Neurology & Neurosurgery

Newborn baby in a crib

Pioneering research center aims to revolutionize prenatal and neonatal health

Catherine Limperopoulos, Ph.D., was drawn to understanding the developing brain, examining how early adverse environments for a mother can impact the baby at birth and extend throughout its entire lifetime. She has widened her lens – and expanded her team – to create the new Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital.

“Despite the obvious connection between mothers and babies, we know that conventional medicine often addresses the two beings separately. We want to change that,” said Dr. Limperopoulos, who also directs the Developing Brain Institute. “Given the current trajectory of medicine toward precision care and advanced imaging, we thought this was the right moment to channel our talent and resources into understanding this delicate and highly dynamic relationship.”

Moving the field forward

Since its establishment in July 2023, the new research center has gained recognition through high-impact scientific publications, featuring noteworthy studies exploring the early phases of human development.

Dr. Limperopoulos has been at the forefront of groundbreaking research, directing attention to the consequences of maternal stress on the unborn baby and the placenta. In addition, under the guidance of Kevin Cook, Ph.D., investigators published a pivotal study on the correlation between pain experienced by premature infants in the Neonatal Intensive Care Unit and the associated risks of autism and developmental delays.

Another area of research has focused on understanding the impact of congenital heart disease (CHD) on prenatal brain development, given the altered blood flow to the brain caused by these conditions during this period of rapid development. Led by Josepheen De Asis-Cruz, M.D., Ph.D., a research team uncovered variations in the functional connectivity of the brains of infants with CHD. In parallel, Nickie Andescavage, M.D., and her team employed advanced imaging techniques to identify potential biomarkers in infants with CHD, holding promise for guiding improved diagnostics and postnatal care. Separately, she is investigating the impact of COVID-19 on fetal brain development.

In the months ahead, the team plans to concentrate its efforts on these areas and several others, including the impact of infectious disease, social determinants of health and protecting developing brains from the negative impacts of maternal stress, pre-eclampsia and other conditions prevalent among expectant mothers.

Assembling a team

Given its robust research plan and opportunities for collaboration, the center pulled together expertise from across the hospital’s faculty and has attracted new talent from across the country, including several prominent faculty members:

  • Daniel Licht, M.D., has joined Children’s National to build a noninvasive optical device research group to better care for children with CHD. Dr. Licht brings decades of experience in pediatric neurology, psychiatry and critical care and is recognized internationally for his expertise in neurodevelopmental outcomes in babies with CHD.
  • Katherine L. Wisner, M.S., M.D., has accumulated extensive knowledge on the impact of maternal stress on babies throughout her career, and her deep background in psychiatry made her a natural addition to the center. While Dr. Wisner conducts research into the urgent need to prioritize maternal mental health, she will also be treating mothers as part of the DC Mother-Baby Wellness Initiative — a novel program based at Children’s National that allows mothers to more seamlessly get care for themselves and participate in mother-infant play groups timed to align with their clinical appointments.
  • Catherine J. Stoodley, B.S., M.S., D.Phil., brings extensive research into the role of the cerebellum in cognitive development. Dr. Stoodley uses clinical studies, neuroimaging, neuromodulation and behavioral testing to investigate the functional anatomy of the part of the brain responsible for cognition.
  • Katherine M. Ottolini, M.D., attending neonatologist, is developing NICU THRIVE – a research program studying the effects of tailored nutrition on the developing newborn brain, including the impact of fortifying human milk with protein, fat and carbohydrates. With a grant from the Gerber Foundation, Dr. Ottolini is working to understand how personalized fortification for high-risk babies could help them grow.

Early accolades

The new center brings together award-winning talent. This includes Yao Wu, Ph.D., who recently earned the American Heart Association’s Outstanding Research in Pediatric Cardiology award for her groundbreaking work in CHD, particularly for her research on the role of altered placental function and neurodevelopmental outcomes in toddlers with CHD. Dr. Wu became the third Children’s National faculty member to earn the distinction, joining an honor roll that includes Dr. Limperopoulos and David Wessel, M.D., executive vice president and chief medical officer.

Interim Chief Academic Officer Catherine Bollard, M.D., M.B.Ch.B., said the cross-disciplinary collaboration now underway at the new center has the potential to make a dramatic impact on the field of neonatology and early child development. “This group epitomizes the Team Science approach that we work tirelessly to foster at Children’s National,” Dr. Bollard said. “Given their energetic start, we know these scientists and physicians are poised to tackle some of the toughest questions in maternal-fetal medicine and beyond, which will improve outcomes for our most fragile patients.”

Before and after pictures of the patient's improved gait

Next-generation genomics testing holds key to undiagnosed rare disease

Before and after pictures of the patient's improved gaitSeth Berger, M.D., Ph.D., felt the pull to dig deeper when he started reading the chart. An 11-year-old boy had an abnormal gait and couldn’t even walk in a straight line down the sidewalk to go trick-or-treating. Yet workups with neurology, orthopedics and an exome analysis of the patient’s genetic code did not provide a diagnosis. He had been getting worse for roughly three years.

With one of the largest clinical genetics departments in the country, Children’s National Hospital receives more than 10,000 visits a year from patients like this middle schooler. Often, they are children and caregivers who are searching for answers and follow-up support for diagnoses of genetic disorders, which impact so few people that only highly trained geneticists and genetic counselors can get to the root of the disorder.

“In genetics, we are finding layers of understanding. A negative clinical test is not always the final answer because the significance of variants can often be missed or misunderstood,” said Dr. Berger, a medical geneticist and principal investigator in the Center for Genetics Medicine Research at Children’s National. “It can take extensive research and a deep knowledge of the limits of certain tests to reach a diagnosis.”

The fine print

On page 4 of the patient’s genetics report, Dr. Berger found a reference to a pair of variants with no known clinical impact. Dr. Berger recognized that the genes referenced could affect proteins that drive potentially treatable neurological outcomes.

Dr. Berger ordered further testing, including biochemical testing of the patient’s blood and a phenylalanine loading challenge, a test that measures how the body metabolizes certain amino acids. With the results, he confirmed a recessive GCH1 deficiency in the patient was causing a condition called DOPA-responsive dystonia, a disorder that causes involuntary muscle contractions, tremors and uncontrolled movements. Laura Schiffman Tochen, M.D., director of the Movement Disorders Program at Children’s National, started the patient on levodopa-carbidopa — a drug combination used to treat Parkinson’s disease and other neurological disorders — and within two hours the boy showed improvement. His gait was almost normal.

Why we’re excited

Dr. Berger presents at conferences on this case and several other medical mysteries that he’s recently solved in his clinical practice and his role at the Pediatric Mendelian Genomics Research Center, a Children’s National program immersed in a federally funded research study to better understand how differences in genetic material can affect human health. As part of his work, he’s joined the GREGoR project (Genomic Research to Elucidate the Genetics of Rare Disease), which hopes to increase the number of genetic disorders where a cause can be identified. The elite genetics consortium includes nationally recognized research centers – the University of California at Irvine, Broad Institute, University of Washington, Baylor University, Stanford University, Invitae and Children’s National – which are working together to harness cutting-edge genomics sequencing capabilities. They hope to enroll thousands in their research, funded by the National Institutes of Health.

“It’s truly stunning what genetic sequencing can find. The outcomes can be life-changing,” said Dr. Berger. “These cases with life-altering diagnoses don’t come along every day, but when they do, they make the hunt to find answers all the more worthwhile.”

Members of the Columbia Zika virus research team

School entry neurodevelopmental outcomes of Zika-exposed Colombian children

Members of the Columbia Zika virus research team

The Children’s National Hospital Zika Research Team and collaborators from Biomelab, in Barranquilla, Colombia take a picture after a study visit in Sabanalarga, Colombia following the neurodevelopmental outcomes of children who had in utero exposure to Zika virus. Pictured from Children’s National Hospital: Dr. Sarah Mulkey, Regan Andringa-Seed, Margarita Arroyave-Wessel, and Dr. Madison Berl.

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been followed to the age of starting primary school.

In a new study published in Pathogens, researchers found children with in utero ZIKV exposure appear to have an overall positive developmental trajectory at 4 to 5 years of age but may experience risks to neurodevelopment in areas of emotional regulation and adaptive mobility.

The hold up in the field

Children who were born during the ZIKV epidemic and who had in utero exposure to ZIKV are only now at the age to start school. Child neurodevelopmental outcome data has not been reported at the age of school entry for children with antenatal ZIKV exposure who do not have the severe birth defects of CZS.

“As these children approach the early school-age years, we aim to examine whether there are neurodevelopmental differences in executive function, motor ability, language development or scholastic skills as compared to a group of unexposed control participants from the same communities in Colombia,” says Sarah Mulkey, M.D., Ph.D., prenatal-neonatal neurologist in The Zickler Family Prenatal Pediatrics Institute at Children’s National Hospital and lead author of the study.

Moving the field forward

Building on previous findings, this study presents the longitudinal outcomes of a well-characterized Colombian cohort of ZIKV-exposed children without CZS at ages 4 to 5 years. These children have been seen for neurodevelopmental follow-up as infants and toddlers at approximately 6 months, 18 months and 3 years of age as part of an international collaboration between researchers in Barranquilla, Colombia and at Children’s National beginning in 2016. The objective of this study was to assess the multi-domain neurodevelopmental outcomes in 4 to 5-year-old children with antenatal ZIKV exposure without CZS compared to unexposed controls in Colombia.

Why we’re excited

Many of the children who had antenatal ZIKV exposure are making good progress in multiple areas of their neurodevelopment. However, the researchers found that children with antenatal ZIKV exposure have differences in areas of emotional regulation, executive function, mood and behavior which may relate to virus exposure during their early brain development.

“These areas of brain function are important for future academic achievement, employment, mental health and social relationships,” says Dr. Mulkey. “So, it will be important to continue to follow these children at older ages when they start school.”

Children’s National leads the way

Children’s National is a leader in conducting outcome studies of children born following antenatal ZIKV exposure. This study follows children in Colombia who are now 5 years old who were first studied while they were in the womb. These children have contributed unique longitudinal understanding to early child neurodevelopment following in utero exposure to ZIKV.

Dr. Mulkey is committed to studying the long-term neurodevelopmental impacts that viruses like Zika and SARS-CoV-2 have on infants born to mothers who were infected during pregnancy through research with the Congenital Infection Program at Children’s National and in collaboration with colleagues in Colombia.

Additional Children’s National authors include Meagan Williams M.S.P.H., C.C.R.C., senior research coordinator; Regan Andringa-Seed, clinical research coordinator, Margarita Arroyave-Wessel, clinical research coordinator; L. Gilbert Vezina, M.D., director, Neuroradiology Program; Dorothy Bulas, M.D., chief, Diagnostic Imaging and Radiology; Robert Podolsky, biostatistician.

Researchers showing paintings of zika virus

Dr. Sarah Mulkey and Children’s National clinical research coordinators in the Prenatal Pediatrics Institute and the Division of Pediatric Infectious Diseases display their paintings of the Zika virus. Pictured from left to right: Manuela Iglesias, Elizabeth Corn, Dr. Sarah Mulkey, Emily Ansusinha and Meagan Williams.

The endovascular embolic hemispherectomy team.

New hemimegalencephaly procedure is all about teamwork

Children’s National experts pioneered a novel approach of inducing strokes to stop seizures and improve neurodevelopmental outcomes in newborns under three months old with hemimegalencephaly (HME). The procedure, called an endovascular embolic hemispherectomy, can be safely used to provide definitive treatment of HME-related epilepsy in neonates and young infants. Monica Pearl, M.D., neurointerventional radiologist, and Panagiotis Kratimenos, M.D., Ph.D., neonatologist, discuss why having a multidisciplinary team skilled at this procedure is the reason we’re the only center in the world capable of providing this treatment.

baby with brain monitor

The history behind the novel hemimegalencephaly procedure

Traditionally, when a baby is diagnosed with hemimegalencephaly (HME), doctors turn to a hemispherectomy at 3 months of age, which involves surgically removing half of a baby’s brain. At Children’s National Hospital, our doctors pioneered the endovascular embolic hemispherectomy, an approach using induced controlled strokes to eliminate the affected part of the brain, halting seizures. Monica Pearl, M.D., neurointerventional radiologist, and Tammy Tsuchida, M.D., Ph.D., neonatal neurologist, talk about this life-changing procedure.

Angelique and family pose in front of their house

Inducing strokes to better treat babies with hemimegalencephaly

When a family from Texas received a shocking diagnosis for their newborn daughter, they knew there was one place they needed to go – Children’s National Hospital in Washington, D.C. At birth, Angelique was diagnosed with a rare and devastating condition known as hemimegalencephaly (HME) which causes uncontrollable and frequent seizures. Monica Pearl, M.D., neurointerventional radiologist, and the team at Children’s National have pioneered an approach to treat HME, where they induce controlled strokes to eliminate the affected part of the brain, halting seizures in their tracks. They’re the only team in the world doing this work. Angelique’s parents knew the clock was ticking — every day they waited meant irreversible damage to their daughter’s developing brain.

pregnant woman talking to doctor

Prenatal COVID exposure associated with changes in newborn brain

pregnant woman talking to doctor

The team found differences in the brains of both infants whose mothers were infected with COVID while pregnant, as well as those born to mothers who did not test positive for the virus.

Babies born during the COVID-19 pandemic have differences in the size of certain structures in the brain, compared to infants born before the pandemic, according to a new study led by researchers at Children’s National Hospital.

The team found differences in the brains of both infants whose mothers were infected with COVID while pregnant, as well as those born to mothers who did not test positive for the virus, according to the study published in Cerebral Cortex.

The findings suggest that exposure to the coronavirus and being pregnant during the pandemic could play a role in shaping infant brain development, said Nickie Andescavage, M.D., the first author of the paper and associate chief for the Developing Brain Institute at Children’s National.

The fine print

The study’s authors looked at three groups of infants: 108 born before the pandemic; 47 exposed to COVID before birth; and 55 unexposed infants. In all cases, researchers performed magnetic resonance imaging (MRI) scans of the newborns’ brains during the first few weeks of life. The MRI scans, which are non-invasive and do not expose patients to radiation, provided 3D images of the brain, allowing doctors to calculate the volume of different areas.

Researchers found several differences in the brains of babies exposed to COVID. They had larger volumes of the gray matter that makes up the brain’s outermost layer, compared to the two other groups. In contrast, an inner area of the brain, known as deep gray matter, was smaller than in unexposed babies. These are areas that contain large numbers of neurons that generate and process signals throughout the brain. “Their brains formed differently if they were exposed to COVID,” said Dr. Andescavage, adding that “those exposed to COVID had unique signatures” in the brain.

Doctors also measured the depths of the folds in the babies’ brains – a way to determine how the brain is maturing during early development. Babies born to mothers who had COVID in pregnancy had deeper grooves in the frontal lobe, while babies born during the pandemic – even without being exposed to COVID – had increased folds and grooves throughout the brain, compared to babies born before the pandemic. “There was something about being born during the pandemic that changed how the brain developed,” Dr. Andescavage said.

What’s ahead

The study authors can’t fully explain what caused the differences in brain development in these babies, Dr. Andescavage said. But other studies have linked maternal stress and depression to changes in the newborn brain. In a future study, Dr. Andescavage and her colleagues will examine the relationship between infant brain development and how stress and anxiety during the pandemic may have played a role in early development.

Because the babies in the study were just a few weeks old, researchers don’t know if their altered brain development will affect how they learn or behave. Researchers plan to follow the children until age 6, allowing them to observe whether pandemic-era babies hit key developmental milestones on time, such as walking, talking, holding a crayon and learning the alphabet.

Researchers have been worried about the effect of COVID on the fetus since the beginning of the pandemic. Studies show that babies exposed to COVID in the womb may experience developmental impacts, and research is underway to better understand long-term outcomes.

Although the coronavirus rarely crosses the placenta to infect the fetus directly, there are other ways maternal infection can influence the developing baby. Dr. Andescavage said inflammation is one potential harm to a developing baby. In addition, if a pregnant woman becomes so sick that the levels of oxygen in her blood fall significantly, that can deprive the fetus of oxygen, she added.

In recent decades, studies of large populations have found that maternal infections with influenza and other viruses increased the risk of serious problems in children even years later, including autism, attention deficit hyperactivity disorder and schizophrenia, although the reasons behind the association are not well understood. Technology may allow doctors to answer a number of questions about COVID and the infant brain.

“With advanced imaging and MRI, we’re in a position now to be able to understand how the babies are developing in ways we never previously could,” Dr. Andescavage said. “That will better allow us to identify the exposures that may be harmful, and at what times babies may be especially vulnerable, to better position us to promote maternal wellness. This, in turn, helps infant wellness.”

desktop computer showing the CNRI Annual Report

Driving pediatric breakthroughs through 2023

desktop computer showing the CNRI Annual ReportThe Children’s National Research Institute released its 2022-2023 Academic Annual Report. In the report, a summary of the past academic year highlights the accomplishments of each of the institute’s research centers, provides research funding figures and exalts some of the institute’s biggest milestones.

The stories in the report are a testament to the hard work and dedication of everyone at the Children’s National Research Institute.

We celebrated five decades of leadership and mentorship of Naomi Luban, M.D., and her incredible accomplishments in the W@TCH program, which have been instrumental in shaping the future of pediatric research.

We also celebrated innovation, highlighting our recent FDA award to lead a pediatric device consortium, which recognizes our commitment to developing innovative medical devices that improve the lives of children.

Breakthroughs at the Research & Innovation Campus continued as our researchers worked tirelessly to develop new treatments and therapies that will transform the lives of children and families around the world.

Taking a look at the breakthroughs happening in our now six research centers, we spotlighted the following stories:

  • Reflecting on decades of progress in the blood, marrow and cell therapy programs at Children’s National. Our researchers have made significant strides in this field, and we are proud to be at the forefront of these life-saving treatments.
  • In genetic medicine, we continue to be a beacon of hope for families facing rare and complex conditions. Our researchers are making incredible breakthroughs that are changing the landscape of pediatric medicine.
  • We are also proud to share the $90 million award received from an anonymous donor to support pediatric brain tumor research. The predominant focus of this award is to develop new treatments that will improve outcomes for children with this devastating disease.
  • This year, we opened a new Center that enhances our research capabilities in the field of Prenatal, Neonatal & Maternal Health Research. We are excited about the possibilities this new center will bring and look forward to the discoveries that will emerge from it.
  • In addition, we are driving future pandemic readiness with the NIH funded Pediatric Pandemic Network. Our researchers are using cutting-edge technology and innovative approaches to prepare for the next pandemic and protect children.
  • We are also exploring the potential of artificial intelligence (AI) in pediatric breakthroughs. Our researchers are using machine learning and other AI techniques to develop new treatments and therapies that will transform the lives of children.
Daniel J. Licht, M.D.

Q&A with Daniel J. Licht, M.D.: The future of medicine is in light

Daniel J. Licht, M.D.

A pediatric neurologist who specializes in children with congenital heart disease, Dr. Licht initially came to this area of research as he considered ways to ensure children’s brains have adequate oxygen delivery during heart care, preserving neurological health and improving long-term outcomes.

Daniel J. Licht, M.D., joins Children’s National Hospital with a vision: He believes non-invasive devices built using biomedical optics – or instruments using light – can give clinicians invaluable information about how the brain and other organs are functioning.

A pediatric neurologist who specializes in children with congenital heart disease, Dr. Licht initially came to this area of research as he considered ways to ensure children’s brains have adequate oxygen delivery during heart care, preserving neurological health and improving long-term outcomes. He sees countless applications for using the properties of light in pediatric medicine.

Dr. Licht, whose name coincidentally also means “light” in German, is planning to establish a program for biomedical optics at Children’s National, built on the pillars of education, innovation and commercialization. He wants to tap into the resources of the Sheik Zayed Institute of Pediatric Surgical Innovation and expertise across the hospital. He is launching this effort as part of the new Center for Prenatal, Neonatal & Maternal Health Research.

Q: How can light be used diagnostically?

A: I believe that light is truly the future of biomedical devices, especially in children. Light can penetrate human tissues deeply, whether it’s muscle, liver or kidney. For example, you can put a light at the end of an endoscope and someday do virtual biopsies. It’s all a matter of understanding the properties of light, and how to manipulate light to give you the answers that you need. The applications are truly infinite.

Q: What has your initial work in neurology shown?

A: One of the instruments that we have developed can measure cerebral blood flow and quantitatively show the oxygen use of the brain. That’s important because it’s easy to measure oxygen delivery, but it’s hard to balance supply-and-demand without knowing the patient’s unique demand. We now have preclinical data and information from about 500 patients.

In terms of what’s ahead, many therapies today aren’t targeted to the individual, so Johnny’s brain-oxygen demand may not be the same as Sarah’s brain-oxygen demand, even if they both have congenital heart disease. As a patient waits for surgery, we also have found that the brain-oxygen demand increases, but if the demand is not met, this can lead to pre-operative brain injury. This technology could change the whole conversation about the timing of surgery. In addition, we can measure the brain-oxygen demand intraoperatively. We are finding that we can actually define the right perfusion strategy for each patient, rather than making uniform decisions for all patients with a shared diagnosis.

Lastly, beyond the operating room, we can use this technology for countless conditions. It would help with the treatment of almost any disease in the critical care unit, when we are using tools like ECMO (extracorporeal membrane oxygenation, a salvage technique), and we need to monitor a patient’s status. We can also use it to measure intracranial pressure. In very simple terms, if a child with a shunt comes into the emergency room with a headache, we can noninvasively measure the pressure and see how it’s changed without a head CT. We can decide who needs to go to the operating room – and who doesn’t – without radiation.

Q: How did your career bring you to this point?

A: My interest has always been in brain injury and kids with congenital heart disease. Years ago, I started out using MRI because it was the technology that was bright and shiny at the time. I was part of a team that developed an MRI sequence for measuring cerebral blood flow. We made some discoveries that indicated the culprit for brain injury was not the surgeries. Instead, there was something with the babies.

Unfortunately, with MRI, it’s a big, expensive instrument, and you have to take the baby to the machine for a single point-in-time measurement. So I started working with a physicist at the University of Pennsylvania to develop a way to measure the motion of particles, specifically red blood cells, to study cerebral blood flow. We found ways to use light, and this is what I hope to build and commercialize at Children’s National. By the end of my career, I hope to be able to say that we got this into clinical care.

A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.

Measuring preschoolers’ cognitive development in Latin America

A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.A blue background showcases a brain made of gears, symbolizing the intricate workings of the mind.

Neurodevelopment occurs at a rapid pace during the preschool years, research shows.

Measuring and tracking development in early childhood is important for understanding how to best support long-term positive health outcomes for children. However, the art of selecting measurement tools that are appropriate for a given study sample is complex; variations in language, cultural relevance and adaptations, availability of normative data, and more can impact the administration and interpretation of study findings.

In a recent study published in the Journal of Pediatric Psychology, the authors systematically review the standardized neurodevelopmental assessments used to study preschool-aged children’s cognitive development in Spanish-speaking Latin America.

“Thinking critically about the ways we measure these outcomes is an important first step in conducting ethical and accurate global research,” said Meagan Williams, M.S.P.H., C.C.R.C., senior clinical research coordinator for the division of Infectious Diseases and the Zickler Family Prenatal Pediatrics Institute at Children’s National Hospital and corresponding author of the study.

The hold-up in the field

The field of child development research is complicated by the presence and use of many different neurodevelopmental assessment tools, only some of which are standardized and use norms to allow researchers to compare their cohorts’ performance with population-level data.

“Many cognitive assessments, including some of the most commonly used assessments identified in our review of research conducted in Spanish-speaking Latin America, have only been officially normed in the United States,” Williams added. “Others have been translated into Spanish and normed in large countries such as Mexico or Spain, but Latin America is a large and culturally diverse region, and it is unclear whether these normative samples are generalizable and culturally relevant to other regions of Spanish-speaking Latin America.”

This systematic review outlined 41 different neurodevelopmental assessments used in 97 studies, including information about each study’s sample, use of each measurement tool and findings related to child cognitive development. The review goes into detail about the most widely used assessments, including background information of each assessment and trends in how authors of the studies in this review reported their methods and results.

Moving the field forward

When researchers use similar methods and valid outcome measures across studies, it becomes possible to combine data between cohorts and draw stronger conclusions about child outcomes. For example, The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) was identified as the most used tool to measure intelligence of young children ages 2-6 in the systematic review. The WPPSI is also one of many assessments that Williams’s research team, led by Sarah Mulkey, M.D., is using to measure neurodevelopment among children exposed to Zika virus in utero.

“If researchers studying longitudinal outcomes after Zika virus exposure also use the WPPSI for their study samples – and if they openly report on their methods, adaptations, and sample characteristics – then it may be possible to harmonize data from multiple cohorts and draw stronger conclusions across studies,” Williams said.

But even the most popular and widespread assessments such as the WPPSI are not without their limitations. While norms exist for regions such as the United States and Mexico, additional work needs to be done to appropriately adapt and validate these tools for use in other populations.

Benefiting patients

Neurodevelopment occurs at a rapid pace during the preschool years. The earlier neurodevelopmental delays can be identified, the earlier experts can administer interventions to respond to these delays and help children get back on track with their peers.

This is particularly salient for research conducted in low- and middle-income countries, where socioeconomic, environmental and other exposures that are known to impact child development differ from those in higher-resource settings. Internationally, there appears to be significant variability in not only the assessment tools which are selected for use, but also in the methods reported across studies to conduct and interpret these assessments.

“By coming together as a field and prioritizing the use and validation of common and culturally appropriate assessments, we can better understand child outcome data on both an individual study level as well as on a broader population level, which will lead to a better understanding of the unique needs and strengths of the children we serve,” Williams said.

The team at Children’s National has been studying the neurodevelopment of children exposed to the Zika virus in Colombia since the beginning of the Zika epidemic.

“As our study on Zika virus has overlapped with the COVID-19 pandemic, we have had the opportunity to collect child outcome data at a very interesting time in history. We are excited that this review revealed that we chose a popular and well-studied assessment for our data collection in this region and we look forward to publishing our 5-year outcome data (which will include WPPSI data) in the coming year,” Williams and Mulkey concluded.

Dr. Mulkey is committed to studying the long-term neurodevelopmental impacts that viruses like Zika and SARS-CoV-2 have on infants born to mothers who were infected during pregnancy through research with the Congenital Infection Program at Children’s National and in collaboration with colleagues in Colombia.

Additional Children’s National authors include Madison Berl, Ph.D.

Doctors performing bilateral high intensity focused ultrasound (HIFU) pallidotomy on a patient with dyskinetic cerebral palsy.

Children’s National performs first ever HIFU procedure on patient with cerebral palsy

Doctors performing bilateral high intensity focused ultrasound (HIFU) pallidotomy on a patient with dyskinetic cerebral palsy.

HIFU is a non-invasive therapy that utilizes focused ultrasound waves to thermally ablate a focal area of tissue.

In January, a team of multidisciplinary doctors performed the first case in the world of using bilateral high intensity focused ultrasound (HIFU) pallidotomy on Jesus, a 22-year-old patient with dyskinetic cerebral palsy.

The procedure is part of a clinical trial led by Chima Oluigbo, M.D., pediatric neurosurgeon at Children’s National Hospital.

“The primary objective of the study is to evaluate the safety of ExAblate Transcranial MRgFUS as a tool for creating bilateral or unilateral lesions in the globus pallidus (GPi) in patients with treatment-refractory secondary dystonia due to dyskinetic cerebral palsy,” Dr. Oluigbo explained. “The secondary purpose is to assess the impact of HIFU pallidotomy on dyskinetic cerebral palsy movement disorder in pediatric and young adult patients.”

In addition, the impact of bilateral pallidotomy on motor development, pain perception, speech, memory, attention and cognition in these patients will be assessed.

“We hope that the trial will help us find results that lead to treatments that can reduce the rigidity and stiffness which occurs in cerebral palsy so we can help these children who do not have any effective treatment,” Dr. Oluigbo added.

“This new, first of its kind, non-invasive therapeutic approach – without even a skin incision – will open the door to offering hope for a number of kids with movement disorders who have failed conventional therapy,” said Robert Keating, M.D., chief of neurosurgery at Children’s National. “We are at the beginning of a new era for treating functional disorders in the pediatric patient.”

How it works

HIFU is a non-invasive therapy that utilizes focused ultrasound waves to thermally ablate a focal area of tissue. In the past, Children’s National successfully used HIFU to treat low-grade type tumors located in difficult locations of the brain, such as hypothalamic hamartomas and pilocytic astrocytoma, as well as for epilepsy and other movement disorders.

This most recent procedure was another successful milestone for the hospital, discharging Jesus the following day without any complications.

The team comprised neurosurgeons, MRI techs, anesthesiologists and radiologists, to name a few.

Originally, Jesus came to Children’s National in 2006 when he started working with the Physical Medicine and Rehabilitation team to help him with his muscle hypertonia management as well as equipment, orthoses and therapy concerns.

“As he continued to grow, his muscle hypertonia became more pronounced and caused difficulty with his care, positioning and comfort,” said Olga Morozova, M.D., pediatric rehabilitation specialist at Children’s National. “We have tried multiple oral medications however he has had significant side effects from the majority of the medications.”

Dr. Morozova and Julie Will, M.S.N., F.N.P., the nurse practitioner that worked with Jesus, referred him to Dr. Oluigbo after they learned about HIFU being an option to treat Jesus using a non-invasive approach.

Moving the field forward

This clinical trial highlights the expanding indications for focused ultrasound.

“We are excited about the potential for these innovative treatment strategies in neurosurgery to transform the lives of pediatric patients who suffer from challenging diseases, such as brain tumors, epilepsy, and movement disorders,” said Hasan Syed, M.D., co-director of the Focused Ultrasound Program at Children’s National. “We are redefining what is possible in neurosurgery.”

From low-intensity focused ultrasound (LIFU) treatments for our young DIPG patients to now the groundbreaking research on HIFU for pediatric movement disorders, the dedication to cutting-edge techniques highlights the team’s commitment to patients and transforming pediatric neurosurgical care.

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Children’s National in the News: 2023

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Explore some of the notable medical advancements and stories of bravery that defined 2023, showcasing the steadfast commitment of healthcare professionals at Children’s National Hospital and the resilient spirit of the children they support. Delve into our 2023 news highlights for more.

1. COVID during pregnancy dramatically increases the risk of complications and maternal death, large new study finds

According to a study published in British Medical Journal Global Health, women who get COVID during pregnancy are nearly eight times more likely to die and face a significantly elevated risk of ICU admission and pneumonia. Sarah Mulkey, M.D., prenatal-neonatologist neurologist, discussed findings based on her work with pregnant women and their babies.
(Fortune)

2. Rest isn’t necessarily best for concussion recovery in children, study says

A study led by Christopher Vaughan, Psy.D., pediatric neuropsychologist, suggests that — despite what many people may presume — getting kids back to school quickly is the best way to boost their chance for a rapid recovery after a concussion.
(CNN)

3. Pediatric hospital beds are in high demand for ailing children. Here’s why

David Wessel, M.D., executive vice president, chief medical officer and physician-in-chief, explained that one reason parents were still having trouble getting their children beds in a pediatric hospital or a pediatric unit after the fall 2022 respiratory surge is that pediatric hospitals are paid less by insurance.
(CNN)

4. Anisha Abraham details impact of social media use on children: ‘True mental health crisis’

Anisha Abraham, M.D., M.P.H., chief of the Division of Adolescent and Young Adult Medicine, joined America’s Newsroom to discuss the impact social media access has had on children’s mental health.
(FOX News)

5. Saving Antonio: Can a renowned hospital keep a boy from being shot again?

After 13-year-old Antonio was nearly killed outside his mom’s apartment, Children’s National Hospital went beyond treating his bullet wounds. Read how our Youth Violence Intervention Program team supported him and his family during his recovery.
(The Washington Post)

6. Formerly conjoined twins reunite with doctors who separated them

Erin and Jade Buckles underwent a successful separation at Children’s National Hospital. Nearly 20 years later they returned to meet with some of the medical staff who helped make it happen.
(Good Morning America)

7. Asthma mortality rates differ by location, race/ethnicity, age

Shilpa Patel, M.D., M.P.H., medical director of the Children’s National IMPACT DC Asthma Clinic, weighed in on a letter published in Annals of Allergy, Asthma & Immunology, asserting that the disparities in mortality due to asthma in the United States vary based on whether they occurred in a hospital, ethnicity or race and age of the patient.
(Healio)

8. How one Afghan family made the perilous journey across the U.S.-Mexico border

After one family embarked on a perilous journey from Afghanistan through Mexico to the U.S.-Mexico border, they eventually secured entry to the U.S. where Karen Smith, M.D., medical director of Global Services, aided the family’s transition and provided their daughter with necessary immediate medical treatment.
(NPR)

9. When a child is shot, doctors must heal more than just bullet holes

With the number of young people shot by guns on the rise in the U.S., providers and staff at Children’s National Hospital are trying to break the cycle of violence. But it’s not just the physical wounds though that need treating: young victims may also need help getting back on the right track — whether that means enrolling in school, finding a new group of friends or getting a job.
(BBC News)

10. This 6-year-old is a pioneer in the quest to treat a deadly brain tumor

Callie, a 6-year-old diagnosed with diffuse intrinsic pontine glioma, was treated with low-intensity focused ultrasound (LIFU) at Children’s National Hospital and is the second child in the world to receive this treatment for a brain tumor. LIFU is an emerging technology that experts like Hasan Syed, M.D., and Adrianna Fonseca, M.D., are trialing to treat this fatal childhood brain tumor.
(The Washington Post)

11. F.D.A. approves sickle cell treatments, including one that uses CRISPR

The FDA approved a new genetic therapy, giving people with sickle cell disease new opportunities to eliminate their symptoms. David Jacobsohn, M.B.A., M.D., confirmed that Children’s National Hospital is one of the authorized treatment centers and talked about giving priority to the sickest patients if they are on Vertex’s list.
(The New York Times)

12. 6-year-old fulfils wish to dance in the Nutcracker

After the potential need for open-heart surgery threatened Caroline’s Nutcracker performance, Manan Desai, M.D., a cardiac surgeon, figured out a less invasive procedure to help reduce her recovery time so she could perform in time for the holidays.
(Good Morning America)

2023 with a lightbulb

The best of 2023 from Innovation District

2023 with a lightbulbAdvanced MRI visualization techniques to follow blood flow in the hearts of cardiac patients. Gene therapy for pediatric patients with Duchenne muscular dystrophy. 3D-printed casts for treating clubfoot. These were among the most popular articles we published on Innovation District in 2023. Read on for our full list.

1. Advanced MRI hopes to improve outcomes for Fontan cardiac patients

Cardiac imaging specialists and cardiac surgeons at Children’s National Hospital are applying advanced magnetic resonance imaging visualization techniques to understand the intricacies of blood flow within the heart chambers of children with single ventricle heart defects like hypoplastic left heart syndrome. The data allows surgeons to make critical corrections to the atrioventricular valve before a child undergoes the single ventricle procedure known as the Fontan.
(3 min. read)

2. Children’s National gives first commercial dose of new FDA-approved gene therapy for Duchenne muscular dystrophy

Children’s National Hospital became the first pediatric hospital to administer a commercial dose of Elevidys (delandistrogene moxeparvovec-rokl), the first gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD). Elevidys is a one-time intravenous gene therapy that aims to delay or halt the progression of DMD by delivering a modified, functional version of dystrophin to muscle cells.
(2 min. read)

3. New model to treat Becker Muscular Dystrophy

Researchers at Children’s National Hospital developed a pre-clinical model to test drugs and therapies for Becker Muscular Dystrophy (BMD), a debilitating neuromuscular disease that is growing in numbers and lacks treatment options. The work provides scientists with a much-needed method to identify, develop and de-risk drugs for patients with BMD.
(2 min. read)

4. First infants in the U.S. with specially modified pacemakers show excellent early outcomes

In 2022, five newborns with life-threatening congenital heart disease affecting their heart rhythms were the first in the United States to receive a novel modified pacemaker generator to stabilize their heart rhythms within days of birth. Two of the five cases were cared for at Children’s National Hospital. In a follow-up article, the team at Children’s National shared that “early post-operative performance of this device has been excellent.”
(2 min. read)

5. AI: The “single greatest tool” for improving access to pediatric healthcare

Experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere came together to discuss how pediatric specialties can use AI to provide medical care to kids more efficiently, more quickly and more effectively at the inaugural symposium on AI in Pediatric Health and Rare Diseases, hosted by Children’s National Hospital and the Fralin Biomedical Research Institute at Virginia Tech.
(3 min. read)

6. AAP names Children’s National gun violence study one of the most influential articles ever published

The American Academy of Pediatrics (AAP) named a 2019 study led by clinician-researchers at Children’s National Hospital one of the 12 most influential Pediatric Emergency Medicine articles ever published in the journal Pediatrics. The findings showed that states with stricter gun laws and laws requiring universal background checks for gun purchases had lower firearm-related pediatric mortality rates but that more investigation was needed to better understand the impact of firearm legislation on pediatric mortality.
(2 min. read)

7. Why a colorectal transition program matters

Children’s National Hospital recently welcomed pediatric and adult colorectal surgeon Erin Teeple, M.D., to the Division of Colorectal and Pelvic Reconstruction. Dr. Teeple is the only person in the United States who is board-certified as both a pediatric surgeon and adult colorectal surgeon, uniquely positioning her to care for people with both acquired and congenital colorectal disease and help them transition from pediatric care to adult caregivers.
(3 min. read)

8. First-of-its-kind holistic program for managing pain in sickle cell disease

The sickle cell team at Children’s National Hospital received a grant from the Founders Auxiliary Board to launch a first-of-its-kind, personalized holistic transformative program for the management of pain in sickle cell disease. The clinic uses an inter-disciplinary approach of hematology, psychology, psychiatry, anesthesiology/pain medicine, acupuncture, mindfulness, relaxation and aromatherapy services.
(3 min read)

9. Recommendations for management of positive monosomy X on cell-free DNA screening

Non-invasive prenatal testing using cell-free DNA (cfDNA) is currently offered to all pregnant women regardless of the fetal risk. In a study published in the American Journal of Obstetrics and Gynecology, researchers from Children’s National Hospital provided context and expert recommendations for maternal and fetal evaluation and management when cfDNA screening is positive for monosomy X or Turner Syndrome.
(2 min. read)

10. Innovation in clubfoot management using 3D anatomical mapping

While clubfoot is relatively common and the treatment is highly successful, the weekly visits required for Ponseti casting can be a significant burden on families. Researchers at Children’s National Hospital are looking for a way to relieve that burden with a new study that could eliminate the weekly visits with a series of 3D-printed casts that families can switch out at home.
(1 min. read)

11. Gender Self-Report seeks to capture the gender spectrum for broad research applications

A new validated self-report tool provides researchers with a way to characterize the gender of research participants beyond their binary designated sex at birth. The multi-dimensional Gender Self-Report, developed using a community-driven approach and then scientifically validated, was outlined in a peer-reviewed article in the American Psychologist, a journal of the American Psychological Association.
(2 min. read)

12. Cardiovascular and bone diseases in chronic kidney disease

In a study published by Advances in Chronic Kidney Disease, a team at Children’s National Hospital reviewed cardiovascular and bone diseases in chronic kidney disease and end-stage kidney disease patients with a focus on pediatric issues and concerns.
(1 min. read)

Adelaide Robb

Changing the game in pediatric psychopharmacology

Adelaide Robb

“I realized adequate treatment in youth can prevent many of the harmful outcomes in adults who were never treated properly for their symptoms,” says Adelaide Robb, M.D.

Over three decades ago, Adelaide Robb, M.D., sat in her office with a clear goal in mind: follow a career in adult psychiatry. Her patients displayed all sorts of symptoms: generalized anxiety, depression, bipolar disorder, autism, schizophrenia.

“In the early 1990s, my patients would tell me other doctors didn’t believe in their children having bipolar disorder,” she says.

These adult patients had been sick for 5, 10 and even 15 years but had not been diagnosed or treated properly. Eventually, they started bringing their children with them, who also had similar symptoms.

“I realized adequate treatment in youth can prevent many of the harmful outcomes in adults who were never treated properly for their symptoms,” Dr. Robb says.

She soon came to another realization: there was a massive gap in the health care world – pediatric psychopharmacology. She felt the need to bridge this gap and help children, motivating her to change the course of her career. Since joining Children’s National Hospital in 1994, she’s been an unstoppable force in the pediatric psychopharmacology world, quickly changing the rules of the game.

The big picture

Pediatricians in the United States continue to grapple with a mental health crisis that was exacerbated by the COVID-19 pandemic and declared a national emergency in 2021.

Mental health plays a key role in a child’s mental, emotional and behavioral well-being. It affects the way they think, feel and act while also impacting how they handle stress, relate to their peers and make choices.

According to the Centers for Disease Control and Prevention, attention deficit hyperactivity disorder (ADHD), anxiety, behavior problems and depression are the most commonly diagnosed mental health disorders in children. While available treatments vary, over the years, data has proven how medications can play a role in improving most mental health conditions.

Children’s National leads the way

For decades, Dr. Robb has led research focused on pediatric psychopharmacology with more than 80 clinical trials. Children’s National is one of only a few sites nationwide to participate in federally funded mental health clinical trials. Major trials she has led include:

  • Lexapro for major depression in youth
  • Prozac for obsessive compulsive disorder
  • Abilify for pediatric bipolar and schizophrenia
  • Latuda for pediatric bipolar depression
  • Concerta for ADHD

Dr. Robb also co-chaired the American Academy of Child and Adolescent Psychiatry’s Pediatric Psychopharmacology Initiative Committee for more than 8 years. She has also been active for more than 15 years in the American Academy of Pediatrics Committee on drugs (pharmacology).

“Since its inception in the ‘90s, pediatric psychopharmacology has changed in two major ways: First, we started to do regular testing of new medications in children and not just adults. Second, there’s been congressional and FDA mandates for testing of all medications that can be used in kids,” says Dr. Robb. “It’s no longer a guessing game – we have an evidence-based approach to children with mental illness using psychopharmacology.”

Currently, Dr. Robb is the principal investigator on several open clinical trials at Children’s National, including a study that compares the effectiveness of treating a parent with ADHD medication plus behavioral parent training (BPT) versus BPT alone on their child’s ADHD related symptoms.

Moving the field forward

Earlier this year, Dr. Robb moderated a panel on mental health and precision genomics which touched on what we know about depression, anxiety and other disorders and the future of pediatric behavioral health care.

“The goal is to give people with depression and other mental health illnesses the opportunity to go to school and function, whether they have depression, ADHD or any other disorder. This can make a huge difference in someone’s life,” Dr. Robb says.

Children’s National is uniquely positioned with a dedicated pharmacokinetic clinical team – which has greatly aided its ADHD and Learning Differences Program and most recent Addictions Program.

“We changed how ADHD was treated because our patients had early access to new trialed drugs,” says Dr. Robb. “This makes a big difference and gives children the opportunity to have better control of their symptoms so they’re paying attention and learning in school.”

Read more about our advances in Behavioral Health.

Drs. Catherine Limperopoulos, Yao Wu and David Wessel

AHA’s Outstanding Research Award: Three generations of pediatric cardiac excellence

Drs. Catherine Limperopoulos, Yao Wu and David Wessel

Catherine Limperopoulos, Ph.D., Yao Wu, Ph.D., and David Wessel, M.D.

Children’s National Hospital is celebrating a remarkable milestone as three of its faculty members have been honored over 15 years with the American Heart Association’s Outstanding Research in Pediatric Cardiology Award. Yao Wu, Ph.D., became the latest researcher to earn the accolade for her groundbreaking work into congenital heart disease (CHD).

A research faculty member with the newly established Center for Prenatal, Neonatal & Maternal Health Research, Dr. Wu received the award specifically for her studies on the role of altered placental function, measured by advanced in utero imaging, and neurodevelopmental outcomes in toddlers with CHD.

Honored at the association’s annual meeting in Philadelphia, Dr. Wu returned to Children’s National to warm congratulations from her colleagues who had previously won the award: David Wessel, M.D., executive vice president and chief medical officer, and Catherine Limperopoulos, Ph.D., director of the new center.

“I am thrilled to pass the baton to one of our own,” Dr. Limperopoulos said. “Dr. Wu’s recognition speaks to the outstanding and innovative research happening at Children’s National among junior faculty who are focusing on advancing our understanding of congenital heart disease and its long-term neurodevelopmental outcomes.”

Why we’re excited

The prestigious award represents more than individual accomplishments; it symbolizes three generations of mentorship and collaboration at the hospital. In 2007, Dr. Wessel joined Children’s National to enhance the care of newborns across specialty services by expanding programs and research, with a focus on critically ill newborns with heart disease. He recruited and mentored Dr. Limperopoulos in 2010, who became one of his research partners and creator of the hospital’s Center for Prenatal, Neonatal & Maternal Health Research. Dr. Limperopoulos, in turn, recruited and mentored Dr. Wu, providing her with the tools to conduct advanced imaging on in-utero brains and placentas, as well as the development of children with CHD.

“Each one of us is in different phases of our careers, yet we are connected by our deep interest in advancing cardiac care for critically ill newborns,” Dr. Wessel said. “In this collaborative environment, we learn from each other to improve entire lifetimes for our patients.”

Dr. Wu said she believes in sharing scientific developments for the advancement of the entire medical community. “It was an honor to be chosen to join this esteemed club, which has a relentless focus on improving health outcomes,” she said.

Children’s National leads the way

The award winners shared five collaborations published in leading journals to contribute to the ongoing dialogue in the field and the innovative work happening at Children’s National:

baby in the NICU

Painful NICU procedures change neurological development in preterm babies

baby in the NICU

Premature infants exposed to pain while in the Neonatal Intensive Care Unit (NICU) are at greater risk for motor delays, language deficits and autism, even in the absence of structural brain injuries, according to findings from the new Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital.

Premature infants exposed to pain while in the Neonatal Intensive Care Unit (NICU) are at greater risk for motor delays, language deficits and autism, even in the absence of structural brain injuries, according to findings from the new Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital.

The research sheds light on the potential outcomes of routine medical interventions – such as heel pricks, venipunctures and IV placements – and correlates these skin breaks to changes in neurological connectivity in the preterm infants’ brains. Published in BMC Medicine, the work provides valuable insights about the far-reaching impact of early medical care.

“We know that premature babies are often exposed to repeated medical interventions, light, sound and other stimuli that they would not experience in utero, and we wanted to better understand the long-term effect,” said Kevin Cook, Ph.D., research faculty at the new center and an expert in fetal and neonatal neurology. “Through this study, we can see that early and repeated exposure to pain appears to alter brain development and put children at risk for poor neurodevelopmental outcomes.”

The big picture

Globally, nearly 1 in 10 babies is born preterm, and the Children’s National team was particularly interested in the experience of those born “very” and “extremely” preterm, which is considered any delivery earlier than 32 and 28 weeks of gestation, respectively. While rates of prematurity have been relatively stable, survival rates of these babies have increased remarkably in recent decades, thanks to improved interventions and therapies for preterm infants. Yet neurodevelopmental challenges among these children persist, with noteworthy risks of autism and other neurological deficits.

At Children’s National, researchers are working to understand the mechanism behind those challenges. Given that the late second trimester and the third trimester are critical periods for brain development, the team wanted to study the effects of exposing babies to the world outside the womb early.

The fine print

Dr. Cook and his colleagues collected resting-state functional MRI (fMRI) scans from 148 infants born at least four weeks prematurely, along with 99 infants born full term. The fMRI scans, uniquely suited for studying the resting state of the brain in non-responsive infants, revealed significant hyperconnectivity within the cerebellum, which coordinates muscle activity, and the limbic and paralimbic regions, which govern emotions, motivation and cognitive functions.

Notably, the hyperconnectivity correlated with the number of skin break procedures, including heel pricks, venipunctures and IV placements. When the children returned for developmental evaluations at 18 months, the skin breaks were strongly associated with an increased risk of autism and lower motor and language scores. The toddlers identified at risk for autism had an average of 118 skin breaks, which is significantly more than the average of 65 skin breaks in those who were not at risk.

What’s ahead

Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal & Maternal Health Research, said the findings have important implications for understanding how painful NICU procedures can impact long-term outcomes and how physicians conceptualize the risks of care given to preterm babies. She and her team at the center recommend further research into managing pain in premature babies, especially given the limits of current options and the known risk of opioids.

“With this foundational study, we should consider ways to improve pain management for preterm infants and methods to better weigh the interventions used on these incredibly vulnerable patients,” Dr. Limperopoulos said. “Saving their lives is certainly the priority, and the quality of that life should also be forefront of our minds.”

illustration of neurons with electrical impulses

Children’s National at the American Epilepsy Society Annual Meeting

illustration of neurons with electrical impulsesSeveral experts from Children’s National Hospital will be sharing their knowledge at the upcoming American Epilepsy Society Annual Meeting in Orlando, December 1-5. Here’s a sample of what you can expect.

  • Chima Oluigbo, M.D., a pediatric neurosurgeon, will be on panel with other surgeons discussing different surgical techniques and approaches related to epilepsy surgery followed by hands-on practice at teaching stations. He will focus on extra-temporal epilepsy scenarios and will be presenting on Nuances of Temporal Lobe Surgery in the Pediatric Population at the Neurosurgery Symposium highlighting Surgical Controversies in Temporal Lobe Epilepsies.
  • Ersida Buraniqi, M.D., a child neurologist, will be part of a special interest group on critical care and discuss advances in electroencephalography (EEG) and multimodal neuro-monitoring for seizures in the intensive care unit (ICU). Dr. Buranigui will be doing a special presentation on EEG features to predict electrographic seizures and mortality in the pediatric intensive care unit (PICU).
  • Dana Harrar, M.D., director of Pediatric Stroke Program and co-director of Critical Care Neurology, is presenting at an invitation-only resident EEG course, providing an interactive structured curriculum on pediatric and adult EEG. Dr. Harrar will be focusing on doing an ICU-EEG nomenclature overview.
  • Madison Berl, Ph.D., director of Neuropathy Research and of the Intellectual and Developmental Disabilities Research Center Program, will be presenting during the AES Annual Course. The topic “It’s About Time” will focus on the critical importance the timing in epilepsy care plays in patient outcome. Dr. Berl will be presenting on neuropsych outcomes.
  • Leigh Sepeta, Ph.D., director of Inpatient Neuropsychology, is the vice-chair of the special interest group on neuropsychology. Additionally, Freya Prentice, M.Sc., will be doing a presentation during this session on functional mapping of the cognitive memory circuit in pediatric epilepsy.
Date Time Presenter(s) Title
12/2/23 8:00 am Chima Oluigbo, M.D., FRCSC, FAANS Skills Workshop | Epilepsy Surgery Workshop: Techniques and Clinical Scenarios
12/2/23 5:30 pm Chima Oluigbo, M.D., FRCSC, FAANS SIG | Epilepsy Surgery: Homunculus Revisited: Managing Central Lobe Epilepsies
12/2/23 5:30 pm Ersida Buraniqi, M.D. SIG | Critical Care: Advances in EEG and Multimodal Neuro-monitoring for Seizures in the ICU
12/2/23 7:00am Dana Harrar M.D. Resident EEG Course
12/3/23 9:00 am Chima Oluigbo, M.D., FRCSC, FAANS Neurosurgery Symposium | Surgical Controversies in Temporal Lobe Epilepsies
12/3/23 8:45 am Madison Berl, Ph.D. Annual Course | It’s About Time: Timing in Epilepsy Evaluation and Treatment
12/4/23 7:00 am Leigh Sepeta, M.D. SIG | Neuropsychology: Mapping Cognition in Epilepsy: From the Lab to the Clinic
12/4/23 7:00 am Freya Prentice, M.D. SIG | Neuropsychology: Mapping Cognition in Epilepsy: From the Lab to the Clinic
12/5/23 7:00 am Dana Harrar M.D. SIG | Epilepsy Education: Epilepsy Education Throughout the Training Pipeline

 

Dr. Panagiotis Kratimenos in the lab

Understanding mechanisms of injury due to prematurity in human cerebellum

Dr. Panagiotis Kratimenos in the lab

“There is no better model to study preterm injury than the human brain. Our team, along with the expertise of the scientific advisory board of the Raynor Cerebellum Project, will approach this project in multiple ways to extract the most possible information from the extremely precious human tissues,” says Dr. Kratimenos.

Children’s National Hospital has received $1 million in funding as part of the Raynor Cerebellum Project, whose mission is to improve the lives of those with cerebellar disease in seven to ten years. Panagiotis Kratimenos, M.D., Ph.D., principal investigator and Co-Director of Research in the Division of Neonatology at Children’s National, says the goal of this work is to understand the mechanisms of injury due to prematurity in human cerebellum and identify opportunities for intervention.

Why the research is unique

This project is unique because it focuses on postmortem human cerebellum, addressing the effect of the immune dysregulation of the mother during preterm labor. “We have established a large cohort of human term and preterm subjects and we will leverage cutting edge techniques to understand how the immune system of the mother during preterm labor shapes the cerebellum in a way that becomes more vulnerable to subsequent insults,” says Dr. Kratimenos.

Why this research matters for critical newborns

“There is no better model to study preterm injury than the human brain. Our team, along with the expertise of the scientific advisory board of the Raynor Cerebellum Project, will approach this project in multiple ways to extract the most possible information from the extremely precious human tissues. This will give us insight into the real mechanisms of preterm birth induced injury due to maternal immune dysregulation,” says Dr. Kratimenos.

illustration of the brain with concussion

20 years of leadership in the concussion space

illustration of the brain with concussion

The concussion space has evolved, especially in the pediatric field, more than ever before.

For the past two decades, the concussion space has evolved, especially in the pediatric field where more than ever before, experts are specializing in the evaluation and management of concussions in children. Gerard Gioia, Ph.D., is a neuropsychologist and the director of the Safe Concussion Outcome, Recovery & Education (SCORE) Program at Children’s National Hospital. He has been at the forefront of this work and is a leading expert in traumatic brain injury research and education.

For 20 years, Dr. Gioia has lent his expertise to CDC’s HEADS UP campaign providing clinical and research insights on concussion prevention, recognition and response. Here’s what we’ve learned.

Q: What has been the biggest change you have seen in the concussion landscape over the last 20 years?

A: The biggest change is awareness. Most people now recognize concussions as a serious issue. The second change is how we treat concussions. People used to think that if you got a concussion, you had to sit in a dark room and not do anything after a concussion. Now, we know better. This is where care plans (such as the ACE care plan) come in. Healthcare providers now tell people with a concussion that they need to be progressively active (physically, socially, cognitively) and that appropriate activity can speed and improve recovery. Related to active recovery management, we now provide explicit guidance to schools in supporting the returning student from day one.

Q: How have you and Children’s National been involved with CDC’s HEADS UP campaign?

A: I was excited when CDC released educational materials for physicians in 2003 on identifying mild traumatic brain injury (mTBI) and concussions. I soon realized that they were not robust enough. In 2005, CDC released a tool kit for high school coaches (HEADS UP to High School Coaches). That was great — a robust toolkit full of ideas for what to do if a kid gets a brain injury. I reached out to Jean Langlois and then Kelly Sarmiento at CDC. That kicked off several efforts with CDC to create educational materials for physicians (HEADS UP: Brain Injury in Your Practice), youth sports coaches (HEADS UP: Concussion in Youth Sports) and school professionals (HEADS UP to Schools: Know Your Concussion ABCs).

Q: What do you envision for the next 20 years of concussion research and education?

A: Treatment and prevention are the ultimate goals for us. I am looking forward to refining active treatment using biomarkers, the biological underpinnings of injury. Expanding and refining our understanding of these biomarkers will change the game for concussion treatment. We also need to focus efforts on preventing these injuries and modifying how we teach/coach youth sports with greater safety in a developmentally-appropriate manner.

pregnant woman looking at sonogram

Babies with congenital heart disease display disrupted brain function before birth

pregnant woman looking at sonogram

In their study, the team at Children’s National Hospital found that specific brain regions become especially vulnerable to injury around 24 weeks of pregnancy when developing babies begin to have high energy demands and rapid neurovascular changes.

For the first time, researchers have found that babies born with congenital heart disease (CHD) have alterations to the emerging functional connectivity of their brains in utero. The changes are related to the subtype of their CHD and their oxygen status before they have lifesaving surgery to treat their cardiac malformation, according to new findings published in the American Heart Association’s Circulation Research.

In their study, the team at Children’s National Hospital found that specific brain regions become especially vulnerable to injury around 24 weeks of pregnancy when developing babies begin to have high energy demands and rapid neurovascular changes. That leaves certain parts of the brain, including the brainstem, more susceptible to injury from cardiac complications and poor circulation.

“We used a special type of magnetic resonance imaging to safely study the brains of these unborn babies, and we found that they have weakened connectivity in the deep grey structures, which are responsible for sensation, movement, alertness and other core functions,” said Josepheen De Asis-Cruz, M.D., Ph.D., assistant professor at the Developing Brain Institute at Children’s National and an author of the study. “This offers an important clue in utero to the type of care the babies will eventually need when they are born.”

The big picture

In the past decade, the survival rate for fetuses with CHD has greatly improved. About 80% of cases – even some of the most high-risk heart defects – can be successfully treated or palliated with surgery and survive. Yet Dr. Cruz said researchers are finding that the rates of poor neurodevelopmental outcomes are about the same. That’s why she and her colleagues are looking at what precisely may be injuring the brains of these newborns prior to surgery, offering a possible roadmap to interventions.

The fine print

The research team studied 107 healthy, low-risk pregnancies and 75 pregnancies known to be complicated by CHD. They used functional connectivity magnetic resonance imaging (fcMRI) to examine the emerging connections of the brains of unborn babies, given fcMRI’s unique ability to query the brain in a resting state when a patient is unable to respond to tasks. They also studied the oxygen saturation levels of the babies after they were born and then mapped all of this information to the type of CHD that they were diagnosed with.

“Our findings indicate that the compromised connectivity in the brains of CHD patients before delivery is linked to hypoxia after birth,” Cruz said. “There were important differences in the low- and high-risk CHD groups. Babies born with transposition of the great arteries or hypoplastic left heart syndrome – two of the most high-risk diagnoses – have notable changes in their brain function, which could someday be used as biomarkers to guide their care.”

What’s ahead

Researchers at Children’s National are working together, using a variety of modalities, to move toward precision imaging in utero to help predict a child’s neurodevelopmental outcomes. The ultimate goal: better interventions sooner.

“This work is foundational. As we fine-tune more techniques to identify babies at risk, we can understand how environmental, genetic and epigenetic factors impact brain development and guide care decisions,” said Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal & Maternal Health Research and a senior author of the paper. “We can imagine a day where we can offer pregnant mothers highly detailed and personalized information about their unborn baby, and individualized interventions that lead to healthier lifetimes.”