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

Abstract

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.

Sex differences in stroke across the lifespan: The role of T lymphocytes

“…HIE is the primary cause of preterm birth (Lauterbach et al 2001), neonatal death, and long-term disability, and is one of the most important causes of cerebral palsy and seizures (Caffarelli et al 2016). Neonates with HIE present with abnormalities shortly after delivery, principally in muscle tone, posturing, and the development of seizures (Kharoshankaya et al 2016). Clinically, HIE is a sexually dimorphic disease as boys have been shown to have a higher incidence and poorer post-HIE outcome than girls (Mayoral et al 2009).…”

The independent role of neonatal seizures in epilepsy and other long‐term neurological outcomes

“…Collecting sound information on seizure burden, status epilepticus, and refractoriness to antiseizure medications (among others) would be meaningful, as a dose‐response relationship between seizure burden and outcome, including epilepsy, has been repeatedly unraveled in hospital‐based and experimental research. As an example, a seizure burden greater than 40 minutes and an hourly seizure burden greater than 13 minutes an hour (but not the mere presence/absence of seizures) were recently found to be independently associated with unfavourable outcome in newborn infants with hypoxic‐ischemic encephalopathy …”

“…As an example, a seizure burden greater than 40 minutes and an hourly seizure burden greater than 13 minutes an hour (but not the mere presence/absence of seizures) were recently found to be independently associated with unfavourable outcome in newborn infants with hypoxicischemic encephalopathy. 4 Intriguingly, the intracellular signaling cascades (excitotoxicity and neuroinflammation) initiated by prolonged or recurrent seizures, by promoting persistent inflammation, might link acute seizures to the pathogenesis of both epilepsy and cerebral palsy. 5…”

Prognostication and the unpredictable nature of HIV encephalopathy

“…The complexity of the brain and its capacity for adaptation never cease to amaze as well as confound. Recent papers exploring the outcomes of neonates with hypoxic–ischemic encephalopathy (HIE) indicate that the presence of moderate to severe HIE when accompanied by prolonged/severe seizures may contribute to an abnormal outcome irrespective of treatment with hypothermia, albeit at somewhat reduced odds …”