Advances in Neonatal Neurology
Preface Advances in Neonatal Neurology
Praveen Ballabh, MD
Stephen A. Back, MD, PhD Editors
We are extremely pleased to introduce this issue of Clinics in Perinatology, which focuses on “Advances in Neonatal Neurology.” The last decade has witnessed remarkable progress in neonatal neurology that has come in part from major advances in neuroimaging, the introduction of cerebral hypothermia, and a wealth of basic science insights that have positioned us for sustained accelerated progress in the diagnosis and treatment of numerous disorders of preterm and term neonates. Our challenge in compiling this issue was, thus, to select from a wide spectrum of recent advances that span from bench to bedside. The 16 articles in this issue draw on the expertise of internationally recognized experts who have collectively provided cross-cutting reviews with a broad perspective on the current state of the field. We are very grateful to the authors for providing succinct, up-to-date clinical perspectives and for highlighting current controversies and future challenges. Thanks to them, we are able to offer you a cutting-edge compendium of this complex and fast-moving field. Throughout the issue, the reader is encouraged to acquire a more comprehensive perspective by drawing connections between earlier and later articles that are thematically grouped around issues dealing with pathogenesis, diagnosis, and therapy. The issue begins by addressing two common problems in neonatal neurology from the perspectives of pathogenesis and neuroimaging: cerebral gray and white matter injury and intraventricular hemorrhage. The first article addresses the pathogenesis of cerebral injury in the premature infant. The considerable recent progress in the care of preterm infants has translated to substantial changes in the spectrum of cerebral injury sustained by these babies. The shift from predominantly destructive lesions to dysmature lesions has raised new challenges to define insults to the developing brain, which do not strictly adhere to our long-standing concepts about cerebral injury. Inherent in these challenges are complex issues related to disruption of the timing and progression of key neurodevelopmental events that progress rapidly in the last trimester of gestation. The first article is complemented by a second article Clin Perinatol 41 (2014) xvii–xix http://dx.doi.org/10.1016/j.clp.2013.11.002 perinatology.theclinics.com 0095-5108/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
xviii
Preface
by Dr Serena Counsell, Dr David Edwards, and their colleagues that provides a comprehensive review of the application of advanced MRI techniques to define the evolution of the events that underlie brain development in the preterm and term infants through diffusion and functional MRI. The application of these advanced neuroimaging techniques provides powerful noninvasive surrogate measures to define how perturbations in brain development affect cellular maturation and neuronal connectivity. This information also provides another avenue to accelerate progress toward improved preventive strategies and new directions in rehabilitation that will harness the intrinsic plasticity of the neonatal brain for regeneration and repair. Later in the issue, Dr Flora Vaccarino and her colleagues return to this exciting new direction to examine how prematurity and perinatal insults influence neurogenesis in the brain of premature infants and in experimental models with resultant microstructural and functional changes that translate to enduring changes in neurodevelopment. In the third article on intraventricular hemorrhage, advances in the understanding of the pathogenesis and prevention of this common problem have been thoroughly reviewed. The article draws on a wealth of new insights into the complex developmental changes in the preterm vasculature as derived from both experimental models and human autopsy studies. This article is complemented by the fourth article by Dr Linda De Vries and her colleagues, which integrates the application of multiple neuroimaging modalities to define the progression of white matter injury and intraventricular hemorrhage. In the next article, Dr Steven Miller and his colleagues grapple with the on-going controversies and challenges to define the pathogenesis of white matter injury in terms of the relative contributions of maternal chorioamnionitis and postnatal infection. Several authors were invited to address state-of-the-art diagnostic and neuroprotective strategies for the term neonate with hypoxic-ischemic encephalopathy. Dr Sidhartha Tan analyzes the application of clinical and MRI biomarkers for earlier detection of hypoxic-ischemic injury. Three articles address current advances in the prevention of hypoxic-ischemic injury to the term neonate by means of pharmacological strategies and cerebral hypothermia—a topic that Dr Donna Ferriero refreshingly refers to as cocktails and ice! Remarkably, as adult neurologists continue to struggle to develop viable therapies for stroke and other forms of hypoxicischemic brain injury, neonatal neurology is exploring new avenues to fine-tune the approach of combination therapies to augment the therapeutic efficacy of cerebral hypothermia with adjunctive pharmacological agents. Drs Sunny Juul and Donna Ferriero provide a highly current perspective on the most promising agents for neuroprotection. Dr Pierre Gressens and his coauthors have provided a comprehensive summary of the current status of both preclinical testing of stem cells in animal models and the current status of clinical trials with various forms of stem cell therapy. In her article, Dr Seetha Shankaran navigates through the outcome data on childhood hypoxic-ischemic encephalopathy to provide an up-to-date perspective on the current status of the efficacy and limitations of cerebral hypothermia. Dr Alistair Gunn and his colleagues have discussed molecular mechanisms of hypothermic neuroprotection, which may help clinicians to design effective combination therapies for hypothermia. Three articles address timely and controversial issues related to management of preterm or term infants. Neonatal seizures frequently pose challenging diagnostic and management issues. Dr Hannah Glass has provided a valuable compendium of recent advances related to both the diagnosis and the management of neonatal seizures. Dr Barbara Stonestreet and her colleagues have extensively studied glucocorticoids and their impact on brain development and injury. They provide valuable
Preface
insights into the physiological basis for the use of prenatal and postnatal glucocorticoids and discuss the risks and benefits of these agents in the preterm neonate. Drs Ruth Grunau and Christopher McPherson have contributed the article on neonatal pain control and the neurologic effects of anesthetics and sedatives in preterm infants. They assess the potential deleterious effects of analgesics and anesthetics for management of both acute and chronic pain in neonates in intensive care. The issue concludes with two complementary articles that examine long-term outcomes in preterm and term neonates. Dr Betty Vohr has framed the problem with an outstanding article assessing the current status of neurodevelopmental outcomes of extremely preterm infants. Drs Petra Huppi, Laura Ment, and colleagues address the application of sophisticated MRI strategies, including diffusion tensor imaging, resting state functional connectivity, and magnetic resonance spectroscopy to better predict the prognosis for premature newborns and assist in early intervention services. We are extremely grateful to Elsevier for the opportunity to serve as the guest editors for this issue that we expect will offer much valuable insight into the current management of the neurology problems of the preterm and term neonate. This issue underscores the vital importance of continued support to encourage and nurture collaboration among clinicians and scientists. We hope that this issue will serve as testimony to the passionate pursuit of progress achieved by our colleagues. We hope it will also inspire others to sustain the tremendous potential for further advances to optimize brain development for newborns in neonatal units throughout the world. Praveen Ballabh, MD Professor of Pediatrics and Cell Biology and Anatomy Regional Neonatal Center Maria Fareri Children’s Hospital at Westchester Medical Center and New York Medical College Valhalla, New York 10595, USA Stephen A. Back, MD, PhD Professor of Pediatrics and Neurology Oregon Health & Science University Clyde and Elda Munson Professor of Pediatric Research Director, Neuroscience Section, Pape´ Family Pediatric Research Institute Mail Code: L481 Biomedical Research Building 317 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098, USA E-mail addresses: [email protected] (P. Ballabh) [email protected] (S.A. Back)
xix
Preface Advances in Neonatal Neurology
Praveen Ballabh, MD
Stephen A. Back, MD, PhD Editors
We are extremely pleased to introduce this issue of Clinics in Perinatology, which focuses on “Advances in Neonatal Neurology.” The last decade has witnessed remarkable progress in neonatal neurology that has come in part from major advances in neuroimaging, the introduction of cerebral hypothermia, and a wealth of basic science insights that have positioned us for sustained accelerated progress in the diagnosis and treatment of numerous disorders of preterm and term neonates. Our challenge in compiling this issue was, thus, to select from a wide spectrum of recent advances that span from bench to bedside. The 16 articles in this issue draw on the expertise of internationally recognized experts who have collectively provided cross-cutting reviews with a broad perspective on the current state of the field. We are very grateful to the authors for providing succinct, up-to-date clinical perspectives and for highlighting current controversies and future challenges. Thanks to them, we are able to offer you a cutting-edge compendium of this complex and fast-moving field. Throughout the issue, the reader is encouraged to acquire a more comprehensive perspective by drawing connections between earlier and later articles that are thematically grouped around issues dealing with pathogenesis, diagnosis, and therapy. The issue begins by addressing two common problems in neonatal neurology from the perspectives of pathogenesis and neuroimaging: cerebral gray and white matter injury and intraventricular hemorrhage. The first article addresses the pathogenesis of cerebral injury in the premature infant. The considerable recent progress in the care of preterm infants has translated to substantial changes in the spectrum of cerebral injury sustained by these babies. The shift from predominantly destructive lesions to dysmature lesions has raised new challenges to define insults to the developing brain, which do not strictly adhere to our long-standing concepts about cerebral injury. Inherent in these challenges are complex issues related to disruption of the timing and progression of key neurodevelopmental events that progress rapidly in the last trimester of gestation. The first article is complemented by a second article Clin Perinatol 41 (2014) xvii–xix http://dx.doi.org/10.1016/j.clp.2013.11.002 perinatology.theclinics.com 0095-5108/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
xviii
Preface
by Dr Serena Counsell, Dr David Edwards, and their colleagues that provides a comprehensive review of the application of advanced MRI techniques to define the evolution of the events that underlie brain development in the preterm and term infants through diffusion and functional MRI. The application of these advanced neuroimaging techniques provides powerful noninvasive surrogate measures to define how perturbations in brain development affect cellular maturation and neuronal connectivity. This information also provides another avenue to accelerate progress toward improved preventive strategies and new directions in rehabilitation that will harness the intrinsic plasticity of the neonatal brain for regeneration and repair. Later in the issue, Dr Flora Vaccarino and her colleagues return to this exciting new direction to examine how prematurity and perinatal insults influence neurogenesis in the brain of premature infants and in experimental models with resultant microstructural and functional changes that translate to enduring changes in neurodevelopment. In the third article on intraventricular hemorrhage, advances in the understanding of the pathogenesis and prevention of this common problem have been thoroughly reviewed. The article draws on a wealth of new insights into the complex developmental changes in the preterm vasculature as derived from both experimental models and human autopsy studies. This article is complemented by the fourth article by Dr Linda De Vries and her colleagues, which integrates the application of multiple neuroimaging modalities to define the progression of white matter injury and intraventricular hemorrhage. In the next article, Dr Steven Miller and his colleagues grapple with the on-going controversies and challenges to define the pathogenesis of white matter injury in terms of the relative contributions of maternal chorioamnionitis and postnatal infection. Several authors were invited to address state-of-the-art diagnostic and neuroprotective strategies for the term neonate with hypoxic-ischemic encephalopathy. Dr Sidhartha Tan analyzes the application of clinical and MRI biomarkers for earlier detection of hypoxic-ischemic injury. Three articles address current advances in the prevention of hypoxic-ischemic injury to the term neonate by means of pharmacological strategies and cerebral hypothermia—a topic that Dr Donna Ferriero refreshingly refers to as cocktails and ice! Remarkably, as adult neurologists continue to struggle to develop viable therapies for stroke and other forms of hypoxicischemic brain injury, neonatal neurology is exploring new avenues to fine-tune the approach of combination therapies to augment the therapeutic efficacy of cerebral hypothermia with adjunctive pharmacological agents. Drs Sunny Juul and Donna Ferriero provide a highly current perspective on the most promising agents for neuroprotection. Dr Pierre Gressens and his coauthors have provided a comprehensive summary of the current status of both preclinical testing of stem cells in animal models and the current status of clinical trials with various forms of stem cell therapy. In her article, Dr Seetha Shankaran navigates through the outcome data on childhood hypoxic-ischemic encephalopathy to provide an up-to-date perspective on the current status of the efficacy and limitations of cerebral hypothermia. Dr Alistair Gunn and his colleagues have discussed molecular mechanisms of hypothermic neuroprotection, which may help clinicians to design effective combination therapies for hypothermia. Three articles address timely and controversial issues related to management of preterm or term infants. Neonatal seizures frequently pose challenging diagnostic and management issues. Dr Hannah Glass has provided a valuable compendium of recent advances related to both the diagnosis and the management of neonatal seizures. Dr Barbara Stonestreet and her colleagues have extensively studied glucocorticoids and their impact on brain development and injury. They provide valuable
Preface
insights into the physiological basis for the use of prenatal and postnatal glucocorticoids and discuss the risks and benefits of these agents in the preterm neonate. Drs Ruth Grunau and Christopher McPherson have contributed the article on neonatal pain control and the neurologic effects of anesthetics and sedatives in preterm infants. They assess the potential deleterious effects of analgesics and anesthetics for management of both acute and chronic pain in neonates in intensive care. The issue concludes with two complementary articles that examine long-term outcomes in preterm and term neonates. Dr Betty Vohr has framed the problem with an outstanding article assessing the current status of neurodevelopmental outcomes of extremely preterm infants. Drs Petra Huppi, Laura Ment, and colleagues address the application of sophisticated MRI strategies, including diffusion tensor imaging, resting state functional connectivity, and magnetic resonance spectroscopy to better predict the prognosis for premature newborns and assist in early intervention services. We are extremely grateful to Elsevier for the opportunity to serve as the guest editors for this issue that we expect will offer much valuable insight into the current management of the neurology problems of the preterm and term neonate. This issue underscores the vital importance of continued support to encourage and nurture collaboration among clinicians and scientists. We hope that this issue will serve as testimony to the passionate pursuit of progress achieved by our colleagues. We hope it will also inspire others to sustain the tremendous potential for further advances to optimize brain development for newborns in neonatal units throughout the world. Praveen Ballabh, MD Professor of Pediatrics and Cell Biology and Anatomy Regional Neonatal Center Maria Fareri Children’s Hospital at Westchester Medical Center and New York Medical College Valhalla, New York 10595, USA Stephen A. Back, MD, PhD Professor of Pediatrics and Neurology Oregon Health & Science University Clyde and Elda Munson Professor of Pediatric Research Director, Neuroscience Section, Pape´ Family Pediatric Research Institute Mail Code: L481 Biomedical Research Building 317 3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098, USA E-mail addresses: [email protected] (P. Ballabh) [email protected] (S.A. Back)
xix
