Precision medicine and therapies of the future

Abstract

Precision medicine in the epilepsies has gathered much attention, especially with gene discovery pushing forward new understanding of disease biology. Several targeted treatments are emerging, some with considerable sophistication and individual‐level tailoring. There have been rare achievements in improving short‐term outcomes in a few very select patients with epilepsy. The prospects for further targeted, repurposed, or novel treatments seem promising. Along with much‐needed success, difficulties are also arising. Precision treatments do not always work, and sometimes are inaccessible or do ...

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

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Tensor‐valued diffusion MRI differentiates cortex and white matter in malformations of cortical development associated with epilepsy

Abstract

Objective

Delineation of malformations of cortical development (MCD) is central in presurgical evaluation of drug‐resistant epilepsy. Delineation using magnetic resonance imaging (MRI) can be ambiguous, however, because the conventional T1‐ and T2‐weighted contrasts depend strongly on myelin for differentiation of cortical tissue and white matter. Variations in myelin content within both cortex and white matter may cause MCD findings on MRI to change size, become undetectable, or disagree with histopathology. The novel tensor‐valued diffusion MRI (dMRI) technique maps microscopic diffusion anisotropy, ...

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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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