Seminars in Pediatric Neurology

Introduction

Adre J. du Plessis — 2009-12-01

Confronted with the task of selecting topics for a neonatal neurology issue of Seminars in Pediatric Neurology, I was struck by the plethora of recent review articles, many of them superb, covering the spectrum of today's important issues in the field. This situation is a testament to the vigor of neonatal neurology and the many bright minds that have come to populate the field. However, clearly this was not the time to further saturate the literature with reviews of current progress and future directions. Instead, I made the decision to focus on the current state of the field of neonatal neurology, and more importantly, on how we got to this point.

The Encephalopathy of Prematurity—Brain Injury and Impaired Brain Development Inextricably Intertwined

Joseph J. Volpe — 2009-12-01

The field of neonatal neurology, and specifically its focus on the premature infant, had its inception in neuropathologic studies. Since then, the development of advanced imaging techniques has guided our developing understanding of the etiology and nature of neonatal brain injury. This review promotes the concept that neonatal brain injury has serious and diverse effects on subsequent brain development, and that these effects likely are more important than simple tissue loss in determining neurologic outcome. Brain injury in the premature infant is best illustrative of this concept. This “encephalopathy of prematurity” is reviewed in the context of the remarkable array of developmental events actively proceeding during the last 16-20 weeks of human gestation. Recent insights into the brain abnormalities in survivors of preterm birth obtained by both advanced magnetic resonance imaging and neuropathologic techniques suggest that this encephalopathy is a complex amalgam of destructive and developmental disturbances. The interrelations between destructive and developmental mechanisms in the genesis of the encephalopathy are emphasized. In the future, advances in neonatal neurology will likely reiterate the dependence of this field on neuropathologic studies, including new cellular and molecular approaches in developmental neurobiology.

The Encephalopathy of Prematurity: One Pediatric Neuropathologist's Perspective

Hannah C. Kinney — 2009-12-01

A major challenge in understanding brain injury in the premature brain is the establishment of the precise human neuropathology at the cellular and molecular levels, as such knowledge is the foundation upon which the elucidation of the cause(s), scientific experimentation, and therapies in the field is by necessity based. In this essay, I provide my perspective as a pediatric neuropathologist upon pathologic studies in the developing human brain itself, including a review of past, present, and future aspects. My focus is upon the path that has brought us to the current recognition that preterm brain injury is a complex of white and gray matter damage that results in the modification of key developmental pathways during a critical period, which in turn defines the adverse clinical outcomes as important as the primary insult itself. The evolution of this recognition, as well as the introduction of the term “encephalopathy of prematurity” for the complex of gray and white matter damage because of acquired and developmental mechanisms, is discussed. Our enhanced understanding of the fundamental neuropathology of the human preterm brain should bring us closer to more effective therapy as the need to prevent and treat injury to developing oligodendrocytes and neurons in combination is appreciated.

The Relationship Between Systemic Hemodynamic Perturbations and Periventricular-Intraventricular Hemorrhage—A Historical Perspective

Jeffrey M. Perlman — 2009-12-01

Periventricular-intraventricular hemorrhage (PV–IVH) remains the major cause of injury to the developing brain. Predisposing factors include a germinal matrix with an immature vasculature, a pressure passive cerebral circulation, and hemodynamic perturbations in sick premature infants. Intact cerebral autoregulation has been documented in stable premature infants; however, it functions within a limited blood pressure range and is likely to be absent in the sick hypotensive infant, which increases the risk for PV–IVH with perturbations in blood pressure. The risk for PV–IVH is markedly increased in the absence of antenatal glucocorticoid exposure in the intubated low birthweight infant <1000 g with respiratory distress syndrome; ± other complications. Although surfactant administration reduces the severity of respiratory distress syndrome, it has not led to a reduction in PV–IVH. Early postnatal administration of indomethacin has been associated with a reduction in PV–IVH, although this has not translated into long-term neurocognitive benefits.

The Discovery of Hypothermic Neural Rescue Therapy for Perinatal Hypoxic-Ischemic Encephalopathy

A. David Edwards — 2009-12-01

The development of the concepts of delayed post-ischaemic neuronal death and neural rescue brought about a search for clinical treatments to reduce brain damage after birth asphyxia. Cooling had long been an unproven empyrical therapy, and a 20 year programme of careful laboratory and clinical research has proved that hypothermia reduces neurological damage in infants suffering perinatal asphyxial encephalopathy.

To Autoregulate or Not to Autoregulate—That is No Longer the Question

Gorm Greisen — 2009-12-01

In the late 1970s, high cerebral blood flow was perceived as a cause of intracranial hemorrhage in the preterm infant. Intracranial hemorrhage was diagnosed by computed tomography and ultrasound found to be frequent not only in babies who died. Hemorrhage was soon linked to cerebral palsy in survivors. The analogy was hypertensive hemorrhagic stroke in the adult. Cerebral hemorrhage was perceived as the major (preventable) cause of brain injury in the preterm baby. An immature cerebral autoregulation or a vulnerability of the autoregulation exposed by preceding hypoxia or ischemia therefore became a focus of neonatal brain research in the 1980s. Over the years the focus has changed, first to the pathogenesis of hypoxic-ischemic brain injury, then to the effects of pCO2, and now 30 years later to a more comprehensive, less clearly hypothesis-driven exploration of the multitude of factors involved in cerebral blood flow and oxygenation. Meanwhile, some basic questions regarding autoregulation remain unanswered, and some concepts from the 1970s still direct clinical practice.

Evolving Understanding of Hypoxic-Ischemic Encephalopathy in the Term Infant

Linda S. de Vries, Frances M. Cowan — 2009-12-01

Our aim was to document changes in the evaluation and prognosis of term-born infants with neonatal encephalopathy of hypoxic-ischemic origin, with particular reference to our own experiences and influences, and to summarize the debate on causation and the relative importance of antenatal and perinatal factors. High quality neonatal cranial ultrasound and magnetic resonance imaging and spectroscopy have enabled the accurate early visualization of different patterns of hypoxic-ischemic brain injury and prediction of their associated outcomes. Long-term follow-up shows that cognitive and memory difficulties may follow even in children without motor deficits. The very early use of electrophysiologic methods has allowed broad prognostic categorization of infants when this is not possible from clinical assessment or imaging, providing a rationale for entry into intervention trials, such as therapeutic hypothermia. This work has also shown that most of these infants have evidence of acute hypoxic-ischemic brain injury that explains their symptoms and outcomes.

A History of Our Understanding of Cerebral Vascular Development and Pathogenesis of Perinatal Brain Damage Over the Past 30 Years

Sachio Takashima, Masayuki Itoh, Akira Oka — 2009-12-01

This article reviews our studies focusing on cerebral vascular development, the pathogenesis of subependymal/intraventricular hemorrhage (SEH/IVH), periventricular leukomalacia (PVL), and pontosubicular neuron necrosis (PSN). Their pathogenesis consists of predisposing developmental and causal factors. SEH/IVH may be caused by reperfusion or overperfusion following ischemia in the subependymal germinal matrix with characteristic vasculature. The cause of PVL is multifactorial (ie, ischemia and inflammation), predisposed by the maturational status of the vasculature and oligodendroglia in the white matter. Focal PVL is ischemic necrosis, and diffuse PVL or white matter injury may include cytotoxic damage. PSN has an apoptotic character, and may be induced by ischemic and oxidative stress on specific immature neurons. Further studies on preventive and therapeutic measures are necessary in clinical, pathologic, and experimental fields. The monitoring and control methods of brain hemodynamics and cellular stability should be more developed to prevent brain damages.

Author-Subject Index

2009-12-01