P‐glycoprotein overactivity in epileptogenic developmental lesions measured in vivo using (R)‐[11C]verapamil PET

Abstract

Objective

Overexpression of the drug transporter P‐glycoprotein (P‐gp) is thought to be involved in drug‐resistance in epilepsy by extrusion of antiepileptic drugs (AEDs). We used positron emission tomography (PET) and the P‐gp substrate radiotracer (R)‐[11C]verapamil (VPM) together with the third‐generation P‐gp inhibitor tariquidar (TQD) to evaluate P‐gp function in individuals with drug‐resistant epileptogenic developmental lesions.

Methods

Twelve healthy controls (7 male, median age 45, range 35‐55 years), and two patients with epileptogenic developmental lesions (2 male, aged 24 and 62 years) underwent VPM‐PET scans before ...

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Temporal‐plus epilepsy in children: A connectomic analysis in magnetoencephalography

Abstract

Objective

Seizure recurrence following surgery for temporal lobe (TL) epilepsy may be related to extratemporal epileptogenic foci, so‐called temporal‐plus (TL+) epilepsy. Here, we sought to leverage whole brain connectomic profiling in magnetoencephalography (MEG) to identify neural networks indicative of TL+ epilepsy in children.

Methods

Clinical and MEG data were analyzed for 121 children with TL and TL+ epilepsy spanning 20 years at the Hospital for Sick Children. Resting‐state connectomes were derived using the weighted phase lag index from neuromagnetic oscillations. Multidimensional associations between patient ...

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A perspective on the physicochemical and biopharmaceutic properties of marketed antiseizure drugs—From phenobarbital to cenobamate and beyond

Abstract

The success rate from first time in man to regulatory approval of central nervous system (CNS) drugs is lower than the overall success rate across all therapeutic indications (eg, cardiovascular, infectious diseases). To understand the reasons for drug‐candidate failure and to capture trends in antiseizure drug (ASD) design, we have analyzed the physicochemical and biopharmaceutical properties of marketed ASDs in comparison with new ASDs in development. Our comparative analysis included molecular weight (MW), logP, polar surface area (PSA), the “Lipinski ...

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Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid

Abstract

In January 2019, a new plant‐derived purified cannabidiol preparation, approved by the US Food and Drug Administration, became commercially available for patients ≥2 years old with Lennox‐Gastaut syndrome or Dravet syndrome. Among our patients who were prescribed the new cannabidiol formulation, we observed several cases of thrombocytopenia and therefore embarked on this study. We conducted a single‐center systematic chart review of all pediatric patients (<21 years old) who were prescribed cannabidiol from January to August 2019. We evaluated salient features of the ...

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Effect of combined physical training on cognitive function in people with epilepsy: Results from a randomized controlled trial

Abstract

Objective

To examine the effect of 12‐week exercise program on cognitive function in people with epilepsy.

Methods

Twenty‐one physically inactive subjects were randomized into two groups: the exercise group (EG) or the control group (CG). EG performed 12 weeks of combined physical training. CG was advised to maintain usual daily activities. EG received a structured, individually supervised exercise program with two 60‐minute sessions per week. Each session included warmup (5‐minutes), aerobic (15‐20 minutes at 14‐17 on Borg scale), strength (2‐3 sets, 10‐15 repetitions), and 5‐minute ...

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Zebrafish model of posttraumatic epilepsy

Abstract

Objective

Posttraumatic epilepsy (PTE) is defined as recurrent and unprovoked seizures occurring >1 week after traumatic brain injury (TBI). Animal studies of PTE are lengthy and expensive. In this study, we developed a cost‐effective PTE animal model using zebrafish to bridge the gap between in vitro studies and low‐throughput animal studies.

Methods

We used two different sets of parameters (G1 and G2) to induce closed‐head TBI in adult zebrafish using pulsed high‐intensity focused ultrasound. Injured fish and naive controls were evaluated for behavioral deficits ...

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Interictal intracranial electroencephalography for predicting surgical success: The importance of space and time

Abstract

Objective

Predicting postoperative seizure freedom using functional correlation networks derived from interictal intracranial electroencephalography (EEG) has shown some success. However, there are important challenges to consider: (1) electrodes physically closer to each other naturally tend to be more correlated, causing a spatial bias; (2) implantation location and number of electrodes differ between patients, making cross‐subject comparisons difficult; and (3) functional correlation networks can vary over time but are currently assumed to be static.

Methods

In this study, we address these three challenges using ...

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