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Inflammation and the Newborn Brain

INTRODUCTION A preponderance of clinical and experimental evidence suggests that systemic inflammation and its neurobiological consequences are involved importantly in brain injury and subsequent impairments of brain maturation in both term and preterm newborns, The central nervous system (CNS) is considered an immune-privileged site, although inflammation severely affects this privilege. In addition, peripheral and central immune signals can affect inflammatory responses within the CNS during the…

Pathophysiology: General Principles

Hypoxic-ischemic encephalopathy (HIE) in the perinatal period represents an important portion of neonatal neurology. To understand the features of HIE, which are discussed extensively in this unit, it is necessary to be cognizant of the physiological and biochemical derangements that lead to the structural and functional manifestations of this encephalopathy. In this chapter, we first deal with the major modes of cell death in the setting…

Neonatal Seizures

INTRODUCTION Seizures are distinctive and frequent manifestations of neurological disease in the neonatal period. The incidence of seizures varies with gestational age and birth weight. Estimated incidences range from 5 to 15/1000 live births in very-low-birth-weight infants to 1 to 3.5/1000 live births in term infants. Compared with seizures at later developmental stages, seizures in the newborn differ in clinical appearance, electroencephalographic (EEG) characteristics, etiologies, management,…

Neurodevelopmental Follow-Up of High-Risk Newborns

INTRODUCTION Though progress in newborn medicine since the 1960s has led to the dramatic increase of survival in treated patients, it may be offset by an increase in neurodevelopmental impairments in these patients. Moreover, these developmental issues are not always evident in the neonatal period but appear throughout the first year of life as neuromotor deficits or later in childhood as cognitive, educational, and socioemotional deficits.…

Specialized Neurological Studies

CEREBROSPINAL FLUID EXAMINATION Examination of the cerebrospinal fluid (CSF) is an important part of the evaluation of a wide variety of neurological disorders, as noted in appropriate chapters throughout this book. In this section, we focus principally on normal CSF in the newborn, particularly the newborn considered at high risk for such neurological disorders. The principal components of the CSF examination include measurement of intracranial pressure,…

Neurological Examination: Normal and Abnormal Features

INTRODUCTION The neurological evaluation of the newborn comprises, as it does at other ages in pediatric medicine, the history, physical examination, and appropriate specialized studies. Appropriate neurodevelopmental follow-up is the critical next step in the neurological evaluation. The history is discussed best in the context of essentially every chapter of this book and is not repeated in detail here. Appropriate specialized studies (see Chapter 13 )…

Maternal and Fetal Conditions With Consequences for the Fetal Brain

ENDOCRINE DISORDERS IN PREGNANCY AND THE DEVELOPING FETAL BRAIN Normal fetal brain development is dependent on a highly orchestrated and dynamic endocrine milieu that evolves across gestation. Early in gestation the endocrine environment of the fetus is supported and regulated by maternal and placental systems. Understanding of this complex field is far from complete but is more advanced for some hormones, such as insulin, thyroid hormone,…

Placental Conditions With Consequences for the Fetal Brain

DEVELOPMENT OF NORMAL PLACENTAL STRUCTURE AND FUNCTION The normal placenta is far more than a mere conduit for nutrient and waste exchange between the mother and fetus. Rather, it is a highly specialized organ with multiple complex and interrelated functions, including hormonal and trophic factor synthesis and transfer and immunological (both tolerance and barrier) functions. These complex physiological functions are served by an anatomical structure that…

Specialized Diagnostic Studies for Assessment of the Fetal Central Nervous System

INTRODUCTION Evaluation of the fetal brain is, for obvious reasons, heavily dependent on specialized imaging techniques that have entered the clinical domain over the past five decades. Since its entry into the clinical domain in the late 1960s and early 1970s, obstetrical ultrasound (US) has secured its status as the first-line screening and diagnostic technique for evaluating the fetal brain. Almost three decades later, “modern” fetal…

Myelination Events

Myelination is characterized by the acquisition of the highly specialized myelin membrane around axons. The time period of myelination in the human is long, beginning mainly in the second trimester of pregnancy and continuing into adult life. Myelination in the brain begins before birth within the caudal brainstem and progresses rostrally to the forebrain, with the most rapid and dramatic period of human central myelination within…

Organizational Events

NORMAL DEVELOPMENT Organizational events occur in a peak time period from approximately the fifth month of gestation to several years after birth. However, these complex processes may continue for many more years in human cerebrum. The major developmental features include (1) establishment and differentiation of the subplate neurons; (2) attainment of proper alignment, orientation, and layering (lamination) of cortical neurons; (3) gyral development; (4) elaboration of…

Neuronal Migration

MIGRATION As progenitor cells proliferate and differentiate into neurons and glia (see Chapter 5 ), these cells migrate to form the cerebral cortex in an elaborate and still not completely understood series of genetically influenced processes. Neurodevelopmental studies and disorders of brain development have informed our knowledge of these processes. In fact, the period of early migration overlaps with neuronal proliferation, and the period of late…

Neuronal Proliferation

The awesome complexity of the human brain begins its evolution after the essential external form is established by the events described in Chapters 1 and 2 . The events that follow are proliferation of the brain’s total complement of neurons, estimated at 86 billion, the migration of these neurons to specific sites throughout the central nervous system (CNS), the series of organizational events that result in…

Normal and Abnormal Development of the Posterior Fossa Structures

As is the case for development of the prosencephalic structures discussed in Chapter 2 , the most critical time for development of the form and cellular structure of the brainstem and cerebellum is in the second and third months of gestation. The widespread implementation of prenatal screening protocols that include fetal anatomical ultrasound (US) surveys has made suspected posterior fossa anomalies in the fetus one of…

Ventricular Development, Ventriculomegaly, and Hydrocephalus in the Fetus and Newborn

Introduction The terms ventriculomegaly and hydrocephalus are often used inconsistently and imprecisely in the literature. In this discussion we use ventriculomegaly (VM) as an overarching term to describe enlarged cerebral ventricles without reference to etiopathogenesis, natural history, or outcome. Ventriculomegaly may be subcategorized in a number of ways, based on the underlying pathogenetic mechanism, clinical course, and associated features ( Fig. 3.1 ). Hydrocephalus is one…

Prosencephalic Development

Normal Prosencephalic Development The major event following neurulation is development of the prosencephalon, which results in the fundamental structure of the central nervous system. The prosencephalon lies rostral to the other major vesicles of the brain—that is, the midbrain (mesencephalon) and hindbrain (rhombencephalon)—and will ultimately form the cerebral hemispheres and diencephalic structures (i.e., the thalamus and hypothalamus). Prosencephalic development peaks between the second and third months…

Neural Tube Development

Introduction An understanding of the development of the nervous system is essential for an understanding of fetal and neonatal neurology. An obvious reason for this contention is the wide variety of disturbances of neural development that are flagrantly apparent in the neonatal period and increasingly diagnosed in the fetal period. In addition, all of the insults that affect the fetus and newborn, which are the subject…

Principles of Human Biomechanics

KEY POINTS The direction and magnitude of forces affect the form of the developing fetus. Abnormal mechanical forces give rise to deformation in humans in much the same fashion as abnormal forces may deform a tree. The tissues of a human fetus are especially pliable and easily molded, especially as a fetus fills out the uterus in late gestation. Many factors can lead to an aberrant…

Fetal Disruption

KEY POINTS Fetal vascular disruption defects refer to structural defects that occur after a structure has formed normally, and they are usually limited to tissues within a defined area that are supplied by the affected blood vessels. Decreased blood flow to the affected area leads to hypoxia, endothelial cell damage, hemorrhage, tissue loss, and repair. Defects attributed to vascular defects included amniotic band defects, terminal transverse…

First-Trimester Vascular Disruption

KEY POINTS The underlying mechanism for most defects related to problems associated with failed first-trimester obstetric procedures is vascular disruption. With chorionic villus sampling, removal of villi may result in embryonic hypotension, hypoxia, endothelial damage, hemorrhage, and necrosis with tissue loss involving distal structures in the upper body (hands and tongue), with middle digital rays more affected than medial or lateral rays. Failed dilatation and uterine…