Amplitude-integrated Electroencephalography Research Articles

Trends in Amplitude-Integrated Electroencephalography in the Smallest Preterm Neonates.

Amplitude-integrated electroencephalography is increasingly used for the neuromonitoring of premature infants. However, it is still not clear how bioelectrical activity changes in the smallest gestational age newborns. The aim of our study was to evaluate the bioelectrical activity of amplitude-integrated electroencephalograms in premature newborns of different gestational age to assess how gestational age and postnatal age influence patterns of amplitude-integrated electroencephalograms and to test the hypothesis of whether the bioelectrical activity of the brain matures faster after the birth of premature newborns than in utero. We prospectively included infants born before 32 weeks of gestational age between June 2020 and July 2022. Serial recordings of amplitude-integrated electroencephalograms were performed at three time points of age (days 1-3, 13-15, and 27-29). Recordings were analyzed for background patterns, the onset and appearance of cyclicity, and lower amplitude border and bandwidth, which were used to derive a composite Burdjalov score. In total, 140 premature neonates were included in the study, and 112 of them completed the study. The median gestational age of the newborns enrolled in the study was 29 (27-30) weeks, and the mean weight was 1206 (350) g. Burdjalov scores increased with increasing gestational age. Higher scores were observed in every dimension of the amplitude-integrated electroencephalograms for newborns of lower gestational age when compared to newborns of higher gestational age of the same postmenstrual age. There was a significant correlation between gestational age and parameters of amplitude-integrated electroencephalograms at all time points. A higher gestational age has a positive effect on the bioelectrical activity of amplitude-integrated electroencephalograms. Increasing postnatal age affected amplitude-integrated electroencephalograms more than gestational age. Our hypothesis that the bioelectrical activity of the brain matures faster for premature newborns after birth than in the womb was confirmed.

A biochemical feedback signal for hypothermia treatment for neonatal hypoxic-ischemic encephalopathy: focusing on central nervous system proteins in biofluids.

Hypothermia has been widely used to treat moderate to severe neonatal hypoxic-ischemic encephalopathy (HIE), yet evaluating the effects of hypothermia relies on clinical neurology, neuroimaging, amplitude-integrated electroencephalography, and follow-up data on patient outcomes. Biomarkers of brain injury have been considered for estimating the effects of hypothermia. Proteins specific to the central nervous system (CNS) are components of nervous tissue, and once the CNS is damaged, these proteins are released into biofluids (cerebrospinal fluid, blood, urine, tears, saliva), and they can be used as markers of brain damage. Clinical reports have shown that CNS-specific marker proteins (CNSPs) were early expressed in biofluids after brain damage and formed unique biochemical profiles. As a result, these markers may serve as an indicator for screening brain injury in infants, monitoring disease progression, identifying damage region of brain, and assessing the efficacy of neuroprotective measures. In clinical work, we have found that there are few reports on using CNSPs as biological signals in hypothermia for neonatal HIE. The aim of this article is to review the classification, origin, biochemical composition, and physiological function of CNSPs with changes in their expression levels after hypothermia for neonatal HIE. Hopefully, this review will improve the awareness of CNSPs among pediatricians, and encourage future studies exploring the mechanisms behind the effects of hypothermia on these CNSPs, in order to reduce the adverse outcome of neonatal HIE.

Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas: a multicenter clinical research protocol

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.

Amplitude-integrated electroencephalography showed no differences in cerebral activity between preterm singletons and twins in the first 4 weeks of life.

Genetic influences on cerebral activity have been described previously, but data are scarce in preterms. We aimed to investigate whether a genetic influence causes amplitude-integrated electroencephalography (aEEG) signals to differ between singletons and twin preterm newborns. This was a retrospective single-centre study conducted at Innsbruck Medical University Hospital, Austria. Preterm infants born before 32 weeks of gestation between 6 November 2010 and 6 December 2022 were eligible for the study. The aEEG was analysed for the total maturation score, its component scores and the number of sleep-wake cycles per hour. We enrolled 240 preterm twin infants (57.5% male) with a mean gestational age of 30 (range: 24-32) weeks and a mean birth weight of 1324 (range: 600-2116) grams. We compared 240 singleton matched preterms. No differences were found between preterm singletons and twin preterm infants regarding the total maturation and component scores, or the number of sleep-wake cycles. aEEG showed no difference between monozygotic and dizygotic twins. Compared to singletons, twin infants born preterm showed no differences in aEEG signals in the first 4 weeks of life. Future studies should include more complex non-invasive functional neuroimaging methods to gain more insight into this important topic.

Early Brain Activity in Very Preterm Infants of Mothers with Gestational Diabetes Mellitus: A Pilot Study

Introduction: Neurological consequences of preterm infants born to mothers with gestational diabetes mellitus (GDM) are unclear. In this pilot study, we investigated the effect of GDM on brain activity in very preterm infants. Methods: Preterm infants <32 gestational weeks of mothers with GDM compared to gestational age- and sex-matched controls born between 2011 and 2018 were included. Amplitude-integrated electroencephalography (aEEG) was assessed for total maturation and individual component scores according to Burdjalov and colleagues, the dominating visual background, and the presence of sleep-wake cycles per hour in the first 72 h of life and weekly at days 7, 14, 21, and 28. Results: We included 47 infants of mothers with GDM and 94 control infants. Both the aEEG total maturation score and its individual component scores, as well as the percentage of continuous background pattern, increased equally during the first 4 weeks after birth in both groups. GDM-exposed infants showed a slightly but significantly higher number of sleep-wake cycles per hour. Conclusion: We found normal maturation of brain activity in the first 4 weeks after birth in very preterm infants born to mothers with GDM, not differing from a very preterm control group. The higher number of sleep-wake cycles per hour in GDM-exposed infants could indicate transiently enhanced maturation. Further studies on brain activity and brain development in very preterm infants of mothers with GDM are needed to validate our results.

Association Between Seizures and Neurodevelopmental Outcome at Two and Five Years in Asphyxiated Newborns With Therapeutic Hypothermia

ObjectiveTo investigate the association between the presence and severity of seizures in asphyxiated newborns and their neurodevelopmental outcome at ages two and five years. MethodsRetrospective data analysis from a prospectively collected multicenter cohort of 186 term-born asphyxiated newborns undergoing therapeutic hypothermia (TH) in 11 centers in the Netherlands and Belgium. Seizures were diagnosed by amplitude-integrated electroencephalography (EEG) and raw EEG signal reading up to 48 hours after rewarming. Neurodevelopmental outcome was assessed by standardized testing at age two and five years. Primary outcome was death or long-term neurodevelopmental impairment (NDI) including cerebral palsy. Associations were calculated using univariate and multivariate logistic regression analyses adjusting for Thompson score and a validated brain magnetic resonance imaging (MRI) score. ResultsSeventy infants (38%) had seizures during TH or rewarming, and 44 (63%) of these needed two or more antiseizure medications (ASMs). Overall mortality was 21%. Follow-up data from 147 survivors were available for 137 infants (93%) at two and for 94 of 116 infants (81%) at five years. NDI was present in 26% at two and five years. Univariate analyses showed a significant association between seizures and death or NDI, but this was no longer significant after adjusting for Thompson and MRI score in the multivariate analysis; this was also true for severe seizures (need for two or more ASMs) or seizures starting during rewarming. ConclusionThe presence or severity of seizures in newborns undergoing TH for hypoxic-ischemic encephalopathy was not independently associated with death or NDI up to age five years after adjusting for several confounders.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderateand severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

APPLICATION OF AMPLITUDE-INTEGRATED ELECTROENCEPHALOGRAPHY IN PATIENTS OF NEONATAL INTENSIVE CARE UNITS

Intriduction. Amplitude-integrated electroencephalography is a technique for monitoring continuous cerebral function, when electroencephalographic signal is filtered, scaled and compressed in time.&#x0D; Objective of the study is to elucidate peculiarities of interpreting findings of the amplitude-integrated electroencephalography in patients of neonatal intensive care units, and represent a clinical case of establishing diagnosis by using the amplitude-integrated electroencephalography for a critically sick neonate.&#x0D; Materials and methods. A comprehensive literature review was conducted across international and national databases, including Elsevier, PubMed, Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Google Scholar, covering the period from 2019 to 2023. The search focused on the keywords "amplitude-integrated electroencephalography" and/or "aEEG" and "neonates" and/or "term infants" and/or "preterm infants." The clinical case presented took place at the neonatal intensive care unit of the Maternity Home "Central Municipal Clinical Hospital", Chernivtsi, Ukraine. Permission for publication was obtained from both parents of the child.&#x0D; Results. The main indications for conducting the amplitude-integrated electroencephalography in neonates include the assessment of the cerebral function and the degree of cerebral damage with hypoxic-ischemic encephalopathy or asphyxia at birth (often combined with therapeutic hypothermia); assessment of sleep-wake cycle; identification of seizures; assessment of cerebral function maturity in preterm neonates.&#x0D; The underlying cerebral activity is estimated according to the amplitude-integrated electroencephalography findings by means of a simple recognition of visual images corresponding to the five main patterns: Continuous Normal Voltage, Discontinuous Normal Voltage, Burst Suppression, Low Voltage, and Flat Trace. A typical neonatal single seizure fit on the amplitude-integrated electroencephalography looks like a “hump” or lower edge elevation interrupting the background recording. Repeated fits (epileptic status) look like a “saw” of repeated “humps”, one of each represents one attack. The article presents a clinical case of the diagnostic search in the neonate with congenital pneumonia and development of multiple organ failure syndrome including seizure syndrome. Clinical tonic-clonic seizures of the infant were associated with electroencephalographic criteria of status epilepticus both on the amplitude-integrated electroencephalography (repeated symmetrical elevations of the lower edge in the left and right) and on the standard electroencephalography (different variations of seizure graphic elements in the right and left). Considering the results of the clinical and instrumental examination, an adequate anticonvulsant therapy was administered.&#x0D; Conclusions. Continuous recording of the video-amplitude-integrated electroencephalography and standard electroencephalography in infants from the risk group is a good strategy of the neurological status effective monitoring. It enables to assess the underlying cerebral electric activity and it maturity, diagnose seizures and manage anticonvulsant therapy correctly. An adequate training of the staff who are at the patient’s bedside 24/7 is an important part of the interdisciplinary collaboration which is essential for a safe and effective management of patients in the neonatal intensive care units, prevention of early complications and disability in the future.

Efficacy of Levetiracetam as Add-On Therapy in the Treatment of Seizures in Neonates

Introduction: There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy of add-on therapy with LEV for achieving >80% seizure reduction after phenobarbital (PB) treatment. Methods: Retrospective cohort study of near term neonates admitted to the neonatal intensive care unit with EEG-confirmed seizures despite treatment with PB as first-line therapy and using LEV as 2nd-, 3rd- or 4th-line treatment. Antiseizure medication was administered according to national guidelines. All neonates were monitored with 2-channel amplitude-integrated electroencephalography. The total seizure burden in minutes, 2 h before and 4 h after administration of LEV, was calculated using raw EEG. Primary outcome was the efficacy of LEV in achieving >80% seizure reduction. The efficacy of additional midazolam (MDZ) and lidocaine (LDC) was also calculated. Results: A total of 47 full-term neonates were included. The mean total loading dose of LEV was 40 mg/kg (36–44 mg/kg). Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 11), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 8), genetic (n = 8), metabolic disorders (n = 3), and unknown (n = 1). Following LEV administration, >80% seizure reduction was observed in 17% (8/47) of neonates, whereas it was 23% (6/26) after MDZ and 92% (23/25) after LDC administration. Discussion: Although the cumulative loading dose of LEV was low and the group of infants studied was heterogeneous, the efficacy of LEV as add-on therapy for the treatment of seizures in neonates was limited. The highest seizure reduction rate was seen after LDC administration.

The Association of Therapeutic Hypothermia With Seizure Burden in Neonates With Hypoxic-Ischemic Encephalopathy

ObjectivesTo compare seizure burden between newborn infants treated with therapeutic hypothermia (TH) and those that were not and to compare the need for antiseizure medications (ASM) in a cohort of infants who were diagnosed with neonatal hypoxic-ischemic encephalopathy (HIE). MethodsThis was a retrospective cohort study on infants born after 35 weeks’ gestation, diagnosed with moderate to severe HIE, monitored with amplitude-integrated electroencephalography (aEEG) and eligible for TH. Infants born before the implementation of TH in 2008 were compared with infants born thereafter who received TH. Seizure burden was assessed from aEEG as total time in minutes of seizures activity per hour of recording. Other clinical and demographic data were retrieved from a prospective local database of infants with HIE. ResultsOverall, 149 of 207 infants were included in the study: 112 exposed to TH and 37 not exposed. Cooled infants had a lower seizure burden overall (0.4 vs 2.3 min/h, P < 0.001) and were also less likely to be treated with ASM (74% vs 100%, P < 0.001). In multivariable regression models, not exposed to TH, having a depressed aEEG background, and having higher Apgar scores were associated with higher seizure burden (incidence rate ratio: 4.78 for noncooled infants, P < 0.001); also, not exposed to TH was associated with a higher likelihood of multidrug ASM (odds ratio: 4.83, P < 0.001). ConclusionsTH in infants with moderate to severe HIE is associated with significant reduction of seizure burden and ASM therapy.

Relationship between Brain Function and Microstructural Brain Maturation in Preterm Infants

Introduction: Preterm infants are at risk for impairment in brain maturation at term equivalent age (TEA). Diffusion tensor imaging (DTI) is a powerful magnetic resonance imaging (MRI) technique, quantitatively reflecting microstructural brain development of white matter regions with parameters such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Amplitude-integrated electroencephalography (aEEG) assesses electrocortical activity and brain function. Methods: Aim of this study was to investigate a possible correlation between functional and microstructural brain maturation using neonatal aEEG and DTI-MRI at TEA. The study was conducted as a retrospective single-center study in 446 infants born below 32 gestational weeks. Spearman rank’s correlation coefficients were calculated between aEEG (total maturation score) and FA/ADC value. To compare aEEG and DTI-MRI to neurodevelopmental outcome at 24 months of corrected age, we performed a multivariate linear regression analysis. Results: Analysis showed an all-time significant correlation between total maturation score and FA/ADC values of the corpus callosum at TEA with the strongest correlation at day 2, day 3, week 3, and week 4. After including perinatal variables in the model, this correlation remained highly significant at day 2 and 3. When comparing the association of aEEG and DTI-MRI to outcome, both the total maturation score at day 2, day 3, and FA/ADC of the splenium of the corpus callosum showed a significant correlation. Conclusion: This study indicates that early monitoring of functional brain maturation may predict later assessment of microstructural brain development of corpus callosum in preterm infants with a relation to neurodevelopmental outcome.

No neuroprotective effect of therapeutic hypothermia following lipopolysaccharide-sensitized hypoxia-ischemia: a newborn piglet study

IntroductionTherapeutic hypothermia is the only proven neuroprotective treatment for hypoxic-ischemic encephalopathy. However, studies have questioned whether therapeutic hypothermia may benefit newborns subjected to infection or inflammation before a hypoxic-ischemic insult. We aimed to compare newborn piglets with lipopolysaccharide-sensitized hypoxia-ischemia treated with and without therapeutic hypothermia with regards to measures of neuroprotection.MethodsA total of 32 male and female piglets were included in this randomized experimental study. Lipopolysaccharides from Escherichia coli were infused intravenously before initiation of a standardized global hypoxic-ischemic insult. The piglets were then randomized to either normothermia or therapeutic hypothermia. After 14 h, the piglets were evaluated. Our primary outcome was brain lactate/N-acetylaspartate ratio assessed by magnetic resonance spectroscopy. Secondary outcomes included measures of magnetic resonance imaging, amplitude-integrated electroencephalography, immunohistochemistry, and concentration of blood cells and cytokines.ResultsPiglets treated with and without therapeutic hypothermia were subjected to comparable global hypoxic-ischemic insults. We found no difference between the two groups with regards to measures of magnetic resonance spectroscopy and imaging, amplitude-integrated electroencephalography, immunohistochemistry, and concentration of blood cells and cytokines.ConclusionWe found no indication of neuroprotection by therapeutic hypothermia in newborn piglets following lipopolysaccharide-sensitized hypoxia-ischemia. However, interpretation of the results is limited by the short observation period. Further studies are required to determine the potential clinical implications of these findings.

Multisensory stimulation bundles on sleep and neurobehavioral development in the first year after birth in very preterm infants: a randomized crossover controlled study protocol

BackgroundDisrupted sleep is believed to contribute to short- and long-term neurodevelopmental problems in very preterm infants (VPIs). This study presents a protocol for an evaluator-blinded, randomized crossover trial. It aims to assess the sleep efficiency of hospitalized VPIs by providing multisensory stimulation bundles. Furthermore, it aims to observe the intervention impacts on sleep during hospitalization of the VPIs and their sleep and neurodevelopmental outcomes during the first year of post-discharge follow-up.MethodsThe study will be conducted in the neonatology department of a tertiary pediatric teaching hospital. All the eligible VPIs will undergo two types of care in random order: “standard care” (2 weeks) and “standard care plus multisensory stimulation bundles,” each lasting 2 weeks. A generated list of random numbers will be used for case sequence allocation. Sleep outcomes will be evaluated using the Actiwatch-2 Actigraph. Moreover, the amplitude-integrated electroencephalography and the Griffiths Mental Development Scales will be used to measure the neurodevelopmental outcomes during hospitalization and in the first year of follow-up of the VPIs.DiscussionThe intervention protocol of this study differs from that of other traditional interventions by producing precise and consistent supportive stimulations, similar to maternal tactile, auditory, posture, and visual effects for hospitalized VPIs. This protocol could be an effective measure to facilitate sleep and early neurodevelopment of VPIs. The expected outcomes will help confirm the implementation and generalization of the multisensory stimulation bundles’ care protocol in neonatology departments. We expect that the study will positively impact hospitalized VPIs, especially in their sleep and early neurodevelopmental outcomes. It will also provide a new perspective regarding parent and infant interaction strategies, particularly for newborn intensive care units that limit visits because of the global spread of COVID-19.Trial registrationChinese Clinical Trial Registry ChiCTR 2200059099. Registered on 25 April 2022, https://www.chictr.org.cn/showproj.html?proj=166980; the Hospital Research Ethics Committee (approval number: SCMCIRB-K2021086-1, Version 01), approved on 21 January 2022.

Remote Monitoring for Seizures During Therapeutic Hypothermia in Neonates With Hypoxic-Ischemic Encephalopathy

Neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) frequently experience seizures, which are associated with adverse outcomes. Efforts to rapidly identify seizures and reduce seizure burden may positively change neurologic and neurodevelopmental outcomes. To describe the onset, treatment, and evolution of seizures in a large cohort of newborns with HIE during TH assisted by a telehealth model and remote neuromonitoring approach. This was a prospective, observational, multicenter cohort study performed between July 2017 and December 2021 in 32 hospitals in Brazil. Participants were newborns with HIE meeting eligibility criteria and receiving TH. Data were analyzed from November 2022 to April 2023. Infants with HIE receiving TH were remotely monitored with 3-channel amplitude-integrated electroencephalography (aEEG) including raw tracing and video imaging, and bedside clinicians received assistance from trained neonatologists and neurologists. Data on modified Sarnat examination, presence, timing and seizure type, aEEG background activity, sleep-wake cycling, and antiepileptic drugs used were collected. Descriptive statistical analysis was used with independent t test, χ2, Mann-Whitney test, and post hoc analyses applied for associations. A total of 872 cooled newborns were enrolled; the median (IQR) gestational age was 39 (38-40) weeks, 518 (59.4%) were male, and 59 (6.8%) were classified as having mild encephalopathy by modified Sarnat examination, 504 (57.8%) as moderate, and 180 (20.6%) as severe. Electrographic seizures were identified in 296 newborns (33.9%), being only electrographic in 213 (71.9%) and clinical followed by electroclinical uncoupling in 50 (16.9%). Early abnormal background activity had a significant association with seizures. Infants with flat trace had the highest rate of seizures (58 infants [68.2%]) and the greatest association with the incidence of seizures (odds ratio [OR], 12.90; 95% CI, 7.57-22.22) compared with continuous normal voltage. The absence of sleep-wake cycling was also associated with a higher occurrence of seizures (OR, 2.22; 95% CI, 1.67-2.96). Seizure onset was most frequent between 6 and 24 hours of life (181 infants [61.1%]); however, seizure occurred in 34 infants (11.5%) during rewarming. A single antiepileptic drug controlled seizures in 192 infants (64.9%). The first line antiepileptic drug was phenobarbital in 294 (99.3%). In this cohort study of newborns with HIE treated with TH, electrographic seizure activity occurred in 296 infants (33.9%) and was predominantly electrographic. Seizure control was obtained with a single antiepileptic drug in 192 infants (64.9%). These findings suggest neonatal neurocritical care can be delivered at remote limited resource hospitals due to innovations in technology and telehealth.

Distinctive Amplitude-Integrated EEG Ictal Pattern and Targeted Therapy with Carbamazepine in KCNQ2 and KCNQ3 Neonatal Epilepsy: A Case Series.

Carbamazepine (CBZ) is effective in treating KCNQ2/3-related seizures, which may present with a distinctive amplitude-integrated electroencephalography (aEEG) pattern. To assess how improved recognition of the distinctive aEEG ictal pattern associated with KCNQ2/3 variants has enabled early and effective targeted therapy with CBZ. Retrospective descriptive study of five neonates with KCNQ2/3 pathogenic gene variants admitted at a level 3 neonatal intensive care unit (NICU) over an 8-year period. The distinctive ictal aEEG pattern was recognized in four neonates after an average of 61.5 hours (minimum 12 hours, maximum 120 hours) from the first electroclinical seizure and prompted the use of CBZ that was effective in all. The two most recently diagnosed patients could avoid polytherapy as they received CBZ as the first and second antiseizure medication, respectively. Three out of five patients with continuous normal voltage (CNV), sleep-wake cycling (SWC), and shorter postictal suppression had normal neurodevelopmental outcome. Regarding the remaining two infants, one was not trialed with CBZ and had a high seizure burden, both presented with a prolonged postictal suppression, no SWC, and had moderate-to-severe developmental delay. Genetic results became available after the neonatal period in all but one of the infants, who had a prenatal diagnosis. Recognition of the distinctive ictal aEEG pattern in the NICU allowed early and effective targeted therapy with CBZ in four neonates, well before genetic results became available. Furthermore, a CNV background pattern with SWC and short postictal suppression were associated with normal developmental outcomes.

Association of aEEG and brain injury severity on MRI at term-equivalent age in preterm infants.

Measures to detect and monitor brain injury in preterm infants are amplitude-integrated electroencephalography (aEEG) and magnetic resonance imaging (MRI). To investigate the association between aEEG and MRI in a large cohort of preterm infants. Five hundred and twenty-three preterm infants were included in the study. AEEG was interpreted for the total maturation score (TMS) according to Burdjalov. Cerebral MRI was evaluated using a validated scoring system by Kidokoro. One hundred and forty-six infants (27.9%) showed some form of brain injury, with 111 infants (21.2%) showing mild injury and 35 (6.7%) showing severe injury. TMS were significantly higher in infants without injury compared to severe injury. When comparing infants with isolated intraventricular haemorrhage to infants without brain injury, TMS were significantly lower. Prediction of adverse outcome is an important aspect of neonatal care. The combination of diagnostic measures evaluating brain injury might enhance our abilities in neonatal care to provide accurate information about later outcome. Early aEEG is predictive for the severity of brain injury detected by MRI at term-equivalent age. Whether aEEG is also predictive for neurodevelopmental outcome needs to be further investigated in relation to the various patterns of preterm brain injury.

Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.

Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs. Midazolam and phenobarbital as anti-epileptics were evaluated with a systematic literature search on neonatal pharmacokinetic (PK) and/or pharmacodynamic [PD, (amplitude-integrated) electroencephalography effect] studies. With the GAPPS system, two evaluators graded the current level of evidence. Inter-rater agreement was assessed for dosing evidence score (DES), quality of evidence (QoE), and strength of recommendation (REC). Seventy-two studies were included. DES scores 4 and 9 were most frequently used for PK, and scores 0 and 1 for PD. Inter-rater agreements on DES, QoE, and REC ranged from moderate to very good. A final REC was provided for all PK studies, but only for 25% (midazolam) and 33% (phenobarbital) of PD studies. There is a reasonable level of evidence concerning midazolam and phenobarbital PK in neonates, although using a predefined target without integrated PK/PD evaluation. Further research is needed on midazolam use in term neonates with therapeutic hypothermia, and phenobarbital treatment in preterms. There is a reasonable level of evidence concerning pharmacotherapy of midazolam and phenobarbital in neonates. Most evidence is however based on PK studies, using a predefined target level or concentration range without integrated, combined PK/PD evaluation. Using the GAPPS system, final strength of recommendation could be provided for all PK studies, but only for 25% (midazolam) to 33% (phenobarbital) of PD studies. Due to the limited PK observations of midazolam in term neonates with therapeutic hypothermia, and of phenobarbital in preterm neonates these subgroups can be identified for further research.

Nurses’ experiences and perspectives on aEEG monitoring in neonatal care: A qualitative study

PurposeThis study aimed to gather nurses’ experiences and perspectives regarding the amplitude-integrated electroencephalogram (aEEG) monitoring system in neonatal intensive care units (NICUs) and to explore potential avenues for future improvements. Design and MethodsThis study employed a descriptive qualitative design. Semi-structured interviews were conducted with 20 nurses from the level-III NICU of a Dutch medical center. The collected interview data were analyzed using thematic analysis. ResultsSeven main themes emerged: training in aEEG monitoring, proficiency in aEEG electrode placement and pattern interpretation, usual practices of using aEEG, neonatologist-nurse cooperation on aEEG, the performance of the automated seizure detection software, the usefulness of aEEG monitoring in the NICU, and feedback about the current aEEG monitoring system. ConclusionsNurses confirmed that aEEG is a valuable tool for cerebral function monitoring in the NICU; however, improvements are necessary. For better utilization of aEEG in the NICU, it is recommended to enhance nurses’ aEEG knowledge and skills and apply state-of-art techniques to improve the monitoring system. Practice implicationsTo enhance the aEEG knowledge of NICU nurses, we suggest introducing structured training programs, conducting routine case-centered discussions, and creating readily available reference resources. To optimize the aEEG monitoring system, it is essential to incorporate innovative electrodes, provide remote accessibility, integrate advanced algorithms, and develop an intuitive graphical user interface.

A preliminary study on a new method for evaluating brain maturation in preterm infants

To establish a new method for evaluating the brain maturation of preterm infants based on the features of electroencephalographic activity. A prospective study was conducted on the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) recordings within 7 days after birth of preterm infants who had a postmenstrual age (PMA) of 25-36 weeks and met the inclusion criteria. The background activity of aEEG+conventional electroencephalography (cEEG) was scored according to the features of brain maturation as a new evaluation system and was compared with the aEEG evaluation system. The correlations of the evaluation results of the two methods with gestational age (GA), PMA, and head circumference were evaluated. The intervals of the total scores of aEEG+cEEG and aEEG were calculated for preterm infants with different PMAs and were compared between groups. The consistency of the new scoring system was evaluated among different raters. A total of 52 preterm infants were included. The total scores of aEEG+cEEG and aEEG were positively correlated with GA, PMA, and head circumference (P<0.05), and the correlation coefficient between the total scores of the two systems and PMA and GA was >0.9. The normal score intervals for aEEG+cEEG and aEEG scoring systems were determined in preterm infants with different PMAs as follows: infants with a PMA of less than 28 weeks had scores of 13.0 (11.0, 14.0) points for aEEG+cEEG and 6.0 (4.0, 7.0) points for aEEG; infants with a PMA between 28 and 29+6 weeks had scores of 16.0 (14.5, 17.0) points for aEEG+cEEG and 8.0 (6.0, 8.0) points for aEEG; infants with a PMA between 30 and 31+6 weeks had scores of 18.0 (17.0, 21.0) points for aEEG+cEEG and 9.0 (8.0, 10.0) points for aEEG; infants with between 32 and 33+6 weeks had scores of 22.0 (20.0, 24.5) points for aEEG+cEEG and 10.0 (10.0, 10.8) points for aEEG; infants with a PMA between 34 and 36 weeks had scores of 26.0 (24.5, 27.5) points for aEEG+cEEG and 11.0 (10.0, 12.0) points for aEEG. There were significant differences in the total scores of aEEG+cEEG and aEEG among the different PMA groups (P<0.05). There was a high consistency between different raters when using the scoring system to evaluate the brain maturation of preterm infants (κ=0.86). The aEEG+cEEG scoring system established in this study can quantitatively reflect the brain maturation of preterm infants, with a good discriminatory ability between preterm infants with different PMAs and high consistency between different raters.

Amplitude-Integrated Electroencephalography Evolution and Magnetic Resonance Imaging Injury in Mild and Moderate to Severe Neonatal Encephalopathy.

This study aimed to describe the evolution of amplitude-integrated electroencephalography (aEEG) in neonatal encephalopathy (NE) during therapeutic hypothermia (TH) and evaluate the association between aEEG parameters and magnetic resonance imaging (MRI) injury. aEEG data of infants who underwent TH were reviewed for background, sleep wake cycling (SWC), and seizures. Conventional electroencephalography (cEEG) background was assessed from the reports. Discordance of background on aEEG and cEEG was defined if there was a difference in the severity of the background. MRI injury (total score ≥ 5) was assessed by using the Weeke scoring system. A total of 46 infants were included; 23 (50%) with mild NE and 23 (50%) with moderate to severe NE. Comparing mild NE with moderate to severe NE, the initial aEEG background differed with more mild being continuous (70 vs. 52%), with fewer being discontinuous (0 vs. 22%) and flat tracing (0 vs. 4%), whereas burst suppression (4 vs. 4%) and low voltage (26 vs. 18%) did not differ. There was a notably common discordance between the background assessment on cEEG with aEEG in 82% with continuous and 40% low voltage aEEG background. MRI abnormalities were identified in four infants with mild NE and seven infants with moderate to severe NE. MRI injury was associated with aEEG seizures in infants with moderate to severe NE. aEEG seizures are useful to predict MRI injury in moderate to severe NE infants. There is a large discrepancy between aEEG, cEEG, and MRI in neonates treated by TH. · MRI injury was identified in 29% of moderate NE infants and in 50% of severe NE infants.. · aEEG seizures were associated with MRI injury in the moderate to severe NE infants.. · MRI injury was identified in 16% infants with mild NE.. · Mild NE infants with normal aEEG were unlikely to have MRI injury.. · There was a large discrepancy between aEEG, cEEG, and MRI in infants treated by TH..