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 remark-
able progress in neonatal neurology that has come in part from major advances in neu-
roimaging, 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 re-
views 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 devel-
oping 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

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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 pertur-
bations in brain development affect cellular maturation and neuronal connectivity.
This information also provides another avenue to accelerate progress toward im-
proved 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 develop-
mental 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 col-
leagues grapple with the on-going controversies and challenges to define the path-
ogenesis 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 neuropro-
tective 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 pharma-
cological 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 hypoxic-
ischemic 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 neuro-
protection. 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 gluco-
corticoids and their impact on brain development and injury. They provide valuable
 Preface xix

insights into the physiological basis for the use of prenatal and postnatal glucocorti-
coids 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 man-
agement 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 out-
comes 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 interven-
tion 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, Papé 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:
pballabh@msn.com (P. Ballabh)
backs@ohsu.edu (S.A. Back)