Epilepsia
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Randomized Controlled Trial Multicenter Study
Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial.
To evaluate the safety and tolerability of adjunctive brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A (SV2A) ligand, in adults with uncontrolled epilepsy. Efficacy was also assessed in patients with focal seizures as a secondary objective, and explored by descriptive analysis in patients with generalized seizures. ⋯ Adjunctive BRV given at individualized tailored doses (20-150 mg/day) was well tolerated in adults with uncontrolled epilepsy, and our results provided support for further evaluation of efficacy in reducing focal and generalized seizures.
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Randomized Controlled Trial Multicenter Study
Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial.
Brivaracetam (BRV) is a novel high-affinity synaptic vesicle protein 2A ligand currently being investigated for the treatment of epilepsy. The purpose of this phase III study was to evaluate the efficacy and safety/tolerability of adjunctive BRV in adults with uncontrolled partial-onset (focal) seizures. ⋯ Adjunctive BRV at a daily dose of 50 mg was associated with statistically significant reductions in seizure frequency compared with PBO. All doses of BRV showed good tolerability throughout the study.
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Randomized Controlled Trial Multicenter Study
Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial.
Brivaracetam (BRV) is a novel high-affinity synaptic vesicle protein 2A ligand in clinical development for the treatment of epilepsy. This phase III study (N01252; NCT00490035) evaluated the efficacy and safety/tolerability of BRV (20, 50, and 100 mg/day) compared with placebo (PBO) in patients aged 16-70 years with uncontrolled focal seizures with/without secondary generalization, despite treatment with one to two concomitant antiepileptic drugs at a stable and optimal dosage. ⋯ In this study of adjunctive BRV (20-100 mg/day) in adults with uncontrolled focal seizures, the primary efficacy analysis based on the 50 mg/day dose was not statistically significant. However, BRV 100 mg/day reduced baseline-adjusted focal seizure frequency/week by 11.7% over PBO, achieving statistical significance (p = 0.037). Secondary efficacy analyses (percent reduction from baseline in focal seizure frequency/week, ≥50% responder rate) provided supportive evidence for the efficacy of BRV 100 mg/day. BRV 20-100 mg/day was well tolerated without up-titration, with a high completion rate.
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Temporal lobe epilepsy (TLE) affects brain areas beyond the temporal lobes due to connections of the hippocampi and other temporal lobe structures. Using functional connectivity magnetic resonance imaging (MRI), we determined the changes of hippocampal networks in TLE to assess for a more complete distribution of abnormality. ⋯ The observed connectivity changes in TLE indicate dysfunctional networks that underlie widespread brain involvement in TLE. There are identifiable differences in the connectivity of the hippocampi between left and right TLE.
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The contribution of glial cells, mainly astrocytes and microglia, to the pathophysiology of epilepsy is increasingly appreciated. Glia play a pivotal role in the initiation and maintenance of the central nervous system (CNS) immune response and neuronal metabolic and trophic supply. Recent clinical and experimental evidence suggests a direct relationship between epileptic activity and CNS inflammation, which is characterized by accumulation, activation, and proliferation of microglia and astrocytes. Concomitant glia-mediated mechanisms of action of several antiepileptic drugs (AEDs) have been proposed. However, their direct effects on glial cells have been rarely investigated. We aimed to investigate the effect of commonly used AEDs on glial viability, the gap junctional network, the microglial activation, and cytokine expression in an in vitro astroglia/microglia co-culture model. ⋯ CNS inflammation is characterized by a disturbance of glial cell functions. Strong microglial activation, a typical hallmark of inflammation, was induced by VPA in M5 and continued in M30 co-cultures. With regard to the direct relation between CNS inflammation and seizures, VPA seems to be unsuitable for reducing inflammatory conditions. The reverse effect was achieved after CBZ. We noticed significant microglial inactivation, after incubation of the M30 co-cultures. In conclusion, we suggest that AEDs with antiinflammatory glial features are beneficial for seizures caused by persistent brain inflammation.