Dataset Information

Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

ABSTRACT:

Objective

Visual hyperexcitability in the form of abnormal contrast gain control has been shown in photosensitive epilepsy and idiopathic generalized epilepsies. We assessed the accuracy and reliability of measures of visual contrast gain control in discerning individuals with idiopathic generalized epilepsies from healthy controls.

Methods

Twenty-four adult patients with idiopathic generalized epilepsy and 32 neurotypical control subjects from two study sites participated in a prospective, cross-sectional study. We recorded steady-state visual evoked potentials to a wide range of contrasts of a flickering grating stimulus. The resultant response magnitude vs. contrast curves were fitted to a standard model of contrast response function, and the model parameters were used as input features to a linear classifier to separate patients from controls. Additionally we compared the relative contribution of model parameters towards the classification using a sparse feature-selection approach.

Results

Classification accuracy was 80% or better. Sensitivity and specificity both were 80-85%. Cross validation confirmed robust classifier performance generalizable across the data from the two samples. Patients' relative lack of gain control at high contrasts was the most important information distinguishing patients from controls.

Conclusions

Individuals with idiopathic generalized epilepsy were distinguishable from the neurotypical with a high degree of accuracy and reliability by a reduction in gain control at high contrasts.

Significance

Gain control is an essential neural operation that regulates neuronal sensitivity to stimuli and may represent a novel biomarker of hyperexcitability.

SUBMITTER: Won D

PROVIDER: S-EPMC5823846 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

Won Daehan D Kim Wonsuk W Chaovalitwongse W Art WA Tsai Jeffrey J JJ

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 20161218 2

<h4>Objective</h4>Visual hyperexcitability in the form of abnormal contrast gain control has been shown in photosensitive epilepsy and idiopathic generalized epilepsies. We assessed the accuracy and reliability of measures of visual contrast gain control in discerning individuals with idiopathic generalized epilepsies from healthy controls.<h4>Methods</h4>Twenty-four adult patients with idiopathic generalized epilepsy and 32 neurotypical control subjects from two study sites participated in a pr ...[more]

PMID: 28056389

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Project description:Objective: The objective of this study is to explore the role of GRIN2A gene in idiopathic generalized epilepsies and the potential underlying mechanism for phenotypic variation. Methods: Whole-exome sequencing was performed in a cohort of 88 patients with idiopathic generalized epilepsies. Electro-physiological alterations of the recombinant N-methyl-D-aspartate receptors (NMDARs) containing GluN2A mutants were examined using two-electrode voltage-clamp recordings. The alterations of protein expression were detected by immunofluorescence staining and biotinylation. Previous studies reported that epilepsy related GRIN2A missense mutations were reviewed. The correlation among phenotypes, functional alterations, and molecular locations was analyzed. Results: Three novel heterozygous missense GRIN2A mutations (c.1770A > C/p.K590N, c.2636A > G/p.K879R, and c.3199C > T/p.R1067W) were identified in three unrelated cases. Electrophysiological analysis demonstrated R1067W significantly increased the current density of GluN1/GluN2A NMDARs. Immunofluorescence staining indicated GluN2A mutants had abundant distribution in the membrane and cytoplasm. Western blotting showed the ratios of surface and total expression of the three GluN2A-mutants were significantly increased comparing to the wild type. Further analysis on the reported missense mutations demonstrated that mutations with severe gain-of-function were associated with epileptic encephalopathy, while mutations with mild gain of function were associated with mild phenotypes, suggesting a quantitative correlation between gain-of-function and phenotypic severity. The mutations located around transmembrane domains were more frequently associated with severe phenotypes and absence seizure-related mutations were mostly located in carboxyl-terminal domain, suggesting molecular sub-regional effects. Significance: This study revealed GRIN2A gene was potentially a candidate pathogenic gene of idiopathic generalized epilepsies. The functional quantitative correlation and the molecular sub-regional implication of mutations helped in explaining the relatively mild clinical phenotypes and incomplete penetrance associated with GRIN2A variants.

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Dataset Information

Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

Objective

Methods

Results

Conclusions

Significance

Publications

Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

Similar Datasets

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