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EEG Discontinuity as a Predictor of Cerebral Tissue Injury in Cooled Term Neonates with Hypoxic-Ischaemic Encephalopathy

Presented at the Neonatal Society 2014 Autumn Meeting.

Dunne JM, Wertheim D, Kapellou O, Clarke P, Boardman JP, Shah DK

Barts and The London School of Medicine and Dentistry, Kingston University, Kingston University, Homerton University Hospital, Norfolk and Norwich University Hospitals, University of Edinburgh, Royal London Hospital.

Background: Neonatal encephalopathy is associated with both high neonatal morbidity and mortality, with therapeutic hypothermia (TH) having a beneficial effect on both outcomes in resource-rich settings. Prior to the adoption of TH, the prognostic value of early EEG recordings in term babies was demonstrated (1,2); continuous limited channel EEG monitoring is routinely used and provides an indication of cerebral function. However, the predictive value of early EEG as a prognostic indicator in therapeutically cooled babies is unclear. We thus tested the hypothesis that early EEG background continuity in term neonates undergoing TH for neonatal encephalopathy is predictive of cerebral tissue injury detectable on later MRI.

Methods: Term neonates receiving 72 hours of TH at three centres were selected for study if they had continuous 2 channel EEG with amplitude-integrated EEG (aEEG) monitoring and cerebral MRI. A two hour seizure-free period, with minimum artefact, at 24 and 48 hours after birth were selected for analysis. Single channel crosscerebral (P3-P4) EEG data were exported and continuity was analysed in one minute epochs using software that we developed using MATLAB (The MathWorks, Inc., USA). The system detected an interval if the absolute amplitude of the EEG was less than 15 μV with respect to the baseline for at least 6 seconds; the analysis was repeated with a 10 μV threshold. For each recording the mean of the total interval length per epoch, the discontinuity, was calculated. MRIs were graded by the severity of injury using a system that has been shown to be predictive of outcome in this group of infants (3). MRIs were rated independently by two blinded experts.

Results: Of 49 term neonates receiving TH after HIE, 17 (35%) had cerebral tissue injury on MRI predictive of abnormal outcome. On univariate analysis factors associated with abnormal MRI outcome were high seizure burden (p=0.003), mean discontinuity at 24 hours (p<0.001) and at 48 hours (p<0.001) at 15 μV threshold. In multivariate logistic regression high seizure burden (OR 4.2, 95% CI 1.01–17.48; p=0.05), mean discontinuity at 24 hours (OR 1.04, 95% CI 1.01–1.08; p=0.01) and at 48 hours (OR 1.05, 95% CI 1.01-1.10; p=0.01) were associated with severe cerebral tissue injury on MRI. A mean discontinuity >30s per minute epoch has a positive predictive value of 90% and 86% at 24 and 48 hours respectively (10 μV threshold) and of 75% and 80% at 24 and 48 hours (15 μV threshold) for cerebral tissue injury on MRI.

Conclusion: Our study indicates that, in addition to seizure burden (4), excessive EEG discontinuity in infants undergoing therapeutic cooling after hypoxic-ischaemic encephalopathy is associated with increased cerebral tissue injury on MRI predictive of abnormal neurodevelopmental outcome. The EEG remains a valuable tool for monitoring cerebral function in this group of patients and provides an early prognostic indicator.

Corresponding author: divyen.shah@bartshealth.nhs.uk

References
1. Wertheim et al., Arch Dis Child, 1994, Volume 71(2): 97-102.
2. Menache et al., Pediatric Neurology, 2002, Volume 27(2): 93-101.
3. Rutherford et al., Lancet Neurology, 2010, Volume 9(1): 39-45.
4. Shah et al., Arch Dis Child Neontatal, 2014, Volume 99: 219-224.

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