Risk factors for EEG seizures in neonates treated with hypothermia: A multicenter cohort study

Published on Apr 8, 2014in Neurology8.77
· DOI :10.1212/WNL.0000000000000282
Hannah C. Glass37
Estimated H-index: 37
(UCSF: University of California, San Francisco),
Courtney J. Wusthoff28
Estimated H-index: 28
(Stanford University)
+ 6 AuthorsTaeun Chang30
Estimated H-index: 30
(Children's National Medical Center)
Objective: To assess the risk factors for electrographic seizures among neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). Methods: Three-center observational cohort study of 90 term neonates treated with hypothermia, monitored with continuous video-EEG (cEEG) within the first day of life (median age at onset of recording 9.5 hours, interquartile range 6.3–14.5), and continued for >24 hours (total recording 93.3 hours, interquartile range 80.1–112.8 among survivors). A pediatric electroencephalographer at each site reviewed cEEGs for electrographic seizures and initial EEG background category. Results: A total of 43 (48%) had electrographic seizures, including 9 (10%) with electrographic status epilepticus. Abnormal initial EEG background classification (excessively discontinuous, depressed and undifferentiated, burst suppression, or extremely low voltage), but not clinical variables (including pH Conclusions: Electrographic seizures are common among neonates with HIE undergoing hypothermia and are difficult to predict based on clinical features. These results justify the recommendation for cEEG monitoring in neonates treated with hypothermia.
Figures & Tables
📖 Papers frequently viewed together
252 Citations
97 Citations
200 Citations
#1Elena Isaeva (Dartmouth College)H-Index: 16
#2Dmytro Isaev (Dartmouth College)H-Index: 20
Last. Gregory L. Holmes (Dartmouth College)H-Index: 74
view all 3 authors...
Summary Seizures in newborns are associated with a high risk for subsequent epilepsy and adverse neurodevelopmental consequences. Understanding the mechanisms by which neonatal seizures adversely disturb the immature brain is important in developing therapeutic strategies. Using the convulsant agent flurothyl to mimic repetitive neonatal seizures we show that early-life seizures result in long-term alteration in the maintenance phase of long-term potentiation (LTP) in layer IV to layer II/III sy...
22 CitationsSource
#1Preethi Srinivasakumar (WashU: Washington University in St. Louis)H-Index: 5
#2John M. Zempel (WashU: Washington University in St. Louis)H-Index: 19
Last. Amit M. Mathur (WashU: Washington University in St. Louis)H-Index: 28
view all 6 authors...
Objective To evaluate the electrographic seizure burden in neonates with hypoxic ischemic encephalopathy (HIE) treated with or without therapeutic hypothermia and stratified results by severity of HIE and severity of injury as assessed by magnetic resonance imaging (MRI). Study design Between 2007 and 2011, video-electroencephalography (EEG) monitoring was initiated in neonates with moderate to severe HIE. Seizure burden (in seconds) was calculated, and brain MRI scans were quantitatively scored...
82 CitationsSource
#1Evonne Low (UCC: University College Cork)H-Index: 8
#2Geraldine B. Boylan (UCC: University College Cork)H-Index: 47
Last. Janet M. RennieH-Index: 38
view all 8 authors...
Objective To investigate any possible effect of cooling on seizure burden, the authors quantified the recorded electrographic seizure burden based on multichannel video-EEG recordings in term neonates with hypoxic-ischaemic encephalopathy (HIE) who received cooling and in those who did not. Study design Retrospective observational study. Patients Neonates >37 weeks gestation born between 2003 and 2010 in two hospitals. Methods Off-line analysis of prolonged continuous multichannel video-EEG reco...
90 CitationsSource
#1Hannah C. Glass (UCSF: University of California, San Francisco)H-Index: 37
#2Jessica Kan (UCSF: University of California, San Francisco)H-Index: 1
Last. Donna M. Ferriero (UCSF: University of California, San Francisco)H-Index: 109
view all 4 authors...
Neonatal seizures are common clinical conditions in both term and preterm neonates, yet no clinical management guidelines for direct care exist. We surveyed 193 international neurologists, neonatologists, and specialists in neonatal neurology or neonatal neurocritical care to assess management practices for seizures in preterm and term neonates. We found high reported rates of electroencephalogram and amplitude-integrated electroencephalogram (aEEG) monitoring to detect neonatal seizures, preval...
96 CitationsSource
#1Renée A. Shellhaas (UM: University of Michigan)H-Index: 32
#2Taeun Chang (Children's National Medical Center)H-Index: 30
Last. Robert R. Clancy (UPenn: University of Pennsylvania)H-Index: 88
view all 9 authors...
This article offers the preferred methods and indications for longterm, conventional electroencephalography (EEG) monitoring for selected, high-risk neonates of postmenstrual age less than 48 weeks. The authors recognize that there may be significant practical barriers to the implementation of these recommendations for many caregivers and institutions, particularly with regard to the availability of equipment, and technical and interpretive personnel. A wide range of clinical circumstances dicta...
252 CitationsSource
#1Hannah C. Glass (UCSF: University of California, San Francisco)H-Index: 37
#2Kendall B. Nash (UCSF: University of California, San Francisco)H-Index: 10
Last. Maria Roberta Cilio (UCSF: University of California, San Francisco)H-Index: 37
view all 7 authors...
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 resona...
78 CitationsSource
#1Nofrat Frenkel (BGU: Ben-Gurion University of the Negev)H-Index: 1
#2Michael Friger (BGU: Ben-Gurion University of the Negev)H-Index: 45
Last. Eilon Shany (BGU: Ben-Gurion University of the Negev)H-Index: 13
view all 7 authors...
Abstract Objectives This study aims to detect seizures by amplitude-integrated electroencephalography (EEG) (aEEG) as compared with conventional EEG (cEEG) by clinicians with different levels of expertise. Methods Simultaneous 10 min aEEG/cEEG recordings were time-locked and assessed for seizure activity. aEEG was assessed by a neonatologist, a fellow and a medical student and cEEG by two child neurologists and a neonatologist. Results A total of 265 paired epochs from 38 simultaneous recording ...
39 CitationsSource
#1Courtney J. Wusthoff (Imperial College London)H-Index: 28
#2Dennis J. Dlugos (Children's Hospital of Philadelphia)H-Index: 55
Last. Nicholas S. Abend (Children's Hospital of Philadelphia)H-Index: 46
view all 8 authors...
Electrographic seizures are common in neonates with hypoxic-ischemic encephalopathy, but detailed data are not available regarding seizure incidence during therapeutic hypothermia. The objective of this prospective study was to determine the incidence and timing of electrographic seizures in term neonates undergoing whole-body therapeutic hypothermia for hypoxic-ischemic encephalopathy as detected by conventional full-array electroencephalography for 72 hours of therapeutic hypothermia and 24 ho...
97 CitationsSource
#1Geraldine B. Boylan (UCC: University College Cork)H-Index: 47
#2Louise Burgoyne (UCC: University College Cork)H-Index: 10
Last. Janet M. Rennie (UCL: University College London)H-Index: 38
view all 5 authors...
Objective: To examine the extent of EEG monitoring in neonatal intensive care units (NICUs), and to survey the level of experience and training of those using it. Study design: A web-based survey, the link to which was circulated via e-mail, personal contact, specialist societies and professional groups. Survey data were exported to SPSS for analysis. Results: In total 210 surveys were analysed; 124 from Europe, 54 from the US. Ninety percent of respondents had access to either EEG or aEEG monit...
73 CitationsSource
#1Aileen Malone (UCC: University College Cork)H-Index: 1
#2C. Anthony Ryan (UCC: University College Cork)H-Index: 30
Last. Geraldine B. Boylan (UCC: University College Cork)H-Index: 47
view all 6 authors...
Summary Objectives: Accurate diagnosis of neonatal seizures is critically important and is often made clinically, without EEG (electroencephalography) monitoring. This observational study aimed to determine the accuracy and interobserver reliability of healthcare professionals in distinguishing clinically manifested seizures from other neonatal movements, when presented with clinical histories and digital video recordings only. Methods: Twenty digital video recordings of paroxysmal movements in ...
111 CitationsSource
Cited By62
#2Janette Mailo (Glenrose Rehabilitation Hospital)
Last. Taeun Chang (GW: George Washington University)H-Index: 30
view all 10 authors...
Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half of neonates treated with therapeutic hypothermia for NE have EEG-confirmed seizures. These seizures are best identified with continuous EEG monitoring, as clinical diagnosis leads to under-diagnosis of subclinical seizures and over-treatment of events that are not seizures. High seizure burden, especially status epilepticus, is thought to augment brain injury. Treatment, therefore, is aimed at minimi...
1 CitationsSource
#1Lina F. Chalak (UTSW: University of Texas Southwestern Medical Center)H-Index: 24
#2Lena Hellström-Westas (Uppsala University Hospital)H-Index: 57
view all 9 authors...
Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated electroencephalogram (aEEG) and EEG], 2) cerebral oxygenation delivery and consumption [near-infrared spectroscopy (NIRS)] and 3) blood and cerebrospinal fluid biomarkers. The aim of the review is to provide the role of neuromonitoring in understanding the development of brain injury in these newborns and better predict their long-term outcome....
#1Neil Marlow (UCL: University College London)H-Index: 89
#2Seetha Shankaran (WSU: Wayne State University)H-Index: 88
Last. Christopher D. Smyser (WashU: Washington University in St. Louis)H-Index: 27
view all 5 authors...
In randomized trials, therapeutic hypothermia (TH) is associated with reduced prevalence of the composite outcome mortality or neurodevelopmental morbidity in infants with neonatal encephalopathy (NE). Following systematic review, the reduction in prevalence of both mortality and infant neuromorbidity is clear. Among three trials reporting school age outcomes, the effects of NE and TH suggest that such benefit persists into middle childhood, but none of the major trials were powered to detect di...
#1Courtney J. Wusthoff (Stanford University)H-Index: 28
#2Vandana Sundaram (Stanford University)H-Index: 25
Last. Renée A. Shellhaas (UM: University of Michigan)H-Index: 32
view all 15 authors...
OBJECTIVE To determine whether screening continuous EEG monitoring (cEEG) is associated with greater odds of treatment success for neonatal seizures. METHODS We included term neonates with acute symptomatic seizures enrolled in the Neonatal Seizure Registry (NSR), a prospective, multicenter cohort of neonates with seizures. We compared two cEEG approaches: (1) Screening cEEG, initiated for indications of encephalopathy or paralysis without suspected clinical seizures, and (2) Confirmatory cEEG, ...
#1M. Asjid Tanveer (National University of Science and Technology)H-Index: 2
#2Muhammad Jawad Khan (National University of Science and Technology)H-Index: 14
Last. Noman Naseer (Air University (Islamabad))H-Index: 17
view all 4 authors...
Abstract Background Neonatal seizures are a common occurrence in clinical settings, requiring immediate attention and detection. Previous studies have proposed using manual feature extraction coupled with machine learning, or deep learning to classify between seizure and non-seizure states. New method In this paper a deep learning based approach is used for neonatal seizure classification using electroencephalogram (EEG) signals. The architecture detects seizure activity in raw EEG signals as op...
Objective Prolonged continuous video-electroencephalography (cEEG) is recommended for neonates at risk of seizures. The cost and expertise required to provide a real-time response to detected seizures often limits its utility. We hypothesised that the first hour of cEEG could predict subsequent seizures. Design and setting Retrospective multicentre diagnostic accuracy study. Patients 266 term neonates at risk of seizure or with suspected seizures. Intervention The first hour of cEEG was graded b...
1 CitationsSource
#1Valerie Y. Chock (Stanford University)H-Index: 17
#2Seo-Ho Cho (Stanford University)H-Index: 2
Last. Adam Frymoyer (Stanford University)H-Index: 19
view all 3 authors...
Neonates with hypoxic–ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied. A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum cr...
6 CitationsSource
Seizures are the most common neurological disorder in newborns and are most prevalent in the neonatal period. They are mostly caused by severe disorders of the central nervous system (CNS). However, they can also be a sign of the immaturity of the infant’s brain, which is characterized by the presence of specific factors that increase excitation and reduce inhibition. The most common disorders which result in acute brain damage and can manifest as seizures in neonates include hypoxic-ischemic en...
#1Charles Lechner (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 1
#2Melanie A. McNally (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 6
Last. Raul Chavez-Valdez (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 18
view all 7 authors...
Abstract Since neonatal hypoxia-ischemia (HI) disrupts the hippocampal (Hp) GABAergic network in the mouse and Hp injury in this model correlates with flurothyl seizure susceptibility only in male mice, we hypothesized that GABAergic disruption correlates with flurothyl seizure susceptibility in a sex-specific manner. C57BL6 mice were exposed to HI (Vannucci model) versus sham procedures at P10, randomized to normothermia (NT) or therapeutic hypothermia (TH), and subsequently underwent flurothyl...
#1Jennifer L. Griffith (WashU: Washington University in St. Louis)H-Index: 6
#2Stuart T. Tomko (WashU: Washington University in St. Louis)H-Index: 1
Last. Réjean M. Guerriero (WashU: Washington University in St. Louis)H-Index: 11
view all 3 authors...
Abstract Continuous EEG-video (CEEG) monitoring of critically ill infants and children has expanded rapidly in recent years. Indications for CEEG include evaluation of patients with altered mental status, characterization of paroxysmal events, and detection of electrographic seizures, including monitoring of patients with limited neurologic exam or conditions that put them at high risk for electrographic seizures (for example, cardiac arrest or ECMO cannulation). Depending on the inclusion crite...
2 CitationsSource