First clinical postmarketing experiences in the treatment of epilepsies with brivaracetam: a retrospective observational multicentre study.

OBJECTIVES: Brivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting. DESIGN: Retrospective, observational multicentre study. SETTING: We retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist. PARTICIPANTS: Data of 615 epilepsy patients treated with BRV were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Efficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed. RESULTS: Overall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV. CONCLUSIONS: The present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

Recent advances in the pharmacotherapy of epilepsy: brivaracetam and perampanel as broad-spectrum antiseizure drugs for the treatment of epilepsies and status epilepticus.

Introduction: Antiseizure drugs (ASDs) play a central and crucial role in the treatment of epilepsy patients, as the majority require anticonvulsant treatment for an extended period of time. Since up to 30% of patients are refractory to medical treatment, new therapeutic options are necessary. Perampanel (PER) and brivaracetam (BRV) are the latest approved ASDs that may be considered in a variety of epilepsy syndromes. PER has a distinct and selective mode of action on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and is licensed for use in focal and generalized epilepsies. BRV is a derivative of levetiracetam but exhibits a 20-fold higher affinity and a faster brain entry time as a synaptic vesicle glycoprotein 2A (SV2A) ligand. Areas covered: This article reviews the advances in the epileptic treatment and provides a comparison of PER and BRV. Both drugs have shown comparable results in randomized controlled trials, and both are well tolerated. Expert opinion: PER and BRV have the potential to perform as important, broad-spectrum ASDs with significant market shares. BRV's intravenous formulation and fast penetration into the brain and PER's unique mode of action will result in the more frequent use of both drugs in status epilepticus.

Prevalence, risk factors and therapeutic aspects of injuries and accidents in women with epilepsy.

BACKGROUND: Epilepsy-related injuries and accidents (ERIA) are a frequent cause of hospitalisation and represent a relevant burden for patients with epilepsy. In particular, osteoporosis and other gender-specific aspects may increase the risk of seizure-related fractures and injuries in women with epilepsy. AIM AND SCOPE: The aim of this analysis is to determine the prevalence and clinical nature of ERIA in a cohort of women with epilepsy, to identify possible determinants including osteoporosis and to give an overview of the current knowledge of clinically important prophylactic and therapeutic aspects. RESULTS: In total, 167 women (mean age 39.0 years, range 18-67 years) with established diagnosis of epilepsy (mean disease duration 18.2 years, range 0-64) were analysed for the occurrence of ERIA. Overall, 22 patients (13.2%) reported at least one ERIA (mean number 3.4, ± 3.1) during the last three months prior to enrollment. The most frequent types of ERIA were lacerations (n = 7/22; 31.8%), abrasions, cuts, bruises or hematoma (n = 6/22, 27.3%), burns (n = 3/22, 13.6%), and fractures (n = 3/22, 13.6%). Moreover, one seizure-related road traffic accident with consecutive trauma (4.5%) was reported. Ictal falls, periictal abnormalities of behaviour and missing seizure freedom were associated with ERIA. Furthermore, female patients with ERIA had a significantly reduced quality of life (QoL, p = 0.002) and increased anxiety (p = 0.008) compared to patients without ERIA. A review of the pertinent literature suggests decreased bone mineral density and use of enzyme-inducing AEDs to be risk factors for ERIA in women with epilepsy. CONCLUSION: ERIA represent relevant complications for women with epilepsy and are associated with a lower QoL and anxiety compared with non-affected controls. Improvement of anticonvulsive treatment and therapy for osteoporosis or osteomalacia may help to decrease ERIA and the associated burden.

Functional and structural properties of dentate granule cells with hilar basal dendrites in mouse entorhino-hippocampal slice cultures.

During postnatal development hippocampal dentate granule cells (GCs) often extend dendrites from the basal pole of their cell bodies into the hilar region. These so-called hilar basal dendrites (hBD) usually regress with maturation. However, hBDs may persist in a subset of mature GCs under certain conditions (both physiological and pathological). The functional role of these hBD-GCs remains not well understood. Here, we have studied hBD-GCs in mature (≥18 days in vitro) mouse entorhino-hippocampal slice cultures under control conditions and have compared their basic functional properties (basic intrinsic and synaptic properties) and structural properties (dendritic arborisation and spine densities) to those of neighboring GCs without hBDs in the same set of cultures. Except for the presence of hBDs, we did not detect major differences between the two GC populations. Furthermore, paired recordings of neighboring GCs with and without hBDs did not reveal evidence for a heavy aberrant GC-to-GC connectivity. Taken together, our data suggest that in control cultures the presence of hBDs on GCs is neither sufficient to predict alterations in the basic functional and structural properties of these GCs nor indicative of a heavy GC-to-GC connectivity between neighboring GCs.