The long-term effects of limbic non-convulsive status epilepticus in peri-adolescent rats.

To optimize the clinical approach to non-convulsive status epilepticus (NCSE), it is essential to gain insight into its long-term effects on cognition and behaviors. Here, we investigated limbic NCSE-induced hippocampal injury and behavioral deficits in peri-adolescent rats. NCSE was induced in P43 Sprague Dawleyrats with intrahippocampal subconvulsive doses of kainic acid (NCSE group, n = 14) under continuous epidural cortical electroencephalography (EEG).

Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder.

Purpose: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations.

Methods: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies.

High Diagnostic Yield and Clinical Utility of Next-Generation Sequencing in Children with Epilepsy and Neurodevelopmental Delays: A Retrospective Study.

Advances in genetics led to the identification of hundreds of epilepsy-related genes, some of which are treatable with etiology-specific interventions. However, the diagnostic yield of next-generation sequencing (NGS) in unexplained epilepsy is highly variable (10-50%). We sought to determine the diagnostic yield and clinical utility of NGS in children with unexplained epilepsy that is accompanied by neurodevelopmental delays and/or is medically intractable.

Inkjet-Printed, Flexible Organic Electrochemical Transistors for High-Performance Electrocorticography Recordings.

Organic electrochemical transistors (OECTs) have emerged as powerful tools for biosignal amplification, including electrocorticography (ECoG). However, their widespread application has been limited by the complexities associated with existing fabrication techniques, restricting accessibility and scalability. Here, we introduce a novel all-planar, all-printed high-performance OECT device that significantly enhances the accuracy and sensitivity of ECoG recordings.

Imiquimod Reverses Chronic Toxoplasmosis-Associated Behavioral and Neurocognitive Anomalies in a Rat Model.

is the etiologic agent of toxoplasmosis, a highly prevalent parasitosis. () transits in the brain from acute (AT) to chronic toxoplasmosis (CT), under host immune control. In immunocompromised patients, reactivation of CT is potentially life-threatening.

Lestaurtinib (CEP-701) reduces the duration of limbic status epilepticus in periadolescent rats.

Background: The timely abortion of status epilepticus (SE) is essential to avoid brain damage and long-term neurodevelopmental sequalae. However, available anti-seizure treatments fail to abort SE in 30% of children. Given the role of the tropomyosin-related kinase B (TrkB) receptor in hyperexcitability, we investigated if TrkB blockade with lestaurtinib (CEP-701) enhances the response of SE to a standard treatment protocol and reduces SE-related brain injury.

Role of Early Intravenous Immunoglobulins in Halting Clinical and Radiographic Disease Progression in Rasmussen Encephalitis.

Background: Rasmussen encephalitis (RE) is a rare progressive presumed autoimmune disorder characterized by pharmacoresistant epilepsy and progressive motor and cognitive deterioration. Despite immunomodulation, more than half of the patients with RE ultimately require functional hemispherotomy. In this study, we evaluated the potential beneficial effects of early initiation of immunomodulation in slowing disease progression and preventing the need for surgical interventions.

Causes of New-Onset Seizures and Their Treatment in Children With Non-CNS Malignancies: A Retrospective Study in a Tertiary Care Center.

Background: Seizures occur in up to 13% of children with non-central nervous system (CNS) malignancies, but little is known about their causes and optimal diagnostic and therapeutic approaches. Here we sought to determine etiologies and clinical trajectories of new-onset seizures in this patient population.

Methods: A retrospective chart review over a 10-year period was conducted at the American University of Beirut Medical Center to identify children with non-CNS malignancies and at least one new-onset seizure.

Hippocampal injury and learning deficits following non-convulsive status epilepticus in periadolescent rats.

The effects of non-convulsive status epilepticus (NCSE) on the developing brain remain largely elusive. Here we investigated potential hippocampal injury and learning deficits following one or two episodes of NCSE in periadolescent rats. Non-convulsive status epilepticus was induced with subconvulsive doses of intrahippocampal kainic acid (KA) under continuous EEG monitoring in postnatal day 43 (P43) rats.

A Modified Two-Way Active Avoidance Test for Combined Contextual and Auditory Instrumental Conditioning.

Available two-way active avoidance paradigms do not provide contextual testing, likely due to challenges in performing repetitive trials of context exposure. To incorporate contextual conditioning in the two-way shuttle box, we contextually modified one of the chambers of a standard two-chamber rat shuttle box with visual cues consisting of objects and black and white stripe patterns. During the 5 training days, electrical foot shocks were delivered every 10 s in the contextually modified chamber but were signaled by a tone in the plain chamber.

Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits.

Post-traumatic epilepsy (PTE) and neurocognitive deficits are devastating sequelae of head injuries that are common in adolescents. Investigating desperately needed treatments is hindered by the difficulties in inducing PTE in rodents and the lack of established immature rat models of pediatric PTE. Hemorrhage is a significant risk factor for PTE, but compared to humans, rats are less prone to bleeding because of their rapid blood coagulation system.

High-Dose Levetiracetam for Neonatal Seizures: A Retrospective Review.

Background: Neonatal seizures are frequently encountered in the neonatal intensive care unit and may be associated with serious long-term neurological sequelae. Response to treatment continues to be modest, and treatment guidelines remain unclear. The use of levetiracetam has been on the rise in the past several years due to its favorable safety profile in the face of limited data on its efficacy and optimal dosing regimens.

Dysfunctional cerebrovascular tone contributes to cognitive impairment in a non-obese rat model of prediabetic challenge: Role of suppression of autophagy and modulation by anti-diabetic drugs.

Prediabetes is a highly prevalent stage of early metabolic dysfunction that poses a high risk for cardiovascular and cognitive impairment without a clear pathological mechanism. Here, we used a non-obese prediabetic rat model previously developed in our laboratory to examine this mechanism. These rats were subjected to a mild metabolic challenge leading to hyperinsulinemia without hyperglycemia or obesity.

Methods in Electrode Implantation and Wiring for Long-Term Continuous EEG Monitoring in Rodent Models of Epilepsy and Behavioral Disturbances.

Rodent seizure models that pathologically and behaviorally recapitulate age-tailored epileptic disorders are used by us and others to advance our understanding of the chronobiology and mechanisms of epileptic seizure emergence and their comorbidities and to investigate potential novel treatment strategies. Obtaining prolonged continuous electroencephalogram (EEG) tracings over months is essential in this line of translational research, particularly to assess the relation between electrographic changes and the development of seizures and their various psychiatric and cognitive comorbidities in models where seizures gradually emerge over weeks following brain insults. Here we describe our approach to electrode implantation and wiring in order to successfully obtain high-quality continuous EEG tracings in rats for prolonged periods.

Methods in Emotional Behavioral Testing in Immature Epilepsy Rodent Models.

Pediatric epilepsy is associated with prominent comorbid psychiatric and cognitive disturbances. Neurobehavioral testing is employed to characterize the cognitive and emotional behavioral derangements that accompany seizures in age-tailored and clinically relevant immature rodent seizure models. In addition to dissecting the causes of the etiologically multifaceted psychiatric and cognitive comorbidities of the epilepsies, neurobehavioral panels are essential in investigating potential neuroprotective strategies, especially during neurodevelopment.

Enhanced setup for wired continuous long-term EEG monitoring in juvenile and adult rats: application for epilepsy and other disorders.

Background: The electroencephalogram (EEG) is a widely used laboratory technique in rodent models of epilepsy, traumatic brain injury (TBI), and other neurological diseases accompanied by seizures. Obtaining prolonged continuous EEG tracings over weeks to months is essential to adequately answer research questions related to the chronobiology of seizure emergence, and to the effect of potential novel treatment strategies. Current EEG recording methods include wired and the more recent but very costly wireless technologies.

Lestaurtinib (CEP-701) modulates the effects of early life hypoxic seizures on cognitive and emotional behaviors in immature rats.

Hypoxic encephalopathy of the newborn is a major cause of long-term neurological sequelae. We have previously shown that CEP-701 (lestaurtinib), a drug with an established safety profile in children, attenuates short-term hyperexcitability and tropomyosin-related kinase B (TrkB) receptor activation in a well-established rat model of early life hypoxic seizures (HS). Here, we investigated the potential long-term neuroprotective effects of a post-HS transient CEP-701 treatment.

A child with hyperekplexia and epileptic myoclonus.

Hyperekplexia is a rare neurogenetic disorder characterized by startle. Accurate diagnosis of this notorious mimicker of epilepsy is important to prevent life-threatening apnoea. We report a novel case of concomitant GLRA1-related hyperkeplexia and myoclonic epilepsy.

Seizures Induced by Exiting Water: A Unique Form of Reflex Epilepsy.

Introduction: Reflex epilepsies represent a form of epilepsy in which unique modes of seizure precipitation are characterized by endogenous or exogenous stimuli. Hot water epilepsy represents a subtype of reflex epilepsy in which seizure precipitation arises from the act of immersing the head with hot water. Bathing epilepsy represents another subtype of reflex epilepsy in which seizure precipitation arises from the immersion with water at lukewarm temperatures.

Treatable Genetic Metabolic Epilepsies.

In the absence of a culprit epileptogenic lesion, pharmacoresistant seizures should prompt the physician to consider potentially treatable metabolic epilepsies, especially in the presence of developmental delays. Even though the anti-seizure treatment of the epilepsies remains symptomatic and usually tailored to an electroclinical phenotype rather than to an underlying etiology, a thorough metabolic workup might reveal a disease with an etiology-specific treatment. Early diagnosis is essential in the case of treatable metabolic epilepsies allowing timely intervention.

Glucose Transporter 1 Deficiency: A Treatable Cause of Opsoclonus and Epileptic Myoclonus.

Background: Epileptic myoclonus in infancy is associated with various pathological conditions. In the absence of an identifiable central nervous system lesion, an underlying metabolic genetic cause is often suspected.

Patients: We describe two infants with glucose transporter 1 deficiency syndrome who presented with epileptic myoclonus.