Cannabinoid regulation of neurons in the dentate gyrus during epileptogenesis. Role of CB1R‐associated proteins and downstream pathways

Abstract

The hippocampal formation plays a central role in the development of temporal lobe epilepsy (TLE), a disease characterized by recurrent, unprovoked epileptic discharges. TLE is a neurologic disorder characterized by acute long-lasting seizures (i.e. abnormal electrical activity in the brain) or seizures that occur in close proximity without recovery, typically after a brain injury or status epilepticus. After status epilepticus, epileptogenic hyperexcitability develops gradually over the following months to years resulting in the emergence of chronic, recurrent seizures. Acting as ...

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Reasons for ineligibility for clinical trials of patients with medication resistant epilepsy

Abstract

Selection criteria for clinical trials for medication resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criteria on medication resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication resistant focal- or generalized-onset epilepsy who attended outpatient clinic over a consecutive 3-month period. We assessed each patient’s eligibility of ...

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Distinct genetic basis of common epilepsies and structural magnetic resonance imaging measures

Abstract

Focal and generalized epilepsies are associated with robust differences in magnetic resonance imaging (MRI) measures of subcortical structures, gray matter, and white matter. However, it is unknown whether such structural brain differences reflect the cause or consequence of epilepsy or its treatment. Analyses of common genetic variants underlying both common epilepsy risk and variability in structural brain measures can give further insights, as such inherited variants are not influenced by disease or treatment. Here, we performed genetic correlation analyses using ...

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Ketamine as advanced second‐line treatment in benzodiazepine‐refractory convulsive status epilepticus in children

Abstract

Status epilepticus (SE) is one of the most common neurological emergencies in children. To date, there is no definitive evidence to guide treatment of SE refractory to benzodiazepines. The main objectives of treatment protocols are to expedite therapeutic decisions and to use fast- and short-acting medications without significant adverse effects. Protocols differ among institutions, and most frequently valproate, phenytoin, and levetiracetam are used as second-line treatment. After failure of first- and second-line medications, admission to the intensive care unit and ...

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Relative entropy is an easy‐to‐use invasive electroencephalographic biomarker of the epileptogenic zone

Abstract

Objective

High-frequency oscillations are considered among the most promising interictal biomarkers of the epileptogenic zone in patients suffering from pharmacoresistant focal epilepsy. However, there is no clear definition of pathological high-frequency oscillations, and the existing detectors vary in methodology, performance, and computational costs. This study proposes relative entropy as an easy-to-use novel interictal biomarker of the epileptic tissue.

Methods

We evaluated relative entropy and high-frequency oscillation biomarkers on intracranial electroencephalographic data from 39 patients with seizure-free postoperative outcome (Engel Ia) from three institutions. ...

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Metabolomic, proteomic, and transcriptomic changes in adults with epilepsy on modified Atkins diet

Abstract

Objective

High-fat and low-carbohydrate diets can reduce seizure frequency in some treatment-resistant epilepsy patients, including the more flexible modified Atkins diet (MAD), which is more palatable, mimicking fasting and inducing high ketone body levels. Low-carbohydrate diets may shift brain energy production, particularly impacting neuron- and astrocyte-linked metabolism.

Methods

We evaluated the effect of short-term MAD on molecular mechanisms in adult epilepsy patients from surgical brain tissue and plasma compared to control participants consuming a nonmodified higher carbohydrate diet (n = 6 MAD, mean age = 43.7 years, range = 21–53, ...

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A pharmacokinetic model of anti‐seizure medication load to guide care in the Epilepsy Monitoring Unit

Abstract

Objective

Evaluating patients with drug-resistant epilepsy often requires inducing seizures by tapering anti-seizure medications (ASMs) in the Epilepsy Monitoring Unit (EMU). The relationship between ASM taper strategy, seizure timing and severity remains unclear. In this study, we developed and validated a pharmacokinetic model of total ASM load and tested its association with seizure occurrence and severity in the EMU.

Methods

We studied 80 patients who underwent intracranial EEG recording for epilepsy surgery planning. We developed a first-order pharmacokinetic model of the ASMs administered ...

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Comorbidities and predictors of health‐related quality of life in Dravet syndrome: A 10‐year, prospective follow‐up study

Abstract

Objective

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy, leading to reduced health-related quality of life (HRQOL). Prospective outcome data on HRQOL are sparse, and this study investigated long-term predictors of HRQOL in DS.

Methods

One hundred thirteen families of SCN1A-positive patients with DS, who were recruited as part of our 2010 study were contacted at 10-year follow-up, of which 68 (60%) responded. The mortality was 5.8%. Detailed clinical and demographic information was available for each patient. HRQOL was evaluated with ...

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