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Purpose: To determine the feasibility of using epileptiform events detected by continuous electrocorticographic monitoring via a brain-responsive neurostimulation system to supplement patient-maintained seizure diaries., Methods: Data were retrospectively analyzed from a randomized controlled trial of brain-responsive neurostimulation (RNS® System) for adjunctive treatment of medically intractable focal onset seizures in 191 subjects. The long-term (≥3 months) correspondence between daily counts of diary-reported seizures and device-recorded "long epileptiform events" (LEs), a proxy for electrographic seizures (ESs), was assessed using cross-correlation and logistic generalized estimating equation models., Results: Diary-reported seizures and LEs significantly co-varied across days in 124 patients whose detection settings were held constant, with a significantly higher correlation in 54 patients (44 %) whose LEs were usually ESs (high concordance patients). There were more days in which LEs were detected than days in which patients reported a seizure (positive predictive value (PPV): 34 %). On days when there were no LEs, there were typically no diary-reported seizures (negative predictive value (NPV): 90 %). In patients with a high concordance between LEs and ESs, the PPV and NPV were both slightly higher, 43 % (35-52 %) and 93 % (95 % CI: 86-97 %) respectively., Conclusion: Although LEs can substantially outnumber diary reported seizures, the high across-day correlation and strong NPV between LEs and diary seizures suggests that LEs recorded by the RNS® System could potentially supplement seizure diaries by providing an objective biomarker for relative seizure burden., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To study the relationship of glucose metabolism and volume of the temporal lobes with age at epilepsy onset, epilepsy duration, and seizure frequency in patients with mesial temporal sclerosis (MTS)., Methods: We evaluated the pre-surgical 18 F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) of 18 patients with epilepsy and MRI findings of MTS, who were seizure-free for at least 2-years after temporal lobectomy. We calculated the volume of the hippocampi and amygdalae on MRI. On PET we studied their mean standard uptake values (SUV), and relative metabolic activity as compared to normal subjects in terms of Z-scores. We compared the PET and MRI metrics in the bilateral structures using the Wilcoxon sign rank test. We studied the relationship between the imaging metrics and age of epilepsy onset, epilepsy duration, and seizure frequency via Spearman correlation analyses., Results: Younger age at onset correlated with decreased hippocampal glucose metabolism (rs=0.64, p=0.008). Longer epilepsy duration correlated with decreased hippocampal glucose metabolism (rs=-0.55, p=0.024). There was no correlation between age at onset of epilepsy, epilepsy duration, or seizure frequency and volumetrics. Z-score in the sclerotic hippocampus (-3.51±2.2vs -0.7±1.7) and amygdala (-3.26±2.3 vs -0.68±1.8) was smaller than the contralateral (p<0.001). The diseased hippocampus (2.84±0.49 vs 3.52±0.4ml) and ipsilateral amygdala (1.49±0.24 vs 1.72±0.3ml) were significantly smaller than the contralateral (p<0.02)., Significance: Earlier epilepsy onset correlated with hippocampal hypometabolism. Longer epilepsy duration correlated with amygdalar hypometabolism suggesting an ongoing progressive disease in MTLE., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To assess the multiple-dose pharmacokinetics of levetiracetam and its major metabolite ucb L057 in children with partial-onset seizures and determine whether it is affected by adjunctive carbamazepine or valproate. To correlate levetiracetam concentrations in plasma and saliva and to assess its safety and clinical response., Methods: Design was an open-label, multicenter study. Twenty-one children (4-12 years old) with epilepsy taking carbamazepine (13) or valproate (8) received adjunctive levetiracetam. Levetiracetam was initiated at 20 mg/(kg day) and titrated at 2-week intervals to 40 and then 60 mg/(kg day). Twelve-hour pharmacokinetics were determined at the end of each 2-week period. Efficacy was estimated from the partial seizure frequency per week and Global Evaluation Scale., Results: Levetiracetam was rapidly absorbed following oral dosing, with median t(max) of 0.5 h. Dose proportional increases were observed for C(max) and AUC((0-12)) over the dose range; t(1/2) was 4.9 h. Pharmacokinetics of levetiracetam and ucb L057 were not markedly different with concomitant carbamazepine or valproate; clearance was only 7-13% faster and AUC was decreased by only 15-24% in those on carbamazepine compared to valproate. Levetiracetam did not affect trough carbamazepine or valproate. Concentration in saliva and plasma were strongly correlated. Seizure frequency declined by 50% or more in 43% of subjects in the intent-to-treat population (n=21) and in 56% of those with seizures at baseline (n=16). Marked or moderate improvement occurred in 80% and 75% of patients based on Global Evaluation Scale ratings by investigators and parents/guardians, respectively. Levetiracetam was well tolerated., Conclusion: Levetiracetam exhibits simple pharmacokinetics in children, with rapid absorption and dose-proportional kinetics. Small but not clinically relevant differences were observed between subjects receiving carbamazepine and valproate, suggesting significant dose adjustment is usually not necessary. This substantiates prior assessments that levetiracetam clearance is higher in children than adults, necessitating a higher dose in children on a mg/kg basis, and suggests it is useful add-on therapy for children with partial-onset seizures regardless of baseline therapy.