Long‐term safety, efficacy, and quality of life outcomes with adjunctive brivaracetam treatment at individualized doses in patients with epilepsy: An up to 11‐year, open‐label, follow‐up trial

Abstract

Objective

To evaluate long‐term safety/tolerability of brivaracetam at individualized doses ≤200 mg/d (primary) and maintenance of efficacy over time (secondary) in adults with focal seizures or primary generalized seizures (PGS) enrolled in phase 3, open‐label, long‐term follow‐up trial N01199 (NCT00150800).

Methods

Patients ≥16 years of age who had completed double‐blind, placebo‐controlled adjunctive brivaracetam trials NCT00175825, NCT00490035, NCT00464269, or NCT00504881 were eligible. Outcomes included safety, efficacy, and quality of life.

Results

The safety set included 667 patients (focal seizures, 97.8%; PGS, 2.2%); the efficacy set included 648 patients ...

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Posttraumatic epilepsy in intensive care unit–treated pediatric traumatic brain injury patients

Abstract

Objective

Posttraumatic epilepsy (PTE) is a well‐described complication of traumatic brain injury (TBI). The majority of the available data regarding PTE stem from the adult population. Our aim was to identify the clinical and radiological risk factors associated with PTE in a pediatric TBI population treated in an intensive care unit (ICU).

Methods

We used the Finnish Intensive Care Consortium database to identify pediatric (<18 years) TBI patients treated in four academic university hospital ICUs in Finland between 2003 and 2013. Our primary outcome ...

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Forecasting cycles of seizure likelihood

Abstract

Objective

Seizure unpredictability is rated as one of the most challenging aspects of living with epilepsy. Seizure likelihood can be influenced by a range of environmental and physiological factors that are difficult to measure and quantify. However, some generalizable patterns have been demonstrated in seizure onset. A majority of people with epilepsy exhibit circadian rhythms in their seizure times, and many also show slower, multiday patterns. Seizure cycles can be measured using a range of recording modalities, including self‐reported electronic seizure ...

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Somatic variants in new candidate genes identified in focal cortical dysplasia type II

Summary

Objective

Focal cortical dysplasia type II (FCDII) is a malformation of cortex development commonly found in children with drug‐resistant epilepsy. FCDII has been associated with somatic mutations in mammalian target of rapamycin (mTOR)‐related pathway genes and an upregulation of mTOR. Somatic mutations were found in 10%‐63% of FCDII samples; the frequency of the mutant allele was 0.93%‐33.5%. This study aimed to find new candidate genes involved in FCDII.

Methods

We collected resected FCD lesions, perilesional brain tissues, and peripheral blood from 17 children ...

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Upregulation of lactate dehydrogenase A in a chronic model of temporal lobe epilepsy

Abstract

The ketogenic diet treatment is effective for drug‐resistant epilepsy. Because its antiepileptic effect is associated with lactate dehydrogenase (LDH), drug development is possible by targeting LDH enzymes. Seizures in rodent models are suppressed by inhibiting LDH; however, it remains unclear whether LDH in the brain is changed by seizures. In the present study, we examined the expression of LDH subunits (LDHA and LDHB) in a chronic model of temporal lobe epilepsy, in which seizures were induced by the microinjection of ...

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Understanding the challenge of comparative effectiveness research in focal epilepsy: A review of network meta‐analyses and real‐world evidence on antiepileptic drugs

Abstract

Objective

Head‐to‐head randomized controlled trials (RCTs) are the gold standard for assessing comparative treatment effects. In the absence of direct comparisons between all possible antiepileptic drugs (AEDs), however, clinical decision‐making in focal (partial onset) epilepsy relies on alternative evidence borne from indirect comparisons including network meta‐analyses (NMAs) and from real‐world evidence (RWE) studies. We review NMAs and observational RWE studies comparing AEDs in the adjunctive setting to compare the robustness of these methods and to formulate recommendations for future evidence development.

Methods

A ...

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Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval

Abstract

Objective

To determine electrical changes in the heart in a chronic, nonstatus model of epilepsy.

Methods

Electrocorticography (ECoG) and electrocardiography (ECG) of nine animals (five made epileptic by intrahippocampal injection of tetanus neurotoxin (TeNT) and four controls), are monitored continuously by radiotelemetry for up to 7 weeks.

Results

Epileptic animals develop a median of 168 seizures, with postictal tachycardias reaching a mean of 487 beats/min and lasting a mean of 661 seconds. Ictal changes in heart rate include tachycardia and in the case of convulsive seizures, bradyarrhythmias ...

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Shared hippocampal abnormalities in sporadic temporal lobe epilepsy patients and their siblings

Abstract

Objective

To examine the shared familial contribution to hippocampal and extrahippocampal morphological abnormalities in patients with sporadic temporal lobe epilepsy (TLE) and their unaffected siblings.

Methods

We collected clinical, electrophysiological, and T1‐weighted magnetic resonance imaging (MRI) data of 18 sporadic patients with TLE without lesions other than hippocampal sclerosis (12 right, 6 left), their 18 unaffected full siblings, and 18 matched healthy volunteers. We compared between‐group differences in cortical thickness and volumes of five subcortical areas (hippocampus, amygdala, thalamus, putamen, and pallidum). We ...

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