Seizure-associated brain injury in term newborns with perinatal asphyxia

Miller, Steven P.; Weiss, Jennifer M.; Barnwell, Alison; Ferriero, Donna M.; Latal-Hajnal, B.; Ferrer-Rogers, A.; Newton, Nancy; Partridge, John Colin; Glidden, David V.; Vigneron, Daniel B.; Barkovich, A. James

doi:10.1212/wnl.58.4.542

Cited by 335 publications

(232 citation statements)

References 37 publications

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“…The importance of neonatal seizure burden for outcome has been highlighted by many researchers,2, 7, 9, 22 but in HIE it has not been fully quantified for long‐term outcome 7, 12, 14. In critically ill children with diseases of mixed aetiologies, including neonates with HIE, MSB of more than 12 minutes per hour was found to be associated with an increase in short‐term neurological decline, independent of the diagnosis or severity of illness 22.…”

Section: Discussionmentioning

confidence: 99%

Seizure burden and neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy

Kharoshankaya

Stevenson

Livingstone

et al. 2016

Develop Med Child Neuro

200

149

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AimTo examine the relationship between electrographic seizures and long‐term outcome in neonates with hypoxic–ischemic encephalopathy (HIE).MethodFull‐term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre‐hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome.ResultsContinuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5–80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43–37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06–31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome.InterpretationIn HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia.

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Section: Discussionmentioning

confidence: 99%

Seizure burden and neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy

Kharoshankaya

Stevenson

Livingstone

et al. 2016

Develop Med Child Neuro

200

149

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“…8,9 Animal data reveal that commonly used anticonvulsants may have deleterious effects on the developing brain. 4,[10][11][12] NSs are most commonly associated with perinatal hypoxic ischemic encephalopathy (HIE), accounting for more than 60% of early onset NS. 1,2 Although neurodevelopmental outcome in term infants with seizures is highly influenced by the underlying etiology, and a diagnostic MRI scan is essential to delineate underlying brain injury, 13 increasing evidence from animal models and human studies reveals that seizures in themselves may adversely impact the immature brain.…”

Section: What This Study Addsmentioning

confidence: 99%

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

Srinivasakumar¹,

Zempel²,

et al. 2015

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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.

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“…Furthermore, those who developed neonatal seizures might also as a result have impaired cerebral energy metabolism. 19 In 22q11.2DS, proneness to seizures, perhaps related to aberrant neurodevelopment, appears to be relatively prevalent. 1 Patients with more severe neonatal hypocalcemia and/or those exposed to events that further lower the seizure threshold, such as surgery, in the neonatal period may be at increased risk of poor intellectual outcomes.…”

Section: Potential Mechanismmentioning

confidence: 99%

Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

Cheung

George

Andrade

et al. 2014

Genetics in Medicine

103

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Seizure-associated brain injury in term newborns with perinatal asphyxia

Abstract: The severity of seizures in human newborns with perinatal asphyxia is independently associated with brain injury and is not limited to structural damage detectable by MRI.

Cited by 335 publications

References 37 publications

Seizure burden and neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy

Seizure burden and neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy

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

Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome

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