Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis

Abstract

Objective

Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan‐drebrin) isoforms, respectively.

Methods

Hippocampal sections from drug‐resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 ...

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Statistical efficiency of patient data in randomized clinical trials of epilepsy treatments

Abstract

Objective

Previous research suggests that natural fluctuations in seizure rates within individuals have a quantifiable impact on therapeutic clinical trial outcomes.

Methods

A trial simulator estimated the statistical power of clinical trials with a typical trial design with and without patients included who exhibited a range of means (1‐15 seizures/mo) and standard deviations (1‐15 seizures/mo) in their baseline seizure rates. Trial outcomes were evaluated using 50% responder rates, median percentage change, and time to prerandomization.

Results

Patients with higher seizure frequencies and lower standard deviations ...

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Real‐world experience with direct brain‐responsive neurostimulation for focal onset seizures

Abstract

Objective

The RNS System is a direct brain‐responsive neurostimulation system that is US Food and Drug Administration–approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real‐world safety and effectiveness of the RNS System.

Methods

Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device‐related ...

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Quantifying the burden of generalized tonic‐clonic seizures in patients with drug‐resistant epilepsy

Abstract

Objective

Compared to other seizure types, generalized tonic‐clonic (GTC) seizures may be disproportionately related to increased morbidity, and reducing seizure frequency could translate into improvements across measures of morbidity in medically treated patients with drug‐resistant epilepsy (DRE). The primary objective of this analysis was to quantify the burden of patients with DRE who experience GTC seizures (GTC+) compared to patients with DRE who do not experience GTC seizures (GTC−).

Methods

Adult patients from the Cleveland Clinic Epilepsy Center‐Neurological Institute from 2012‐2016 with DRE ...

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Functional and behavioral signatures of Kv7 activator drug subtypes

Abstract

Objective

Voltage‐gated potassium channels of the KCNQ (Kv7) family are targeted by a variety of activator compounds with therapeutic potential for treatment of epilepsy. Exploration of this drug class has revealed a variety of effective compounds with diverse mechanisms. In this study, we aimed to clarify functional criteria for categorization of Kv7 activator compounds, and to compare the effects of prototypical drugs in a zebrafish larvae model.

Methods

In vitro electrophysiological approaches with recombinant ion channels were used to highlight functional properties important ...

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Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug‐resistant temporal lobe epilepsy and comorbid depression

Abstract

Objective

Depressive disorders are common among about 50% of the patients with drug‐resistant temporal lobe epilepsy (TLE). The underlying etiology remains elusive, but hypothalamus‐pituitary‐adrenal (HPA) axis activation due to changes in glucocorticoid receptor (GR) protein expression could play an important role. Therefore, we set out to investigate expression of the GR in the hippocampus, an important brain region for HPA axis feedback, of patients with drug‐resistant TLE, with and without comorbid depression.

Methods

GR expression was studied using immunohistochemistry on hippocampal sections from ...

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Photoplethysmographic evaluation of generalized tonic‐clonic seizures

Abstract

Objective

Photoplethysmography (PPG) is an optical technique measuring variations of blood perfusion in peripheral tissues. We evaluated alterations in PPG signals in relationship to the occurrence of generalized tonic‐clonic seizures (GTCSs) in patients with epilepsy to evaluate the feasibility of seizure detection.

Methods

During electroencephalographic (EEG) long‐term monitoring, patients wore portable wristband sensor(s) on their wrists or ankles recording PPG signals. We analyzed PPG signals during three time periods, which were defined with respect to seizures detected on EEG: (1) baseline (>30 minutes prior ...

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Defining the phenotype of FHF1 developmental and epileptic encephalopathy

Abstract

Fibroblast growth‐factor homologous factor (FHF1 ) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients with pathogenic FHF1 variants. We retrospectively collected clinical, genetic, neurophysiologic, and neuroimaging data of 17 patients with FHF1‐DEE. Sixteen patients had recurrent heterozygous FHF1 missense variants: 14 had the recurrent p.Arg114His variant and two had a novel likely ...

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