Diagnosis and management of status epilepticus: improving the status quo.

Status epilepticus is a common neurological emergency that is characterised by prolonged or recurrent seizures without recovery between episodes and associated with substantial morbidity and mortality. Prompt recognition and targeted therapy can reduce the risk of complications and death associated with status epilepticus, thereby improving outcomes. The most recent International League Against Epilepsy definition considers two important timepoints in status epilepticus: first, when the seizure does not self-terminate; and second, when the seizure can have long-term consequences, including neuronal injury.

Lack of association of first and second-line medication dosing and progression to refractory status epilepticus in children.

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children.

Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given as the first single-dose) using a logistic regression model, adjusting for confounders such as time to ASMs.

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.

The significance of multimodality approach in the management of non-lesional drug-resistant focal parietal lobe epilepsies.

Due to extensive connectivity of the parietal lobe, non-lesional drug-resistant (DRE) parietal lobe epilepsies (PLEs) are difficult to localize and often imitate other epilepsies. Therefore, patients with PLEs have low rates of seizure freedom following epilepsy surgery. Previous studies have highlighted the need to combine EEG and semiology for more accurate localization of PLEs.

Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.

Purpose: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants.

Methods: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells.

Results: Biallelic variants in CRELD1 were found in 18 participants from 14 families.

Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort).

Purpose: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE).

Methods: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020.

Pediatric Status Epilepticus: Treat Early and Avoid Delays.

Pediatric convulsive status epilepticus (cSE) is a neurologic emergency with potential for morbidity and mortality. Rapid treatment and escalation of therapies to achieve early seizure control is paramount in preventing complications and providing the best patient outcomes. Although guidelines recommend early treatment, cessation of out-of-hospital SE is undermined by treatment delay and inadequate dosing.

Persistent Diarrhea and Eosinophilic Esophagitis Resulting From Chronic Cannabidiol Usage for Refractory Epilepsy.

Cannabidiol is used in the care of treatment-resistant epilepsy. It has been associated with varying side effects, ranging from somnolence to diarrhea and weight loss. We present a patient on chronic cannabidiol therapy who had persistent diarrhea, abdominal pain, weight loss, and esophageal eosinophilia that improved with cannabidiol dose adjustment.

Preclinical pharmacokinetics and tolerability of a novel meglumine-based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus.

Objective: For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain.

Reduced expression of perineuronal nets in the normotopic somatosensory cortex of the tish rat.

The tish (telencephalic internal structural heterotopia) rat is a naturally occurring and unique model of a malformation of cortical development (MCD) arising from a sponeantous mutation in the Eml1 gene. Tish rats are characterized by a macroscopic bilateral heterotopic dysplastic cortex (HDCx) and an overlaying, intact normotopic neocortex (NNCx). These two cortices are functional and have been reported to innervate and establish connections with subcortical regions including the thalamus, resulting in a dual-cortical representation.

Altered closed state inactivation gating in Kv4.2 channels results in developmental and epileptic encephalopathies in human patients.

Kv4.2 subunits, encoded by KCND2, serve as the pore-forming components of voltage-gated, inactivating I K channels expressed in the brain. I channels inactivate without opening in response to subthreshold excitatory input, temporarily increasing neuronal excitability, the back propagation of action potentials, and Ca influx into dendrites, thereby regulating mechanisms of spike timing-dependent synaptic plasticity.

Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2): A novel health-related quality of life prompt for children with epilepsy.

Objective: Pediatric epilepsy is often associated with diminished health-related quality of life (HRQOL). Our aim was to establish the validity of the Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2) questions, a novel two-item HRQOL prompt for children with epilepsy, primarily for use in clinical care.

Methods: We performed a multicenter cross-sectional study to validate the PELHS-QOL-2.

Results of the First GNAO1-Related Neurodevelopmental Disorders Caregiver Survey.

Background: We sought to expand our knowledge of the clinical spectrum of GNAO1-related neurodevelopmental disorders through a caregiver survey reviewing medical and developmental history and development of epilepsy and movement disorders.

Methods: An online survey was administered to caregivers of individuals diagnosed with GNAO1 pathogenic variants.

Results: Eighty-two surveys were completed.

Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.

Objectives: To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients.

Design: Retrospective cohort study with prospectively collected data between June 2011 and January 2019.

Setting: Seventeen academic hospitals in the United States.

Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort).

Objective: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE).

Methods: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology.

Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy.

Objective: Sudden unexpected death in epilepsy (SUDEP) is an unpredictable and devastating comorbidity of epilepsy that is believed to be due to cardiorespiratory failure immediately after generalized convulsive seizures.

Methods: We performed cardiorespiratory monitoring of seizure-induced death in mice carrying either a p.Arg1872Trp or p.

Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system.

Objective: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data-driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy.

The Need to Intervene Before Time Point 2: Evidence From Clinical and Animal Data That Status Epilepticus Damages the Brain.

Status epilepticus, a condition characterized by abnormally prolonged seizures, has the potential to cause irreversible, structural or functional, injury to the brain. Unfavorable consequences of these seizures include mortality, the risk of developing epilepsy, and cognitive impairment. We highlight key findings of clinical and laboratory studies that have provided insights into aspects of cell death, and anatomical and functional alterations triggered by status epilepticus that support the need to intervene before time point 2, the time after which the risk of these long-term consequences increases.

Implementation of an Intravenous Dihydroergotamine Protocol for Refractory Migraine in Children.

Objective: Retrospective chart review to assess the effectiveness of an institutional intravenous (IV) dihydroergotamine (DHE) therapy protocol for refractory migraine in the pediatric population.

Background: Limited high-quality evidence exists to guide the approach to treatment of refractory migraine with IV DHE, particularly in the pediatric population. This study reviews our institutional experience in implementing an IV DHE protocol in children to identify areas for improvement.

Association of guideline publication and delays to treatment in pediatric status epilepticus.

Objective: To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review.

Methods: We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE.

Results: We studied 328 patients (56% male) with median (25th-75th percentile [p-p]) age of 3.