A multiorganism pipeline for antiseizure drug discovery: Identification of chlorothymol as a novel γ‐aminobutyric acidergic anticonvulsant

Abstract

Objective

Current medicines are ineffective in approximately one‐third of people with epilepsy. Therefore, new antiseizure drugs are urgently needed to address this problem of pharmacoresistance. However, traditional rodent seizure and epilepsy models are poorly suited to high‐throughput compound screening. Furthermore, testing in a single species increases the chance that therapeutic compounds act on molecular targets that may not be conserved in humans. To address these issues, we developed a pipeline approach using four different organisms.

Methods

We sequentially employed compound library screening in ...

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Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

Abstract

Objective

To identify postinjury physiologic, behavioral, and cognitive biomarkers for posttraumatic epilepsy to enrich study populations for long‐term antiepileptogenesis studies.

Methods

The EPITARGET cohort with behavioral follow‐up and 1‐month 24/7 video‐electroencephalography (vEEG) monitoring included 115 adult male Sprague‐Dawley rats with lateral fluid‐percussion–induced traumatic brain injury (TBI), 23 sham‐operated controls, and 13 naive rats. Animals underwent assessment of somatomotor performance (composite neuroscore), anxiety‐like behavior (elevated plus maze, open field), spatial memory (Morris water maze), and depression‐like behavior (Porsolt forced swim, sucrose preference). Impact force, ...

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Pregnancy‐related complications and risk of postpartum readmission for seizures and epilepsy: A national study

Abstract

Objective

Peripartum seizures remain a leading cause of maternal morbidity and mortality worldwide. Therefore, recognition of high‐risk individuals is essential. We aimed to determine the rate and identify risk factors for postpartum seizure/epilepsy readmissions.

Methods

In this retrospective cohort study, the Nationwide Readmissions Database was used to identify index admissions for delivery and readmissions for seizures in the year 2013, defined by International Classification of Disease, Ninth Revision, Clinical Modification codes for epilepsy, convulsions, and eclampsia in the primary diagnostic position. Logistic regression ...

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Transcranial magnetic stimulation as a tool to understand genetic conditions associated with epilepsy

Abstract

Advances in genetics may enable a deeper understanding of disease mechanisms and promote a shift to more personalised medicine in the epilepsies. At present, understanding of consequences of genetic variants mainly relies on preclinical functional work; tools for acquiring similar data from the living human brain are needed. Transcranial magnetic stimulation (TMS), in particular paired‐pulse TMS protocols which depend on the function of cortical GABAergic interneuron networks, has the potential to become such a tool. For this report, we identified ...

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Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery

Abstract

Objective

To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects.

Methods

Pre‐ and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug‐resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, ...

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The development of an epilepsy electronic patient portal: Facilitating both patient empowerment and remote clinician‐patient interaction in a post‐COVID‐19 world

Abstract

Objectives

The current coronavirus disease 2019 (COVID‐19) pandemic stresses an urgency to accelerate much‐needed health service reform. Rapid and courageous changes being made to address the immediate impact of the pandemic are demonstrating that the means and technology to enable new models of health care exist. For example, innovations such as electronic patient portals (ePortal) can facilitate (a) radical reform of outpatient care; (b) cost containment in the economically constrained aftermath of the pandemic; (c) environmental sustainability by reduction of unnecessary ...

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Stereotactic MRI‐guided laser interstitial thermal therapy for extratemporal lobe epilepsy

Abstract

Objective

Magnetic resonance imaging (MRI)–guided laser interstitial thermal therapy (MRg‐LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg‐LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection.

Methods

We retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg‐LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ...

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