Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open‐label study

Abstract

Objective

To report long-term post hoc efficacy and safety data from 10 US study sites from an open-label Phase 3 study of adjunctive cenobamate (NCT02535091).

Methods

Patients with uncontrolled focal seizures taking stable doses of 1–3 antiseizure medications (ASMs) were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day). Further increases to 400 mg/day by 50-mg/day increments biweekly were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. ...

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Post hoc analysis of a phase 3, multicenter, open‐label study of cenobamate for treatment of uncontrolled focal seizures: Effects of dose adjustments of concomitant antiseizure medications

Abstract

Objective

To report post hoc results on how adjustments to baseline antiseizure medications (ASMs) in a subset of study sites (10 US sites) from a long-term, open-label phase 3 study of adjunctive cenobamate affected tolerability, efficacy, and retention.

Methods

Patients with uncontrolled focal seizures taking stable doses of one to three ASMs were administered increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day). Further increases to 400 mg/day by 50 mg/day biweekly increments were allowed during ...

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Continuous seizure emergency evoked in mice with pharmacological, electrographic, and pathological features distinct from status epilepticus

Summary

Objectives

Benzodiazepines are the standard of care for the management of sustained seizure emergencies, including status epilepticus (SE) and seizure clusters. Seizure clusters are a variably defined seizure emergency wherein a patient has multiple seizures above a baseline rate, with intervening periods of recovery, distinguishing clusters from SE. Although these seizure emergencies are phenotypically distinct, the precise pathophysiological and mechanistic differences between SE and seizure clusters are understudied. Emergency-specific preclinical models may differentiate the behavioral and pathological mechanisms that are acutely ...

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OV329, a novel highly potent γ‐aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala‐kindled rats

Summary

Objective

An attractive target to interfere with epileptic brain hyperexcitability is the enhancement of γ-aminobutyric acidergic (GABAergic) inhibition by inactivation of the GABA-metabolizing enzyme GABA aminotransferase (GABA-AT). GABA-AT inactivators were designed to control seizures by raising brain GABA levels. OV329, a novel drug candidate for the treatment of epilepsy and addiction, has been shown in vitro to be substantially more potent as a GABA-AT inactivator than vigabatrin, an antiseizure drug approved as an add-on therapy for adult patients with refractory complex ...

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Long‐term efficacy, tolerability, and retention of brivaracetam in epilepsy treatment: A longitudinal multicenter study with up to 5 years of follow‐up

Abstract

Objective

This study was undertaken to evaluate the long-term efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice.

Methods

A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021.

Results

Long-term data for 262 patients (mean age = 40 years, range = 5–81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients ...

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Functional cognitive and language outcomes after cerebral hemispherectomy for hemimegalencephaly

Abstract

Objective

Hemispheric surgeries are an effective treatment option to control seizures for children with hemimegalencephaly (HME); however, not enough is known about their cognitive outcomes. This study aimed to delineate the cognitive and language outcomes after hemispherectomy for HME and identify the clinical characteristics associated with cognition and language.

Methods

Data came from the Global Pediatric Epilepsy Surgery Registry, a patient-driven web-based registry for epilepsy surgery. We focused on children’s functional status, assessed through parent-reports of cognitive and language skills. Parents also reported ...

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Recurrent febrile seizures alter intrahippocampal temporal coordination but do not cause spatial learning impairments

Abstract

Objective

Febrile seizures (FSs) are the most common form of seizures in children. Single short FSs are benign, but FSs lasting longer than 30 min, termed febrile status epilepticus, may result in neurological sequelae. However, there is little information about an intermediary condition, brief recurrent FSs (RFSs). The goal of this study was to determine the role of RFSs on spatial learning and memory and the properties of spontaneous hippocampal signals.

Methods

A hippocampus-dependent active avoidance task was used to assess spatial learning and ...

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Reasons for not having epilepsy surgery

Abstract

Objective

This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course.

Methods

We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period. Multivariate logistic ...

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Activated N‐methyl‐D‐aspartate receptor ion channels detected in focal epilepsy with [18F]GE‐179 positron emission tomography

Summary

Objective

Imaging activated glutamate N-methyl-D-aspartate receptor ion channels (NMDAR-ICs) using positron emission tomography (PET) has proved challenging due to low brain uptake, poor affinity and selectivity, and high metabolism and dissociation rates of candidate radioligands. The radioligand [18F]GE-179 is a known use-dependent marker of NMDAR-ICs. We studied whether interictal [18F]GE-179 PET would detect foci of abnormal NMDAR-IC activation in patients with refractory focal epilepsy.

Methods

Ten patients with refractory focal epilepsy and 18 healthy controls had structural magnetic resonance imaging (MRI) followed by ...

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The effect of lamotrigine and other antiepileptic drugs on respiratory rhythm generation in the pre‐Bötzinger complex

Abstract

Objective

Lamotrigine and other sodium-channel blocking agents are among the most commonly used antiepileptic drugs (AEDs). Because other sodium channel blockers, such as riluzole, can severely alter respiratory rhythm generation during hypoxia, we wanted to investigate if AEDs can have similar effects. This is especially important in the context of sudden unexpected death in epilepsy (SUDEP), the major cause of death in patients suffering from therapy-resistant epilepsy. Although the mechanism of action is not entirely understood, respiratory dysfunction after generalized tonic-clonic ...

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