Little is known about the mechanisms that generate epileptic spasms following perinatal brain injury. Recent studies have implicated reduced levels of Insulin-like Growth Factor 1 (IGF-1) in these patients' brains. Other studies have reported low levels of the inhibitory neurotransmitter, GABA.
View Article and Find Full Text PDFThe human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time.
View Article and Find Full Text PDFObjective: We sought to examine the effects of acute seizures and respiratory derangement on the cardiac electrical properties reflected on the electrocardiogram (ECG); and to analyze their potential interactions with a diagnosis of epilepsy in children.
Methods: Emergency center (EC) visits with seizure or epilepsy diagnostic codes from 1/2011-12/2013 were included if they had ECG within 24 h of EC visit. Patients were excluded if they had pre-existing cardiac conditions, ion channelopathy, or were taking specific cardiac medications.
J Clin Neurophysiol
September 2024
Purpose: Cardiac abnormalities resulting from chronic epilepsy ("the epileptic heart") constitute a well-recognized comorbidity. However, the association of cardiac alterations with epilepsy duration remains understudied. We sought to evaluate this association using electrocardiogram (ECG).
View Article and Find Full Text PDFExpression of immediate early genes (IEGs) in the brain is important for synaptic plasticity, and probably also in neurodegenerative conditions. To understand the cellular mechanisms of the underlying neuropathophysiological processes in epilepsy, we need to pinpoint changes in concentration of synaptic plasticity-related proteins at subsynaptic levels. In this study, we examined changes in synaptic expression of Activity-regulated cytoskeleton-associated (Arc) and Brai Derived Neurotrophic Factor (BDNF) in a rat model of kainate-induced temporal lobe epilepsy (TLE).
View Article and Find Full Text PDFObjective: Infantile spasms are associated with a wide variety of clinical conditions, including perinatal brain injuries. We have created a model in which prolonged infusion of tetrodotoxin (TTX) into the neocortex, beginning in infancy, produces a localized lesion and reproduces the behavioral spasms, electroencephalogram (EEG) abnormalities, and drug responsiveness seen clinically. Here, we undertook experiments to explore the possibility that the growth factor IGF-1 plays a role in generating epileptic spasms.
View Article and Find Full Text PDFHyperactivation of the mTOR pathway during foetal neurodevelopment alters neuron structure and function, leading to focal malformation of cortical development and intractable epilepsy. Recent evidence suggests a role for dysregulated cap-dependent translation downstream of mTOR signalling in the formation of focal malformation of cortical development and seizures. However, it is unknown whether modifying translation once the developmental pathologies are established can reverse neuronal abnormalities and seizures.
View Article and Find Full Text PDFBackground: Angelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics.
View Article and Find Full Text PDFObjective: Cardiac alterations represent a potential epilepsy-associated comorbidity. Whether cardiac changes occur as a function of epilepsy duration is not well understood. We sought to evaluate whether cardiac alterations represented a time-dependent phenomenon in pediatric epilepsy.
View Article and Find Full Text PDFThe presence of unprovoked, recurrent seizures, particularly when drug resistant and associated with cognitive and behavioral deficits, warrants investigation for an underlying genetic cause. This article provides an overview of the major classes of genes associated with epilepsy phenotypes divided into functional categories along with the recommended work-up and therapeutic considerations. Gene discovery in epilepsy supports counseling and anticipatory guidance but also opens the door for precision medicine guiding therapy with a focus on those with disease-modifying effects.
View Article and Find Full Text PDFAngelman syndrome (AS) is a neurodevelopmental disorder with unique behavioral phenotypes, seizures, and distinctive electroencephalographic (EEG) patterns. Recent studies identified motor, social communication, and learning and memory deficits in a CRISPR engineered rat model with a complete maternal deletion of the gene. It is unknown whether this model recapitulates other aspects of the clinical disorder.
View Article and Find Full Text PDFThe goal of these studies was to use quantitative (q)EEG techniques on data from children with Angelman syndrome (AS) using spectral power analysis, and to evaluate this as a potential biomarker and quantitative method to evaluate therapeutics. Although characteristic patterns are evident in visual inspection, using qEEG techniques has the potential to provide quantitative evidence of treatment efficacy. We first assessed spectral power from baseline EEG recordings collected from children with AS compared to age-matched neurotypical controls, which corroborated the previously reported finding of increased total power driven by elevated delta power in children with AS.
View Article and Find Full Text PDFObjective: Epileptic spasms are a hallmark of severe seizure disorders. The neurophysiological mechanisms and the neuronal circuit(s) that generate these seizures are unresolved and are the focus of studies reported here.
Methods: In the tetrodotoxin model, we used 16-channel microarrays and microwires to record electrophysiological activity in neocortex and thalamus during spasms.
Status epilepticus (SE) is a prevalent disorder associated with significant morbidity, including the development of epilepsy and mortality. Cardiac arrhythmias (i.e.
View Article and Find Full Text PDFAngelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype.
View Article and Find Full Text PDFPurpose: We aimed to determine whether clinical EEG reports obtained from children in the intensive care unit with refractory status epilepticus could provide data for comparative effectiveness research studies.
Methods: We conducted a retrospective descriptive study to assess the documentation of key variables within clinical continuous EEG monitoring reports based on the American Clinical Neurophysiology Society's standardized EEG terminology for children with refractory status epilepticus from 10 academic centers. Two pediatric electroencephalographers reviewed the EEG reports.
Excitotoxicity caused by excessive stimulation of glutamate receptors, resulting in pathologically increased Ca-concentrations, is a decisive factor in neurodegenerative diseases. We investigated long-term changes in synaptic contents of AMPA receptor subunits that play important roles in calcium regulation in chronic epilepsy. Such plastic changes may be either adaptive or detrimental.
View Article and Find Full Text PDFObjective: Sympathetic predominance and ventricular repolarization abnormalities represent epilepsy-associated cardiac alterations and may underlie seizure-induced ventricular arrhythmias. Myocardial ion channel and electrical remodeling have been described early in epilepsy development and may contribute to ventricular repolarization abnormalities and excitability. Using the pilocarpine-induced acquired epilepsy model we sought to examine whether altered myocardial ion channel levels and electrophysiological changes also occur in animals with long-standing epilepsy.
View Article and Find Full Text PDFCortical dysplasia (CD) is a common cause for intractable epilepsy. Hyperactivation of the mechanistic target of rapamycin (mTOR) pathway has been implicated in CD; however, the mechanisms by which mTOR hyperactivation contribute to the epilepsy phenotype remain elusive. Here, we investigated whether constitutive mTOR hyperactivation in the hippocampus is associated with altered voltage-gated ion channel expression in the neuronal subset-specific Pten knockout (NS-Pten KO) mouse model of CD with epilepsy.
View Article and Find Full Text PDFObjective: Convulsive status epilepticus can exert profound cardiovascular effects in adults including ventricular depolarization-repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus.
View Article and Find Full Text PDFNeuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long-lasting inflammatory response in hippocampal microglia associated with a concomitant upregulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic AMP-gated channel type 1 (HCN1) protein level while Kv4.
View Article and Find Full Text PDFAngelman syndrome (AS) is a genetic neurodevelopmental disorder, most commonly caused by deletion or mutation of the maternal allele of the UBE3A gene, with behavioral phenotypes and seizures as key features. Currently no treatment is available, and therapeutics are often ineffective in controlling AS-associated seizures. Previous publications using the Ube3a maternal deletion model have shown behavioral and seizure susceptibility phenotypes, however findings have been variable and merit characterization of electroencephalographic (EEG) activity.
View Article and Find Full Text PDFMitochondrial dysfunction plays a central role in the neuropathology associated with status epilepticus (SE) and is implicated in the development of epilepsy. While excitotoxic mechanisms are well-known mediators affecting mitochondrial health following SE, whether hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1) also contributes to SE-induced mitochondrial dysfunction remains to be examined. Here we first evaluated the temporal evolution of poly-ADP-ribosylated protein levels in hippocampus following kainic acid-induced SE as a marker for PARP-1 activity, and found that PARP-1 was hyperactive at 24 h following SE.
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