Neurology and Neurosurgery Research

Multidisciplinary approach to hydrocephalus care

February 23, 2017

Reflective of the myriad symptoms and complications that can accompany hydrocephalus, a multidisciplinary team at Children’s National works with patients and families for much of childhood.

The Doppler image on the oversized computer screen shows the path taken by blood as it flows through the newborn’s brain, with bright blue distinguishing blood moving through the middle cerebral artery toward the frontal lobe and bright red depicting blood coursing away. Pitch black zones indicate ventricles, cavities through which cerebrospinal fluid usually flows and where hydrocephalus can get its start.

The buildup of excess cerebrospinal fluid in the brain can begin in the womb and can be detected by fetal magnetic resonance imaging. Hydrocephalus also can crop up after birth due to trauma to the head, an infection, a brain tumor or bleeding in the brain, according to the National Institutes of Health. An estimated 1 to 2 per 1,000 newborns have hydrocephalus at birth.

When parents learn of the hydrocephalus diagnosis, their first question tends to be “Is my child going to be OK?” says Suresh Magge, M.D., a pediatric neurosurgeon at Children’s National Health System.

“We have a number of ways to treat hydrocephalus. It is one of the most common conditions that pediatric neurosurgeons treat,” Dr. Magge adds.

Unlike fluid build-up elsewhere in the body where there are escape routes, with hydrocephalus spinal fluid becomes trapped in the brain. To remove it, surgeons typically implant a flexible tube called a shunt that drains excess fluid into the abdomen, an interim stop before it is flushed away. Another surgical technique, called an endoscopic third ventriculostomy has the ability to drain excess fluid without inserting a shunt, but it only works for select types of hydrocephalus, Dr. Magge adds.

For the third year, Dr. Magge is helping to organize the Hydrocephalus Education Day on Feb. 25, a free event that offers parents an opportunity to learn more about the condition.

Reflective of the myriad symptoms and complications that can accompany hydrocephalus, such as epilepsy, cerebral palsy, cortical vision impairment and global delays, a multidisciplinary team at Children’s National works with patients and families for much of childhood.

Neuropsychologist Yael Granader, Ph.D., works with children ages 4 and older who have a variety of developmental and medical conditions. Granader is most likely to see children and adolescents with hydrocephalus once they become medically stable in order to assist in devising a plan for school support services and therapeutic interventions. Her assessments can last an entire day as she administers a variety of tasks that evaluate how the child thinks and learns, such as discerning patterns, assembling puzzles, defining words, and listening to and remembering information.

Neuropsychologists work with schools in order to help create the most successful academic environment for the child. For example, some children may struggle to visually track across a page accurately while reading; providing a bookmark to follow beneath the line is a helpful and simple accommodation to put in place. Support for physical limitations also are discussed with schools in order to incorporate adaptive physical education or to allow use of an elevator in school.

“Every child affected by hydrocephalus is so different. Every parent should know that their child can learn,” Granader says. “We’re going to find the best, most supportive environment for them. We are with them on their journey and, every few years, things will change. We want to be there to help with emerging concerns.”

Another team member, Justin Burton, M.D., a pediatric rehabilitation specialist, says rehabilitation medicine’s “piece of the puzzle is doing whatever I can to help the kids function better.” That means dressing, going to the bathroom, eating and walking independently. With babies who have stiff, tight muscles, that can mean helping them through stretches, braces and medicine management to move muscles smoothly in just the way their growing bodies want. Personalized care plans for toddlers can include maintaining a regular sleep-wake cycle, increasing attention span and strengthening such developmental skills as walking, running and climbing stairs. For kids 5 and older, the focus shifts more to academic readiness, since those youths’ “full-time job” is to become great students, Dr. Burton says.

The area of the hospital where children work on rehabilitation is an explosion of color and sounds, including oversized balance balls of varying dimensions in bright primary colors, portable basketball hoops with flexible rims at multiple heights, a set of foam stairs, parallel bars, a climbing device that looks like the entry to playground monkey bars and a chatterbox toy that lets a patient know when she has opened and closed the toy’s doors correctly.

“We end up taking care of these kids for years and years,” he adds. “I always love seeing the kids get back to walking and talking and getting back to school. If we can get them back out in the world and they’re doing things just like every other kid, that’s success.”

Meanwhile, Dr. Magge says research continues to expand the range of interventions and to improve outcomes for patients with hydrocephalus, including:

Fluid dynamics of cerebrospinal fluid
Optimal ways to drain excess fluid
Improving understanding of why shunts block
Definitively characterizing post-hemorrhagic ventricular dilation.

Unlike spina bifida, which sometimes can be corrected in utero at some health institutions, hydrocephalus cannot be corrected in the womb. “While we have come a long way in treating hydrocephalus, there is still a lot of work to be done. We continue to learn more about hydrocephalus with the aim of continually improving treatments,” Dr. Magge says.

During a recent office visit, 5-year-old Abagail’s head circumference had measured ¼ centimeter of growth, an encouraging trend, Robert Keating, M.D., Children’s Chief of Neurosurgery, tells the girl’s mother, Melissa J. Kopolow McCall. According to Kopolow McCall, who co-chairs the Hydrocephalus Association DC Community Network, it is “hugely” important that Children’s National infuses its clinical care with the latest research insights. “I have to have hope that she is not going to be facing a lifetime of brain surgery, and the research is what gives me the hope.”

Michael Bell to head Division of Critical Care

February 22, 2017

Michael J. Bell, M.D., will join Children’s National as Chief of the Division of Critical Care Medicine, in April 2017.

Dr. Bell is a nationally known expert in the field of pediatric neurocritical care, and established the pediatric neurocritical care program at the Children’s Hospital of UPMC in Pittsburgh.

He is a founding member of the Pediatric Neurocritical Care Research Group, an international consortia of 40 institutions dedicated to advancing clinical research for children with critical neurological illnesses. Prior to joining the University of Pittsburgh, Dr. Bell served on the faculty at Children’s National and simultaneously conducted research on the impact of inflammation on the developing brain at the National Institute of Neurological Disorders and Stroke (NINDS), within the laboratory of the Chief of the NINDS Stroke Branch.

Dr. Bell also leads the largest study to date evaluating the impact of interventions on the outcomes of infants and children with severe traumatic brain injury (TBI) and analyzing findings to improve clinical practice across the world. The Approaches and Decisions for Acute Pediatric Traumatic Brain Injury (ADAPT) Trial, funded by NINDS, has enrolled 1,000 children through 50 clinical sites across eight countries and compiled an unmatched database, which will be used to develop new guidelines for clinical care and research on TBIs. Dr. Bell is currently working on expanding the scope and continuing the trial for at least the next 5 years.

In his time at Children’s National, he played a critical role in building one of the first clinical pediatric neuro-critical care consult services in the country, which established common protocols between Children’s Divisions of Critical Care Medicine, Neurology, and Neurosurgery aimed at improving clinical care of children with brain injuries. Dr. Bell’s current research interests include: barriers to implementation of traumatic brain injury guidelines, the effect of hypothermia on various brain injuries and applications for neurological markers in a clinical setting.

The Children’s National Division of Critical Care Medicine is a national leader in the care of critically ill and injured infants and children, with clinical outcomes and safety measures among the best in the country across the pediatric, cardiac, and neuro critical care units.

Javad Nazarian named scientific director of the Brain Tumor Institute

February 8, 2017

Javad Nazarian

Javad Nazarian, Ph.D., has been named scientific director of the Brain Tumor Institute of the Children’s National Health System. Since 2006, Dr. Nazarian has been an active member of the Brain Tumor Institute, contributing to the advancement in understanding pediatric brain tumors.

He has been instrumental in his role as a Principal Investigator in the Center for Cancer and Immunology Research where his laboratory actively investigates the molecular mechanisms of diffuse intrinsic pontine gilomas (DIPGs) and establishes preclinical models of pediatric brain tumors.

Dr. Nazarian has also contributed to the expansion of the comprehensive biorepository at Children’s National, growing from 12 samples six years ago to more than 3,000 specimens donated by more than 900 patients with all types of pediatric brain tumors, including DIPG. Recently he was appointed Scientific Co-chair of the Children’s Brain Tumor Tissue Consortium.

Congenital heart disease and cortical growth

February 7, 2017

The cover of Science Translational Medicine features a new study of the cellular-level changes in the brain induced by congenital heart disease. Reprinted with permission from AAAS. Not for download

Disruptions in cerebral oxygen supply caused by congenital heart disease have significant impact on cortical growth, according to a research led by Children’s National Health System. The findings of the research team, which include co-authors from the National Institutes of Health, Boston Children’s Hospital and Johns Hopkins School of Medicine, appear on the cover of Science Translational Medicine. The subventricular zone (SVZ) in normal newborns’ brains is home to the largest stockpile of neural stem/progenitor cells, with newly generated neurons migrating from this zone to specific regions of the frontal cortex and differentiating into interneurons. When newborns experience disruptions in cerebral oxygen supply due to congenital heart disease, essential cellular processes go awry and this contributes to reduced cortical growth.

The preliminary findings point to the importance of restoring these cells’ neurogenic potential, possibly through therapeutics, to lessen children’s long-term neurological deficits.

“We know that congenital heart disease (CHD) reduces cerebral oxygen at a time when the developing fetal brain most needs oxygen. Now, we are beginning to understand the mechanisms of CHD-induced brain injuries at a cellular level, and we have identified a robust supply of cells that have the ability to travel directly to the site of injury and potentially provide help by replacing lost or damaged neurons,” says Nobuyuki Ishibashi, M.D., Director of the Cardiac Surgery Research Laboratory at Children’s National, and co-senior study author.

The third trimester of pregnancy is a time of dramatic growth for the fetal brain, which expands in volume and develops complex structures and network connections that growing children rely on throughout adulthood. According to the National Heart, Lung, and Blood Institute, congenital heart defects are the most common major birth defect, affecting 8 in 1,000 newborns. Infants born with CHD can experience myriad neurological deficits, including behavioral, cognitive, social, motor and attention disorders, the research team adds.

Cardiologists have tapped noninvasive imaging to monitor fetal hearts during gestation in high-risk pregnancies and can then perform corrective surgery in the first weeks of life to fix damaged hearts. Long term neurological deficits due to immature cortical development also have emerged as major challenges in pregnancies complicated by CHD.

“I think this is an enormously important paper for surgeons and for children and families who are affected by CHD. Surgeons have been worried for years that the things we do during corrective heart surgery have the potential to affect the development of the brain. And we’ve learned to improve how we do heart surgery so that the procedure causes minimal damage to the brain. But we still see some kids who have behavioral problems and learning delays,” says Richard A. Jonas, M.D., Chief of the Division of Cardiac Surgery at Children’s National, and co-senior study author. “We’re beginning to understand that there are things about CHD that affect the development of the brain before a baby is even born. What this paper shows is that the low oxygen level that sometimes results from a congenital heart problem might contribute to that and can slow down the growth of the brain. The good news is that it should be possible to reverse that problem using the cells that continue to develop in the neonate’s brain after birth.”

Among preclinical models, the spatiotemporal progression of brain growth in this particular model most closely parallels that of humans. Likewise, the SVZ cytoarchitecture of the neonatal preclinical model exposed to hypoxia mimics that of humans in utero and shortly after birth. The research team leveraged CellTracker Green to follow the path traveled by SVZ derived cells and to illuminate their fate, with postnatal SVZ supplying the developing cortex with newly generated neurons. SVZ derived cells were primarily neuroblasts. Superparamagnetic iron oxide nanoparticles supplied answers about long term SVZ migration, with SVZ derived cells making their way to the prefrontal cortex and the somatosensory cortex of the brain.

“We demonstrated that in the postnatal period, newly generated neurons migrate from the SVZ to specific cortices, with the majority migrating to the prefrontal cortex,” says Vittorio Gallo, Ph.D., Director of the Center for Neuroscience Research at Children’s National, and co-senior study author. “Of note, we revealed that the anterior SVZ is a critical source of newborn neurons destined to populate the upper layers of the cortex. We challenged this process through chronic hypoxia exposure, which severely impaired neurogenesis within the SVZ, depleting this critical source of interneurons.”

In the preclinical model of hypoxia as well as in humans, brains were smaller, weighed significantly less and had a significant reduction in cortical gray matter volume. In the prefrontal cortex, there was a significant reduction in white matter neuroblasts. Taken as a whole, according to the study authors, the findings suggest that impaired neurogenesis within the SVZ represents a cellular mechanism underlying hypoxia induced, region specific reduction in immature neurons in the cortex. The prefrontal cortex, the region of the brain that enables such functions as judgment, decision making and problem solving, is most impacted. Impairments in higher order cognitive functions involving the prefrontal cortex are common in patients with CHD.

Congenital heart disease and white matter injury

February 6, 2017

Although recent advances have greatly improved the survival of children with congenital heart disease, up to 55 percent will be left with injury to their brain’s white matter – an area that is critical for aiding connection and communication between various regions in the brain.

What’s known

Eight of every 1,000 children born each year have congenital heart disease (CHD). Although recent advances have greatly improved the survival of these children, up to 55 percent will be left with injury to their brain’s white matter – an area that is critical for aiding connection and communication between various regions in the brain. The resulting spectrum of neurological deficits can have significant costs for the individual, their family and society. Although studies have demonstrated that white matter injuries due to CHD have many contributing factors, including abnormal blood flow to the fetal brain, many questions remain about the mechanisms that cause these injuries and the best interventions.

What’s new

A Children’s National Health System research team combed existing literature, reviewing studies from Children’s as well as other research groups, to develop an article detailing the current state of knowledge on CHD and white matter injury. The scientists write that advances in neuroimaging – including magnetic resonance imaging, magnetic resonance spectroscopy, Doppler ultrasound and diffusion tensor imaging – have provided a wealth of knowledge about brain development in patients who have CHD. Unfortunately, these techniques alone are unable to provide pivotal insights into how CHD affects cells and molecules in the brain. However, by integrating animal models with findings in human subjects and in postmortem human tissue, the scientists believe that it will be possible to find novel therapeutic targets and new standards of care to prevent developmental delay associated with cardiac abnormalities.

For example, using a porcine model, the Children’s team was able to define a strategy for white matter protection in congenital heart surgery through cellular and developmental analysis of different white matter regions. Another study from Children’s combined rodent hypoxia with a brain slice model to replicate the unique brain conditions in neonates with severe and complex congenital heart disease. This innovative animal model provided novel insights into the possible additive effect of preoperative hypoxia on brain insults due to cardiopulmonary bypass and deep hypothermic circulatory arrest.

The Children’s research team also recently published an additional review article describing the key windows of development during which the immature brain is most vulnerable to CHD-related injury.

Questions for future research

Q: Can we create an animal model that recapitulates the morphogenic and developmental aspects of CHD without directly affecting other organs or developmental processes?
Q: What are the prenatal and neonatal cellular responses to CHD in the developing brain?
Q: What are the molecular mechanisms underlying white matter immaturity and vulnerability to CHD, and how can we intervene?
Q: How can we accurately assess the dynamic neurological outcomes of CHD and/or corrective surgery in animal models?
Q: Prenatal or postnatal insults to the developing brain: which is most devastating in regards to developmental and behavioral disabilities?
Q: How can we best extrapolate from, and integrate, neuroimaging findings/correlations in human patients with cellular/molecular approaches in animal models?

Source: Reprinted from Trends in Neurosciences, Vol. 38/Ed. 6, Paul D. Morton, Nobuyuki Ishibashi, Richard A. Jonas and Vittorio Gallo, “Congenital cardiac anomalies and white matter injury,” pp. 353-363, Copyright 2015, with permission from Elsevier.

Thrasher to fund Children’s project

February 1, 2017

The Thrasher Research Fund will fund a Children’s National Health System project, “Defining a new parameter for post-hemorrhagic ventricular dilation in premature infants,” as part of its Early Career Award Program, an initiative designed to support the successful training and mentoring of the next generation of pediatric researchers.

The proposal was submitted by Rawad Obeid, M.D., a neonatal neurology clinical research fellow at Children’s National who will serve as the project’s principal investigator. The competition for one-year Thrasher Research Fund awards is highly competitive with just two dozen granted across the nation. Research clinicians at Children’s National received two awards this funding cycle, with another awarded to support a neurologic outcomes study about Zika-affected pregnancies led by Fetal-Neonatal Neurologist Sarah B. Mulkey, M.D., Ph.D.

“Preterm infants born earlier than the 29th gestational week are at high risk for developing cerebral palsy and other brain injuries,” Dr. Obeid says. “Infants with intraventricular hemorrhage (IVH) followed by hydrocephalus (post-hemorrhagic hydrocephalus) face the highest risks of such brain injuries.”

Dr. Obeid hypothesizes that measuring distinct frontal and temporal horn ratio trajectories in extremely premature infants with and without IVH will help to definitively characterize post-hemorrhagic ventricular dilation (PHVD). Right now, experts disagree about the degree of PHVD that should trigger treatment to avoid life-long impairment.

He will be mentored by Anna A. Penn, M.D., Ph.D., Director, Translational Research for Hospital-Based Services & Board of Visitors Cerebral Palsy Prevention Program; Taeun Chang, M.D., Director of the Neonatal Neurology Program within the Division of Neurophysiology, Epilepsy & Critical Care; and Dorothy Bulas, M.D., F.A.C.R., F.A.I.U.M., F.S.R.U., Vice Chief of Academic Affairs.

In the award nomination letter, Dr. Penn noted that in “clinical settings and in the laboratory, I have supervised many trainees, but a trainee like Dr. Obeid is rare. He has pursued his research interests with great commitment. Before coming to Children’s National, he already had multiple job offers, but chose further training to enhance his research skills. While I have worked with many accomplished students, residents and fellows, Dr. Obeid stands out not only for his strong clinical skills, but also for his eagerness to learn and his dedication to both his patients and his research.”

New Children’s National and Inova collaboration

January 13, 2017

A new research collaboration will streamline completion of retrospective and prospective research studies, shedding light on myriad conditions that complicate pregnancies.

A new three-year, multi-million dollar research and education collaboration in maternal, fetal and neonatal medicine aims to improve the health of pregnant women and their children. The partnership between Children’s National Health System and Inova will yield a major, nationally competitive research and academic program in these areas that will leverage the strengths of both health care facilities and enhance the quality of care available for these vulnerable populations.

The collaboration will streamline completion of retrospective and prospective research studies, shedding light on a number of conditions that complicate pregnancies. It is one of several alliances between the two institutions aimed at improving the health and well-being of children in Northern Virginia and throughout the region.

“The Washington/Northern Virginia region has long had the capability to support a major, nationally competitive research and academic program in maternal and fetal medicine,” says Adre du Plessis, M.B.Ch.B., Director of the Fetal Medicine Institute at Children’s National and a co-Principal Investigator for this partnership. “The Children’s National/Inova maternal-fetal-neonatal research education program will fill this critical void.

“This new partnership will help to establish a closer joint education program between the two centers, working with the OB/Gyn residents at Inova and ensuring their involvement in Children’s National educational programs and weekly fetal case review meetings,” Dr. du Plessis adds.

Larry Maxwell, M.D., Chairman of Obstetrics and Gynecology at Inova Fairfax Medical Campus and a co-Principal Investigator for the collaboration, further emphasizes that “Inova’s experience in caring for women and children — combined with genomics- and proteomics-based research — will synergize with Children National’s leadership in neonatal pediatrics, placental biology and fetal magnetic resonance imaging (MRI) to create an unprecedented research consortium. This will set the stage for developing clinically actionable interventions for mothers and babies in metropolitan District of Columbia.”

Children’s National, ranked No. 3 nationally in neonatology, has expertise in pediatric neurology, fetal and neonatal neurology, fetal and pediatric cardiology, infectious diseases, genetics, neurodevelopment and dozens of additional pediatric medical subspecialties. Its clinicians are national leaders in next-generation imaging techniques, such as MRI. Eighteen specialties and 50 consultants evaluate more than 700 cases per year through its Fetal Medicine Institute. In mid-2016, Children’s National created a Congenital Zika Virus Program to serve as a dedicated resource for referring clinicians and pregnant women. The hospital performs deliveries in very high-risk, complex situations, but does not offer a routine labor and delivery program.

Inova Fairfax Medical Campus is home to both Inova Women’s Hospital and Inova Children’s Hospital. Inova Women’s Hospital is the region’s most comprehensive and highest-volume women’s hospital — delivering more than 10,000 babies in 2016. Inova Children’s Hospital serves as Northern Virginia’s children’s hospital —providing expert care in pediatric and fetal cardiology, cardiac surgery, genetics, complex general surgery, neurology, neurosurgery and other medical and surgical specialties. Its 108-bed Level IV neonatal intensive care unit is one of the largest and most comprehensive in the nation. Inova’s Translational Medicine Institute includes a genomics lab, as well as a research Institute focused on studies designed to build genetic models that help answer questions about individual disease. Each of these specialties is integrated into the Inova Fetal Care Center — which serves as a connection point between Inova Women’s and Children’s Hospitals. The Inova Fetal Care Center provides complex care coordination for women expecting infants with congenital anomalies or with other fetal concerns. Because Inova Women’s Hospital and Inova Children’s Hospital are co-located, women are able to deliver their babies in the same building where their children will receive care.

The research collaboration will support research assistants; tissue technicians; a placental biologist; as well as support for biomedical engineering, fetal-neonatal imaging, telemedicine, regulatory affairs and database management. The joint research projects that will take place under its auspices include:

Fetal growth restriction (FGR), which occurs when the failing placenta cannot support the developing fetus adequately. FGR is a major cause of stillbirth and death, and newborns who survive face numerous risks for multiple types of ailments throughout their lives. A planned study will use quantitative MRI to identify signs of abnormal brain development in pregnancies complicated by FGR.
Placental abnormalities, including placenta accreta. A planned study will combine quantitative MRI studies on the placenta during the third trimester and other points in time with formal histopathology to identify MRI signals of placenta health and disease.
Microcephaly, a condition that is characterized by babies having a much smaller head size than expected due to such factors as interrupted brain development or brain damage during pregnancy. While the global Zika virus epidemic has heightened awareness of severe microcephaly cases, dozens of pregnancies in the region in recent years have been complicated by the birth defect for reasons other than Zika infection. A planned study will examine the interplay between MRI within the womb and head circumference and weight at birth to examine whether brain volume at birth correlates with the baby’s developmental outcomes.

Using fMRI for assessment prior to neurosurgery

January 12, 2017

For more than 20 years, Children’s National has explored the use of non-invasive fMRI as an alternative to more invasive testing to assess children’s language and memory.

A new Practice Guideline Summary published in Neurology, the journal of the American Academy of Neurology, contains the first complete, objective assessment of available data on the efficacy of functional magnetic resonance imaging (fMRI) to assess baseline language and memory, brain hemisphere dominance and to predict postsurgical impacts prior to surgery in patients with epilepsy.

According to contributing author William D. Gaillard, M.D., chief of Child Neurology, Epilepsy and Neurophysiology, and director of the Comprehensive Pediatric Epilepsy Program at Children’s National Health System, the report outlines several cases in which fMRI presents an effective alternative to the current standard of care, intracarotid amobarbital procedure (IAP). In IAP, medication is injected through the carotid artery to isolate one hemisphere of the brain at a time, followed by the patient performing memory or language tasks. The approach requires catheterization via a major artery. While minimally invasive, the procedure still carries the standard risks of vascular catheter procedures and requires recovery time.

“This publication took six years to complete,” Dr. Gaillard notes, “but we are happy to finally have the practice parameters that will make the case for the use of fMRI in an evidence-based way.”

Though the Practice Guidelines focus on adults, the evidence assessment included all available pediatric data as well, says Dr. Gaillard. A great deal of that data were contributed by Children’s National faculty, who lead the nation in clinical applications of fMRI. More than 20 years ago, Dr. Gaillard and his team began studying fMRI as a viable alternative to IAP to collect accurate language assessments in children, particularly those with epilepsy. Today, Children’s National is at the forefront of clinical application of fMRI, having performed about 1,000 pediatric assessments in the last two decades — more than nearly every other institution.

An 11-member panel of international experts conducted the analyses for the Practice Guidelines. Overall, the report indicates:

fMRI is a viable option for measuring lateralized language functions in place of IAP in medial temporal lobe epilepsy, temporal epilepsy in general or extratemporal epilepsy.
Evidence was insufficient to recommend fMRI over IAP for patients with temporal neocortical epilepsy or temporal tumors.
Pre-surgical fMRI can serve as an adequate alternative to IAP memory testing for predicting verbal memory outcome.

In closing, the authors also explicitly recommend that clinicians carefully advise every patient of the risks and benefits of both fMRI and IAP before recommending either approach.

Vittorio Gallo named Chief Research Officer

January 12, 2017

As chief research officer, Vittorio Gallo, Ph.D., will be instrumental in developing and realizing Children’s Research Institute’s long-term strategic vision.

Children’s National Health System has appointed the longtime director of its Center for Neuroscience Research, Vittorio Gallo, Ph.D., as Chief Research Officer. Gallo’s appointment comes at a pivotal time for the institution’s research strategic plan, as significant growth and expansion will occur in the next few years. Gallo is a neuroscientist who studies white matter disorders, with particular focus on white matter growth and repair. He is also the Wolf-Pack Chair in Neuroscience at Children’s Research Institute, the academic arm of Children’s National.

As Chief Research Officer, Gallo will be instrumental in developing and realizing Children’s Research Institute’s long-term strategic vision, which includes building out the nearly 12-acre property once occupied by Walter Reed National Military Medical Center to serve as a regional innovation hub and to support Children’s scientists conducting world-class pediatric research in neuroscience, genetics, clinical and translational science, cancer and immunology. He succeeds Mendel Tuchman, M.D., who has had a long and distinguished career as Children’s Chief Research Officer for the past 12 years and who will remain for one year in an emeritus role, continuing federally funded research projects and mentoring junior researchers.

“I am tremendously pleased that Vittorio has agreed to become Chief Research Officer as of July 1, 2017, at such a pivotal time in Children’s history,” says Mark L. Batshaw, M.D., Physician-in-Chief and Chief Academic Officer at Children’s National. “Since Mendel announced plans to retire last summer, I spent a great deal of time talking to Children’s Research Institute investigators and leaders and also asking colleagues around the nation about the type of person and unique skill sets needed to serve as Mendel’s successor. With each conversation, it became increasingly clear that the most outstanding candidate for the Chief Research Officer position already works within Children’s walls,” Dr. Batshaw adds.

“I am deeply honored by being selected as Children’s next Chief Research Officer and am excited about being able to play a leadership role in defining the major areas of research that will be based at the Walter Reed space. The project represents an incredible opportunity to maintain the core nucleus of our research strengths – genetics, immunology, neurodevelopmental disorders and disabilities – and to expand into new, exciting areas of research. What’s more, we have an unprecedented opportunity to form new partnerships with peers in academia and private industry, and forge new community partnerships,” Gallo says. “I am already referring to this as Walter Reed ‘Now,’ so that we are not waiting for construction to begin to establish these important partnerships.”

Gallo’s research focus has been on white matter development and injury, myelin and glial cells – which are involved in the brain’s response to injury. His past and current focus is also on neural stem cells. His work in developmental neuroscience has been seminal in deepening understanding of cerebral palsy and multiple sclerosis. He came to Children’s National from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) intramural program. His intimate knowledge of the workings of the National Institutes of Health (NIH) has helped him to establish meaningful collaborations between both institutions. During his tenure, he has transformed the Center for Neuroscience Research into one of the nation’s premier programs. The Center is home to the prestigious NIH/NICHD-funded District of Columbia Intellectual and Developmental Disabilities Research Center, which Gallo directs.

Children’s research scientists working under the auspices of Children’s Research Institute conduct and promote highly collaborative and multidisciplinary research within the hospital that aims to better understand, treat and, ultimately, prevent pediatric disease. As Chief Research Officer, Gallo will continue to establish and enhance collaborations between research and clinical programs. Such cross-cutting projects will be essential in defining new mechanisms that underlie pediatric disease. “We know, for instance, that various mechanisms contribute to many genetic and neurological pediatric diseases, and that co-morbidities add another layer of complexity. Tapping expertise across disciplines has the potential to unravel current mysteries, as well as to better characterize unknown and rare diseases,” he says.

“Children’s National is among the nation’s top seven pediatric hospitals in NIH research funding, and the extraordinary innovations that have been produced by our clinicians and scientists have been put into practice here and in hospitals around the world,” Dr. Batshaw adds. “Children’s leadership aspires to nudge the organization higher, to rank among the nation’s top five pediatric hospitals in NIH research funding.”

Gallo says the opportunity for Children’s research to expand beyond the existing buildings and the concurrent expansion into new areas of research will trigger more hiring. “We plan to grow our research enterprise through strategic hires and by attracting even more visiting investigators from around the world. By expanding our community of investigators, we aim to strengthen our status as one of the nation’s leading pediatric hospitals,” he says.

Harnessing progenitor cells in neonatal white matter repair

December 21, 2016

The sirtuin protein Sirt1 plays a crucial role in the proliferation and regeneration of glial cells from an existing pool of progenitor cells — a process that rebuilds vital white matter following neonatal hypoxic brain injury. Although scientists do not fully understand Sirt1’s role in controlling cellular proliferation, this pre-clinical model of neonatal brain injury outlines for the first time how Sirt1 contributes to development of additional progenitor cells and maturation of fully functional oligodendrocytes.

The findings, published December 19 in Nature Communications, suggest that modulation of this protein could enhance progenitor cell regeneration, spurring additional white matter growth and repair following neonatal brain injury.

“It is not a cure. But, in order to regenerate the white matter that is lost or damaged, the first steps are to identify endogenous cells capable of regenerating lost cells and then to expand their pool. The glial progenitor cells represent 4 to 5 percent of total brain cells,” says Vittorio Gallo, Ph.D., Director of the Center for Neuroscience Research at Children’s National, and senior author of the study. “It’s a sizable pool, considering that the brain is made up of billions of cells. The advantage is that these progenitor cells are already there, with no requirement to slip them through the blood-brain barrier. Eventually they will differentiate into oligodendrocyte cells in white matter, mature glia, and that’s exactly what we want them to do.”

The study team identified Sirt1 as a novel, major regulator of basal oligodendrocyte progenitor cell (OPC) proliferation and regeneration in response to hypoxia in neonatal white matter, Gallo and co-authors write. “We demonstrate that Sirt1 deacetylates and activates Cdk2, a kinase which controls OPC expansion. We also elucidate the mechanism by which Sirt1 targets other individual members of the Cdk2 signaling pathway, by regulating their deacetylation, complex formation and E2F1 release, molecular events which drive Cdk2-mediated OPC proliferation,” says Li-Jin Chew, Ph.D., research associate professor at Children’s Center for Neuroscience Research and a study co-author.

Hypoxia-induced brain injury in neonates initiates spontaneous amplification of progenitor cells but also causes a deficiency of mature oligodendrocytes. Inhibiting Sirt1 expression in vitro and in vivo showed that loss of its deacetylase activity prevents OPC proliferation in hypoxia while promoting oligodendrocyte maturation – which underscores the importance of Sirt1 activity in maintaining the delicate balance between these two processes.

The tantalizing findings – the result of four years of research work in mouse models of neonatal hypoxia – hint at the prospect of lessening the severity of developmental delays experienced by the majority of preemies, Gallo adds. About 1 in 10 infants born in the United States are delivered preterm, prior to the 37^th gestational week of pregnancy, according to the Centers for Disease Control and Prevention. Brain injury associated with preterm birth – including white matter injury – can have long-term cognitive and behavioral consequences, with more than 50 percent of infants who survive prematurity needing special education, behavioral intervention and pharmacological treatment, Gallo says.

Time is of the essence, since Sirt1 plays a beneficial role at a certain place (white matter) and at a specific time (while the immature brain continues to develop). “We see maximal Sirt1 expression and activity within the first week after neonatal brain injury. There is a very narrow window in which to harness the stimulus that amplifies the progenitor cell population and target this particular molecule for repair,” he says.

Sirt1, a nicotinamide adenine dinucleotide-dependent class III histone deacetylase, is known to be involved in normal cell development, aging, inflammatory responses, energy metabolism and calorie restriction, the study team reports. Its activity can be modulated by sirtinol, an off-the-shelf drug that inhibits sirtuin proteins. The finding points to the potential for therapeutic interventions for diffuse white matter injury in neonates.

Next, the research team aims to study these processes in a large animal model whose brains are structurally, anatomically and metabolically similar to the human brain.

“Ideally, we want to be able to promote the timely regeneration of cells that are lost by designing strategies for interventions that synchronize these cellular events to a common and successful end,” Gallo says.

Thrasher Research Fund supports Zika virus neurologic outcomes study

December 19, 2016

The Thrasher Research Fund will fund a Children’s National project, “Neurologic Outcomes of Apparently Normal Newborns From Zika Virus-Positive Pregnancies,” as part of its Early Career Award Program, an initiative designed to support the successful training and mentoring of the next generation of pediatric researchers.

The project was submitted by Sarah B. Mulkey, M.D., Ph.D., a fetal-neonatal neurologist who is a member of the Congenital Zika Virus Program at Children’s National. During the award period, Dr. Mulkey will be mentored by Adre du Plessis, M.B.Ch.B., director of the Fetal Medicine Institute, and Roberta L. DeBiasi, M.D., M.S., chief of the Division of Pediatric Infectious Diseases. Drs. du Plessis and DeBiasi co-direct the multidisciplinary Zika program, one of the nation’s first.

In the award letter, the fund mentioned Children’s institutional support for Dr. Mulkey, as demonstrated by the mentors’ letter of support, as “an important consideration throughout the funding process.”

Doctors working together to find treatments for autoimmune encephalitis

Shining light on autoimmune encephalitis

November 22, 2016

Experts at Children’s National Health System brought together over 40 specialists from around the world to talk about autoimmune encephalitis (AE) and how the present institutions can better align their research priorities with the goal of finding more effective treatment for children with AE.

About autoimmune encephalitis

AE is a serious and rare medical condition in which the immune system attacks the brain, significantly impairing function and causing the loss of the ability to perform basic actions such as walking, talking or eating. If diagnosed quickly and treated appropriately, many patients recover most or all functions within a few years. However, not all patients will fully recover, or even survive, if the condition is not diagnosed early. AE is mainly seen in female young adults, but is increasingly being seen more in males and females of all ages.

The condition is often difficult to diagnose. Symptoms can vary and include psychosis, tremors, multiple seizures, and uncontrollable bodily movements. Once diagnosed, AE is treated by steroids and neuro-immunology treatments such as plasmapheresis, the removal and exchange of infected plasma with healthy plasma.

The Neuro-Immunology Clinic at Children’s National treats infants, children, and adolescents with several neurologic autoimmune conditions including AE. The multidisciplinary team consists of neurologists, neuropsychologists, physical and rehabilitation medicine experts, and complex care physicians.

A look at the pediatric autoimmune encephalitis treatment consensus meeting

Children’s National, along with Autoimmune Encephalitis Alliance and the Childhood Arthritis and Rheumatology Research Alliance, hosted the first International Pediatric Autoimmune Encephalitis Treatment Consensus Meeting at the Carnegie Endowment for International Peace in Washington, DC, this month. Several leading children’s hospitals and health institutions including Duke University Medical Center, Texas Children’s Hospital, and Alberta Children’s Hospital also co-hosted the event with Children’s National.

“This meeting gathered experts from around the world to discuss our current efforts to standardize approaches to diagnosis, treatment, and research for pediatric autoimmune encephalitis with the common goal of discovering new ways to provide more effective care to children and adolescents with AE,” says Elizabeth Wells, MD, director of the Neuro-Immunology Clinic at Children’s National.

The following were the three main objectives of the meeting:

Beginning the formation of treatment roadmaps for initial treatment and maintenance therapy for pediatric AE
Discussing current work to standardize approaches to diagnosis, initial treatment, maintenance immunotherapy, disease surveillance, biomarker discovery, supportive care, and multidisciplinary coordination
Aligning research priorities and planning future collaborative work

Three families who have children with AE also shared their stories of diagnosis and journeys to recovery, putting the need for more research into perspective for the experts in the room.

“We are very hopeful for the future of autoimmune encephalitis research and are proud to be at the forefront of it so we are able to provide the best possible care to our patients,” says Dr. Wells.

Children’s National spin-off ReveraGen announces agreement with actelion for Duchenne Muscular Dystrophy treatment

November 22, 2016

Earlier this month, ReveraGen BioPharma announced an exclusive option agreement with Actelion Ltd for lead compound vamorolone, a non-hormonal steroid modulator that is primarily used for the treatment of Duchenne Muscular Dystrophy (DMD). ReveraGen, the first Children’s National private spin-off company, is engaged in the discovery and development of proprietary therapeutic products for neuromuscular and inflammatory diseases.

Under the terms of the license agreement, Actelion and ReveraGen will partner to research and co-develop the novel compound vamorolone, which holds the potential to preserve muscle function and prolong ambulation in DMD patients, without some of the side effects that are commonly associated with glucocorticoid therapy. Those commonly associated include growth stunting and immune suppression, which can pose significant challenges for very young patients.

ReveraGen completed Phase I clinical trials for vamorolone in late 2015, and a Phase IIa program is currently underway to investigate the safety and efficiency of vamorolone in male DMD patients between four and seven years of age who have not taken deflazacort or prednisone. A Phase IIb program is also in early planning stages.

ReveraGen Co-Founder and CEO Eric Hoffman, PhD, has worked on DMD since the late 1980’s and has led his own research group for nearly 20 years at Children’s National. He co-founded ReveraGen back in 2008 with John McCall, PhD and Kanneboyina Nagaraju, PhD, DVM, before being named CEO in 2014. Children’s National maintains a 38 percent stake in ReveraGen.

Brain tumor expert from Children’s National speaks at Society for Neuro-Oncology’s scientific meeting and Education Day

November 8, 2016

Roger Packer

Roger Packer, M.D., Senior Vice President for the Center of Neuroscience and Behavioral Medicine and Director of the Brain Tumor Institute at Children’s National Health System, will be speaking at the 21st Annual Meeting and Education Day of the Society for Neuro-Oncology. From November 17-20, 2016, the conference will gather neuro-oncologists, medical oncologists, adult and pediatric neurosurgeons, pediatric neuro-oncologists, neuroradiologists, neuropathologists, radiation oncologists, neuropsychologists, and epidemiologists from across the country to discuss the future of neuro-oncology. Dr. Packer will be sharing his expertise in treating neurofibromatosis and pediatric brain tumors. He also will be part of a working group to discuss guidelines for response assessment in PDCT-13 medulloblastoma and other leptomeningeal seeding tumors.

2016 Neurobiology of Disease in Children Symposium: neurofibromatosis features Children’s National expert

November 8, 2016

Roger Packer, M.D., Senior Vice President for the Center of Neuroscience and Behavioral Medicine and Director of the Gilbert Neurofibromatosis Institute at Children’s National Health System, was an invited speaker at the 2016 Neurobiology of Disease in Children Symposium: Neurofibromatosis (NF). This conference brought together experts from around the world to discuss the newest developments in the understanding and treatment of children with NF. While at the conference, which was held on October 26, 2016, Dr. Packer gave an update of the Department of Defense-sponsored Neurofibromatosis Clinical Trial Consortium. The Neurofibromatosis Clinical Trials Consortium, of which Dr. Packer is the group chair, was established by the Department of Defense Neurofibromatosis Research Program to develop and perform clinical trials for the treatment of NF complications in children and adults.

Brain Tumor Institute Director Speaks at Coalition against Childhood Cancer Meeting

November 8, 2016

Roger Packer, MD, Senior Vice President for the Center of Neuroscience and Behavioral Medicine and Director of the Brain Tumor Institute at Children’s National Health System, was an invited speaker at the Coalition Against Childhood Cancer meeting at Cold Springs Harbor Laboratory on October 31 and November 1, 2016. This international conference was a unique collaborative effort between multiple foundations, the National Cancer Institute, and industry experts to develop a new path forward for the treatment of childhood cancer. Dr. Packer spoke on “Pediatric Brain Tumors: Where Are We Now” and shared his expertise in treating pediatric brain tumors and what he hopes the future of pediatric brain tumor research will look like. Pediatric brain tumors recently surpassed leukemia as the most deadly form of childhood cancer.

How technology can predict vision loss in neurofibromatosis patients

November 6, 2016

For the first time, scientists have been able to definitively connect tumor volume and vision loss for children with neurofibromatosis type 1 (NF1). The first study to use quantitative imaging technology to accurately assess the total volume of individual optic nerve glioma (OPG) in NF1 was published in the November 4, 2016 issue of Neurology.

NF1 is a genetic condition that occurs in one in 3,500 births. Children with NF1 develop tumors in multiple locations across the nervous system. About 20 percent of children with NF1 will develop optic pathway gliomas, or tumors that occur in the visual system. Half of those with OPG will have irreversible vision loss, which occurs at a very young age, usually before age 3.

“Neuroradiologists typically assess these tumors through a measurement of the tumor’s radii using magnetic resonance images (MRI) of the patient,” said Marius George Linguraru, D.Phil., M.A., M.S., Principal Investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System, who is senior author on the study.

“These measurements aren’t detailed enough to serve as a good indicator of whether an OPG will cause vision loss for a child. Through automated computerized analysis, however, we’ve taken the MRI data and systematically analyzed the size and shape, as well as documented changes over time, all in 3-D, to pinpoint the volume of each tumor.”

A look inside the study

The study included children with NF1-related OPGs who are currently cared for at the Gilbert Family Neurofibromatosis Institute at Children’s National. Investigators compared the MRI analysis to the patients’ retinal nerve fiber layer (RNFL), a measure of the health of the visual system. The analysis showed a quantifiable negative relationship between increasing tumor volume within the structures of the anterior visual pathway (the optic nerve, chiasm, and tract) and decreasing thickness of the RNFL, indicating damage to the visual system and vision loss.

“Measuring the tumors in a precise, systematic manner, along with knowing how they grow, is the first step in recognizing which children are at highest risk for vision loss and to potentially identifying them before they suffer any visual symptoms,” added Dr. Linguraru. “If we know which children will probably lose vision, we can treat earlier, and perhaps improve how patients respond to treatment.”

A multicenter collaborative study to validate the findings will begin in 2017.

Every day fetuses remain in utero critical to preserving normal brain development

October 28, 2016

preemieimage

If it does not jeopardize the health of the pregnant mother or her fetus, pregnancies should be carried as close to full term as possible to avoid vulnerable preemies experiencing a delay in brain development, study results published October 28 in Pediatrics indicate.

Some 15 million infants around the world – and 1 in 10 American babies – are born prematurely. While researchers have known that preemies’ brain growth is disturbed when compared with infants born at full term, it remained unclear when preemies’ brain development begins to veer off course and how that impairment evolves over time, says Catherine Limperopoulos, Ph.D., Director of the Developing Brain Research Laboratory at Children’s National Health System and senior study author.

A look at the research

In order to shine a spotlight on this critical phase of fetal brain development, Limperopoulos and colleagues studied 75 preterm infants born prior to the 32th gestational week who weighed less than 1,500 grams who had no evidence of structural brain injury. These preemies were matched with 130 fetuses between 27 to 39 weeks gestational age.

The healthy fetal counterparts are part of a growing database that the Children’s National Developing Brain Research Laboratory has assembled. The research lab uses three-dimensional magnetic resonance imaging to carefully record week-by-week development of the normal in utero fetal brains as well as week-by-week characterizations of specific regions of the fetal brain.

The availability of time-lapsed images of normally developing brains offers a chance to reframe research questions in order to identify approaches to prevent injuries to the fetal brain, Limperopoulos says.

“Up until now, we have been focused on examining what is it about being born too early? What is it about those first few hours of life that leaves preemies more vulnerable to brain injury?” she says. “What is really unique about these study results is for the very first time we have an opportunity to better understand the ways in which we care for preemies throughout their hospitalization that optimize brain development and place more emphasis those activities.”

When the research team compared third-trimester brain volumes, preemies showed lower volumes in the cerebrum, cerebellum, brainstem, and intracranial cavity. The cerebrum is the largest part of the brain and controls speech, thoughts, emotions, learning, as well as muscle function. The cerebellum plays a role in learning and social-behavioral functions as well as complex motor functions; it also controls the balance needed to stand up and to walk. The brainstem is like a router, ferrying information between the brain, the cerebellum, and the spinal cord.

“What this study shows us is that every day and every week of in utero development is critical. If at all possible, we need to keep fetuses in utero to protect them from the hazards that can occur in the extra uterine environment,” she says.

Transgender adolescents on the autism spectrum, and the first clinical guidelines for care

October 24, 2016

Evidence indicates a link between transgenderism and autism spectrum disorders (ASD). John Strang, Psy.D., a neuropsychologist in the Center for Autism Spectrum Disorders at Children’s National Health System, has dedicated his career to learning more about this co-occurrence and led a group of experts who recently released the first clinical guidelines for the care of transgender adolescents with ASD.

Through a comprehensive international search procedure, the research team, led by Dr. Strang, identified 22 experts in the care of transgender youth with autism. The expert group from around the world worked together for one year to create guidelines, putting processes in place to avoid interpersonal influence or bias.

The findings, published in the Journal of Clinical Child and Adolescent Psychology, outline the first initial clinical guidelines for treating transgender adolescents with ASD.

With overall 89.6 percent consensus achieved among the identified experts, key recommendations include the importance of assessing for ASD among transgender youth, and assessing for gender concerns among youth on the autism spectrum.

More study findings and recommendations

The study also indicates that gender-related medical treatments, including cross-sex hormone therapy, are appropriate for some youth with ASD, but emphasizes the importance of providing more extended time and supports in many cases to allow an adolescent with autism to explore a range of options regarding gender.

The guidelines emphasize that for many transgender youth with autism, parents must play a more active role. “Teens on the autism spectrum often struggle understanding how others perceive them,” Dr. Strang said. “Our study found that many transgender youth on the autism spectrum require specific coaching and supports in how to achieve their gender-related needs regarding gender presentation.”

Several risks for transgender adolescents with autism were emphasized in the study, including around physical safety and obtaining employment. “Trans youth are at increased risk for bullying, persecution, and violence in the community, and those on the autism spectrum are at even higher risk, as they often struggle to read social cues and recognize potentially dangerous social situations,” Dr. Strang said.

The importance of this study

The study group did not achieve consensus around specific guidelines for when an adolescent is appropriate for commencing medical gender treatments (e.g., cross-sex hormones). A majority (about 90 percent) of the expert participants elected to identify themselves as co-authors of the study, including many well-known clinicians across the United States as well as clinicians from The Netherlands.

“Until now, care for individuals with autism and gender concerns has been a matter of individual clinician judgment. This study has allowed for dialogue and discernment between the world’s experts in this field to establish the first recommendations for care,” Dr. Strang said.

Dr. Strang is currently working on a follow-up study to more directly capture the voices and experiences of youth with this co-occurrence, as key stakeholders and collaborators in the research.

At AAP: hands-on simulation training with life-saving technology

October 24, 2016

Recent medical breakthroughs have enabled very premature infants and children with rare genetic and neurological diseases to survive what had once been considered to be fatal conditions. This has resulted in a growing number of children with medically complex conditions whose very survival depends on ongoing use of technology to help their brains function, their lungs take in oxygen, and their bodies remain nourished.

“Many pediatricians care for technology-dependent children with special health needs,” says Neha Shah, M.D., M.P.H., an associate professor of pediatrics in the Division of Hospitalist Medicine at Children’s National Health System. “These kids have unique risks – some of which may be associated with that life-saving device malfunctioning.” Because there is no standard residency training for these devices, many clinicians may feel ill-equipped to address their patients’ device-related issues. To bridge that training gap, Dr. Shah and co-presenters, Priti Bhansali, M.D., M.Ed., and Anjna Melwani, M.D., will lead hands-on simulation training during the American Academy of Pediatrics 2016 National Conference.

“Inevitably, these things happen at 3 in the morning,” Dr. Shah adds. “Individual clinicians’ skill level and comfort with the devices varies. We should all have the same core competency.”

How the training works

During the simulation, the audience is given a specific case. They have eight minutes to troubleshoot and resolve the issue, using mannequins specially fitted with devices, such as trach tubes and feeding tubes, in need of urgent attention. Depending on their actions, the mannequin may decompensate with worsened breathing and racing heartbeats. The high-stakes, hands-on demo is followed by a 12-minute debrief, a safe environment to review lessons learned. Once they complete one simulation, attendees move to the next in the series of four real-life scenarios.

“We’ve done this a few times and my heart rate still goes up,” Dr. Shah admits. After giving similar training sessions at other academic meetings, participants said that having a chance to touch and feel the devices and become familiar with them in a calm environment is a benefit.

Dr. Shah came up with the concept for the hands-on training by speaking with a small group of peers, asking about how comfortable they felt managing kids with medical complex cases. The vast majority favored additional education about common devices, such as gastronomy tubes, tracheostomy tubes, and ventriculoperitoneal shunts. In addition to the in-person training, the team has created a web-based curriculum discussing dysautonomia, spasticity, gastroesophageal reflux disease, enteric feeding tubes, venous thromboembolism, and palliative care, which they described in an article published in the Fall 2015 edition of the Journal of Continuing Education in the Health Professions.

“Most times, clinicians know what they need to do and the steps they need to follow. They just haven’t done it themselves,” Dr. Bhansali adds. “The simulation forces people to put their hands on these devices and use them.”

AAP 2016 presentations:
Saturday, October 22, 2016

W1059- “Emergencies in the Technology-Dependent Child: What Every Pediatrician Should Know” 8:30 a.m. to 10 a.m. (SOLD OUT)

W1131- “Emergencies in the Technology-Dependent Child: What Every Pediatrician Should Know” (Encore) 2 p.m. to 3:30PM