Defining neonatal status epilepticus: A scoping review from the ILAE neonatal task force

Magda L Nunes¹, Elissa G Yozawitz², Courtney J Wusthoff³, Renée A Shellhaas⁴, Efraín Olivas-Peña⁵, Jo M Wilmshurst⁶, Ronit M Pressler⁷, Chahnez C Triki⁸, Hans Hartmann⁹, Terrie Inder¹⁰, Geraldine B Boylan¹¹, Kette Valente¹², Solomon L Moshe^{13

14}, Eli M Mizrahi¹⁵, Nicholas S Abend¹⁶

Affiliations

¹ School of Medicine and Brain Institute (BraIns), Pontifical Catholic University of Rio Grande Do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
² Isabelle Rapin Division of Child Neurology of the Saul R Korey Department of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
³ Department of Neurology, University of California, Davis, Sacramento, California, USA.
⁴ Division of Pediatric Neurology, Department of Neurology, Washington University in St Louis School of Medicine, St Louis, Missouri, USA.
⁵ Department of Neurosciences, National Institute of Perinatology, Mexico City, Mexico. Department of Pediatrics, Women's Hospital, Yautepec Morelos, Mexico.
⁶ Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁷ Clinical Neuroscience, UCL GOS Institute of Child Health and Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁸ Child Neurology Department, Hedi Chaker Hospital, LR19ES15, University of Sfax, Sfax, Tunisia.
⁹ Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany.
¹⁰ Department of Pediatrics, University of California, Irvine; Director, Center for Newborn Research, Children's Hospital of Orange County, California, USA.
¹¹ INFANT Research Centre and Department of Paediatrics & Child Health, University College Cork, Cork, Ireland.
¹² Department of Psychiatry and Pediatrics, Research Center for Complex and Rare Epilepsies, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo, Brazil.
¹³ Laboratory of Clinical Neurophysiology and LIM 21, Department of Psychiatry, Clinics Hospital, University of São Paulo (HC FMUSP), São Paulo, Brazil.
¹⁴ Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology, and Department of Neuroscience and Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA.
¹⁵ Department of Neurology and Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
¹⁶ Department of Neurology and Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 39540265
PMCID: PMC11803272
DOI: 10.1002/epi4.13090

Defining neonatal status epilepticus: A scoping review from the ILAE neonatal task force

Magda L Nunes et al. Epilepsia Open. 2025 Feb.

. 2025 Feb;10(1):40-54.

doi: 10.1002/epi4.13090. Epub 2024 Nov 14.

Authors

Affiliations

¹ School of Medicine and Brain Institute (BraIns), Pontifical Catholic University of Rio Grande Do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
² Isabelle Rapin Division of Child Neurology of the Saul R Korey Department of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA.
³ Department of Neurology, University of California, Davis, Sacramento, California, USA.
⁴ Division of Pediatric Neurology, Department of Neurology, Washington University in St Louis School of Medicine, St Louis, Missouri, USA.
⁵ Department of Neurosciences, National Institute of Perinatology, Mexico City, Mexico. Department of Pediatrics, Women's Hospital, Yautepec Morelos, Mexico.
⁶ Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁷ Clinical Neuroscience, UCL GOS Institute of Child Health and Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁸ Child Neurology Department, Hedi Chaker Hospital, LR19ES15, University of Sfax, Sfax, Tunisia.
⁹ Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany.
¹⁰ Department of Pediatrics, University of California, Irvine; Director, Center for Newborn Research, Children's Hospital of Orange County, California, USA.
¹¹ INFANT Research Centre and Department of Paediatrics & Child Health, University College Cork, Cork, Ireland.
¹² Department of Psychiatry and Pediatrics, Research Center for Complex and Rare Epilepsies, Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo, Brazil.
¹³ Laboratory of Clinical Neurophysiology and LIM 21, Department of Psychiatry, Clinics Hospital, University of São Paulo (HC FMUSP), São Paulo, Brazil.
¹⁴ Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology, and Department of Neuroscience and Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA.
¹⁵ Department of Neurology and Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
¹⁶ Department of Neurology and Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 39540265
PMCID: PMC11803272
DOI: 10.1002/epi4.13090

Abstract

Objective: To review the available literature concerning the definition of neonatal status epilepticus (SE) and/or seizure burden.

Methods: The International League Against Epilepsy Neonatal Task Force performed a scoping review of the definitions of neonatal SE. Following a systematic literature review, articles were screened and data were abstracted regarding: (1) article characteristics (author identification, publication year, journal name, digital object identifier, title, objective, and study design); (2) cohort characteristics (sample size, gestational age, seizure etiology); (3) definition of SE and/or seizure burden; and (4) the method used to identify and classify SE, including routine EEG (EEG), continuous EEG monitoring (cEEG), amplitude-integrated EEG (aEEG), or clinical features.

Results: The scoping review yielded 44 articles containing a definition of neonatal SE. Studies mainly included infants with hypoxic-ischemic encephalopathy or neonates considered at risk for seizures. SE identification and classification most often relied on cEEG. The majority of studies based the definition of SE on seizure duration, including summed duration of seizures comprising ≥50% of any 1-h epoch, recurrent seizures for >50% of the total recording time, or either electrographic seizures lasting >30 min and/or repeated electrographic seizures totaling >50% in any 1-h period. Seizure burden was reported in 20 studies, and the most commonly used approach assessed total seizure burden, defined as total duration of EEG seizures in minutes. Sixteen studies assessed the relationship between seizure burden and outcomes, and most identified a significant association between higher seizure burden and unfavorable outcomes.

Significance: This scoping review demonstrates a substantial variation in neonatal SE definitions across the literature. The most common definitions were based around a 30-min seizure duration criterion, but evidence was insufficient to support that 30 min was a cutoff defining prolonged seizures or that seizures exceeding this burden were more likely to be pharmacoresistant or associated with worse outcomes. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE.

Plain language summary: Prolonged seizures are a neurologic emergency, if untreated, can lead to permanent injury or death. In adults and children, seizures lasting longer than 30 min are believed to cause brain damage. However, it is not clear if this definition can be applied to neonates. The International League Against Epilepsy Neonatal Taskforce performed a scoping literature review which identified 44 articles containing a definition of neonatal status epilepticus. In this article, the authors reviewed the current used definitions for prolonged seizures in neonates to establish a relationship between seizure duration and neurological outcome. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE.

Keywords: neonatal; neurocritical care; outcome; seizure burden; seizures; status epilepticus.

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Conflict of interest statement

M.L.N. is supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)‐Brazil (PQ 306338/2017–3). C.J.W. receives royalties from Cambridge Publishing, receives a stipend as Associate Editor for Neurology, and receives honoraria from ICON and University of Utah for service on Data Safety Monitoring Boards. R.A.S. receives royalties from UpToDate for authorship of topics related to neonatal seizures; serves as a consultant for the Epilepsy Study Consortium; and receives a stipend for her role as President of the Pediatric Epilepsy Research Consortium®. G.B.B. is founder and co‐director of Kephala Ltd. and CergenX Ltd. She has a consultancy agreement through University College Cork with Nihon Kohden. R.M.P. is an associate editor for Epilepsia‐Open; acts as an Investigator for studies with UCB Pharma; has received honoraria from Longboard, Natus, and UCB Pharma for services on advisory boards, teaching, or consultancy work; is supported by the National Institute of Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital, Evelyn Trust, Cambridge Biomedical Research Centre, and NIHR. K.V. receives a stipend as Associate Editor of Epilepsy & Behavior and research grants from FAPESP and CNPq. She receives honorarium as the Director and Coordinator of Clinical Research Center for Clinical Trials in Complex and Rare Epilepsies. JMW is an associate editor for Epilepsia, chief Editor of Pediatric Neurology subsection of Frontiers in Neurology and is on the South African national advisory boards for Sanofi, Roche, and Novartis. She receives honoraria for work related to these activities. S.L.M. is the Charles Frost Chair in Neurosurgery and Neurology and partially funded by grants from NIH U54 NS100064 (EpiBioS4Rx), RO1‐NS43209 and RO1‐ NS127524, US Department of Defense (W81XWH‐22‐1‐0510, W81XWH‐22‐1‐0210), a pilot grant from the NICHD center grant (P50 HD105352) for the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (RFK‐IDDRC), and the Heffer Family and the Segal Family Foundations, and the Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families. E.M.M. receives royalties from Springer Publishing Company, Princeton, NJ, USA. T.E.I. is a scientific advisor for Aspect Imaging, Realta, and Chiese Pharmaceutical. C.C.T., E.O.P., and N.S.A. no conflict of interest to declare. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

**FIGURE 2**
PRISMA Flowchart for the initial search (top) and update search (bottom).

See this image and copyright information in PMC

References

1. Glass HC, Shellhaas RA, Wusthoff CJ, Chang T, Abend NS, Chu CJ, et al. Contemporary profile of seizures in neonates: a prospective cohort study. J Pediatr. 2016;174:98–103. 10.1016/j.jpeds.2016.03.035 - DOI - PMC - PubMed
1. Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, et al. Neonatal seizures: case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019;37(52):7596–7609. - PMC - PubMed
1. Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1349–1397. 10.1111/epi.17239 - DOI - PubMed
1. Pressler RM, Cilio MR, Mizrahi EM, Moshé SL, Nunes ML, Plouin P, et al. The ILAE classification of seizures and the epilepsies: modification for seizures in the neonate. Position paper by the ILAE task force on neonatal seizures. Epilepsia. 2021;62(3):615–628. 10.1111/epi.16815 - DOI - PubMed
1. Pressler RM, Abend NS, Auvin S. Treatment of seizures in the neonate: guidelines and consensus‐based recommendations—special report from the ILAE task force on neonatal seizures. Epilepsia. 2023;00:1–21. 10.1111/epi.17745 - DOI - PubMed

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Defining neonatal status epilepticus: A scoping review from the ILAE neonatal task force

Affiliations

Defining neonatal status epilepticus: A scoping review from the ILAE neonatal task force

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Research Materials