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Seizure Prediction Models in the Neonatal Intensive Care Unit

Sansevere, Arnold J.*; Kapur, Kush; Peters, Jurriaan M.*; Fernández, Ivan Sánchez*; Loddenkemper, Tobias*; Soul, Janet S.

doi: 10.1097/WNP.0000000000000574
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Purpose: Conventional video-EEG monitoring is required to diagnose seizures accurately in neonates. This tool is resource-intense and has limited availability in many centers. Seizure prediction models could help allocate resources by improving efficiency in which conventional video-EEG monitoring is used to detect subclinical seizures. The aim of this retrospective study was to create a neonate-specific seizure prediction model using clinical characteristics and EEG background findings.

Methods: We conducted a 3-year retrospective study of all consecutive neonates who underwent conventional video-EEG monitoring at a tertiary care pediatric hospital. Variables including age, EEG indication, high-risk clinical characteristics, and EEG background informed seizure prediction models based on a multivariable logistic regression model. A Cox proportional hazard regression model was used to construct time to first EEG seizure.

Results: Prediction models with clinical variables or background EEG features alone versus combined clinical and background EEG features were created from 210 neonates who met inclusion criteria. The combined clinical and EEG model had a higher area under the curve for combined sensitivity and specificity to 83.0% when compared to the clinical model (76.4%) or EEG model (66.2%). The same trend of higher sensitivity of the combined model was found for time to seizure outcome.

Conclusions: While both clinical and EEG background features were predictive of neonatal seizures, the combination improved overall prediction of seizure occurrence and prediction of time to first seizure as compared with prediction models based solely on clinical or EEG features alone. With prospective validation, this model may improve efficiency of patient-oriented EEG monitoring.

*Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.; and

Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.

Address correspondence and reprint requests to Janet S. Soul, MD, Department of Neurology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, U.S.A.; e-mail: janet.soul@childrens.harvard.edu.

A. J. Sansevere is supported by an Eleanor and Miles Shore Fellowship for Scholars in Medicine. I. S. Fernández is funded by the Epilepsy Research Fund and was funded by a grant for the study of Epileptic Encephalopathies from Fundación Alfonso Martín Escudero and from the HHV6 foundation. Tobias Loddenkemper serves on the Council (and as President) of the American Clinical Neurophysiology Society, on the American Board of Clinical Neurophysiology, as committee chair at the American Epilepsy Society (Special Interest Group and Investigator Workshop Committees), as founder and consortium principal investigator of the pediatric status epilepticus research group, as an Associate Editor for Seizure, and as an Associate Editor for Wyllie's Treatment of Epilepsy 6th edition and 7th editions. He is part of pending patent applications to detect and predict seizures and to diagnose epilepsy. He receives research support from the National Institutes of Health, Patient Centered Outcomes Research Institute, Epilepsy Research Fund, the Epilepsy Foundation of America, the Epilepsy Therapy Project, the Pediatric Epilepsy Research Foundation, and received research grants from Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Sage, and Pfizer. He serves as a consultant for Zogenix, Engage, Amzell, Upsher Smith, Eisai, and Sunovion. He performs video-EEG long-term and ICU monitoring, EEGs, and other electrophysiological studies at Boston Children's Hospital and affiliated hospitals and bills for these procedures, and he evaluates pediatric neurology patients and bills for clinical care. He has received speaker honorariums from national societies, including the American Academy of Neurology, American Epilepsy Society, and American Clinical Neurophysiology Society, and for grand rounds at various academic centers. His wife, Dr. Karen Stannard, is a pediatric neurologist and she performs video-EEG long-term and ICU monitoring, EEGs, and other electrophysiological studies and bills for these procedures, and she evaluates pediatric neurology patients and bills for clinical care. J. Soul is supported by National Institutes of Health grants R01NS066929, 5R01HD076258, 1R01EB017337, 1R21HD083956, and U54 HD090255 and by grants from the Mooney Family Initiative for Translation and Clinical Studies in Rare Diseases and Patient Centered Outcomes Research Institute. The remaining authors have no funding or conflicts of interest to disclose.

A. J. Sansevere participated in drafting and revising the manuscript for content, including medical writing for content, in study concept and design, and in acquisition, analysis, and interpretation of data. K. Kapur participated in drafting and revising the manuscript for content, including medical writing for content, in study concept and design, in statistical analysis and interpretation of data, and generation of figures and tables. I. S. Fernández participated revising the manuscript for content, including medical writing for content, in analysis and interpretation of data, acquisition of data, and study supervision or coordination. T. Loddenkemper participated revising the manuscript for content, including medical writing for content, in analysis and interpretation of data, acquisition of data, and study supervision or coordination. J. Peters participated in drafting and revising the manuscript for content, including medical writing for content, in study concept and design, in analysis and interpretation of data, and study supervision or coordination. J. Soul participated in drafting and revising the manuscript for content, including medical writing for content, in study concept and design, in analysis and interpretation of data, and study supervision or coordination.

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© 2019 by the American Clinical Neurophysiology Society