Current Pediatric Reviews (v.10, #1)

Conventional (Continuous) EEG Monitoring in the NICU by Taeun Chang, Tammy N. Tsuchida (2-10).
Conventional EEG is being used more frequently in NICUs in the U.S. with the advent of therapeutic hypothermiaand the growth of neurocritical care intensivists & units. Historical applications have included assessing encephalopathy,seizure evaluation and prognosis. Past reluctance or limitation of the use in the NICU are receding with thedigitization of EEG recordings and increasing interest in the neonatal brain. Continuous EEG monitoring is expanding thepotential for its application as a brain monitoring tool to stratify initial injury severity, monitor seizure response to treatment,and detect sentinel neurologic events in the NICU, in addition to guiding neurotherapeutic options. The progressionof the EEG background after an acute insult can also increase its prognostic specificity and provide another immediatemarker of NICU neurologic outcome. The future of EEG monitoring in the NICU holds many possibilities and maygreatly advance the new field of neuroprotection in the NICU.

Amplitude-Integrated EEG and the Newborn Infant by Divyen K. Shah, Amit Mathur (11-15).
There is emerging recognition of the need for continuous long term electrographic monitoring of the encephalopathicneonate. While full-montage EEG with video remains the gold standard for monitoring, it is limited in applicationdue to the complexity of lead application and specialized interpretation of results. Amplitude integrated EEG (aEEG) isderived from limited channels (usually C3-P3, C4-P4) and is filtered, rectified and time-compressed to serve as a bedsideelectrographic trend monitor. It's simple application and interpretation has resulted in increasing use in neonatal unitsacross the world. Validation studies with full montage EEG have shown reliable results in interpretation of EEG backgroundand electrographic seizures, especially when used with the simultaneously displayed raw EEG trace. SeveralaEEG monitors are commercially available and seizure algorithms are being developed for use on these monitors. TheseaEEG monitors, complement conventional EEG and offer a significant advance in the feasibility of long term electrographicmonitoring of the encephalopathic neonate.

Cranial Ultrasound - Optimizing Utility in the NICU by Gerda van Wezel-Meijler, Linda S de Vries (16-27).
Cranial ultrasonography (cUS) is a reliable tool to detect the most frequently occurring congenital and acquiredbrain abnormalities in full-term and preterm neonates.;Appropriate equipment, including a dedicated ultrasound machine and appropriately sized transducers with special settingsfor cUS of the newborn brain, and ample experience of the ultrasonographist are required to obtain optimal imagequality. When, in addition, supplemental acoustic windows are used whenever indicated and cUS imaging is performedfrom admission throughout the neonatal period, the majority of the lesions will be diagnosed with information on timingand evolution of brain injury and on ongoing brain maturation. For exact determination of site and extent of lesions, fordetection of lesions that (largely or partially) remain beyond the scope of cUS and for depiction of myelination, a single,well timed MRI examination is invaluable in many high risk neonates. However, as cUS enables bedside, serial imaging itshould be used as the primary brain imaging modality in high risk neonates.

Magnetic Resonance Imaging in the Encephalopathic Term Newborn by Vann Chau, Kenneth John Poskitt, Christopher Perry Dunham, Glenda Hendson, Steven Paul Miller (28-36).
Neonatal encephalopathy is a neurological emergency with heterogeneous etiologies and several managementchallenges. Neonatal encephalopathy of hypoxic-ischemic origin is associated with high rate of neonatal morbidity andmortality, and the long-term neurodevelopmental outcome of survivors with moderate to severe encephalopathy is poor.Magnetic resonance imaging now provides new insights on the diagnosis and prognosis of this condition. Typical patternsof brain injury have been recognized and in contemporary cohorts of newborns these patterns reflect different risk factorsand clinical presentation, as well as specific patterns of neurodevelopmental outcome. Magnetic resonance spectroscopy,diffusion-weighted imaging, and diffusion tensor imaging are advanced MR techniques that are increasingly used in theassessment of encephalopathic newborns, providing innovative perspectives on neonatal brain metabolism, microstructure,and connectivity. These techniques have been particularly helpful in elucidating the unique time course of neonatalbrain injury and in providing quantitative biomarkers for prognostication. To better refine the prognostic value of thesenew imaging tools, standardization of protocols, imaging modalities and scan timing are needed across centers. It is hopedthat these techniques will permit earlier identification of newborns at risk of neurodevelopmental impairment and complementongoing trials of emerging therapies such as hypothermia and novel pharmacological agents with neuroprotectiveproperties.

Neonatal brain injury remains a devastating condition, with poor outcomes despite the institution of an effectiveneuroprotective strategy of therapeutic hypothermia. There is an urgent need to develop additional neuroprotectivestrategies and to tailor our clinical predictive ability for families and their infants. Such goals could be more readilyachieved if reliable early clinical indicators or biomarkers existed. This review will explore the relation between magneticresonance (MR) imaging biomarkers and the degree of brain pathology observed in our translational piglet model of perinatalasphyxia. We also suggest biomarker relevance at a cellular level. The review will describe the development neededto optimize and simplify the use of biomarkers to speed up future trials of neuroprotection.

Magnetic Resonance Imaging of the Preterm Infant Brain by Valentina Doria, Tomoki Arichi, A. David Edwards (48-55).
Despite improvements in neonatal care, survivors of preterm birth are still at a significantly increased risk ofdeveloping life-long neurological difficulties including cerebral palsy and cognitive difficulties. Cranial ultrasound is routinelyused in neonatal practice, but has a low sensitivity for identifying later neurodevelopmental difficulties. MagneticResonance Imaging (MRI) can be used to identify intracranial abnormalities with greater diagnostic accuracy in preterminfants, and theoretically might improve the planning and targeting of long-term neurodevelopmental care; reducing parentalstress and unplanned healthcare utilisation; and ultimately may improve healthcare cost effectiveness. Furthermore,MR imaging offers the advantage of allowing the quantitative assessment of the integrity, growth and function of intracranialstructures, thereby providing the means to develop sensitive biomarkers which may be predictive of later neurologicalimpairment. However further work is needed to define the accuracy and value of diagnosis by MR and the techniques'sprecise role in care pathways for preterm infants.

Brain development and brain injury in preterm infants are areas of active research. Magnetic resonance imaging(MRI), a non-invasive tool applicable to both animal models and human infants, provides a wealth of information on thisprocess by bridging the gap between histology (available from animal studies) and developmental outcome (availablefrom clinical studies). Moreover, MRI also offers information regarding diagnosis and prognosis in the clinical setting.Recent advances in MR methods - diffusion tensor imaging, volumetric segmentation, surface based analysis, functionalMRI, and quantitative metrics - further increase the sophistication of information available regarding both brain structureand function. In this review, we discuss the basics of these newer methods as well as their application to the study ofpremature infants.

Neurobehavioral Evaluation in the Preterm and Term Infant by Nisha Brown, Alicia Spittle (65-72).
Neurobehavioral examinations of babies, both term and preterm, have been used in neonatology for many decades.However, with the advent of new technologies and, perhaps more “scientific” ways of assessing high risk infants, itseems that neurobehavioral examinations may have become somewhat redundant in some nurseries. Yet these examinationsremain an important part of clinical practice. They help to increase our understanding of an infant's behavior, includingtheir strengths and vulnerabilities, thus enabling us to adjust our care and parent education accordingly. Theseexaminations also assist us to identify those most at risk of developmental disabilities, enabling further assessment andintervention to be considered as early as possible. Whilst it remains a challenge to try and quantify neonatal neurobehavior,there are numerous tools available that can greatly assist us. This review did not find a tool that served all populationsand all assessment purposes. Consequently, the clinician or researcher needs to choose the appropriate assessment dependingon matters such as the infant's gestation and the assessment's goal and training requirements. Further research isneeded to develop neurobehavioral assessment tools, particularly for extremely preterm infants, which are easily accessiblein the clinical setting and can be used from birth.

The neurodevelopmental outcome of at-risk infants in the neonatal intensive care unit (NICU) is concerningdespite steady improvement in the survival rate of these infants. Our current management is often complicated by delayedrealization of cerebral deficits due to late manifestation and lack of effective screening tools and neuroimaging/monitoringtechniques that are suitable for sick neonates at the bedside. Near infrared specstrocopy (NIRS) is a noninvasive, safe, andportable technique providing a wide range of cerebral hemodynamic contrasts for evaluating the brain. The current state ofNIRS technology can be devided into three generations. The first generation represents conventional trend monitoringoximeters that are currently the most widely used in the clinical settings, while the second generation focuses on improvingthe quantitive accuracy of NIRS measurements by advanced optical techniques. The emergence of diffuse optical imaging(DOI) represents a third generation which opens up more potential clinical applications by providing regional comparisonsof brain oximetry and functions either at rest or in response to interventions. Successful integration of NIRS/DOIinto the clinical setting requires matching the different capabilities of each instrument to specific clinical goals.