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Stroke in the Newborn

The presentation and etiologies of stroke in the newborn differ from those of children and adults and, in many cases, remain unrecognized. Perinatal ischemic stroke has been defined as “a group of heterogeneous conditions in which there is a focal disruption of cerebral blood flow secondary to arterial or cerebral venous thrombosis or embolization, between 20 weeks of fetal life through 28th postnatal day confirmed by…

Hypoxic-Ischemic Injury in the Term Infant: Clinical-Neurological Features, Diagnosis, Imaging, Management, and Prognosis

The clinical aspects of neonatal hypoxic-ischemic encephalopathy (HIE) are appropriately discussed after the neuropathology (see Chapter 22 ) and pathophysiology (see Chapter 23 ), because understanding of the clinical phenomena is facilitated greatly by an awareness of the underlying pathological substrates. Moreover, choice of appropriate diagnostic modalities, formulation of rational prognostic statements, and development of appropriate plans of management are based, in many ways, on awareness…

Hypoxic-Ischemic Injury in the Term Infant: Pathophysiology

Introduction This chapter addresses the pathophysiology of hypoxic-ischemic injury. This is a dynamic process, characterized by an evolving cascade of events that may continue for days to weeks, months, and years after the initial insult. The neuropathology following primary, latent, secondary, and tertiary phases of injury include selective neuronal necrosis, parasagittal cerebral injury , and cerebral white matter injury (see Chapter 22 ). Though one or…

Hypoxic-Ischemic Encephalopathy in the Term Infant: Neuropathology

Hypoxic-ischemic brain injury is a very important neurological problem of the perinatal period. This importance relates to the general gravity of the lesions and to the relatively large number of affected infants. In the premature infant, this encephalopathy is often accompanied by intraventricular hemorrhage and its concomitants, which contribute to the neurological morbidity (see Chapter 28 ). Thus it is apparent that a basic understanding of…

Intrauterine and Intrapartum Assessment of the Fetus

The focus in this chapter is the assessment of fetal well-being, particularly as a means for the recognition of the infant that may be at risk of hypoxic-ischemic cerebral injury. The identification of an intrauterine disturbance in gas exchange between the human fetus and mother (i.e., asphyxia) or the likelihood that such a disturbance will occur during labor or delivery is critical, in view of the…

Encephalopathy of the Preterm—Clinical Aspects

INTRODUCTION This chapter addresses the clinical aspects of the encephalopathy of prematurity, a term coined to characterize the multifaceted, nonhemorrhagic white and gray matter lesions in the premature brain that reflect a combination of destructive and dysmaturational effects (see Chapters 18 and 19 ). The central pathology is cerebral white matter injury (WMI)/periventricular leukomalacia (PVL), with a variety of associated neuronal/axonal deficits. The latter principally affect…

Encephalopathy of Prematurity: Pathophysiology

OVERVIEW OF PATHOGENESIS Our understanding of the pathophysiology of the encephalopathy of prematurity continues to evolve significantly. Whereas the focus of this chapter in the prior edition was principally on cerebral white matter injury (WMI), it has become increasingly evident that the encephalopathy also involves dysmaturational processes that affect not only white matter development but also cerebral gray matter maturation. This expanded focus has been driven…

Encephalopathy of Prematurity: Neuropathology

The major neuropathological substrate of human preterm brain injury is the encephalopathy of prematurity , a term coined to characterize the multifaceted gray and white matter lesions in the preterm brain that reflect acquired and developmental factors in combination ( Box 18.1 , Table 18.1 ). The encephalopathy of prematurity is also associated with hemorrhages, notably in the germinal matrix of the ganglionic eminence (GE) (see…

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…