Progesterone receptors regulate susceptibility to spreading depression.

Migraine patients often experience sensory symptoms called auras accompanying the headaches. Cortical spreading depression (CSD), a slow-propagating wave of neuroglial depolarization followed by hyperpolarization is proposed to be the neurological mechanism underlying these auras. We have previously found that progesterone regulates susceptibility to migraine through progesterone receptor (PR) activation.

Preferential superficial cortical layer activation during seizure propagation.

Objective: Focal cortical seizures travel long distances from the onset zone, but the long-distance propagation pathways are uncertain. In vitro and in vivo imaging techniques have investigated the local spread of seizures but did not elucidate long-distance spread. Furthermore, classical studies in slices suggested seizure spread locally along deep cortical layers, whereas more recent in vivo imaging studies posit a role for superficial cortical layers in local spread.

Strategies to innovate emergency care of status epilepticus.

Generalized Convulsive status epilepticus (SE) is a neurological emergency because prolonged convulsions can cause respiratory compromise and neuronal injury. Compromised GABA-mediated inhibition is a defining feature of SE, and many current therapies are benzodiazepines, which are allosteric modulators of GABA-A receptors. Many patients with medically refractory epilepsy are at risk for SE.

Analysis of practical judgment in older adults with epilepsy: An exploratory, multicenter cohort study.

Despite the high prevalence of cognitive deficits in older people with epilepsy (PWE), their ability to judge and make decisions in daily life remains unexplored. In 61 older PWE (55-90 years) from the multicenter BRain Aging and Cognition in Epilepsy (BrACE) study, we examined everyday judgment, as measured by the Test of Practical Judgment (TOP-J: 9 questions, score range = 0-27; higher score = better judgment) and evaluated its association with clinical and demographic characteristics, global cognition, neuropsychological performance, subjective cognition, and quality of life (QOL). In our participants (mean age ± standard deviation [SD] = 66.

Association of Seizure Control with Mortality, Cognition, and Function in People With Dementia.

Objectives: The effects of seizure control on outcomes in persons with dementia (PWD) remain unclear. Our study aimed to investigate the impact of seizure control on mortality, function, cognition, and mood among PWD.

Methods: This longitudinal, multicenter study is based on 39 Alzheimer's disease centers (ADCs) in the United States from September 2005 to December 2021.

QUANTIFYING HIPPOCAMPAL SHAPE ASYMMETRY IN ALZHEIMER'S DISEASE USING OPTIMAL SHAPE CORRESPONDENCES.

Hippocampal atrophy in Alzheimer's disease (AD) is asymmetric and spatially inhomogeneous. While extensive work has been done on volume and shape analysis of atrophy of the hippocampus in AD, less attention has been given to hippocampal asymmetry specifically. Previous studies of hippocampal asymmetry are limited to global volume or shape measures, which don't localize shape asymmetry at the point level.

Association of Seizure Control With Cognition in People With Normal Cognition and Mild Cognitive Impairment.

Background And Objectives: Seizures are common in dementia and associated with accelerated cognitive decline. However, the impact of active vs remote seizures on cognition remains understudied. This study aimed to investigate the impact of active vs remote seizures on cognition in people with normal cognition and mild cognitive impairment (MCI).

A medico-legal perspective on postictal violence: A case study and systematic review of postictal delirium.

Detailed descriptions of violent postictal episodes are rare. We provide evidence from an index case and from a systematic review of violent postictal episodes that demonstrates the encephalopathic features of some violent postictal behaviors. We discuss how these cases may fit in the legal framework of culpability.

Association of the Area Deprivation Index With Dementia Basic Workup and Diagnosis in Central and Western Virginia: A Cross-Sectional Study.

Background And Objectives: The Area Deprivation Index (ADI) provides a validated and multidimensional metric of areal disadvantage. Our goals were to determine if the ADI influences the likelihood of receiving workup based on published guidelines and an etiologic diagnosis of dementia in Central and Western Virginia.

Methods: We collected deidentified data from the electronic health record of individuals aged 50-105 years diagnosed with dementia at the University of Virginia (UVA) Medical Center (2016-2021) and at Carillion Clinic (2018-2021).

Health care disparities in morbidity and mortality in adults with acute and remote status epilepticus: A national study.

Objective: Although disparities have been described in epilepsy care, their contribution to status epilepticus (SE) and associated outcomes remains understudied.

Methods: We used the 2010-2019 National Inpatient Sample to identify SE hospitalizations using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM codes. SE prevalence was stratified by demographics.

Which terms should be used to describe medications used in the treatment of seizure disorders? An ILAE position paper.

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English-language terminology applicable to pharmacological agents currently approved for treating seizure disorders.

Anatomical Substrates of Rapid Eye Movement Sleep Rebound in a Rodent Model of Post-sevoflurane Sleep Disruption.

Background: Previous research suggests that sevoflurane anesthesia may prevent the brain from accessing rapid eye movement (REM) sleep. If true, then patterns of neural activity observed in REM-on and REM-off neuronal populations during recovery from sevoflurane should resemble those seen after REM sleep deprivation. In this study, the authors hypothesized that, relative to controls, animals exposed to sevoflurane present with a distinct expression pattern of c-Fos, a marker of neuronal activation, in a cluster of nuclei classically associated with REM sleep, and that such expression in sevoflurane-exposed and REM sleep-deprived animals is largely similar.

Neuronal plasticity contributes to postictal death.

Repeated generalized tonic-clonic seizures (GTCSs) are the most critical risk factor for sudden unexpected death in epilepsy (SUDEP). GTCSs can cause fatal apnea. We investigated neuronal plasticity mechanisms that precipitate postictal apnea and seizure-induced death.

Progesterone Receptor Activation Regulates Sensory Sensitivity and Migraine Susceptibility.

Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to mechanical stimulus during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone.

Glycolytic lactate production supports status epilepticus in experimental animals.

Objective: Status epilepticus (SE) requires rapid intervention to prevent cerebral injury and mortality. The ketogenic diet, which bypasses glycolysis, is a promising remedy for patients with refractory SE. We tested the role of glycolytic lactate production in sustaining SE.

Progesterone receptor activation regulates sensory sensitivity.

Women develop chronic pain during their reproductive years more often than men, and estrogen and progesterone regulate this susceptibility. We tested whether brain progesterone receptor (PR) signaling regulates pain susceptibility. During the estrous cycle, animals were more sensitive to pain during the estrus stage than in the diestrus stage, suggesting a role for reproductive hormones, estrogen, and progesterone.

Desirability of Outcome Ranking for Status Epilepticus: A Benefit-Risk Approach to Design and Analyses of Clinical SE Trials.

Most clinical trials of treatment efficacy evaluate benefits and harms separately. Investigators generally rate the primary outcome of a trial with a binary outcome measure and consider harms separately as adverse events. This approach fails to recognize finer gradations of patient response, correlations between benefits and harms, and the overall effects on individual patients.

Drug-Inducible Gene Therapy Effectively Reduces Spontaneous Seizures in Kindled Rats but Creates Off-Target Side Effects in Inhibitory Neurons.

Over a third of patients with temporal lobe epilepsy (TLE) are not effectively treated with current anti-seizure drugs, spurring the development of gene therapies. The injection of adeno-associated viral vectors (AAV) into the brain has been shown to be a safe and viable approach. However, to date, AAV expression of therapeutic genes has not been regulated.

Connectivity and Excitability Shape Seizure Circuits.

Mapping neuronal circuits that generate focal to bilateral tonic-clonic seizures is essential for understanding general principles of seizure propagation and modifying the risk of death and injury due to bilateral motor seizures. We used novel techniques developed over the past decade to study these circuits. We propose the general hypothesis that at the mesoscale, seizures follow anatomical projections of the seizure focus, preferentially activating more excitable neurons.

Measuring vagal activity in postictal bradycardia.

Alterations to cardiac electrical conduction are some of the most frequently observed systemic complications of seizures, with autonomic dysregulation cited as the principal driver for these alterations. In this prospective study, we use 6-lead continuous ECG monitoring in hospitalized patients with epilepsy to trend heart rate patterns in the postictal period. A total of 117 seizures in 45 patients met the criteria for analysis.

Limbic progesterone receptors regulate spatial memory.

Progesterone and its receptors (PRs) participate in mating and reproduction, but their role in spatial declarative memory is not understood. Male mice expressed PRs, predominately in excitatory neurons, in brain regions that support spatial memory, such as the hippocampus and entorhinal cortex (EC). Furthermore, segesterone, a specific PR agonist, activates neurons in both the EC and hippocampus.