Use of amplitude-integrated electroencephalography (aEEG) and near infrared spectroscopy findings in neonates with asphyxia during selective head cooling

doi:10.1016/j.braindev.2011.06.005

Brain and Development

Volume 34, Issue 4, April 2012, Pages 280-286

https://doi.org/10.1016/j.braindev.2011.06.005 Get rights and content

Abstract

Background

Amplitude-integrated electroencephalogram (aEEG) at <6 h is the best single outcome predictor in term infants with perinatal asphyxia at normothermia. Hypothermia treatment has changed the cutoff values for outcome prediction by using time at onset of normal trace and SWC. Cerebral hemodynamics and oxygenation changes detected by near infrared spectroscopy (NIRS) during hypothermia treatment in aphyxiated neonates are not a well known issue.

Aim

The aim of this study was to investigate the correlations between brain monitoring (amplitude integrated EEG and NIRS) and outcome in asphyxiated full-term infants with moderate/severe hypoxic–ischemic encephalopathy before, during and after hypothermia treatment.

Method

Ten neonates were recruited for hypothermia treatment by using the cool cap entry criteria. aEEG and NIRS were applied in 10 and 8 patients, respectively with moderate and severe hypoxic–ischemic encephalopathy before, just after brain cooling and rewarming periods. Patterns and voltages of aEEG backgrounds sleep–wake cycles (SWC) and NIRS values (TOI% and FTOE) were recorded. During the follow up their outcomes were assessed by using the Bayley Scales of Infant Development II.

Conclusion

Hypothermia changes the predictive value of early aEEG. Normalization of a baby’s aEEG and the appearance of SWCs while being cooled occurs later. In our study one patient had normal aEEG background pattern at 80 and imminent SWC at 90 h after birth and still had normal Bayley scores at 24 months. Time to normal aEEG and SWC appearance should be carefully evaluated during the cooling period. NIRS values were different due to the clinical presentations of the patients.

Introduction

Since the past two decades, experimental and clinical trials have made up of enough evidence that a 3–4 °C reduction of body temperature maintained for at least 24 h in newborns with hypoxic–ischemic encephalopathy (HIE) either by selective head (SHC) or whole body cooling (WBC) may attenuate cerebral injury and improve neurological outcome. A recent meta-analysis showed a significant improvement of the combined outcome of mortality and neurodevelopmental disability among survivors [1]. The knowledge that amplitude integrated EEG (aEEG) recorded within 6 h after birth in normothermic term babies with asphyxia correctly predicts outcome has resulted in a wide spread use of this method in encephalopathic babies [2], [3]. In some of the randomized controlled trials of induced hypothermia treatment after perinatal asphyxia aEEG was used as inclusion criteria for the selection of the patients [4], [5], [6]. Besides aEEG there is also quite a number of studies considering electroencephalogram recording to be a reliable parameter for predicting clinical outcomes of hypoxic–ischemic babies [7], [8], [9], [10], [11], [12]. However there are only four clinical studies and one case report in which aEEG and EEG recordings have continuously been monitored during the cooling period of both selective and whole body hypothermia treatments [13], [14], [15], [16], [17].

Near infrared spectroscopy (NIRS) is a noninvasive bedside method for evaluating oxy- and deoxy-hemoglobin levels in the brain thus the cerebral hemodynamics and oxygenation and could also be used as a prognostic tool [18], [19], [20]. Determining the type and severity and monitoring an evolving brain injury at the bedside is a challenge, in this respect by using NIRS. It has also been shown that certain patterns of changes in oxygenation of hemoglobin were related to the severity of the brain damage [21]. In one study of severe hypoxic–ischemic injury where both NIRS and aEEG were used; increased cerebral tissue oxygenation in the first 48 h of life was correlated with poor outcomes [20]. There is only one case report about a hypoxic–ischemic neonate of whom the changes in cerebral hemodynamics and aEEG were monitored during and after cool cap treatment [17]. In this study we evaluated the aEEG recordings of 10 and NIRS data of eight asphyxiated neonates before, during and after selective head cooling treatment and gave the short and long term neurological outcomes.

Section snippets

Patients and methods

This is a retrospective review of continuous aEEG and NIRS data from 10 newborns with moderate or severe encephalopathy admitted to Gazi University Medical Faculty, neonatal intensive care unit, which is one of the reference centers in Ankara. In our unit, SHC, using a Cool-Cap System (Olympic MedicalCool Care System, Olympic Medical, Seattle, WA), was introduced as a treatment modality in January 2009. This Cool-Cap device was adopted because its approval by the Federal Food and Drug

Results

All the infants were born at term, all had acidosis, and abnormal neurological examination at the 6 h of age with muscular hyporonia, hyperalertness, absent or weak neonatal reflexes. Seven babies had clinical seizures, and all had AED treatment (one or more). Two babies died both of whom had an abnormal aEEG background pattern with sustained burst suppression (BS) and a continuous low voltage (CLV), flat trace (FT) along with repetitive seizures and saw-tooth appearance (status epilepticus),

Discussion

In this study we analyzed our preliminary data of 10 patients with perinatal asphyxia who had SHC treatment with continuous aEEG and NIRS recordings of eight patients before, just after cooling and rewarming periods. First Hellstrom-Westas showed that infants with CNV/DNV within the first 6 h of their life were likely to survive normally with a predictive value of 96%. On the other hand neonates with BS or FT were at risk of death or neurological sequela with a predictive value of 80% [25]. Then

References (34)

P.S. Shah
Hypothermia: a systematic review and meta-analysis of clinical trials
Semin Fetal Neonatal Med
(2010)
M. Thoresen
Patient selection and prognostication with hypothermia treatment
Semin Fetal Neonatal Med
(2010)
P.D. Gluckman et al.
Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicenter randomized trial
Lancet
(2005)
G. Holmes et al.
Prognostic value of the electroencephalogram in neonatal asphyxia
Electroencephalogr Clin Neurophysiol
(1982)
R.M. Pressler et al.
Early serial EEG in hypoxic ischemic encephalopathy
Clin Neurophysiol
(2001)
E. Mariani et al.
Prognostic value of electroencephalogram in asphyxiated newborns treated with hypothermia
Pediatr Neurol
(2008)
G. Ancora et al.
Changes in cerebral hemodynamics and amplitude integrated EEG in an asphyxiated newborn during and after cool cap treatment
Brain Dev
(2009)
E. Mariani et al.
Prognostic value of electroencephalograms in asphyxiated newborns treated with hypothermia
Pediatr Neurol
(2008)
D.K. Sokol et al.
Near infrared spectroscopy [NIRS] distinguishes seizure types
Seizure
(2000)
M.C. Toet et al.
Amplitude integrated EEG3 and 6 hours after birth in full term neonates with hypoxic–ischaemic encephalopathy
Arch Dis Child Fetal Neonatal Ed
(1999)

R.E. Spitzmiller et al.

Amplitude-integrated EEG is useful in predicting neurodevelopmental outcome in full-term infants with hypoxic–ischemic encephalopathy: a meta-analysis

J Child Neurol

(2007)

D.V. Azzopardi et al.

Moderate hypothermia to treat perinatal asphyxia encephalopathy

N Engl J Med

(2009)

C. Pezzani et al.

Neonatal electroencephalography during the first twenty-four hours of life in full term newborn infants

Neuropediatrics

(1986)

H.B. Van Liseut et al.

The prognostic value of EEG in asphyxiated newborns

Acta Neurol Scand

(1995)

E. Biagioni et al.

Combined use of electroencephalography and magnetic resonance imaging in full term neonates with acute encephalopathy

Pediatrics

(2001)

R. Mandell et al.

Prediction of outcome after hypoxic ischemic encephalopathy: a prospective clinical and electrophysiologic study

J Pediatr

(2002)

S. Sarkar et al.

Should amplitude integrated EEG be used to identify infants suitable for hypothermic neuroprotection?

J Perinato

(2008)

Cited by (26)

Prognostic value of near-infrared spectroscopy in hypoxic-ischaemic encephalopathy
2021, Anales de Pediatria
A pesar del tratamiento con hipotermia, el 40% de los neonatos con encefalopatía hipóxico-isquémica fallecen o sufren discapacidad moderada-grave. La espectroscopia cercana al infrarrojo (NIRS) se propone como una herramienta útil y no invasiva para establecer el pronóstico.
Evaluar el valor pronóstico de la NIRS en el resultado del neurodesarrollo entre los 18-36 meses en neonatos con encefalopatía hipóxico-isquémica, y establecer el tiempo y los puntos de corte de la saturación cerebral de oxígeno que mejor se relacionan con el pronóstico.
Se incluyeron todos los neonatos a término con encefalopatía hipóxico-isquémica, sometidos a hipotermia y NIRS, entre 2013-2016. Con respeto al resultado se constituyeron 3 grupos: neurodesarrollo normal, discapacidad moderada y grave.
Se incluyeron 28 neonatos (edad gestacional mediana: 39 semanas; peso al nacimiento mediano: 3.195 g). La saturación cerebral de oxígeno tendió a aumentar desde una mediana de 65% hasta 85% a las 48 horas de vida. El resultado del neurodesarrollo fue normal en 28,6%, el 35,7% adquirió discapacidad moderada y el 35,7% discapacidad grave (3 fallecieron). Se halló una diferencia estadística entre los grupos a las 48 horas (p = 0,005) y después de la hipotermia (p = 0,03), con valores más altos en los pacientes con discapacidad. Teniendo en cuenta el grupo con discapacidad grave frente a los otros, la curva de ROC a las 48 horas resultó en un área debajo de la curva (AUC) significativa de 0,872 (p = 0,001), con un punto de corte de saturación cerebral de oxígeno de 83,5%. Después de la hipotermia los valores de saturación cerebral de oxígeno por debajo del 66,0% (AUC 0,794; p = 0,017) predijeron el desarrollo normal, mientras que valores por encima del 82% (AUC 0,881; p = 0,001) predijeron discapacidad grave.
El NIRS parece constituir una herramienta útil en la predicción del resultado del neurodesarrollo de pacientes con encefalopatía hipóxico-isquémica, incluso después de la hipotermia, con valores más altos de saturación cerebral de oxígeno en pacientes con discapacidad.
Despite treatment with hypothermia, 40% of newborns with hypoxic-ischaemic encephalopathy die or suffer moderate to severe disability. Near-infrared spectroscopy (NIRS) could be a useful, non-invasive tool to establish the prognosis.
To evaluate the prognostic value of NIRS in predicting neurodevelopmental outcomes at 18 to 36 months in newborns with hypoxic-ischaemic encephalopathy, and to establish the time points and cut-off values of regional cerebral oxygen saturation that exhibit the strongest correlation to these outcomes.
The study included all term newborns with hypoxic-ischaemic encephalopathy managed with hypothermia and NIRS between 2013 and 2016. We established 3 outcome categories: normal neurodevelopment, moderate disability and severe disability.
The sample comprised 28 newborns (median gestational age, 39 weeks; median birth weight, 3195 g). The median regional cerebral oxygen saturation increased from 65% to 85% at 48 hours post birth. Neurodevelopmental outcomes were normal in 28.6%, while 35.7% developed moderate disability and 35.7% severe disability; 3 patients died. We found a statistically significant difference between groups at 48 hours (P = .005) and after hypothermia (P = .03), with higher values in patients with disability. When we compared patients in the severe disability group with the other groups, we found a statistically significant area under the ROC curve at 48 hours of 0.872 (P = .001) applying a regional cerebral oxygen saturation cutoff of 83.5%. After hypothermia, regional cerebral oxygen saturation values below 66.0% (AUC, 0.794; P = .017) predicted normal development, while values above 82% (AUC, 0.881; P = .001) predicted severe disability.
NIRS seems to be a valuable tool to predict neurodevelopmental outcomes in patients with hypoxic-ischaemic encephalopathy, even after hypothermia, with higher cerebral oxygen saturation values in patients with disability.
Automated diagnosis of neonatal encephalopathy on aEEG using deep neural networks
2020, Neurocomputing
Amplitude-integrated electroencephalography, called aEEG clinically, is an effective approach for monitoring neonatal cerebral function. Early aEEG screening is necessary to diagnose neonatal encephalopathy. The electroencephalography (EEG) signal contains lots of information about infant neurological status and prognosis. Traditional computer-aided diagnosis methods pay more attention to process EEG signal data, while doctors referring more to aEEG screening images in clinical diagnosis. In addition, clinical diagnosis of neonatal encephalopathy is a large challenge in low-level medical resource settings where few neonatologists are available to care for those newborns with cerebral disease. As a result, a method of automated diagnosing EEG-related images is requested. This paper presents an automated neonatal encephalopathy diagnosis model for aEEG images, which is divided into two sub-networks. The front part is utilized to extract high-dimensional features from multiple parts of an image. And the second portion aims to accomplish classification. There is a feature combination operator between the two parts. The feature enhancing mechanism can protrude the important region and achieve a better result. The annotated datasets, containing more than 600 aEEG screening images, are established to train and evaluate the novel model. All the annotations in our datasets are verified by case reports. Our proposed method comes up to the performances of professional human neonatologists, which can be applied to clinical diagnosis.
Prognostic Value of Electroencephalography in Hypothermia-Treated Neonates With Hypoxic-Ischemic Encephalopathy: A Meta-Analysis
2019, Pediatric Neurology
Electroencephalography (EEG) background activity is associated with neurological outcome in neonates with hypoxic-ischemic encephalopathy. There is uncertainty about the prognostic value of EEG background activity after hypothermia was introduced.
Searches were made on Pubmed, Embase, and the Cochrane Library, from inception to March 1, 2018. Pooled sensitivities and specificities were calculated to assess the diagnostic power of burst suppression, low voltage, and flat trace background activities in the prediction of an adverse neurological outcome in the follow-up period in hypothermia-treated neonates with hypoxic-ischemic encephalopathy. I² was used to assess heterogeneity, and meta-regression was done to explore the source of heterogeneity.
Eighteen studies with 940 neonates were included. Pooled sensitivities and specificities in predicting the combination of death and neurodevelopmental impairment were burst suppression (sensitivity 0.87 [95% confidence interval (CI) 0.79 to 0.93], specificity 0.60 [95% CI 0.44 to 0.74]), low voltage (sensitivity 0.84 [0.75 to 0.90], specificity 0.80 [0.58 to 0.92]), and flat trace (sensitivity 0.85 [0.75 to 0.92], specificity 0.94 [0.77 to 0.99]). Subgroup analysis revealed the sensitivities of background patterns obtained after 24 hours of life were higher than those within age 24 hours, whereas the specificities were just the reverse. Flat trace performed best on sensitivity 0.93 (0.60 to 0.99) and specificity 0.90 (0.64 to 0.98) in predicting death. Burst suppression demonstrated the highest sensitivity 0.87 (0.58 to 0.97) and flat trace performed best on specificity 0.85 (0.60 to 0.96) in predicting neurodevelopmental impairment.
EEG background activity is predictive of long-term neurological outcome in hypothermia-treated neonates with hypoxic-ischemic encephalopathy. Burst suppression, low voltage, and flat trace are potential predictors of death or neurodevelopmental impairment.
Electrocardiographic and echocardiographic changes during therapeutic hypothermia in encephalopathic infants with long-term adverse outcome
2018, Resuscitation
Citation Excerpt :
We found that the changes in the heart rate, RR and QTc intervals progressively returned to normal after 36 h of therapeutic hypothermia. These data can suggest a progressive recovery of the central nervous and cardiovascular system from the hypoxic ischaemic insult, as shown by Thoresen et al. and Gucuyener et al., who found that heart rate and amplitude-integrated electroencephalography gradually normalized during cooling [20,21]. The present study helps to better understand the hemodynamic changes in the HIE infants, who have long-term adverse outcome.
To assess the electrocardiography and echocardiography changes during therapeutic hypothermia and rewarming period in encephalopathic infants with long-term adverse neurological outcome.
Prospective multicentre longitudinal study. We included 64 consecutive infants with moderate or severe hypoxic ischaemic encephalopathy undergoing therapeutic hypothermia who had 18–24 month-outcome data. We analysed electrocardiography and heart rate changes before, during and after therapeutic hypothermia. Superior vena cava flow, left ventricular cardiac output and stroke volume were studied using echocardiography during and immediately after therapeutic hypothermia. An abnormal outcome was defined as death or moderate/severe disability at 18–24 months.
Neonates with higher superior vena cava flow pre-rewarming had signiﬁcantly higher odds of documented long-term adverse outcome when compared to newborns with good outcome (OR 1.57; 95%CI, 1.1–1.78; p = 0.01 after adjustment). QTc and RR intervals were significantly longer at 12, 24, 36 and 48 h in infants with good outcome compared with those with adverse outcome (p < 0.001). During therapeutic hypothermia, infants with poor outcome had a higher heart rate at 12, 24, 36, 48, 60 h after birth compared with those with good outcome (p < 0.001). From 36 h on, heart rate gradually increased and RR and QTc intervals progressively shortened with values back to normal after rewarming.
Infants with hypoxic ischaemic encephalopathy who have adverse neurological outcome show a preferential cerebral blood flow redistribution during therapeutic hypothermia. Infants with poor outcome have higher heart rate and shorter RR and QTc intervals during therapeutic hypothermia.
Evoked potentials predict psychomotor development in neonates with normal MRI after hypothermia for hypoxic-ischemic encephalopathy
2018, Clinical Neurophysiology
Citation Excerpt :
Reliable outcome measures at bedside in routine neonatal neurology are the severity scores of encephalopathy combined with EEG background activity, but prognosis remains uncertain in mild and moderate cases (Sarnat and Sarnat, 1976; Toet et al., 1999; van de Riet et al., 1999; Pressler et al., 2001; van Handel et al., 2007; Murray et al., 2010). Furthermore, after the introduction of TH, the prognostic role of EEG and clinical scores has been questioned (Thoresen et al., 2010; Hallberg et al., 2010; Gucuyener et al., 2012). In the attempt to improve prognosis, the evoked potentials (EPs) methodology has been successfully explored before and after the advent of TH (De Vries et al., 1991; Suppiej et al., 2010; Kontio et al., 2013; van Laerhoven et al., 2013).
To assess the prognostic role of evoked potentials (EP) in neonates with normal magnetic resonance imaging (MRI) after therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE).
Thirty-five neonates recruited for TH because of HIE, having normal neonatal MRI, performed neonatal somatosensory (SEP), visual (VEP) evoked potentials and electroencephalogram (EEG). The effect of SEP, VEP or EEG abnormalities on Griffith’s developmental scales at 12 and 24 months was measured; positive (PPV) and negative (NPV) predictive value, sensitivity, specificity and accuracy were calculated.
At 24 months, 28% had global psychomotor impairment and 57% had isolated impairments. VEP abnormality was associated with impaired hearing-language score (p = 0.002) and performance score (p < 0.0001). VEP achieved best PPV (0.91, 95% C.I. 0.62–0.99) and specificity (0.93, 95% C.I. 0.70–0.99). The combination of neurophysiological tests achieved the best NPV (0.85, 95% C.I. 0.58–0.96), sensitivity (0.90, 95% C.I. 0.70–0.97), overall accuracy (0.83, 95% C.I. 0.67–0.92).
Psychomotor sequelae may occur in survivors of neonatal HIE with normal MRI. VEP is the single best neurophysiological prognostic marker but the combination of neurophysiological tests has a better value.
When facing the challenge of neurodevelopmental prognosis in infants with normal MRI after TH, EPs are useful prognostic tools, complementary to EEG.
Amplitude-Integrated EEG and Its Potential Role in Augmenting Management Within the NICU
2018, Neurology: Neonatology Questions and Controversies
Electroencephalography (EEG) or amplitude-integrated EEG (aEEG) provides important information on brain function in newborns. It can detect subclinical seizures and assess the effect of antiepileptic medication, and the background activity provides information on the severity of encephalopathy or can be used to monitor brain maturation in preterm infants. Continuous EEG or aEEG monitoring is now used routinely in an increasing number of neonatal intensive care units. However, many aEEG/EEG readers are not confident in their ability to interpret the aEEG/EEG. In this chapter we provide an overview of the literature and discuss how aEEG can be used in the neonatal intensive care unit to improve care in newborns.

View all citing articles on Scopus

View full text

Original articleUse of amplitude-integrated electroencephalography (aEEG) and near infrared spectroscopy findings in neonates with asphyxia during selective head cooling