Final results from a Phase 3, long‐term, open‐label, repeat‐dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy

Abstract

Objective

A Phase 3 open-label safety study (NCT02721069) evaluated long-term safety of diazepam nasal spray (Valtoco) in patients with epilepsy and frequent seizure clusters.

Methods

Patients were 6–65 years old with diagnosed epilepsy and seizure clusters despite stable antiseizure medications. The treatment period was 12 months, with study visits at Day 30 and every 60 days thereafter, after which patients could elect to continue. Doses were based on age and weight. Seizure and treatment information was recorded in diaries. Treatment-emergent adverse events (TEAEs), nasal irritation, and ...

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Benzodiazepine administration patterns before escalation to second‐line medications in pediatric refractory convulsive status epilepticus

Abstract

Objective

This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE).

Methods

This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ...

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Add‐on cannabidiol in patients with Dravet syndrome: Results of a long‐term open‐label extension trial

Abstract

Objective

Add-on cannabidiol (CBD) reduced seizures associated with Dravet syndrome (DS) in two randomized, double-blind, placebo-controlled trials: GWPCARE1 Part B (NCT02091375) and GWPCARE2 (NCT02224703). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or GWPCARE2, were enrolled in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5.

Methods

Patients received a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/ml), titrated from 2.5 to 20 mg/kg/day over a 2-week period, added to ...

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Classification of complications of epilepsy surgery and invasive diagnostic procedures: A proposed protocol and feasibility study

Abstract

Objective

In epilepsy surgery, which aims to treat seizures and thereby to improve the lives of persons with drug-resistant epilepsy, the chances of attaining seizure relief must be carefully weighed against the risks of complications and expected adverse events. The interpretation of data regarding complications of epilepsy surgery and invasive diagnostic procedures is hampered by a lack of uniform definitions and method of data collection.

Methods

Based on a review of previous definitions and classifications of complications, we developed a proposal for a ...

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Short‐term changes in cortical physiological arousal measured by electroencephalography during thalamic centromedian deep brain stimulation

Abstract

Objective

The intralaminar thalamus is well implicated in the processes of arousal and attention. Stimulation of the intralaminar thalamus has been used therapeutically to improve level of alertness in minimally conscious individuals and to reduce seizures in refractory epilepsy, both presumably through modulation of thalamocortical function. Little work exists that directly measures the effects of intralaminar thalamic stimulation on cortical physiological arousal in humans. Therefore, our goal was to quantify cortical physiological arousal in individuals with epilepsy receiving thalamic intralaminar deep ...

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Psychogenic nonepileptic seizures treated as epileptic seizures in the emergency department

Abstract

Objectives

We aimed to estimate the rate of psychogenic nonepileptic seizures (PNES) among patients presenting to an emergency department with presumed seizures. We also wanted to identify factors that can assist health care professionals in determining whether these events are likely to be epileptic or nonepileptic.

Methods

We performed two retrospective audits on patients who were treated for seizures in the department of emergency medicine at the Princess Alexandra Hospital, Brisbane, Australia. Exploratory analyses and logistic regressions were conducted to investigate the characteristics ...

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Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany

Abstract

Objective

Dravet syndrome (DS) is a rare but severe drug-resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP).

Methods

We conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP. Patients received add-on therapy with oral FFA gradually titrated to a target dose between .13 and .7 mg/kg/day.

Results

Overall, 78 patients with DS (median age = 8.0 years, range ...

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Understanding long‐term changes in patient identity 15–20 years after surgery for temporal lobe epilepsy

Abstract

Objective

Following epilepsy surgery, patients can experience complex psychosocial changes. We recently described a longer term adjustment and reframing (“meaning-making”) process 15–20 years following surgery for temporal lobe epilepsy, which could involve an ongoing sense of being a “different” person for some patients. Here, we quantitatively examine identity at long-term follow-up and how this relates to meaning-making and postoperative seizure outcome.

Methods

Eighty-seven participants were included: 39 who underwent anterior temporal lobectomy (ATL) 15–20 years ago (59% female; median age = 49.2 years, interquartile range [IQR] = 10; median follow-up = 18.4 years, ...

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Anticonvulsant dopamine type 2 receptor agonist activates inhibitory parvalbumin interneurons

Abstract

Dopamine type 2 receptor (D2R) agonists have anticonvulsant effect, whereas D2R antagonists increase seizure risk, but the mechanism of this action has not been delineated. We tested whether D2R agonists activate parvalbumin (PV)-containing inhibitory interneurons to suppress seizures. We treated frontal lobe onset seizures with a D2R agonist sumanirole, and it suppressed seizures. We used activity reporter TRAP2 mice and found that injection of D2R agonist led to extensive activation of PV interneurons in the cortex and striatum ipsilateral to the ...

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