Reduced cannabinoid 2 receptor activity increases susceptibility to induced seizures in mice

Abstract

Objective

The endocannabinoid system (ECS) is comprised of cannabinoid receptors 1 and 2 (CB1R and CB2R), endogenous ligands, and regulatory enzymes, and serves to regulate several important physiological functions throughout the brain and body. Recent evidence suggests that the ECS may be a promising target for the treatment of epilepsy, including epilepsy subtypes that arise from mutations in the voltage‐gated sodium channel SCN1A. The objective of this study was to explore the effects of modulating CB2R activity on seizure susceptibility.

Methods

We examined ...

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Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation

Abstract

Objective

To screen a library of potential therapeutic compounds for a woman with Lennox‐Gastaut syndrome due to a Y302C GABRB3 (c.905A>G) mutation.

Methods

We compared the electrophysiological properties of cells with wild‐type or the pathogenic GABRB3 mutation.

Results

Among 1320 compounds, multiple candidates enhanced GABRB3 channel conductance in cell models. Vinpocetine, an alkaloid derived from the periwinkle plant with anti‐inflammatory properties and the ability to modulate sodium and channel channels, was the lead candidate based on efficacy and safety profile. Vinpocetine was administered as a ...

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Lactate reduces epileptiform activity through HCA1 and GIRK channel activation in rat subicular neurons in an in vitro model

Abstract

Objective

Much evidence suggests that the subiculum plays a significant role in the regulation of epileptic activity. Lactate acts as a neuroprotective agent against many conditions that cause brain damage. During epileptic seizures, lactate formation reaches up to ~6 mmol/L in the brain. We investigated the effect of lactate on subicular pyramidal neurons after induction of epileptiform activity using 4‐aminopyridine (4‐AP‐0Mg2+) in an in vitro epilepsy model in rats. The signaling mechanism associated with the suppression of epileptiform discharges by lactate was also ...

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Segregation of seizures and spreading depolarization across cortical layers

Abstract

Objective

Cortical spreading depolarization (SD) and seizures are often co‐occurring electrophysiological phenomena. However, the cross‐layer dynamics of SD during seizures and the effect of SD on epileptic activity across cortical layers remain largely unknown.

Methods

We explored the spatial‐temporal dynamics of SD and epileptic activity across layers of the rat barrel cortex using direct current silicone probe recordings during flurothyl‐induced seizures.

Results

SD occurred in half of the flurothyl‐evoked seizures. SD always started from the superficial layers and spread downward either through all cortical layers ...

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Localization value of subclinical seizures on scalp video‐EEG in epilepsy presurgical evaluation

Abstract

Objective

To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video‐electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery.

Methods

We included 123 consecutive patients who had SCSs and CSs during scalp‐VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1‐year follow‐up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and ...

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Long‐term safety and efficacy of lacosamide and controlled‐release carbamazepine monotherapy in patients with newly diagnosed epilepsy

Abstract

Objective

A large‐scale, double‐blind trial (SP0993; NCT01243177) demonstrated that lacosamide was noninferior to controlled‐release carbamazepine (carbamazepine‐CR) in terms of efficacy, and well tolerated as first‐line monotherapy in patients (≥16 years of age) with newly diagnosed epilepsy. We report primary safety outcomes from the double‐blind extension of the noninferiority trial (SP0994; NCT01465997) and post hoc analyses of pooled long‐term safety and efficacy data from both trials.

Methods

Patients were randomized 1:1 to lacosamide or carbamazepine‐CR. Doses were escalated (lacosamide: 200/400/600 mg/d; carbamazepine‐CR: 400/800/1200 mg/d) based on seizure ...

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The probability of seizures during continuous EEG monitoring in high‐risk neonates

Abstract

Objective

We evaluated the impact of monitoring indication, early electroencephalography (EEG), and clinical features on seizure risk in all neonates undergoing continuous EEG (cEEG) monitoring following a standardized monitoring protocol.

Methods

All cEEGs from unique neonates 34‐48 weeks postmenstrual age monitored from 1/2011‐10/2017 (n = 291) were included. We evaluated the impact of cEEG monitoring indication (acute neonatal encephalopathy [ANE], suspicious clinical events [SCEs], or other high‐risk conditions [OHRs]), age, medication status, and early EEG abnormalities (including the presence of epileptiform discharges and abnormal background continuity, ...

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Comparing the efficacy, exposure, and cost of clinical trial analysis methods

Abstract

This study aimed to compare three commonly used analysis methods for clinical trials in epilepsy in terms of statistical efficiency, nonefficacious exposure, and cost. A realistic seizure diary simulator was employed to produce 102 000 trials, which were analyzed by the 50%‐responder rate method (RR50), median percentage change (MPC), and time to prerandomization (TTP). Half the trials compared a placebo to a drug that was 20% better, and the other half compared two placebos. The former were used to calculate statistical ...

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