Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates

Abstract: Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. Impact: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication.For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury.Continuous multimodal monitoring as well as monitoring of sleep, sleep–wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care

The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group

Improvements in Neonatal Brain Monitoring after Perinatal Asphyxia

Perinatal hypoxic ischemic encephalopathy (HIE) is a major cause of morbidity and mortality world-wide. Common sequelae in survivors include cerebral palsy (CP), epilepsy and sensory as well as cognitive problems. The consequences of HIE impose significant long-term personal and financial burden on the affected families and the society. The most cost-effective approach to reducing neonatal mortality world-wide would be to improve access to antenatal care4. However, even in developed countries, the exact factors triggering perinatal asphyxia as well as the time of onset of brain injury are often difficult to determine, and it remains a major clinical problem. Seizures commonly occur in the neonate with HIE and are often the only sign of serious underlying brain dysfunction6. Animal studies have shown that neonatal seizures in the context of HIE may cause additional brain injury and that their pharmacological suppression may improve outcome9. Monitoring of brain function using the electroencephalogram (EEG), continuously or by serial EEGs is well-suited to give insight into brain function and its dynamic changes in neonatal HIE and helps to guide treatment as well as prognostication. A good understanding of the pathophysiology of HIE is needed not only in the selection of suitable diagnostic tests and treatment methods, but also to develop new therapeutic strategies

Amplitude-integrated EEG assists in detecting cerebral dysfunction in the newborn

Background: Amplitude-integrated encephalography (aEEG) in term-born encephalopathic infants has been shown to be predictive of later neurodevelopmental outcomes, but little is known about the mediating cerebral pathology. In addition, the aEEG is commonly used to monitor electrographic seizures in the newborn, an important manifestation of cerebral pathology, but there is limited data on it’s efficacy for this purpose. It’s clinical application in the preterm infant remains to be explored. Aim: The central aim of this thesis is to prove the hypothesis that the aEEG assists in detecting cerebral dysfunction in the newborn. Methods: 1) In a cohort of term-born infants with encephalopathy and/or seizures digital aEEG background measures of the lower and upper aEEG margins were related to a numeric MRI abnormality score. 2) In at-risk term newborns, the accuracy of two-channel digital aEEG monitoring was compared with continuous concurrent conventional EEG for seizure detection. 3) In preterm infants (gestation at birth < 30 weeks) aEEG measures of lower and upper margin collected in the first week of life were compared in infants with substantial cerebral abnormality to infants without. Results: 1) For all infants in the term cohort, the severity of abnormality of aEEG background was strongly related to severity of abnormality seen on cerebral MRI. 2) Using the aEEG pattern with the raw EEG signal, 76% of electrographic seizures were correctly identified in the term infants. 3) In the preterm cohort, the lower and upper aEEG amplitude margins increased significantly during the first week of life. In the presence of substantial cerebral abnormality, these margins were significantly depressed. Seizures were noted in the smaller and sicker, infants. Conclusion: The central hypothesis of this thesis, that the aEEG assists in detecting cerebral dysfunction in the newborn was proved

Analyzing autonomic activity in neonatal seizures

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 54-55).Recent studies suggest that seizures in the newborn occur more often than previously appreciated. The effect of neonatal seizures remain unclear, however. Do seizures in the newborn cause brain injury, are they a consequence of brain injury, or are they benign? Seizures in the newborn tend to occur without overt clinical correlates, such as convulsions, so their diagnosis requires electroencephalography (EEG). In this thesis, we investigate whether seizure activity is associated with changes in the discharge pattern of the autonomic nervous system, which could be picked up in heart rate (HR) or heart-rate variability (HRV) analysis. More fundamentally, we seek to investigate whether seizures in the neonate are confined to the cerebral cortex or whether they might originate from or propagate to deeper brain structures. Prior studies have provided some evidence that neonatal seizures can result in HR and HRV changes. From these past studies, there seems to be a heart-brain connection, however, this connection is currently poorly understood. Our long term goal is to understand the connection between electro-cortical activity, electro-cardiac activity, and brain injury in newborns with seizures. In this study, we analyzed the EEG and the electrocardiogram (ECG) signals in fourteen newborns with neonatal stroke and three newborns with hypoxemic-ischemic encephalopathy. Furthermore, we used information from magnetic resonance imaging and magnetic resonance spectroscopy reports to identify injury location in these full-term newborns. Our results indicate that some babies show strong changes in HR and HRV during seizure episodes while others tend to respond very weakly. Due to the small sample size of our patient population, no consistent picture emerged whether the location of injury might be responsible for this response pattern. We also explored a spectrogram-based method to determine the occurrence of seizure (on a lead-by-lead basis) and to determine seizure propagation from one region of the cortex to another.by Priya Ramaswamy.M.Eng

Clinicoradiological correlation in birth asphyxia

Background: Hypoxic Ischemic Encephalopathy (HIE) is the most dreaded neurological disease of the new-born. Assessment of severity of HIE would help proper parent counseling and early institution of stimulation therapy for better development of the infant.Methods: This study was conducted between December 2012 and May 2014. 37 term neonates with perinatal asphyxia were the subjects. The cranial ultrasound, EEG and MRI findings of these babies are analysed and correlated with each other and with clinical staging and the neurological condition of the babies at discharge.Results: Among the 37 neonates, 21 were of HIE stage 2 and 16 were of stage 3. Sensitivity of EEG in detecting abnormality in the neurological condition according to our study is 76.9%, specificity 87.5%, positive predictive value 76.9%, negative predictive value 87.5%. Sensitivity of severe pattern of injury in MRI brain in detecting abnormality in neurological condition according to our study is 76.9%, specificity 91.6%, positive predictive value 83.3%, negative predictive value 88%. Involvement of both basal ganglia and cortex in MRI brain had statistically significant correlation with abnormal neurological condition at discharge in our study (P = 0.04).Conclusion: An abnormal EEG and MRI brain in a term new-born with Hypoxic Ischemic Encephalopathy (HIE) is associated with poor neurological outcome. Involvement of basal ganglia/thalamus and cortex together in the MRI are predictors of abnormal outcome.

Study of symptomatic birth asphyxia : its immediate manifestations and long term significance

Despite improvement in healthcare during pregnancy and childbirth, intrapartum asphyxia remains a substantial problem. Mild degrees are common, producing signs of fetal distress during labour and temporary depression of vital function at birth, but, in the absence of neonatal sequelae, are generally benign without longer term implications. More severe degrees of intrapartum asphyxia may be followed by disturbances of function in many body systems, most notably the central nervous system; a situation referred to as symptomatic birth asphyxia. Although such disturbances are often transient, there is a risk of permanent neurological handicap in some cases. Acute, neonatal, neurological consequences of intrapartum asphyxia have long \s been recognised, but,in the literature, differences remain of the detailed neurological findings described, of the interpretation of their immediate significance and of the prognostic significance attributed to such neonatal findings. To look at these aspects, a prospective study of symptomatic birth asphyxia has been conducted. Fifty, mainly mature, infants were identified in the early hours of life by their fulfillment of preselected criteria of symptomatic birth asphyxia. Their general characteristics, antenatal and intrapartum factors, birth condition and the abnormalities of performance and behaviour which the infants displayed are reported. The infants'status over the early neonatal period, carefully assessed by repeated neurological examinations, appropriate investigation, and physiological recording of electroencephalograph, polygraph, and sucking and respiratory patterns, is described and illustrated. The majority of the children have been the subject of regular assessments to primary school age to determine their outcome. Three infants died in the first days of life and a fourth, who was severely brain damaged, in later infancy. Five children have significant handicap, seven mild degrees of neurological or developmental abnormality, while the remaining thirty-four children are considered normal. A number of neonatal events and findings correlated well with outcome. Indicators of condition at birth, the occurrence of apnoeic episodes, prolonged gasping respirations, a phase of apathy, tonic seizures, prolonged depression of feeding reflexes, hypothermia, and certain patterns of neurological abnormality - persistent hypotonia, marked extensor hypertonus with preceding and succeeding hypotonic phases, bulbar palsy and ophthalmo¬ plegia, all bore a highly significant relationship to poor outcome. Of these, the abnormalities of muscle tone and ophthalmoplegia correlated strongly with outcome; the consideration of additional, significant risk factors did not add to their predictive value

Investigation of cardiac dysfunction and hypoxaemia during epileptic seizures

Epileptic seizures are often un-witnessed and can result in hypoxic brain damage or can be fatal due to injuries, status epilepticus or sudden unexpected death in epilepsy (SUDEP). The first aim of this thesis was to investigate some of the physiological parameters that accompany an epileptic seizure and may be useful in a seizure alarm system. The second aim was to investigate aspects of cardiac dysfunction during clinical and sub-clinical seizures that may be potential contributing factors in SUDEP. Percentage heart rate change and oxygen saturation were studied prospectively during 527 epileptic seizures in 50 patients aged from one-day full term neonate to 60 years with a variety of seizure types (absences, generalised tonic clonic seizures, myoclonic seizures, tonic seizures and focal seizures) and in normal physiological events (e.g. coughing, turning in bed). Higher percentage heart rate change occurred during epileptic seizures (21.8%) than during normal physiological events (16.4%) p<0.001. Diagnostic testing of clinically significant seizures i.e seizures that could potentially lead to serious consequences if left undetected (n=61) had a sensitivity of 91% and specificity of 75% when percentage heart rate change and hypoxaemia parameters were combined. Percentage heart rate change and oxygen saturation could be used as reliable indicators of a seizure when set at specific levels and distinguish clinically significant seizures from normal physiological events. These parameters can now be used to develop a reliable alarm system to detect epileptic seizures at night. Prolongation of QTc and increased vagal tone may be possible mechanisms underlying SUDEP. Corrected Q-T cardiac repolarisation time 5 minutes before and throughout 156 epileptic seizures were analysed using four corrective formulae (Bazett, Hodge, Fridericia and Framingham). All formulae indicated statistically significant lengthening of the corrected Q-T during epileptic seizures (p<0.001) compared to pre-seizure values. All formulae agreed that the greatest lengthening of the corrected QT beyond normal limits occurred during right temporal lobe seizures in two patients. Reflex and tonic vagal activity utilising R-R intervals was assessed in 33 sub-clinical seizures occurring during stages 3 or 4 sleep and was compared to matched counts of R-R interval non-ictal baseline studies from the same stage of sleep in each patient. Altered vagal activity occurred during total sub-clinical seizures compared to baseline studies (p<0.001). Lengthening of the corrected Q-T and changes in cardiac vagal tone during epileptic seizures may have a role in the patho-physiology of SUDEP