic causes, in individuals with more than one seizure type, and in those using three or more antiseizure drugs. CONCLUSIONS: This cohort study provides additional evidence that clobazam is an effective and well-tolerable drug with a high seizure-free rate (18.7 %), a significant seizure reduction rate (57.3 %), and with excellent overall therapeutic outcomes with a low seizure relapse rate and considerable reversible benefits in the pediatric population.

HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1ß: novel epilepsy markers?

The purpose of this study was to compare HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels in patients with mild and severe epilepsy with those in a healthy control group. Children aged 4-17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB-1, TLR4, IL-1R1, TNF-α and IL-1ß levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. HMGB-1, TLR4, TNF-α, and IL-1ß levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL-1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). In this first report to identity a possible correlation between HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug-refractory epilepsy.