Common Cause Of Neonatal Seizures Research Articles

Identification of the Long-Term Effects of Mild to Moderate Neonatal Cerebral Hypoxia Based on EEG Signals Analysis

AbstractHypoxic-ischemic encephalopathy (HIE) during perinatal period is the most common cause of neonatal seizures and is associated with an increased risk of epilepsy in later life. Among newborns affected by perinatal brain injury 20-50% die during the newborn period, and 25-60% of the survivors suffer from permanent neurodevelopmental handicap, including cerebral palsy, seizures, mental retardation, and learning disabilities. In the present study EEG data from 11 patients were analysed with power spectra analysis of the principal components of the EEG signals, fractal dimension estimation and sample entropy estimation. The preliminiary results show that the power density properties in the alpha frequency range correlate with learning difficulties of the subjects.

A Novel Approach to the Study of Hypoxia-Ischemia-Induced Clinical and Subclinical Seizures in the Neonatal Rat

Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of acute mortality and chronic neurologic morbidity in infants and children. HIE is the most common cause of neonatal seizures, and seizure activity in neonates can be clinical, with both EEG and behavioral symptoms, subclinical with only EEG activity, or just behavioral. The accurate detection of these different seizure manifestations and the extent to which they differ in their effects on the neonatal brain continues to be a concern in neonatal medicine. Most experimental studies of the interaction between hypoxia-ischemia (HI) and seizures have utilized a chemical induction of seizures, which may be less clinically relevant. Here, we expanded our model of unilateral cerebral HI in the immature rat to include video EEG and electromyographic recording before, during and after HI in term-equivalent postnatal-day-12 rats. We observed that immature rats display both clinical and subclinical seizures during the period of HI, and that the total number of seizures and time to first seizure correlate with the extent of tissue damage. We also tested the feasibility of developing an automated seizure detection algorithm for the unbiased detection and characterization of the different types of seizure activity observed in this model.

Epileptogenesis in the immature brain: Neonatal seizures in hypoxic/ischemic encephalopathy

SummaryNeonatal hypoxic/ischemic encephalopathy is the most common cause of neonatal seizures, and these seizures are refractory to conventional antiseizure drugs and can lead to later life epilepsy and congitive deficits. Data from human tissue studies as well as rodent models suggest unique age‐specific mechanisms underlying these neonatal seizure and their consequences, and are leading to a number of new therapeutic targets. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AC, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books).

Early continuous video electroencephalography in neonatal stroke

Perinatal stroke is the second most common cause of neonatal seizures, and can result in long-term neurological impairment. Diagnosis is often delayed until after seizure onset, owing to the subtle nature of associated signs. We report the early electroencephalographic (EEG) findings in a female infant with a perinatal infarction, born at 41 weeks 2 days and weighing 3.42 kg. Before the onset of seizures, the EEG from 3 hours after delivery demonstrated occasional focal sharp waves over the affected region. After electroclinical seizures, focal sharp waves became more frequent, complex, and of higher amplitude, particularly in 'quiet sleep'. In 'active sleep', sharp waves often disappeared. Diffusion-weighted imaging confirmed the infarct, demonstrating left frontal and parietal diffusion restriction. At 9 months, the infant has had no further seizures, and neurological examination is normal. To our knowledge, this report is the first to describe the EEG findings in perinatal stroke before seizures, and highlights the evolution of characteristic background EEG features.

Management of Neonatal Seizures

Seizures in the newborn period constitute a medical emergency. Subtle seizures are the commonest type of seizures occurring in the neonatal period. Myoclonic seizures carry the worst prognosis in terms of long-term neurodevelopmental outcome. Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Multiple etiologies often co-exist in neonates and hence it is essential to rule out common causes such as hypoglycaemia, hypocalcemia, and meningitis before initiating specific therapy. A comprehensive evidence based approach for management of neonatal seizures has been described in this protocol.

Seizures in the newborn

Seizures in the newborn period constitute a medical emergency. Subtle seizures are the commonest type of neonatal seizures, other types being clonic, tonic, and myoclonic. Myoclonic seizures carry the worst prognosis in terms of long-term neurodevelopmental outcome. Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Multiple etiologies often co-exist in neonates and hence it is essential to rule out conditions such as hypoglycemia, hypocalcemia, and meningitis before initiating specific therapy. A comprehensive approach for management of neonatal seizures has been described.

Apneic Seizures: A Sign of Temporal Lobe Hemorrhage in Full-Term Neonates

Intracranial hemorrhage is a common cause of neonatal seizures in full-term infants. However, only some infants with intracranial hemorrhage come to clinical attention. A right temporal lobe hemorrhage with resulting apneic seizures was described previously in one neonate. In this case report, we review three full-term male neonates with no significant perinatal complications who presented with apneic events and temporal lobe hemorrhage. One neonate had apnea as the sole manifestation of a seizure that was confirmed electrographically. One neonate had motor manifestations of seizures, in addition to apnea, that were confirmed as seizures electrographically. The third neonate had pure apneic events before initiation of electroencephalogram monitoring which were presumed to be seizures, because the electroencephalogram demonstrated epileptiform abnormalities. At follow-up, all three children were neurodevelopmentally normal. This case report emphasizes that, although uncommon, full-term neonates may present with apnea as the initial manifestation of temporal lobe hemorrhage. Because apnea could be a manifestation of a seizure, continuous electroencephalogram monitoring should be considered in a full-term neonate with unexplained apnea.

Persistently Decreased Basal Synaptic Inhibition of Hippocampal CA1 Pyramidal Neurons after Neonatal Hypoxia-Induced Seizures

Hypoxia is the most common cause of neonatal seizures and can lead to epilepsy, but the epileptogenic mechanisms are not yet understood. We have previously shown that hypoxia-induced seizures in the neonatal rat result in acutely decreased amplitudes and frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in hippocampal CA1 pyramidal neurons. In the current study, we asked whether such changes persist for several days following hypoxia-induced seizures. Similar to the acute findings, we observed decreased frequency and amplitudes of sIPSCs and decreased mIPSC amplitudes in CA1 pyramidal neurons at 3–5 days after hypoxia. However, in contrast to the acute findings, we observed no differences between hypoxia-treated and control groups in mIPSC frequency. Additionally, by 7 days after hypoxia, sIPSC amplitudes in the hypoxia group had recovered to control levels, but sIPSC frequency remained decreased. These data indicate that the persistently decreased sIPSC frequency result from decreased firing of presynaptic inhibitory interneurons, with only transient possible changes in postsynaptic responses to GABA release.

Impaired SynGAP expression and long-term spatial learning and memory in hippocampal CA1 area from rats previously exposed to perinatal hypoxia-induced insults: beneficial effects of A68930

Hypoxic encephalopathy is a common cause of neonatal seizures and long-term neurological cognitive deficits. In rats at postnatal days 10–12 (P10–P12), global hypoxia induced spontaneous seizures and chronic brain injury, mimicking clinical aspects of neonatal hypoxia. Synaptic Ras-GTPase activating protein (SynGAP) has important roles in RAS/MAPK-dependent synaptic plasticity and mammalian learning. We investigated possible alterations of SynGAP expression occurring in memory-impaired animals previously exposed to perinatal hypoxia insults. We also evaluated the therapeutic efficacy of A68930, a selective agonist of dopamine D1/D5 receptors, on perinatal hypoxia insults. In the hippocampal CA1 region, perinatal hypoxia insults (P10) led to a reduction in SynGAP expression associated with impairment in long-term spatial learning and memory performance at P45. The use of A68930 (at a dose of 1, 2, 3 mg/kg, P17–P23) effectively attenuated the deleterious effects as described above. Our results may indicate the involvement of SynGAP in certain forms of brain injury, leading to long-term learning and memory deficits. A68930 may have clinical potential as a therapeutic agent for alleviation of long-term cognitive deficits in rats and other animal models.

Decreased Glutamate Receptor 2 Expression and Enhanced Epileptogenesis in Immature Rat Hippocampus after Perinatal Hypoxia-Induced Seizures

Hypoxic encephalopathy is the most common cause of neonatal seizures and can lead to chronic epilepsy. In rats at postnatal days 10-12 (P10-12), global hypoxia induces spontaneous seizures and chronically decreases seizure threshold, thus mimicking clinical aspects of neonatal hypoxia. We have shown previously that the acute and chronic epileptogenic effects of hypoxia are age-dependent and require AMPA receptor activation. In this study, we aimed to determine whether hypoxia-induced seizures and epileptogenesis are associated with maturational and seizure-induced changes in AMPA receptor composition and function. Northern and Western blots indicated that glutamate receptor 2 (GluR2) mRNA and protein expression were significantly lower in neocortex and hippocampus at P10-12 compared with adult. After hypoxia-induced seizures at P10, GluR2 mRNA was significantly decreased within 48 hr, and GluR2 protein was significantly decreased within 96 hr. AMPA-induced Co(2+) uptake by neurons in hippocampal slices indicated higher expression of Ca(2+)-permeable AMPA receptors in immature pyramidal neurons compared with adult. In slices obtained 96 hr after hypoxia-induced seizures, AMPA-induced Co(2+) uptake was significantly increased compared with age-matched controls, and field recordings revealed increased tetanus-induced afterdischarges that could be kindled in the absence of NMDA receptor activation. In situ end labeling showed no acute or delayed cell death after hypoxia-induced seizures. Our results indicate that susceptibility to hypoxia-induced seizures occurs during a developmental stage in which the expression of Ca(2+)-permeable AMPA receptors is relatively high. Furthermore, perinatal hypoxia-induced seizures induce increased expression of Ca(2+)-permeable AMPA receptors and an increased capacity for AMPA receptor-mediated epileptogenesis without inducing cell death.

Unilateral neonatal cerebral infarction in full term infants

AIMSTo determine the prevalence of unilateral neonatal cerebral infarction in infants born at 32 weeks gestation and above; to describe the clinical course, imaging results, and outcome of neonatal cerebral...

Hypoxia-induced hyperexcitability in vivo and in vitro in the immature hippocampus.

Hypoxia is the most common cause of neonatal seizures and encephalopathy. We have previously developed an in vivo experimental model of perinatal hypoxia which exhibits age-dependent acute and chronic epileptogenic effects. Between postnatal day (P) 10-12, the rat exhibits acute seizure activity during global hypoxia, while no seizures are induced at earlier (P5) or older (P60) ages. Rats exposed to hypoxia between P10-12 have reduced seizure thresholds to chemical convulsants in adulthood. The nonNMDA antagonists NBQX appears to suppress both the acute and long term epileptogenic effects of hypoxia. The age-dependency of the hyperexcitable response to hypoxia in vivo can be reproduced in vitro using hippocampal slices. In Mg(2+)-free media, hypoxia induced ictal discharges within 60 s of onset in 79% of slices from normal P10 rat pups compared to 11% of adult slices (p < 0.001). Model systems such as that described here allow for correlation of in vitro and in vivo electrophysiology and should provide data regarding the pharmacological and physiological characteristics of hypoxia-induced seizure activity in the immature brain which could ultimately be applied to therapeutic strategies.