Epilepsia. Official Journal of the International League Against Epilepsy

Abstract

Objective

To pinpoint the earliest cellular defects underlying seizure onset (epileptogenic period) during perinatal brain development in a new zebrafish model of Dravet syndrome (DS) and to investigate potential disease‐modifying activity of the 5HT₂ receptor agonist fenfluramine.

Methods

We used CRISPR/Cas9 mutagenesis to introduce a missense mutation, designed to perturb ion transport function in all channel isoforms, into scn1lab, the zebrafish orthologue of SCN1A (encoding voltage‐gated sodium channel alpha subunit 1). We performed behavioral analysis and electroencephalographic recordings to measure convulsions and epileptiform ...

Abstract

Objective

Voltage‐gated sodium channels (SCNs) share similar amino acid sequence, structure, and function. Genetic variants in the four human brain‐expressed SCN genes SCN1A/2A/3A/8A have been associated with heterogeneous epilepsy phenotypes and neurodevelopmental disorders. To better understand the biology of seizure susceptibility in SCN‐related epilepsies, our aim was to determine similarities and differences between sodium channel disorders, allowing us to develop a broader perspective on precision treatment than on an individual gene level alone.

Methods

We analyzed genotype‐phenotype correlations in large SCN‐patient cohorts and ...

Abstract

Objective

The microscopic review of hematoxylin‐eosin–stained images of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex remains challenging. Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. We trained a convolutional neural network (CNN) to classify both entities and visualize the results. Additionally, we propose a new Web‐based deep learning application as proof of concept of how deep learning could enter ...

Abstract

Objective

Electroencephalographic seizures (ESs) are common in encephalopathic critically ill children, but ES identification with continuous electroencephalography (EEG) monitoring (CEEG) is resource‐intense. We aimed to develop an ES prediction model that would enable clinicians to stratify patients by ES risk and optimally target limited CEEG resources. We aimed to determine whether incorporating data from a screening EEG yielded better performance characteristics than models using clinical variables alone.

Methods

We performed a prospective observational study of 719 consecutive critically ill children with acute encephalopathy ...

Abstract

Excess mortality due to epilepsy is greatest among young adults. However, the relative proportions of sudden unexpected death in epilepsy (SUDEP) and other epilepsy‐related causes of death are not well defined. We prospectively adjudicated cause of death in all 18‐ to 45‐year‐olds with a history of seizure/epilepsy who underwent medicolegal investigation in San Diego County between 2014 and 2017. We identified 108 decedents with definite or probable epilepsy; 62% died from an epilepsy‐related cause. SUDEP accounted for 42.6% (N = 46) of ...

Abstract

Objective

Immediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic‐clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO₂) in low‐risk and high‐risk knockout (KO) mice; and (b) whether blocking receptors for orexin, a cardiorespiratory neuromodulator, influences cardiorespiratory function mice or longevity in high‐risk KO mice.

Methods

Heart rate and SaO₂ were ...

Abstract

Objective

To examine the factors and reasons influencing treatment initiation decisions in patients with newly diagnosed epilepsy.

Methods

We assessed antiseizure medication initiation decisions in adults with newly diagnosed epilepsy seen at first seizure clinics in Western Australia between 1999 and 2016 and followed to 2018.

Results

Of 610 patients (median age 40 years, 61.0% male), 426 (69.8%) were diagnosed after two or more seizures and 184 (30.2%) after a single seizure with risk factors for recurrence. Treatment was commenced in 427 patients (70.0%) at diagnosis, ...

Abstract

Objective

Vascular structures may play a significant role in epileptic pathology. Although previous attempts to characterize vasculature relative to epileptogenic zones and hippocampal sclerosis have been inconsistent, an in vivo method of analysis would assist in resolving these inconsistencies and facilitate a comparison against healthy controls in a human model. Magnetic resonance imaging is a noninvasive technique that provides excellent soft tissue contrast, and the relatively recent development of susceptibility‐weighted imaging has dramatically improved the visibility of small veins.

Methods

We built and ...

Abstract

Objective

The pharmacokinetics (PK) and safety of single oral 750‐mg doses of a plant‐derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the USA and Epidyolex in Europe; 100‐mg/mL oral solution) were assessed in healthy adults following a high‐fat/calorie meal (n = 15), a low‐fat/calorie meal (n = 14), whole milk (n = 15), or alcohol (n = 14), relative to the fasted state (n = 29).

Methods

Blood samples were collected until 96 hours postdose in each period and evaluated by liquid chromatography and tandem mass spectrometry. PK parameters (maximum observed plasma ...