Neonatal EEG Research Articles

Effects of morphine on the electroencephalograms of neonates: a prospective, observational study

Objectives: Although opiates have been reported to profoundly alter the EEG and cause seizures in full-term and premature newborn babies, no prospective study has systematically studied the effects of morphine on the EEG of normal neonates. Methods: A prospective observational study was conducted on 20 neurologically and metabolically normal newborn babies of ≥26 weeks post-conceptional age, with EEG recordings performed while on and off morphine infusions. Results: The recordings performed while the babies were on morphine were all abnormal; the principal abnormalities consisted of prolonged periods of electrical quiescence (PPEQs) and excessive interictal epileptiform activity. After the morphine was discontinued, the PPEQs resolved and the EEG background rhythms were normal for age, but 5 continued to have excessive sharp transients. All babies did well clinically and did not require anti-epileptic drug therapy. Conclusions: Morphine produces a profound, largely reversible alteration of all neonatal EEGs at various post-conceptional ages. The study has implications for caution in formulating conclusions regarding the clinical significance of EEGs of critically ill neonates on morphine infusions.

Duration of rhythmic EEG patterns in neonates: new evidence for clinical and prognostic significance of brief rhythmic discharges

Objective: This study aimed at identifying the characteristics – especially the duration – of rhythmic discharges in neonatal EEG, and their association with clinical neonatal problems. Specifically, we aimed at testing the diagnostic and prognostic validity of using 10 s as minimal duration for defining electroencephalographic seizures. Design and methods: The polysomnographies of 340 neonates were reviewed, and episodes of rhythmic discharges were identified, analyzed, and quantified. The study sample was divided into 3 groups: one in which the maximal duration of rhythmic discharges was shorter than 10 s (brief rhythmic discharges, BRD), a second one in which there were rhythmic discharges longer than 10 s (long rhythmic discharges, LRD), and finally a group in which no rhythmic discharge was found (No-RD). These 3 groups of subjects were compared for the baseline and outcome clinical data. Results: From the 340 neonates studied, 210 did not present any form of rhythmic discharge, 67 (19.7%) had only BRD episodes, and 63 (18.5%) had at least one LRD episode. Prevalence of rhythmic discharges was low among healthy full term newborns, and was significantly higher among preterm and high-risk newborns. Electrophysiological characteristics of rhythmic discharges did not differ between healthy neonates and high-risk ones. Accompanying clinical manifestations were present in 26.3% of the LRD group, but also in 15.9% of the BRD group. The presence of BRD was significantly associated with leukomalacia and with hypoglycemia in the cross-sectional analysis of baseline data, and with an increased risk for abnormal neurodevelopmental outcome after a mean follow-up period of 47 months (adjusted relative risk=4.90, P<0.01). Conclusions: The present data demonstrate an association between BRD and clinical history of hypoxic-ischemic encephalopathy, especially when complicated by leukomalacia, and also with a prognosis of increased risk for abnormal neurodevelopmental outcome. The clinical and prognostic significance of isolated BRD justifies the need to include these brief episodes in future studies of neonatal seizures.

Chapter 36 EEG in neonates. What does the neonatal EEG tell about prognosis?

Publisher Summary The prognosis of the child in the neonatal intensive care unit (NICU) is of paramount importance in the decision to continue or stop treatment. Reliable measures of psychomotor development in the far future are indispensable in such decisions. The electroencephalography (EEG) has the advantage that most technicians can easily apply the method, even in small children. EEG gives not only prognostic features but, in contrast to evoked potentials, gives information on epileptic discharges as well. This chapter discusses a study to evaluate neonatal EEG criteria that are widely used for the prediction of outcome. The study was performed in a large group of children born around term in which follow-up was sufficiently long to give insight into the final performance of the patients. EEGs were recorded on day 2 or 3 of life. Only in very exceptional cases was the EEG made in the first 24 hours of life. This was done only in those patients for whom (suspicion of) epileptic seizures urged early registration. Many children needed drug treatment, in particular anti-epileptic drugs. Blood levels of medication that might have sedative effects were measured. The follow-up of all patients was at least two years and up to six years. The children were regularly seen by a senior pediatrician or a child neurologist for at least the first two years of life. The psychomotor performance of the children was assessed.

Differences in the dynamics of frontal sharp transients in normal and hypoglycemic newborns

Objective: This study focuses on the characteristics of frontal sharp transients (FST), a normal variant of neonatal EEG, in newborns with hypoglycemia. Methods: The EEG from 20 newborns with symptomatic hypoglycemia were compared with a control group of normal newborns matched by conceptional age. The dynamics of these transients were evaluated concerning sleep stages. The density, type and bilateral synchrony of FST were also calculated. The results were compared in the two groups by Student's t test. Results: When compared with controls, hypoglycemic newborns have increased density of frontal sharp transients in all sleep stages but less bilateral synchrony ( P<0.05). FST density was even higher in small for gestational age newborns. Conclusions: The data suggests that normal patterns of neonatal EEG as FST can be influenced by systemic disturbances.

Neonatal EEG: a powerful tool in the assessment of brain damage in preterm infants.

Serial EEG recordings beginning immediately after birth are not only of great diagnostic and prognostic value but also useful to elucidate the timing and the mode of brain injuries in the preterm newborn. It is extremely useful to distinguish between acute stage and chronic stage EEG abnormalities. The former is characterized by findings of acute depression such as increased discontinuity, decreased faster frequency activities, and lowered amplitudes. The latter mainly includes dysmature patterns and disorganized patterns. The timing of brain insult can be assessed by considering EEG findings in relation to the time of birth. Different modes of brain injury are associated with different types of EEG abnormalities and different types of neurological outcome. Sudden strong brain insults are usually associated with findings of severe depression followed by disorganized pattern and later cerebral palsy, while persistent mild insults are usually associated with prolonged mild depression followed by dysmature pattern and later mental retardation. Routine serial EEG studies in preterm infants demonstrated that one fourth of cerebral palsies in these infants were of antenatal origin, two thirds of perinatal origin and postnatal injuries played the least role. Periventricular leucomalacia (PVL) manifesting itself on the ultrasound in the late neonatal period and suggesting postnatal origin was often found to be of antenatal origin with an EEG soon after birth. PVL without apparent causes was often associated with abnormal fetal heart rate patterns and early neonatal EEG abnormalities, and considered to have originated in the antepartum period.

Électroencéphalographie du nouveau-né prématuré et à terme. Aspects maturatifs et glossaire

From the first publication of C. Dreyfus-Brisac and N. Monod, a strong tradition combined with tremendous development of neonatal EEG has taken place in France. After 3 years of collaborative work, 12 clinical neurophysiologists trained at the Port-Royal medical school in Paris detail in this paper the currently available neonatal EEG recording techniques. They have synthesized the criteria of maturational state analysis and have defined the normal and pathological neonatal EEG patterns, including descriptions already present in the French as well as the English literature. In this review one may find a complete description of neonatal EEG patterns according to the states of vigilance and to gestational age. Furthermore, definitions of all normal and pathological patterns are provided in a glossary. Both chapters are illustrated by numerous figures. This detailed terminology in neonatal EEG should allow a better homogeneity in EEG reports, and could lead to multicentric studies on normal, unusual or pathological patterns, according to etiology. Although based on analogic EEG data, this work can equally be applied to digitized EEG tracings.

Adaptable Preprocessing Units and Neural Classification for the Segmentation of EEG Signals

In this contribution, a methodology for the simultaneous adaptation of preprocessing units (PPUs) for feature extraction and of neural classifiers that can be used for time series classification is presented. The approach is based upon an extension of the backpropagation algorithm for the correction of the preprocessing parameters. In comparison with purely neural systems, the reduced input dimensionality improves the generalization capability and reduces the numerical effort. In comparison with PPUs with fixed parameters, the success of the adaptation is less sensitive to the choice of the parameters. The efficiency of the developed method is demonstrated via the use of quadratic filters with adaptable transmission bands as preprocessing units for the segmentation of two different types of discontinuous EEG: discontinuous neonatal EEG (burst-interburst segmentation) and EEG in deep stages of sedation (burst-suppression segmentation).

Analysis of the interrelations between a low-frequency and a high-frequency signal component in human neonatal EEG during quiet sleep

It can be shown that dominant rhythmic signal components of neonatal EEG burst patterns (discontinuous EEG in quiet sleep) are characterised by a quadratic phase coupling (bispectral analysis). A so-called `initial wave' (narrow band rhythm within a frequency range of 3–12 Hz) can be demonstrated within the first part of the burst pattern. The detection of this signal component and of the phase coupling is more successful in the frontal region. By means of amplitude demodulation of the `initial wave' and a subsequent coherence analysis the phase coupling can be attributed to an amplitude modulation, i.e. the envelope curve of the `initial wave' shows for a distinct period of time the same qualitative course as the signal trace of a `lower' frequency component (0.75–3 Hz). The results were derived from six neonates (20 burst patterns for each neonate; 8 channel recordings).

Prognostic value of neonatal electroencephalography in premature newborns less than 33 weeks of gestational age

In a prospective study of 417 premature neonates born before 33 weeks' gestational age, neonatal tracings were reviewed to evaluate the use of EEG in prognosis of neurological injuries. The population was divided into two groups: Group 1, infants who died before the age of 1, and Group 2, survivors in which two categories of motor development were considered. Category A, were abnormal, and Category B, were always normal. Positive rolandic sharp waves (PRSW), which reflect white matter injury, occurred equally in both groups, indicating a similar incidence of white matter damage in Groups 1 and 2. In Group 2, there was a significant correlation of PRSW with developmental motor sequelae (Category A). A frequency of PRSW above 2/min (suggesting more severe periventricular white matter injury) and seizures were significantly more prevalent in Group 1 than in Group 2 and in Category A of Group 2 than in Category B. Background abnormalities occurred equally in both subgroups of extremely premature infants (≤28 weeks' gestation) they were significantly more numerous in the subgroup of very premature infants (between 28 and 33 weeks' gestation) who died, than in the subgroup of very premature infants who survived. This study shows the potential utility of using neonatal EEG in association with transfontanellar ultrasonography in anticipating the neurological development of very (>28 weeks' gestation) and extremely (≤28 weeks' gestation) premature newborns.

Polysomnographic quantification of bioelectrical maturation in preterm and fullterm newborns at matched conceptional ages

We analyzed the relationship between normal neonatal EEG features and gestational age and conceptional age, and evaluated the normal aspects of EEG maturation in preterm babies compared to term babies. We report 46 newborns, divided into two groups. Group I consisted of 11 newborns with gestational age between 30 and 32 weeks, followed with weekly polysomnograms until they reach 42 weeks' conceptional age. Group II (control) consisted of 35 newborns with gestational ages of 34 weeks (n = 5), 36 weeks (n = 10), 38 weeks (n = 10) and 40 weeks (n = 10) evaluated with one polysomnogram in their first 24–48 h of life. In each examination one 5 min epoch in REM and NREM sleep was analyzed to quantify the number of delta brushes, the presence of frontal and temporal sharp transients, the presence of delta frontal rhythmic activity, the grade of concordance between EEG patterns and sleep stages, the percent of interhemispheric synchrony and the duration of interburst interval. The age dependent variability of the EEG patterns was evaluated during the subsequent weeks with group comparisons at weeks 34, 36, 38 and 40. Our results show that the number of delta brushes and the duration of the interburst interval decrease as gestational and conceptional age increase. The percent of interhemispheric synchrony increases with gestational and conceptional age. The presence of frontal sharp transients and delta frontal rhythmic activity suggest that the newborn is fullterm. The presence of temporal sharp transients suggest a preterm newborn. The degree of concordance between behavioral sleep patterns and EEG was more helpful in recognizing sleep stages than in estimating gestational or conceptional age. Although the EEG patterns were comparable between the groups at the same age, analyses of the behavioral patterns of concordance in NREM sleep showed that newborns in Group I had a more immature behavior than newborns in Group II. Our results also suggest that extrauterine life of preterm babies does not seem to accelerate EEG maturation but may influence the acquisition of behavioral patterns during NREM sleep.

Correlation of EEG and cerebral perfusion studies (brain SPECT) in neonates undergoing ECMO therapy

Neuromagnetic fields were evoked by tactile stimuli and detected with a multi-channel biomagnetometer through 72 independent repetitive measurements on a single subject. Each measurement consisted of a somatosensory evoked response (N = 256 stimuli) using a single probe placement. These fields were then analyzed for source localization using an equivalent current dipole model and demonstrated highly reliable localization. The 3 major neuromagnetic somatosensory response components peaking at 35, 65 and 110 msec all localized to the same area of cortex. The relative contributions of intrinsic brain activity, habituation, probe placement, and choice of fiduciary points for headframe determination were quantified. Intrinsic factors were found to constitute the major source of inter-measurement error. Sources localized by magnetic source imaging (MSI) appeared valid relative to neuroanatomical estimation of the central fissure on MRI. Non-invasive presurgical biomagnetic localization of somatosensory cortex produces reliable and valid functional localizations which can be of potential value in risk assessment and may provide a useful guide for invasive functional mapping.

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<h3>SUMMARY</h3> Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex. <h3>HIGHLIGHTS</h3> Early development of human functional neural networks and oscillatory activity can be modeled <i>in vitro</i>. Cortical organoids exhibit phase-amplitude coupling between delta oscillation (2 Hz) and high-frequency activity (100-400 Hz) during network-synchronous events. Differential role of glutamate and GABA in initiating and maintaining oscillatory network activity. Developmental impairment of MECP2-KO cortical organoids impacts the emergence of oscillatory activity. Cortical organoid network electrophysiological signatures correlate with human preterm neonatal EEG features. <h3>eTOC</h3> Brain oscillations are a candidate mechanism for how neural populations are temporally organized to instantiate cognition and behavior. Cortical organoids initially exhibit periodic and highly regular nested oscillatory network events that eventually transition to more spatiotemporally complex activity, capturing features of late-stage preterm infant electroencephalography. Functional neural circuitry in cortical organoids exhibits emergence and development of oscillatory network dynamics similar to those found in the developing human brain.

The contribution of EEG to the understanding of neonatal seizures.

The neonatal EEG is a thread that has linked past and present studies of neonatal seizures that have emerged over the last several decades. Instead of experiencing a waning of value or interest, the neonatal EEG has grown in significance for characterization and quantification of seizures in the neonate. At present, it serves as the ideal theoretical end point of antiepileptic drug (AED) therapy and provides invaluable prognostic information in the analysis of its interictal EEG background. The needs of the near future are to learn the real behavior of the electrographic neonatal seizure (ENS) burden as it erupts on the scene of an acute encephalopathy. The response of the neonatal seizure burden to AED treatment requires careful quantitative description and reliable, automated ENS detection by cerebral function monitors, which are on the technologic horizon.

Estimation of gestational maturity of preterm infants by five fetal sonographic measurements compared with neonatal EEG and the last menstrual period

We previously reported no differences in estimates of gestational maturity between a cumulative score based on sonography/obstetrical measurements and an EEG interpretation for healthy preterm neonates. For the present study, a rank order among 5 fetal sonographic measurements was used to estimate gestational age: head circumference, transcerebellar diameter, biparietal diameter, femur length, and abdominal circumference were compared with an electroencephalographic estimate and an arithmetic estimate of maturity (i.e., the mother's last menstrual period). A fetal sonographic study for each of 13 premature neonates (i.e., born at < 32 weeks estimated gestational age) was followed after birth by a neonatal EEG recording. EEG and sonographic estimates of maturity were assigned without knowledge of other clinical data. The mother's last menstrual period was obtained from the medical record. Principal component analysis determined that 86% of the variance was evenly distributed over the 5 sonographic measurements. Using a regression procedure, 61 % of the variance (adjusted r 2 = 0.61) was explained by EEG when compared with fetal sonographic estimates. Only 19% (adjusted r 2 = 0.19) of the variance was explained by the estimate based on the mother's last menstrual period. Optimal subset selection determined that the rank order for prediction of gestational maturity among the fetal sonographic measurements was as follows: (1) head circumference; (2) transcerebellar diameter; (3) biparietal diameter; (4) femur length; (5) abdominal circumference. Cranial measurements on fetal sonography (i.e., head circumference, transcerebellar diameter, biparietal diameter) compared more closely with EEG estimates than non-cranial measurements (i.e., femur length and abdominal circumference). In conclusion, neonatal EEG estimates of gestational maturity compared more closely with sonographic measurements than estimates based on the time of the last menstrual period. These findings will be useful in situations when dates of conception are unknown or inaccurate, or when intrauterine growth restriction causes discrepancies in growth rates between cranial and non-cranial fetal measurements on sonography.

PS-60-5 Serial neonatal EEGs detect different types of brain injury in preterm infants

PS-60-5 Serial neonatal EEGs detect different types of brain injury in preterm infants

Serial neonatal EEG of infants undergoing ECMO therapy as a predictor of neurologic outcome

Serial neonatal EEG of infants undergoing ECMO therapy as a predictor of neurologic outcome

Somatosensory evoked potentials predict neurologic outcome in full‐term neonates with asphyxia

To investigate the ability of somatosensory evoked potentials (SSEP) to predict neurologic outcome in term neonates with birth asphyxia. Upper limb SSEP were performed on nine infants of 1-7 weeks of age who had perinatal asphyxia and an encephalopathy still present at 7 days of age. Comparison was made between the cranial ultrasound, electroencephalogram (EEG), SSEP and neurologic outcome at 9-36 months. Normal SSEP were found in four infants, all of whom were normal on neurologic follow up at 9-12 months. Neonatal EEG performed on two out of four of these infants were also normal, while cerebral oedema was seen on cranial ultrasound in three of the four studies. No SSEP response was seen initially in three infants, all of whom had adverse outcomes (one death, two with spastic diplegia). In contrast, their neonatal EEG had shown normal background rhythms, while two of the three cranial ultrasounds revealed oedema. For two infants the initial SSEP was absent over one hemisphere and just present over the other. Both children were abnormal on follow up at 10-12 months but did not have a hemiparesis. Upper limb SSEP appear more sensitive than EEG or cranial ultrasounds in predicting the short term neurologic outcome of neonates with asphyxia.

Evaluation of the Cerebro Trac 2500 for monitoring of cerebral function in the neonatal intensive care.

Assessment of brain function is important in predicting long term outcome in sick neonates thus stimulating increasing interest in methods of cerebral surveillance. A report using the Cerebro Trac 2500 in adult intensive care suggested this monitor may provide more information about ongoing cerebral activity than the Cerebral Function Monitor (CFM). Simultaneous recordings in a cross-section of the neonatal population were obtained with multichannel EEG monitor, CFM and Cerebro Trac. Both conventional EEG and CFM determined changes in sleep states and background activity. Seizures of greater than 30 seconds duration were detected by both analyzing monitors, although shorter duration transients were not apparent. Despite the apparent similarity in fixed filters in both CFM and Cerebro Trac, the Cerebro Trac seemed to filter out the lower frequencies that can predominate in the neonatal EEG. The Cerebro Trac did not confer any advantage over the CFM for neonatal cerebral surveillance.

THE EFFECT OF INOTROPIC THERAPY ON THE VERY PRETERM NEONATAL ELECTROENCEPHALOGRAM (EEG)

Computerized analysis of the neonatal EEG provides a measure of cerebral function in the very preterm infant. This method has enabled observation of the effects of inotropic infusions on cerebral function in 13 sick infants between 24 and 30 weeks gestation. Inotropes used included dopamine, dobutamine and nor-adrenaline, either singly or in combination as dictated by the clinicians. On commencement of inotropic therapy, no deterioration in EEG was seen and improvement was noted in only 3 of 18 occasions. Monitoring during a further 12 increases in inotropic therapy showed associated improvement in the EEG in only one of these occasions. However, on reduction of the inotropic treatment, which was no longer deemed clinically necessary, there was an associated improvement in EEG in 12 of 16 occasions monitored. The EEG improvement on reduction in inotropic therapy appeared to be related to the duration of use of inotropes and to tho duration of time normotension had been achieved. These results imply that withdrawal of inotropic therapy should perhaps be considered as soon as clinically feasible as this dolotorious effect of inotropic infusions on cerebral function may be related to enchanced cerebro-vascular sympatho-adrenal tone.

Predictive value of general movements in asphyxiated fullterm infants

The developmental course of spontaneous motility was investigated in a group of 26 fullterm infants, affected by mild to severe hypoxic-ischaemic encephalopathy. Serial 1-h videorecordings were carried out from birth to 15–22 weeks and a quality assessment of general movements (GMs) was made from a replay of the videos. Neurological follow-up of the infants were continued until at least 18 months of age; neonatal EEG and neuro-imaging techniques (US-scan, CT or MRI) were also carried out in all cases. The results indicate that perinatal asphyxia has important effects on the spontaneous motility of fullterm infants. Hypokinesis occurred very frequently during the first days of life, followed by a transient or prolonged (lasting longer than 15–22 weeks) abnormal quality of GMs. In the first 2 weeks the results of GM assessment did not correlate with the simultaneous findings of neurological examination, neuro-imaging and EEG, whereas they did when the results at 15–22 weeks were considered. The changes in spontaneous motility and especially GM developmental trajectories were good predictors of the neurological outcome. The predictive value of GM assessment was found to be similar to that of EEG and neuro-imaging, and better than neurological examination.