Elsevier

The Journal of Pediatrics

Volume 159, Issue 5, November 2011, Pages 731-735.e1
The Journal of Pediatrics

Original Article
Seizures and Magnetic Resonance Imaging–Detected Brain Injury in Newborns Cooled for Hypoxic-Ischemic Encephalopathy

https://doi.org/10.1016/j.jpeds.2011.07.015Get rights and content

Objective

To describe the association between electrographically detected seizures and brain injury evaluated by magnetic resonance imaging in newborns treated with hypothermia.

Study design

A total of 56 newborns treated with hypothermia were monitored using video electroencephalography through cooling and rewarming, and then imaged at a median of 5 days. The electroencephalograms were reviewed for indications of seizure and status epilepticus. Moderate-severe injury detected on magnetic resonance imaging was measured using a classification scheme similar to one predicting abnormal outcome in an analogous population.

Results

Seizures were recorded in 17 newborns (30%), 5 with status epilepticus. Moderate-severe injury was more common in newborns with seizures (relative risk, 2.9; 95% CI, 1.2-4.5; P = .02), and was present in all 5 newborns with status epilepticus. Newborns with moderate-severe injury had seizures that were multifocal and of later onset, and they were more likely to experience recurrent seizures after treatment with 20 mg/kg phenobarbital. Newborns with only subclinical seizures were as likely to have injury as those with seizures with a clinical correlate (57% vs 60%).

Conclusion

Seizures represent a risk factor for brain injury in the setting of therapeutic hypothermia, especially in neonates with status epilepticus, multifocal-onset seizures, and a need for multiple medications. However, 40% of our neonates were spared from brain injury, suggesting that the outcome after seizures is not uniformly poor in children treated with therapeutic hypothermia.

Section snippets

Methods

We examined a cohort of newborns who were treated with therapeutic hypothermia using whole-body cooling at University of California San Francisco between November 2007 and May 2010. A subset of these subjects were reported by Nash et al.19 Inclusion criteria for hypothermia at University of California San Francisco were based on those used in randomized controlled trials1, 20, 21, 22 and have been reported in detail previously.23 Clinical data were extracted from electronic medical records and

Results

During the study period, a total of 61 newborns were treated with hypothermia and monitored with conventional video EEG. Of these, 56 were evaluated with MRI and were included in this study. The clinical characteristics of the subjects with and without seizures are presented in Table I.

Eight newborns were treated with a phenobarbital loading dose of 20 mg/kg before the initiation of monitoring, including 6 for suspected clinical seizures and 2 for seizures on amplitude-integrated EEG. Two of

Discussion

In this cohort of 56 newborns with moderate-severe HIE who were cooled using whole-body hypothermia, status epilepticus, multifocal seizures, and seizures that were resistant to a single loading dose of 20 mg/kg of phenobarbital were associated with moderate-severe injury detected on neonatal MRI. Newborns whose electrographic seizures never had an obvious clinical correlate were as likely to have moderate-severe injury as those who had electrographic seizures with a clinical correlate.

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    • Management of seizures in neonates with neonatal encephalopathy treated with hypothermia

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      Lactate levels increase with increased seizure burden, suggesting a dose-response relationship. Neonates with seizures in addition to NE have more severe injury than those without seizures, even after controlling for NE severity [26–29]. In all, neonatal seizures are associated with worsened biomarkers of injury among neonates with NE.

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    Supported by National Institutes of Health/National Center for Research Resources, University of California, San Francisco, Clinical Translational Science Institute Grant UL1 RR024131 and National Institutes of Health/National Institute of Neurological Disorders and Stroke Grants 5P50NS035902 and NS40117. H.G. is supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke Grant K23NS066137 and the Neonatal Brain Research Institute at University of California San Francisco. M.C. was supported by E-Rare grant EUROBFNS from the European Commission. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest.

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