Pharmacogenetics of KCNQ channel activation in 2 potassium channelopathy mouse models of epilepsy

Summary

Objectives

Antiseizure drugs are the leading therapeutic choice for treatment of epilepsy, but their efficacy is limited by pharmacoresistance and the occurrence of unwanted side effects. Here, we examined the therapeutic efficacy of KCNQ channel activation by retigabine in preventing seizures and neurocardiac dysfunction in 2 potassium channelopathy mouse models of epilepsy with differing severity that have been associated with increased risk of sudden unexpected death in epilepsy (SUDEP): the Kcna1−/− model of severe epilepsy and the Kcnq1A340E/A340E ...

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Modeling pathogenesis and treatment response in childhood absence epilepsy

Summary

Objective

Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ-aminobutyric acid (GABA) receptors and T-type calcium channels implicated in the disorder. Previous studies of T-type calcium channel electrophysiology have shown genetic changes and medications have multiple effects. The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in ...

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Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Summary

The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of ...

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Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Summary

The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of ...

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Is inpatient ictal video-electroencephalographic monitoring mandatory in mesial temporal lobe epilepsy with unilateral hippocampal sclerosis? A prospective study

Summary

Objective

To compare surgical outcome in mesial temporal lobe epilepsy (MTLE) patients with unilateral hippocampal sclerosis (MTLE-HS) who had or did not have preoperative video-electroencephalographic monitoring (VEEG).

Methods

A prospective study was undertaken with 166 consecutive pharmacoresistant unilateral MTLE-HS patients. All patients were investigated with detailed seizure semiology, serial routine outpatient EEG, magnetic resonance imaging, neuropsychological evaluation, and if necessary, other examinations. Postoperative follow-up ranged between 2 and 16 years. Patients were divided into: (1) patients operated on based on ...

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Association between scalp and intracerebral electroencephalographic seizure-onset patterns: A study in different lesional pathological substrates

Summary

Objective

Our purpose was to determine the correlation between scalp electroencephalography (EEG) and intracerebral EEG (iEEG) seizure-onset patterns in patients with focal lesional epilepsy to determine whether scalp seizure-onset patterns can be specific to intracerebral seizure-onset patterns and to lesion type.

Methods

We retrospectively analyzed 61 patients with focal epilepsy and a structural magnetic resonance imaging (MRI)-visible lesion, who first underwent extensive scalp recordings and then iEEG studies (stereo-EEG) for presurgical evaluation, and who showed an iEEG seizure onset ...

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Long-term adherence with psychiatric treatment among patients with psychogenic nonepileptic seizures

Summary

We conducted a prospective cohort study, examining long-term adherence with psychiatric treatment among patients with psychogenic nonepileptic seizures (PNES). Subjects diagnosed with documented PNES were scheduled for 4 psychiatric visits. Survival analysis was performed, and covariates were assessed for association with time to nonadherence using Cox proportional hazard regression analysis. One hundred twenty-three subjects were recruited and followed for up to 17 months. Eighty percent of subjects attended the first outpatient visit, 42% attended the second, 24% ...

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Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring

Summary

Objective

Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video–electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study.

Methods

In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction ...

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Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring

Summary

Objective

Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video–electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study.

Methods

In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction ...

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A longitudinal cohort study on the impact of the clobazam shortage on patients with epilepsy

Summary

Objective

Drug shortages are occurring at an increasing rate. From May to October 2016, there was a shortage of a level I critical antiepileptic drug, clobazam. We aimed to study the impact of this shortage on patients with epilepsy.

Methods

Adult patients from Calgary’s Comprehensive Epilepsy Program who were taking clobazam were approached to participate in the study. Baseline data from the clinic prospective registry included clinical variables and presurvey patient-reported outcomes (PROs) such as the Global Assessment of ...

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