Prolonged Seizures Exacerbate Perinatal Hypoxic-Ischemic Brain Damage

Wirrell, Elaine; Armstrong, Edward A.; Osman, Lyndon D; Yager, Jerome Y.

doi:10.1203/00006450-200110000-00005

Cited by 212 publications

(140 citation statements)

References 62 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…25 Multiple studies have revealed that prolonged seizures induce or worsen already-existing brain injury. 4,12,26 In human studies, it is difficult to measure the effect of seizures on neuronal injury and to distinguish this from the underlying pathogenesis of brain injury and possible effects of AED treatment. Available studies in neonates do suggest that seizures are likely to increase neuronal injury.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial

Srinivasakumar¹,

Zempel²,

et al. 2015

View full text Add to dashboard Cite

BACKGROUND: The impact of treating electrographic seizures in hypoxic ischemic encephalopathy (HIE) is unknown. METHODS:Neonates $36 weeks with moderate or severe HIE were randomly assigned to either treatment of electrographic seizures alone (ESG) or treatment of clinical seizures (CSG). Conventional EEG video was monitored in both groups for up to 96 hours. Cumulative electrographic seizure burden (SB) was calculated in seconds and converted to log units for analysis. MRI scans were scored for severity of brain injury. Infants underwent neurodevelopmental evaluation at 18 to 24 months. Statistical analyses were performed by using SAS 9.3 version (SAS Institute, Inc, Cary, NC).RESULTS: Thirty-five of 69 neonates (51%) who were randomly assigned and included in the study developed seizures (15 in ESG and 20 in CSG). Excluding infants with status epilepticus, median SB (interquartile range) in seconds in ESG (n = 10) was lower than in CSG (n = 16) (449 [113-2070] vs 2226 [760-7654]; P = .02). ESG had fewer seizures with shorter time to treatment (P = .04). Twenty-four of 30 (80%) surviving infants with seizures underwent neurodevelopmental evaluation at 18 to 24 months. Increasing SB in the combined cohort was significantly associated with higher brain injury scores (P , .03) and lower performance scores across all 3 domains on BSID III (P = .03). CONCLUSIONS:In neonates with HIE, EEG monitoring and treatment of electrographic seizures results in significant reduction in SB. SB is associated with more severe brain injury and significantly lower performance scores across all domains on BSID III. WHAT'S KNOWN ON THIS SUBJECT:Continuous conventional EEG video is currently gold standard for identifying neonatal seizures and a substantial proportion of neonatal seizures are electrographic. Currently there is no direct evidence that EEG monitoring, seizure identification, or treatment impacts long-term outcomes. WHAT THIS STUDY ADDS:In neonates with hypoxic ischemic encephalopathy, EEG monitoring and treatment of electrographic seizures results in significant reduction in seizure burden. Increasing seizure burden is associated with more severe brain injury and significantly lower performance scores on Bayley Scales of Infant Development III.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Available studies in neonates do suggest that seizures are likely to increase neuronal injury. 5,14,16,25,26 Understanding whether treatment of electrographic seizures impacts longer term outcome has been difficult because studies have included heterogeneous patient groups.…”

Section: Discussionmentioning

confidence: 99%

Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial

Srinivasakumar¹,

Zempel²,

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The question of whether ongoing neuronal damage during HI blunts the electrographic seizures is a separate issue from the question of whether the acute electrographic seizures augment neuronal death. Previous work that compared HI-mediated brain damage with vs. without kainate-induced seizures reported that seizure activity exacerbates neuronal damage (Wirrell et al 2001). Thus, although neonatal seizures alone do not cause overt neuronal death, seizures may worsen the neuronal damage associated with a prior or ongoing brain insult.…”

Section: Hypoxia-ischemia (Hi)mentioning

confidence: 99%

Ischemic injury suppresses hypoxia-induced electrographic seizures and the background EEG in a rat model of perinatal hypoxic-ischemic encephalopathy

Zayachkivsky

Lehmkuhle

Ekstrand

et al. 2015

Journal of Neurophysiology

View full text Add to dashboard Cite

Zayachkivsky A, Lehmkuhle MJ, Ekstrand JJ, Dudek FE. Ischemic injury suppresses hypoxia-induced electrographic seizures and the background EEG in a rat model of perinatal hypoxic-ischemic encephalopathy. J Neurophysiol 114: 2753-2763, 2015. First published September 9, 2015 doi:10.1152/jn.00796.2014.-The relationship among neonatal seizures, abnormalities of the electroencephalogram (EEG), brain injury, and long-term neurological outcome (e.g., epilepsy) remains controversial. The effects of hypoxia alone (Ha) and hypoxia-ischemia (HI) were studied in neonatal rats at postnatal day 7; both models generate EEG seizures during the 2-h hypoxia treatment, but only HI causes an infarct with severe neuronal degeneration. Single-channel, differential recordings of acute EEG seizures and background suppression were recorded with a novel miniature telemetry device during the hypoxia treatment and analyzed quantitatively. The waveforms of electrographic seizures (and their behavioral correlates) appeared virtually identical in both models and were identified as discrete events with high power in the traditional delta (0.1-4 Hz) and/or alpha (8 -12 Hz) bands. Although the EEG patterns during seizures were similar in Ha-and HI-treated animals at the beginning of the hypoxic insult, Ha caused a more severe electrographic seizure profile than HI near the end. Analyses of power spectral density and seizure frequency profiles indicated that the electrographic seizures progressively increased during the 2-h Ha treatment, while HI led to a progressive decrease in the seizures with significant suppression of the EEG background. These data show that 1) the hypoxia component of these two models drives the seizures; 2) the seizures during Ha are substantially more robust than those during HI, possibly because ongoing neuronal damage blunts the electrographic activity; and 3) a progressive decrease in background EEG, rather than the presence of electrographic seizures, indicates neuronal degeneration during perinatal HI.EEG; hypoxia-ischemia; neonatal; stroke; seizure SEIZURES ARE RELATIVELY COMMON in neonates and are a potential harbinger of intractable epilepsy, cerebral palsy, cognitive deficits, and other negative neurological outcomes. Prolonged periods of hypoxia alone (Ha; e.g., birth asphyxia or apnea) or hypoxia-ischemia (HI; e.g., perinatal stroke) are thought to be a major cause of neonatal seizures, but metabolic disturbances, encephalitis, and genetic abnormalities can also lead to seizures in neonates (Sarnat and Sarnat 1976;Finer et al. 1981; Watanabe et al. 1982a,b;Corey et al. 1988;Mercuri et al. 1999;Marin-Padilla 2000;Nelson and Lynch 2004;Malm 2009;Sorge and Sorge 2010). Although considerable EEG data are available on neonatal seizures, their predictive value is poor because outcomes range from benign to devastating. A definitive causal link between the characteristics of the neonatal EEG and the subsequent neurological outcome is difficult to establish in humans. Thus it is unclear whether acute neonatal seizures ...

show abstract

“…[35][36][37] There are no randomized controlled trials comparing the effects of AED treatment versus no AED treatment on short-or long-term neurodevelopmental outcomes.…”

Section: Benefits Of Aed Treatmentmentioning

confidence: 99%

Neonatal seizures in hypoxic–ischaemic encephalopathy – risks and benefits of anticonvulsant therapy

Shetty

2015

Develop Med Child Neuro

View full text Add to dashboard Cite

The risk of seizures is at its highest during the neonatal period, and the most common cause of neonatal seizures is hypoxic–ischaemic encephalopathy (HIE). This enhanced vulnerability is caused by an imbalance in the expression of receptors for excitatory and inhibitory neurotransmission, which is age dependent. There has been progress in detecting the electrophysiological abnormalities associated with seizures using amplitude‐integrated electroencephalography (aEEG). Data from animal studies indicate a variety of risk factors for seizures, but there are limited clinical data looking at the long‐term neurodevelopmental consequences of seizures alone. Neonatal seizures are also associated with increased risk of further epileptic seizures; however, it is less clear whether or not this results from an underlying pathology, and whether or not seizures confer additional risk. Phenobarbital and phenytoin are still the first‐line antiepileptic drugs (AEDs) used to treat neonatal seizures, although they are effective in only one‐third of affected infants. Furthermore, based on findings from animal studies, there are concerns regarding the risks associated with using these AEDs. Clinicians face a difficult challenge because, although seizures can be easily identified using aEEG, treatment options are limited, and there are uncertainties regarding treatment outcomes. There is a need to obtain long‐term follow‐up data, comparing groups of infants treated with or without current therapies. If these analyses indicate a definite benefit of treating neonatal seizures, then novel therapeutic approaches should be developed.

show abstract

Prolonged Seizures Exacerbate Perinatal Hypoxic-Ischemic Brain Damage

Cited by 212 publications

References 62 publications

Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial

Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial

Ischemic injury suppresses hypoxia-induced electrographic seizures and the background EEG in a rat model of perinatal hypoxic-ischemic encephalopathy

Neonatal seizures in hypoxic–ischaemic encephalopathy – risks and benefits of anticonvulsant therapy

Contact Info

Product

Resources

About