Current Pediatric Reviews - Volume 10, Issue 1, 2014

Conventional EEG is being used more frequently in NICUs in the U.S. with the advent of therapeutic hypothermia and 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 the digitization of EEG recordings and increasing interest in the neonatal brain. Continuous EEG monitoring is expanding the potential 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 progression of the EEG background after an acute insult can also increase its prognostic specificity and provide another immediate marker of NICU neurologic outcome. The future of EEG monitoring in the NICU holds many possibilities and may greatly advance the new field of neuroprotection in the NICU.

There is emerging recognition of the need for continuous long term electrographic monitoring of the encephalopathic neonate. While full-montage EEG with video remains the gold standard for monitoring, it is limited in application due to the complexity of lead application and specialized interpretation of results. Amplitude integrated EEG (aEEG) is derived from limited channels (usually C3-P3, C4-P4) and is filtered, rectified and time-compressed to serve as a bedside electrographic trend monitor. It’s simple application and interpretation has resulted in increasing use in neonatal units across the world. Validation studies with full montage EEG have shown reliable results in interpretation of EEG background and electrographic seizures, especially when used with the simultaneously displayed raw EEG trace. Several aEEG monitors are commercially available and seizure algorithms are being developed for use on these monitors. These aEEG monitors, complement conventional EEG and offer a significant advance in the feasibility of long term electrographic monitoring of the encephalopathic neonate.

Cranial ultrasonography (cUS) is a reliable tool to detect the most frequently occurring congenital and acquired brain abnormalities in full-term and preterm neonates. Appropriate equipment, including a dedicated ultrasound machine and appropriately sized transducers with special settings for cUS of the newborn brain, and ample experience of the ultrasonographist are required to obtain optimal image quality. When, in addition, supplemental acoustic windows are used whenever indicated and cUS imaging is performed from admission throughout the neonatal period, the majority of the lesions will be diagnosed with information on timing and evolution of brain injury and on ongoing brain maturation. For exact determination of site and extent of lesions, for detection 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 it should be used as the primary brain imaging modality in high risk neonates.

Neonatal encephalopathy is a neurological emergency with heterogeneous etiologies and several management challenges. Neonatal encephalopathy of hypoxic-ischemic origin is associated with high rate of neonatal morbidity and mortality, 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 patterns of brain injury have been recognized and in contemporary cohorts of newborns these patterns reflect different risk factors and 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 the assessment 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 neonatal brain injury and in providing quantitative biomarkers for prognostication. To better refine the prognostic value of these new imaging tools, standardization of protocols, imaging modalities and scan timing are needed across centers. It is hoped that these techniques will permit earlier identification of newborns at risk of neurodevelopmental impairment and complement ongoing trials of emerging therapies such as hypothermia and novel pharmacological agents with neuroprotective properties.

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

Despite improvements in neonatal care, survivors of preterm birth are still at a significantly increased risk of developing life-long neurological difficulties including cerebral palsy and cognitive difficulties. Cranial ultrasound is routinely used in neonatal practice, but has a low sensitivity for identifying later neurodevelopmental difficulties. Magnetic Resonance Imaging (MRI) can be used to identify intracranial abnormalities with greater diagnostic accuracy in preterm infants, and theoretically might improve the planning and targeting of long-term neurodevelopmental care; reducing parental stress 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 intracranial structures, thereby providing the means to develop sensitive biomarkers which may be predictive of later neurological impairment. However further work is needed to define the accuracy and value of diagnosis by MR and the techniques’s precise 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 this process by bridging the gap between histology (available from animal studies) and developmental outcome (available from 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, functional MRI, and quantitative metrics – further increase the sophistication of information available regarding both brain structure and function. In this review, we discuss the basics of these newer methods as well as their application to the study of premature infants.

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, it seems that neurobehavioral examinations may have become somewhat redundant in some nurseries. Yet these examinations remain an important part of clinical practice. They help to increase our understanding of an infant’s behavior, including their strengths and vulnerabilities, thus enabling us to adjust our care and parent education accordingly. These examinations also assist us to identify those most at risk of developmental disabilities, enabling further assessment and intervention 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 populations and all assessment purposes. Consequently, the clinician or researcher needs to choose the appropriate assessment depending on matters such as the infant’s gestation and the assessment’s goal and training requirements. Further research is needed to develop neurobehavioral assessment tools, particularly for extremely preterm infants, which are easily accessible in the clinical setting and can be used from birth.

The neurodevelopmental outcome of at-risk infants in the neonatal intensive care unit (NICU) is concerning despite steady improvement in the survival rate of these infants. Our current management is often complicated by delayed realization of cerebral deficits due to late manifestation and lack of effective screening tools and neuroimaging/monitoring techniques that are suitable for sick neonates at the bedside. Near infrared specstrocopy (NIRS) is a noninvasive, safe, and portable technique providing a wide range of cerebral hemodynamic contrasts for evaluating the brain. The current state of NIRS technology can be devided into three generations. The first generation represents conventional trend monitoring oximeters that are currently the most widely used in the clinical settings, while the second generation focuses on improving the 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 comparisons of brain oximetry and functions either at rest or in response to interventions. Successful integration of NIRS/DOI into the clinical setting requires matching the different capabilities of each instrument to specific clinical goals.