Leveraging electrophysiologic correlates of word encoding to map seizure onset zone in focal epilepsy: Task‐dependent changes in epileptiform activity, spectral features, and functional connectivity

Abstract

Objective

Verbal memory dysfunction is common in focal, drug-resistant epilepsy (DRE). Unfortunately, surgical removal of seizure-generating brain tissue can be associated with further memory decline. Therefore, localization of both the circuits generating seizures and those underlying cognitive functions is critical in presurgical evaluations for patients who may be candidates for resective surgery. We used intracranial electroencephalographic (iEEG) recordings during a verbal memory task to investigate word encoding in focal epilepsy. We hypothesized that engagement in a memory task would exaggerate local ...

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Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity

Abstract

Objective

The astroglial enzyme glutamine synthetase (GS) is deficient in small loci in the brain in adult patients with different types of focal epilepsy; however, the role of this deficiency in the pathogenesis of epilepsy has been difficult to assess due to a lack of sufficiently sensitive and specific animal models. The aim of this study was to develop an in vivo approach for precise and specific deletions of the GS gene in the postnatal brain.

Methods

We stereotaxically injected various adeno-associated virus ...

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Blocking receptor for advanced glycation end products (RAGE) or toll‐like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice

Abstract

Objective

Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis.

Methods

In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and ...

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Comparison of the real‐world effectiveness of vertical versus lateral functional hemispherotomy techniques for pediatric drug‐resistant epilepsy: A post hoc analysis of the HOPS study

Abstract

Objective

This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom.

Methods

We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure ...

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Epilepsy centers in China: Current status and ways forward

Summary

Objective

China has the largest population of patients with epilepsy worldwide, which imposes a heavy burden on the public and health care systems. Several epidemiological surveys on epilepsy have been performed in China. Although these surveys grossly describe the prevalence and gap in treatment of epilepsy, the status of epilepsy centers is unclear. The number of epilepsy centers has increased substantially in recent decades. Therefore, a nationwide investigation of the scale and distribution, personnel, equipment, and epilepsy care capacity of each ...

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Soticlestat, a novel cholesterol 24‐hydroxylase inhibitor, reduces seizures and premature death in Dravet syndrome mice

Abstract

Objective

Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) most often caused by de novo pathogenic variants in SCN1A. Individuals with Dravet syndrome rarely achieve seizure control and have significantly elevated risk for sudden unexplained death in epilepsy (SUDEP). Heterozygous deletion of Scn1a in mice (Scn1a
+/−) recapitulates several core phenotypes, including temperature-dependent and spontaneous seizures, SUDEP, and behavioral abnormalities. Furthermore, Scn1a
+/− mice exhibit a similar clinical response to standard anticonvulsants. Cholesterol 24-hydroxlase (CH24H) is a brain-specific enzyme ...

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Atypical functional connectome hierarchy impacts cognition in temporal lobe epilepsy

Abstract

Objective

Drug-resistant temporal lobe epilepsy (TLE) is typically associated with hippocampal pathology. However, widespread network alterations are increasingly recognized and suggested to perturb cognitive function in multiple domains. Here we tested (1) whether TLE shows atypical cortical hierarchical organization, differentiating sensory and higher order systems; and (2) whether atypical hierarchy predicts cognitive impairment.

Methods

We studied 72 well-characterized drug-resistant TLE patients and 41 healthy controls, statistically matched for age and sex, using multimodal magnetic resonance imaging analysis and cognitive testing. To model cortical hierarchical ...

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