Neonatal seizures

Harvard University, Cambridge, Massachusetts, United States
Annals of Neurology (Impact Factor: 9.98). 08/2007; 62(2):112-20. DOI: 10.1002/ana.21167
Source: PubMed


In childhood, the risk for seizures is greatest in the neonatal period. Currently used therapies have limited efficacy. Although the treatment of neonatal seizures has not significantly changed in the past several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. This review includes an overview of current approaches to the diagnosis and treatment of neonatal seizures, identifies some of the critical factors that have limited progress, and highlights recent insights about the pathophysiology of neonatal seizures that may provide the foundation for better treatment.

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    • "Reduced expression of the GluA2 subunit in AMPA receptors leads to an increased permeability to Ca2+ contributing to a lower threshold for seizures [2, 9, 24, 25]. AMPA receptors without the GluA2 subunit are typically expressed in the immature brain and their presence corresponds to an increased risk of excitotoxic cellular injury due to hypoxia-ischemia and of subsequent epileptogenesis both in rats and in humans [11, 12]. "
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    ABSTRACT: Neuronal activity is critical for synaptogenesis and the development of neuronal networks. In the immature brain excitation predominates over inhibition facilitating the development of normal brain circuits, but also rendering it more susceptible to seizures. In this paper, we review the evolution of the subunit composition of neurotransmitter receptors during development, how it promotes excitation in the immature brain, and how this subunit composition of neurotransmission receptors may be also present in the epileptic brain. During normal brain development, excitatory glutamate receptors peak in function and gamma-aminobutiric acid (GABA) receptors are mainly excitatory rather than inhibitory. A growing body of evidence from animal models of epilepsy and status epilepticus has demonstrated that the brain exposed to repeated seizures presents a subunit composition of neurotransmitter receptors that mirrors that of the immature brain and promotes further seizures and epileptogenesis. Studies performed in samples from the epileptic human brain have also found a subunit composition pattern of neurotransmitter receptors similar to the one found in the immature brain. These findings provide a solid rationale for tailoring antiepileptic treatments to the specific subunit composition of neurotransmitter receptors and they provide potential targets for the development of antiepileptogenic treatments.
    Full-text · Article · Sep 2014 · BioMed Research International
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    • "Finally, GABA receptor activation has been shown to result in depolarisation rather than hyperpolarisation in the immature brain, with this state being critical for normal development (Khazipov et al., 2004). This depolarising effect of GABA in early life is, however, thought to impair the efficacy of GABA A receptor inhibition by commonly applied anticonvulsants such as phenobarbital and benzodiazepines, with critical consequences for seizure control (Silverstein and Jensen, 2007). These observations are crucial in understanding the pathophysiology of neonatal seizures as well as the effect of anticonvulsants. "
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    ABSTRACT: Neonatal seizures constitute the most common and distinctive sign of neurological dysfunction in the first weeks of life and reflect a wide variety of underlying central nervous system disorders. Acute symptomatic seizures occur more often during the neonatal period than at any period of life and are associated with adverse long-term neurodevelopmental sequelae and an increased risk of post-neonatal epilepsy. The improvements of neonatal care in the last decades have changed the spectrum of insults to which the immature brain is exposed and facilitated a decrease in mortality of newborns with seizures. However, the prevalence of long-term morbidity in survivors remains unchanged. Whereas aetiology is presumed to be the main predictor of long-term outcome in neonates with seizures, there is converging evidence that specific electroencephalographic (EEG) abnormalities are related to unfavourable outcomes. Interictal EEG abnormalities, especially concerning background activity patterns, thus constitute a major indicator of disease severity and predictor of outcome, while the added value of sequential EEG assessments is so far controversial. Moreover, experimental as well as clinical studies of hypoxic-ischaemic encephalopathy support the notion that recurrent seizures may amplify injury to the developing brain beyond that associated with the underlying aetiology, thus justifying antiepileptic drug treatment. To date, unresolved issues in seizure detection and classification, in addition to the significant variation in gestational ages and brain insults of neonates, still impede clinical research of neonatal seizures. The wider use of long-term EEG or amplitude integrated EEG monitoring may prove crucial for timely neonatal seizure identification and treatment initiation, and thus ultimately improve outcome.
    Full-text · Article · Dec 2013 · Epileptic disorders: international epilepsy journal with videotape
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    • "In the present study, we examine the effects of altered neurodevelopment by manipulating critical perinatal factors (prenatal stress and postnatal maternal care) and assessing male and female offspring seizure susceptibility. Using such a neurodevelopmental approach, as opposed to models that utilize adult animals , provided much more power to make inferences about pediatric epilepsy; a phenomenon that has a well-described strong developmental stage specificity [5] [6] [7]. Further, a large percentage of studies restrict analysis to males, which is problematic for extrapolating findings to females as sex differences in many neurological disorders are now widely accepted [8] [9] [10]. "
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    ABSTRACT: Epilepsy is a heterogeneous and chronic neurological condition of undefined etiology in the majority of cases. Similarly, the pathogenesis of the unprovoked seizures that lead to epilepsy is not known. We are interested in the factors that modify inherent seizure susceptibility, with a particular focus on those occurring during the prenatal and early postnatal periods. Female Sprague-Dawley rats were bred in-house or transported during pregnancy at one of two gestational days (G9 or G16). The effects of transport stress, maternal behavior, and offspring sex were then examined in terms of how they were related to provoked seizure susceptibility to kainic acid (KA) or a model of febrile convulsions (FCs) on postnatal day 14 (P14). We also examined the pattern of neuronal activation in the hippocampus and amygdala as indicated by the density of FosB protein immunoreactivity (FosB-ir). Results demonstrated only a small and inconsistent effect of transport alone, suggesting that the groups differed slightly prior to experimental manipulations. However, the influence of maternal behaviors such as licking and grooming (LG), arched back nursing (ABN), and dam-off time (DO) exerted a much stronger effect on the offspring. Dams designated as high LG gave birth to smaller litters, had pups that weighed less, had greater seizure susceptibility and severity, and had more FosB-ir neurons predominantly in the ventral hippocampus and the medial subnucleus of the amygdala (MeA). We also found a sex-dependent effect such that P14 males were smaller than their female littermates and had a greater seizure susceptibility and severity. Taken together, these results suggest an impact of prenatal and postnatal factors, as well as sex, on seizure susceptibility in young animals.
    Full-text · Article · Aug 2013 · Epilepsy & Behavior
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