Intravenous Ganaxolone for the Treatment of Refractory Status Epilepticus: Results from an Open‐Label, Dose‐Finding, Phase 2 Trial

Abstract

Objective

Patients with refractory status epilepticus (RSE) have failed treatment with benzodiazepines and ≥1 second-line intravenous (IV) anti-seizure medication (ASM). Guidelines recommend IV anesthesia when second-line ASMs have failed, but potential harms can outweigh benefits. Novel treatments are needed to stop and durably control RSE without escalation to IV anesthetics. Ganaxolone is an investigational neuroactive steroid in development for RSE treatment. This study’s objective was to determine the appropriate dosing for IV ganaxolone in RSE and obtain a preliminary assessment of ...

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Superficial and deep white matter diffusion abnormalities in focal epilepsies

SUMMARY

Objective

To evaluate superficial (superficial-WM) and deep white matter (deep-WM) MRI diffusion tensor imaging (DTI) metrics and identify distinctive patterns of microstructural abnormalities in focal epilepsies of diverse etiology, localization and response to antiseizure medications (ASM).

Methods

We examined DTI data for 113 healthy controls and 113 patients with focal epilepsies: 51 patients with temporal lobe epilepsy and hippocampal sclerosis refractory to ASM (refractory-TLE-HS), 27 with pharmacoresponsive TLE-HS, 15 with temporal lobe focal cortical dysplasia (tFCD), and 20 with frontal lobe focal cortical ...

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Temporal lobe interictal spikes disrupt encoding and retrieval of verbal memory: a subregion analysis

Abstract

Objective

The medial temporal lobe (MTL) encodes and recalls memories and can be a predominant site for interictal spikes (IS) in patients with focal epilepsy. It is unclear if memory deficits are due to IS in the MTL producing a transient decline. Here, we investigated whether IS in the MTL subregions and lateral temporal cortex impact episodic memory encoding and recall.

Methods

78 participants undergoing presurgical evaluation for medically refractory focal epilepsy with depth electrodes placed in the temporal lobe participated in a ...

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Anterior Nucleus of the Thalamus Deep Brain Stimulation Versus Temporal Lobe Responsive Neurostimulation for Temporal Lobe Epilepsy

Abstract

Objective

Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are increasingly used in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication for either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare seizure benefits and adverse effects associated with these therapies in this patient population. We therefore examined all patients who underwent ...

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The ILAE consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission

Abstract

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new ...

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High‐resolution hippocampal DTI of Mesial Temporal Sclerosis in Refractory Epilepsy

Abstract

Objective

We explore the possibility of using diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) to discern microstructural abnormalities in the hippocampus indicative of MTS at the subfield level

Methods

We analyzed data from 57 patients with refractory epilepsy who previously underwent 3.0T MRI including DTI as a standard part of presurgical work-up. We collected information about each subject’s seizure semiology, conventional EEG, High Density EEG, PET reports, surgical outcome, and available histopathological findings to assign a final diagnostic ...

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Detection of brain somatic variation in epilepsy‐associated developmental lesions

Abstract

Objective

Epilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified.

Methods

We enrolled 50 children undergoing epilepsy surgery into a translational research study. Resected tissue was divided for clinical neuropathologic evaluation and genomic analysis. We performed exome and RNA-sequencing to identify somatic variation and confirmed our findings using high-depth ...

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Characterizing Thalamic and Basal Ganglia Nuclei in Medically Intractable Focal Epilepsy by MR Fingerprinting

Abstract

Objectives

Magnetic resonance fingerprinting (MRF) is a novel, quantitative and noninvasive technique to measure brain tissue properties. We aim to use MRF for characterizing normal-appearing thalamic and basal ganglia nuclei in the epileptic brain.

Methods

A 3D MRF protocol (1mm3 isotropic resolution) was acquired from 48 patients with unilateral medically refractory focal epilepsy and 39 healthy controls (HCs). Whole-brain T1 and T2 maps (containing T1 and T2 relaxation times) were reconstructed for each subject. Ten subcortical nuclei in the thalamus and basal ganglia ...

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Correlation between fluorodeoxyglucose positron emission tomography brain hypometabolism and posttraumatic stress disorder symptoms in temporal lobe epilepsy

Abstract

The relationship between posttraumatic stress disorder (PTSD) and focal epilepsy is poorly understood. It has been hypothesized that there is a complex and reciprocal potential reinforcement of the symptoms of each condition. In this study, we investigated whether there are PTSD-specific brain changes in temporal lobe epilepsy (TLE). Brain fluorodeoxyglucose positron emission tomography (PET) metabolism was compared between controls and two groups of TLE patients: one group of 15 patients fulfilling the criteria for a potential diagnosis of PTSD (TLE-PTSD+), ...

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Novel animal model of combined generalized and focal epilepsy

Abstract

Thioredoxin, encoded by Txn1, is a critical antioxidant that protects against oxidative damage by regulating the dithiol/disulfide balance of interacting proteins. We recently discovered the Adem rat, an epileptic rat harboring the Txn1-F54L mutation, characterized by wild running and vacuolar degeneration in the midbrain. This study aimed to characterize the classification of epilepsy in Adem rats. We performed simultaneous video-electroencephalographic recordings, magnetic resonance imaging, neurotransmitter measurements using gas chromatography–mass spectrometry (GC-MS), and immunohistochemistry. Adem rats exhibited absence, tonic, and focal seizures. ...

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