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Purkinje cell

Premature birth disrupts Purkinje cell function, resulting in locomotor learning deficits

Purkinje cell

Children’s National Hospital researchers explored how preterm birth disrupts Purkinje cell function, resulting in locomotor learning deficits.

As the care of preterm babies continues to improve, neonatologists face new challenges to ensure babies are protected from injury during critical development of the cerebellum during birth and immediately after birth. How does this early injury affect locomotor function, and to what extent are clinicians able to protect the brain of preterm babies?

A new peer-reviewed study by Aaron Sathyanesan, Ph.D., Panagiotis Kratimenos, M.D., Ph.D., and Vittorio Gallo, Ph.D., published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), explores exactly what neural circuitry of the cerebellum is affected due to complications that occur around the time of birth causing these learning deficits, and finds a specific type of neurons — Purkinje cells — to play a central role.

Up until now, there has been a sparsity of techniques available to measure neuronal activity during locomotor learning tasks that engage the cerebellum. To surmount this challenge, Children’s National used a multidisciplinary approach, bringing together a team of neuroscientists with neonatologists who leveraged their joint expertise to devise a novel and unique way to measure real-time Purkinje cell activity in a pre-clinical model with clinical relevance to humans.

Researchers measured neural circuit function by pairing GCaMP6f fiber photometry, used to measure neuronal activity in the brain of a free moving subject, with an ErasmusLadder, in which it needs to travel from point A to point B on a horizontal ladder with touch-sensitive rungs that register the type and length of steps. By introducing a sudden obstacle to movement, researchers observed how the subject coped and learned accordingly to avoid this obstacle. By playing a high-pitch tone just before the obstacle was introduced, researchers were able to measure how quickly the subjects were able to anticipate the obstacle and adjust their steps accordingly. Subjects with neonatal brain injury and normal models were run through a series of learning trials while simultaneously monitoring brain activity. In this way, the team was able to quantify cerebellum-dependent locomotor learning and adaptive behavior, unlocking a functional and mechanistic understanding of behavioral pathology that was previously unseen in this field.

In addition to showing that normal Purkinje cells are highly active during movement on the ErasmusLadder, the team explored the question of whether Purkinje cells of injured pre-clinical models were generally non-responsive to any kind of stimuli. They found that while Purkinje cells in injured subjects responded to puffs of air, which generally cue the subject to start moving on the ErasmusLadder, dysfunction in these cells was specific to the period of adaptive learning. Lastly, through chemogenetic inhibition, which specifically silences neonatal Purkinje cell activity, the team was able to mimic the effects of perinatal cerebellar injury, further solidifying the role of these cells in learning deficits.

The study results have implications for clinical practice. As the care of premature babies continues to improve, neonatologists face new challenges to ensure that babies not only survive but thrive. They need to find ways to prevent against the lifelong impacts that preterm birth would otherwise have on the cerebellum and developing brain.

Read the full press release here.

Read the full journal article here.

Injury triggered change in ER calcium of a muscle cell

ER maintains ion balance needed for muscle repair

Injury triggered change in ER calcium of a muscle cell

A new study led by Jyoti Jaiswal, M.Sc., Ph.D., principal investigator at Children’s National Hospital, identifies that an essential requirement for the repair of injured cells is to cope with the extracellular calcium influx caused by injury to the cell’s membrane. Credit: Goutam Chandra, Ph.D.

Physical activity can injure our muscle cells, so their ability to efficiently repair is crucial for maintaining muscle health. Understanding how healthy muscle cells respond to injury is required to understand and treat diseases caused by poor muscle cell repair.

A new study led by Jyoti Jaiswal, M.Sc., Ph.D., principal investigator at Children’s National Hospital, identifies that an essential requirement for the repair of injured cells is to cope with the extracellular calcium influx caused by injury to the cell’s membrane.

This study, published in the Journal of Cell Biology, identifies endoplasmic reticulum (ER) – a network of membranous tubules in the cell – as the site where the calcium entering the injured cell is sequestered. Using limb girdle muscular dystrophy 2L (LGMD2L) patient cells and a model for this genetic disease, the study shows impaired ability of diseased muscle cells to cope with this calcium excess. It also shows that a drug to sequester excess calcium counters this ion imbalance and reverses the diseased cell’s repair deficit.

“The study provides a novel insight into how injured cells in our body cope with calcium ion imbalance during injury,” Dr. Jaiswal explained. “This work also addresses how calcium homeostasis is compromised by a genetic defect that leads to LGMD2L. It also offers a proof of principle approach to restore calcium homeostasis, paving the path for future work to develop therapies targeting this disease.”

According to Dr. Jaiswal, this work also addresses the current lack of understanding of the basis for exercise intolerance and other symptoms faced by LGMD2L patients.

“This study opens the path for developing targeted therapies for LGMD2L and provides a fundamental cellular insight into a process crucial for cell survival,” said Goutam Chandra, Ph.D., research fellow and lead author of this study.

The Center for Genetic Medicine Research at Children’s National is among only a handful across the world to study this rare disease. These findings are unprecedented in providing the mechanistic insights needed to develop treatment for it.

In addition to Dr. Jaiswal and Chandra, the study co-authors include Sreetama Sen Chandra, Ph.D., Davi Mazala, Ph.D., and Jack VanderMeulen, Ph.D., from Children’s National, and Karine Charton, Ph.D., and Isabelle Richard, Ph.D., from Université Paris-Saclay.

doctor showing girl with concussion three fingers

Post-traumatic headache phenotype and recovery time after concussion

doctor showing girl with concussion three fingers

In a recent study published by JAMA Network Open, Gerard Gioia, Ph.D., division chief of Neuropsychology and director of Safe Concussion Outcome, Recovery and Education (SCORE) Program at Children’s National Hospital, along with other leading researchers, described the characteristics of youth with post-traumatic headache (PTH) and determine whether the PTH phenotype is associated with outcome.

Concussions and mild traumatic brain injuries (mTBI) are common among children and adolescents and constitute a major public health challenge. While symptoms from a concussion typically resolve days to weeks after injury, 10% to 30% of patients have symptoms that last longer than four weeks, and a smaller proportion have symptoms that persist for much longer.

PTH is defined as significantly worsened head pain attributed to a blow or force to the head. Although adolescents have a higher risk for sustaining concussions and developing persistent symptoms than younger children or adults, there is little data regarding PTH recovery and treatment in youth.

Dr. Gioia founded the multicenter Four Corners Youth Consortium to fill the gap in our understanding of youth concussion and recovery. This study is the first analysis of PTH phenotype and prognosis in this cohort of concussed youth.

The researchers analyzed headache-related symptoms from a validated questionnaire developed by Dr. Gioia and his Children’s National concussion research team. The primary outcomes were time to recovery and concussion-attributable headache three months after injury while the secondary outcome was headache six months after injury. Recovery was defined as resolution of symptoms related to a concussion.

Future large studies validating the classification of posttraumatic headache phenotypes in youth and studying outcomes are essential. PTH phenotyping will improve prognostication of concussion recovery and will enhance the treatment for PTH with more appropriate and targeted therapies to treat and prevent persistent and disabling headaches in youth with a concussion.

Roger Packer at lectern

Roger Packer, M.D., presents keynote address at First International Pakistan Neuro-Oncology Symposium

Roger Packer at lectern

During his presentation, he addressed attendees on the topic of the “Modern Management of Medulloblastoma,” discussing results of recently completed clinical trials and the implications of new molecular insights into medulloblastoma, the most common childhood malignant brain tumor.

In late November 2020,  Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, presented as the inaugural keynote speaker for the First International Pakistan Neuro-Oncology Symposium in Karachi, Pakistan.

During his virtual presentation, he addressed attendees on the topic of the “Modern Management of Medulloblastoma,” discussing results of recently completed clinical trials and the implications of new molecular insights into medulloblastoma, the most common childhood malignant brain tumor.

The symposium attracted participants from 57 countries across the globe. There were over 1,000 attendees and as a result of the success of this symposium, there is now a monthly pediatric neuro-oncology lecture series. Dr. Packer agreed to lecture again to the group in mid-January 2021 on “Pediatric Neural Tumors Associated with NF1” as part of an international lecture series hosted by the Aga Khan University in Pakistan.

This is one of multiple national and international activities led by the Brain Tumor Institute at Children’s National Hospital. Directed by Dr. Packer with Eugene Hwang, M.D. as his co-director, and who is associate division chief of oncology at Children’s National Hospital, the multidisciplinary institute holds a monthly tumor board for colleagues at Dmitry Rogachev National Research Center and the Burdenko Neurosurgery Institute in Moscow, Russia, and a monthly brain tumor board coordinated by the Pediatric Oncology Program for colleagues across São Paulo, Brazil.

This also leads to a bi-monthly regional tumor board, which is attended by staff of the National Cancer Institute, the University of Virginia, Inova Children’s Hospital, the University of Maryland Children’s Hospital, Children’s Hospital of Richmond at VCU, Children’s Hospital of The King’s Daughters Health System, Yale University, Geisinger Medical Center, Georgetown University and Carilion Clinic.

Research & Innovation Campus

Virginia Tech, Children’s National Hospital award $100,000 to fund collaborative cancer research pilot projects

Research & Innovation Campus

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus.

Children’s National Hospital and Virginia Tech have awarded two $50,000 one-year pilot grants to multi-institutional teams of scientists for pediatric brain cancer research.

The inter-institutional program, which launched in December, promotes cross-disciplinary collaborations among researchers at both institutions. At Virginia Tech, the program is part of the Virginia Tech Cancer Research Alliance. Financial support for the program was provided by the Offices of the Physician-in-Chief and Chief Academic Officer at Children’s National, and by Virginia Tech’s Office of the Vice President for Health Sciences and Technology.

“We were delighted to see so many innovative and competitive research proposals for our first round of pilot grants in the area of brain cancer. By forging new research collaborations with our partners at Children’s National, we hope to make major strides in addressing one of the most common and devastating groups of cancers in children,” said Michael Friedlander, Virginia Tech’s vice president for health sciences and technology, and the executive director of the Fralin Biomedical Research Institute at VTC. “The pilot funding will bootstrap several programs to be able to acquire ongoing sustainable funding by providing the opportunity to test novel high impact ideas for new strategies for treating these disorders. There are simply too few good options for children in this space now and this partnership can change that for the better.”

The collaborative research initiative began through an agreement between the Fralin Biomedical Research Institute and the Children’s National Research Institute. The collaborative teams formed through a series of interactive discussions among Virginia Tech’s Cancer Research Alliance faculty members from the university’s Blacksburg and Roanoke campuses, and Children’s National’s neuro-oncology researchers.

“I am extremely excited by this collaboration between VT and CNH that is focused on pediatric brain tumors which is such an area of unmet need,” said Catherine Bollard, M.D., M.B.Ch.B.,, director of Children’s National’s Center for Cancer and Immunology Research. “I am confident that the funded proposals will soon advance our understanding of pediatric brain tumors and, more importantly, facilitate more joint efforts between two world-class institutions which is especially timely with the development of the Children’s National Research & Innovation Campus.”

Yanxin Pei, Ph.D., an assistant professor in the Center for Cancer Immunology Research at Children’s National, and Liwu Li, Ph.D., a professor of biological sciences in Virginia Tech’s College of Science, were awarded one of the pilot research grants to study how white blood cells called neutrophils are involved in metastatic MYC-driven medulloblastoma, an aggressive type of brain tumor in children that often resists conventional radiation and chemotherapies.

Yuan Zhu, Ph.D., the Gilbert Family Professor of Neurofibromatosis Research at Children’s National, and Susan Campbell, Ph.D., an assistant professor of animal and poultry sciences in Virginia Tech’s College of Agriculture and Life Sciences, were awarded funds to study glioma-induced seizures in mice with a genetic mutation that inhibits the production of P53, a key protein involved in suppressing cancer cell growth and division.

The successful applicants will receive funding starting this month and are expected to deliver preliminary data to support an extramural research application by 2024.

This pilot research program represents a growing academic research partnership between Children’s National and Virginia Tech. Last year, the two institutions announced that Virginia Tech will establish a biomedical research facility on the Children’s National Research & Innovation Campus. It will be the first research and innovation campus in the nation focused on pediatrics when it opens later this year and will house newly recruited teams of pediatric brain cancer researchers.

Liwu Li, Yanxin Pei, Susan Campbell, and Yuan Zhu

Liwu Li, Ph.D., Yanxin Pei, Ph.D., Susan Campbell, Ph.D., and Yuan Zhu, Ph.D., were awarded funding through the new pilot research program.

Roger Packer with patient

A lifetime of achievements: Roger Packer, M.D.

Roger Packer with patient

Over the years, Dr. Packer and his team in Washington, D.C., have made meaningful contributions to children all around the world diagnosed with childhood brain tumors, including medulloblastoma and gliomas.

Earlier in December, Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, received the 2020 Lifetime Achievement Award from the International Symposium on Pediatric Neuro-Oncology at the meeting organized in Karuizawa, Japan. The prestigious recognition is a testament to the years of commitment and dedication Dr. Packer has devoted to the care of children with brain tumors and as such, have placed him as a top leader.

This award is a recognition of how the field has grown since the first International Symposium on Pediatric Neuro-Oncology Dr. Packer organized in Seattle in 1989. “It grew from a small gathering of investigators to now a multidisciplinary group of over 2,000 investigators,” Dr. Packer says.

Over the years, Dr. Packer and his team in Washington, D.C., have made meaningful contributions to children all around the world diagnosed with childhood brain tumors, including medulloblastoma and gliomas. These findings have contributed to an increase of the survival rate from 50% to over 80% for children with medulloblastoma. In addition, his contributions have led to newer molecular targeted therapies and improved the quality of life of children who are long-term survivors.

“The field, especially in the last decade, rapidly transitioned to a more biologically informed field,” Dr. Packer explains. “We are now utilizing new, exciting discoveries in biology and genetics to inform new approaches to treatment. This kind of transition gives us great hope for the future.”

In his early career, Dr. Packer worked with two neuro-oncology patients who died and would impact his decision to further study this field. At that time, there was minimal understanding of the nature of neuro-oncology diseases or how to best treat them. As a neurologist, he was frustrated by the lack of understanding and as a pediatrician, he was frustrated at the lack of ability to do success management.

“I saw this as a gap in my personal knowledge and found that the field was struggling to come up with new answers and new approaches,” he says. “But at the same time other, advances were being made in child cancer care, such as with leukemia. However, there was no wide focus on pediatric brain tumors.”

Combining his knowledge of neurology with his curiosity and relying on other leaders that surrounded him in the same field, Dr. Packer worked on driving this new work forward. Today, he is still heavily involved in the development of treatment protocols that are increasingly transitional for a variety of brain tumors, including low-grade and high-grade gliomas.

“With the help of our great colleagues at Children’s National, we continue to try to develop new means to treat these tumors, including immunological approaches and the incorporation in the use of novel means, such as low-intensity and high-intensity focused ultrasound,” he says. “We also have an excellent multidisciplinary team at Children’s National that has grown over the last decade some of whom are acknowledged national leaders in the fields of brain tumors, clinical research and clinical care. We also have a robust program focusing on the neurocognitive outcome of children and ways to intervene to ameliorate intellectual compromise and improve quality of life.”

Maddox and family

Family love and the right care for neurofibromatosis type 1 give Maddox a fresh start

Maddox and family

Maddox and his family in early 2020.

13-year-old Maddox Gibson is learning to cook. He says he wants to be a chef and wants to make meals for people who need it most — the homeless and the hungry.

It makes sense that he’s eager to help people who need it. As a young child growing up in a group home in his native country of China, he knows firsthand how important that support can be. In 2017 at age 10, he found his own endless supply of love and support when he met and was adopted by the Gibson family.

Zhen Chao, now called Maddox, was born in China with a genetic condition called neurofibromatosis type 1 that can cause painful or disfiguring tumors called plexiform neurofibromas. Zhen Chao had two on his head when he arrived — on his scalp and on his left optic nerve — which had been largely untreated for most of his life in China. On top of that, his right leg had been fractured and not fixed properly years before, causing him pain and weakness that left him wheelchair bound.

Adoptive mom Lindsey, a registered nurse, knew he would need special care to meet all the unique challenges he faced, and she’d done her homework — he needed the expertise of Miriam Bornhorst, M.D.,  and the Gilbert Family Neurofibromatosis Institute at Children’s National Hospital to help him thrive in his new life in the U.S. Since shortly after he came to the U.S., Lindsey has been driving Maddox the 6-plus hours from their home in North Carolina to Washington, D.C., regularly, to get care for all of his health challenges.

Maddox’s optic neurofibroma was too large when he arrived at Children’s National for a simple surgical removal. Due to her role as the lead investigator on a cutting edge clinical trial for the orphan drug selumetinib — a so-called MEK inhibitor that has shown early promise at reducing the cell growth of tumors like plexiform neurofibromas, Dr. Bornhorst enrolled Maddox in a compassionate use program for the drug, an opportunity that is not widely available. The drug was initially developed for something completely different — treatment of melanoma and non-small cell lung cancer in adults–but has been adapted through its FDA orphan drug designation for pediatric clinical trials in NF1. In the time since Maddox started taking it, it was approved for use in NF1 patients by the FDA.

The trial drug did its job — in late 2019, Maddox’s tumor had shrunk enough that chief neurosurgeon Robert Keating, M.D., and plastic surgeon Michael Boyajian, M.D., were able to successfully remove it. Follow-up procedures led by that team have also worked to repair the tissue that was impacted by the optic neurofibroma.

In addition to treatment of his neurofibromas, Maddox and his mom are able to see every service they need during one stay in D.C. The Neurofibromatosis Institute works closely across specialties, so his corrective surgery for his leg from Children’s chief of orthopaedics, Matthew Oetgen, M.D., MBA, in September 2019. He was assessed and prescribed physical therapy early in the process and even before surgery, so now he’s stronger than ever and walking. Learning difficulties, including autism and ADHD are common in NF1 patients, and so the NF Institute’s neuropsychology team has evaluated him and worked with the family to find resources and strategies near home that will support him. It should be noted, those learning difficulties only became apparent after Maddox taught himself English from scratch in only two years’ time with the help of his school’s ESOL program.

This kind of full spectrum care, from clinical assessment to surgical treatment and psychological supports, is crucial to the lives of patients with neurofibromatosis type 1 and is only available at a pediatric specialty care institution like Children’s National. The hospital has gathered some of the preeminent researchers, surgeons, and physicians within the NF Institute to make sure that the care families will travel hundreds of miles to receive is the best possible, using the latest evidence-based treatments for every challenge they face.

Though his care and follow-ups will continue at Children’s National Hospital and his condition may pose  new challenges in the future, for now, Maddox is able to focus on exploring new things and doing what he loves — playing outdoors with his family, learning to cook and building with Legos.

graphic abstract for brain tumor paper

First large-scale proteogenomic analysis offers insights into pediatric brain tumor biology

graphic abstract for brain tumor paper

In the first large-scale, multicenter study of its kind, researchers conducted comprehensive analysis yielding a more complete understanding of pediatric brain tumors (PBT), which are the leading cause of cancer-related deaths in children. Researchers from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Children’s Brian Tumor Network (CBTN) generated and analyzed proteomic data, which identifies common biological characteristics among different tumor types. The consortia consist of collaborators from the Icahn School of Medicine at Mount Sinai, National Cancer Institute, Fred Hutchinson Cancer Research Center, Children’s National Hospital and Children’s Hospital of Philadelphia. The study, published in Cell on November 25, 2020, provides a clearer understanding of the molecular basis of pediatric brain tumors and proposes new therapeutic avenues.

The molecular characterization of brain tumors has largely hinged upon the presence of unique alterations in the tumor genome ignoring the many layers of regulation that exist between DNA and the functional biology of the tumor cell that is actuated by proteins. The integration of proteomic data identifies common biological themes that span histologic boundaries, suggesting that treatments used for one histologic type may be applied effectively to other tumors sharing similar proteomic features.

Brian Rood, M.D., medical director of the Brain Tumor Institute and associate professor of pediatrics in the Center for Cancer and Blood Disorders at Children’s National Hospital, participated in this study and explains the importance of what the team discovered.

Q: Why was it important that researchers came together to do this work?

A: Comprehensive characterization of the fundamental biology of pediatric brain tumors, including the proteogenomic analysis done in this study, is essential to better understand and treat pediatric brain tumors.

Our study is based on the recognition that proteomics and phosphoproteomics needs to be integrated with other omics data to gain an improved systems biology view of the molecular features of brain tumors. In addition, characterizing biological themes that cross histologic boundaries and cells of origin can suggest extending treatments shown to be effective in one type of tumor to other histologically disparate tumors sharing the same proteomic features.

Proteomic data further reveal the functional impacts of somatic mutations and copy number variations (CNVs) not evident in transcriptomic data alone. Further, kinase-substrate network analyses identify activated biological mechanisms of tumor biology.

This work was only possible because of a unique collaboration between the CPTAC program of the NCI and the CBTN, of which Children’s National is a member.

Q: How will this work advance understanding and treatment of pediatric brain tumors?

A: Pediatric brain tumors have not benefitted from molecularly targeted drugs as much as other tumor types largely because they harbor relatively few gene mutations. Therefore, identifying key pathways to target in these patients’ tumors has been a challenge. The integration of proteomic and phosphoproteomic data with genomic data allows for the construction of a more comprehensive model of brain tumor biology and nominates specific key pathways to be targeted.

Q: What did you find that excites you?

A: Proteomic data revealed a number of findings that were not present in the genomic data. We found evidence to support a molecularly targeted approach to treating craniopharyngioma, a tumor that has previously been unresponsive to chemotherapy. We also found a prognostic marker for high grade gliomas that do not have a mutation in the H3 histone. We were able to identify specific kinases that may dictate the aggressive nature of certain ependymoma tumors. Importantly, we demonstrated the potential of proteomic studies to uncover unique tumor biology, paving the way for more extensive investigations using this approach.

You can find the full study published in Cell. Learn more about the Brain Tumor Institute at Children’s National.


Dr. Rood recently joined a live panel discussion with researchers from the Children’s Brain Tumor Network and the Clinical Proteomic Tumor Analysis Consortium to explore the impact of their landmark study.

EEG with electrical activity of abnormal brain

Speckle tracking echo reveals possible biomarker for SUDEP risk

EEG with electrical activity of abnormal brain

A study published in the journal Epilepsia used speckle tracking echocardiography to detect subtle changes in heart function found in pediatric patients with refractory epilepsy when compared to controls. Children with refractory epilepsy had impaired systolic ventricular strain compared to controls, not correlated to epilepsy history. These differences in ventricular function may be a biomarker that can indicate someone with epilepsy is at higher risk for Sudden Unexpected Death in Epilepsy (SUDEP).

Speckle tracking echocardiography is a non-invasive technique where software automatically identifies and tracks individual “speckles” of the myocardial wall on a routine echocardiogram in order to directly quantify the extent of contraction.

The study’s first authors, John Schreiber, M.D., medical director of Electroencephalography (EEG) and director of the Epilepsy Genetics program, and Lowell Frank, M.D., advanced imaging cardiologist and director of the Cardiology Fellowship Training program, both at Children’s National Hospital, answered some questions about the study findings.

Why is this important work?

Sudden unexpected death in epilepsy (SUDEP) is a rare but devastating consequence of epilepsy. Some of the proposed mechanisms of SUDEP implicate brain stem, cardiac and respiratory pathways.

This study identified alterations in ventricular function that may serve as one potential biomarker for SUDEP risk that can be evaluated non-invasively and regularly.

How will this work benefit patients?

Identification of children or adults with markedly impaired ventricular strain or diastolic function may provide the opportunity to implement a targeted treatment or monitoring strategy to prevent SUDEP.

What did you find that excites you? What are you hoping to discover?

These differences in cardiac strain were true for all patients with refractory epilepsy as a whole, not one particular group. This suggests that refractory convulsive epilepsy itself, rather than other patient-specific factors, produces these changes. Thanks in part to a grant from the Dravet Syndrome Foundation, the team is currently examining a cohort of patients with epilepsy due to pathogenic variants in sodium channel genes, SCN1A and SCN8A, to determine if these patients have greater degrees of impaired cardiac strain. SCN1A and SCN8A are also expressed in the heart, and patients have a considerably higher risk of SUDEP. It will be particularly exciting to examine for differences in specific genetic epilepsies.

How is this work unique?

Strain has been evaluated in many disease states in adult and pediatric populations and may be more sensitive to early myocardial damage than traditional measures of systolic and diastolic function. Children’s National Hospital has been an innovator in using speckle tracking echocardiography and similar techniques to evaluate subtle changes in heart function. This study is a great example of collaboration between The Comprehensive Pediatric Epilepsy Program and the Children’s National Heart Institute that is driving innovative research at Children’s National Hospital.

MRI of the patient's head close-up

Madison Berl, Ph.D., receives 2020 PERF award for Infrastructure/Registry Research

MRI of the patient's head close-up

The Pediatric Epilepsy Research Foundation Grant (PERF) has awarded Madison Berl, Ph.D., neuropsychologist at Children’s National Hospital, the 2020 PERF award for Infrastructure/Registry Research. The funds will support her work on researching neuropsychological outcomes of children being considered for pediatric epilepsy surgery.

This grant, which provides $200,000 of research funding, will allow Dr. Berl to systematically collect data outcomes and create robust prediction models that are critical to achieving precision medicine that allows for selecting the most effective surgical treatment for an individual child.

“While seizures are a critical outcome, there is increasing recognition that outcomes beyond seizure control is critical to children and their families when evaluating and treating the impact of epilepsy and its treatments,” said Dr. Berl.

Guidelines and consensus statements related to pediatric epilepsy surgery are uniformly lacking high quality published outcome data to support clinical decisions that impact likelihood of seizure freedom and optimizing outcomes beyond seizures (e.g., neuropsychological functioning, quality of life, improved sleep). Despite recognition of the need for standardized collection of data on a multi-institutional basis, the efforts that exist are limited in scope.

Moreover, as new techniques – such as laser ablation and brain stimulation – are approved for pediatric patients, there is little information available to determine which children will benefit from which intervention.

“This project fundamentally is a multi-site registry for epilepsy surgery outcomes,” Dr. Berl added.

“However, this type of infrastructure also fosters growth and active collaboration within a network of pediatric epilepsy clinicians. I am excited because if successful, this will be the start of long-term collaborative effort.”

Illustration of brain hemispheres

Children use both brain hemispheres to understand language

Illustration of brain hemispheres

New research finds young children process language in both hemispheres of the brain, which could help compensation after a neural injury. This is unlike adults who process most language tasks in one side (usually the left) of their brain’s two hemispheres. It suggests a possible reason why children often seem to recover from brain injury more easily than adults.

New research finds young children process language in both hemispheres of the brain, which could help compensate after a neural injury. The study, published Sept. 8, 2020, in PNAS, says this is unlike adults who process most language tasks in one side (usually the left) of their brain’s two hemispheres. It suggests a possible reason why children often seem to recover from brain injury more easily than adults.

We talked with researcher William D. Gaillard, M.D., chief of the Divisions of Child Neurology, Epilepsy and Neurophysiology at Children’s National Hospital, to discuss the importance of this work.

Q: Tell us a little bit about this study.

A: This is a study we did with our colleagues at Georgetown University Medical Center, using fMRI to map brain regions that are used to process language across development. What we found was that younger children have more bilateral “activation” in language processing regions, the traditional left and homotopic regions in the right. With aging there is consolidation that becomes more left lateralized. This process is most clearly seen in the frontal brain regions, called Broca’s area, where the right activation diminishes over age

Q: Why are these findings important?

A: It’s important because this work provides evidence for how cognitive systems, and the neural networks that underlie them, become consolidated and lateralized over time during development. It provides insights into principles of the development of cognitive systems.

The timeline for lateralization of language systems means that the cognitive systems that sustain language are “plastic” – that is the right hemisphere can sustain language functions in the setting of injury to the left hemisphere until around 10 years of age.

Q: What excites you about this work?

A: This is part of a larger collaborative effort that is mapping out the consolidation of cognitive systems across development (language, visual spatial, memory and working memory). This work will help us to understand the limits of brain plasticity in the setting of injury caused by stroke or epilepsy, which could have benefits down the road to helping patients recover from these types of events.

Q: How is Children’s National leading the ongoing discovery in this space?

A: It is a true team effort. We are working with colleagues at Georgetown University Medical Center, MedStar National Rehabilitation Network and Johns Hopkins Medicine. Team members come from diverse backgrounds and scientific skills. We are one of the leading groups using advanced functional imaging to investigate brain development of critical cognitive systems and their response to brain injury.

You can find the full study published in PNAS. Learn more about the Children’s National Research Institute Center for Neuroscience Research.

 

Youssef Kousa

Dr. Youssef Kousa awarded Pediatric Epilepsy Research Grant

zika virus

The Child Neurology Foundation has awarded Youssef A. Kousa, M.S., D.O., Ph.D., the 2020 Pediatric Epilepsy Research Foundation Shields Research Grant. The funds will support his work on identifying genetic risk factors in congenital Zika syndrome.

The Child Neurology Foundation has awarded Youssef A. Kousa, M.S., D.O., Ph.D., physician-scientist within the Division of Neurology at Children’s National Hospital, and founder and director of the Zika Genetics Consortium, the 2020 Pediatric Epilepsy Research Foundation Shields Research Grant. The funds will support his work on identifying genetic risk factors in congenital Zika syndrome.

This prestigious grant provides $100,000 of research funding to help identify treatments and cures for pediatric neurologic diseases. It will allow Dr. Kousa to test the hypothesis that rare genetic variants in individuals contributed to being affected with congenital Zika syndrome and the severity of the phenotype for those who were affected.

“Despite decades of research, identifying those at greatest risk of congenital infection or being severely affected remains an elusive goal,” says Dr. Kousa. “This research is important because identifying genetic risk or protective factors for developmental brain malformations can help teach us how the brain develops.”

Youssef Kousa

In 2015, Dr. Kousa established the Zika Genetic Consortium to investigate whether maternal and fetal genetic factors can modify the risk of brain injury from congenital infections.

Dr. Kousa adds that this work will provide key insights into maternal and fetal genetic factors that can contribute to brain malformations. The hope is that these insights may one day translate into targeted prevention efforts.

“Dr. Kousa’s project is very creative and has a fantastic opportunity to look at factors of Zika on brain development,” says William D. Gaillard, M.D., division chief of both Epilepsy and Neurophysiology, and Neurology at Children’s National. “This is a very competitive award. It’s a tremendous achievement that few accomplish.”

Children’s National is the leading site for this international research study.

In 2015, Dr. Kousa established the Zika Genetic Consortium to investigate whether maternal and fetal genetic factors can modify the risk of brain injury from congenital infections. Dr. Kousa is the principal investigator of the consortium, which includes 19 co-investigators representing 13 different institutions.

The consortium is bringing together cohorts of 12,000 mother-infant participants retrospectively and prospectively. These cohorts come from 15 international health centers in seven countries in collaboration with partners at the National Institutes of Health, and the Centers for Disease Control and Prevention.

“This support gives us the opportunity to test our hypothesis,” says Dr. Kousa. “We also hope what we continue to learn about Zika can play a role in helping us understand other congenital infections and neurodevelopment diseases.”

Neurology infographic

2020 at a glance: Neurology and Neurosurgery at Children’s National

 

The Children’s National Division of Neurology and Neurosurgery is consistently recognized by U.S. News & World Report as one of the top neurology programs in the nation and is currently #3 in the nation.

US News Badges

Children’s National ranked a top 10 children’s hospital and No. 1 in newborn care nationally by U.S. News

US News Badges

Children’s National Hospital in Washington, D.C., was ranked No. 7 nationally in the U.S. News & World Report 2020-21 Best Children’s Hospitals annual rankings. This marks the fourth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide.

In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fourth year in a row.

For the tenth straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“Our number one goal is to provide the best care possible to children. Being recognized by U.S. News as one of the best hospitals reflects the strength that comes from putting children and their families first, and we are truly honored,” says Kurt Newman, M.D., president and CEO of Children’s National Hospital.

“This year, the news is especially meaningful, because our teams — like those at hospitals across the country — faced enormous challenges and worked heroically through a global pandemic to deliver excellent care.”

“Even in the midst of a pandemic, children have healthcare needs ranging from routine vaccinations to life-saving surgery and chemotherapy,” said Ben Harder, managing editor and chief of Health Analysis at U.S. News. “The Best Children’s Hospitals rankings are designed to help parents find quality medical care for a sick child and inform families’ conversations with pediatricians.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

The other three specialties ranked among the top 50 were cardiology and heart surgery, gastroenterology and gastro-intestinal surgery, and urology.

glial cells

Dr. Nathan A. Smith receives $600,000 DOD ARO grant to study the role of glial cells in neural excitability and cognition

glial cells

Microglia are the resident immune cells of the central nervous system that have highly dynamic processes that continuously survey the brain’s microenvironment, making contact with both neurons and astrocytes.

In his pursuit to understand the function of neural circuits within the brain, Nathan A. Smith, M.S., Ph.D., principal investigator at Children’s National Hospital, is examining how specialized glial cells, known as astrocytes and microglia, work together to influence neural networks and potentially enhance neuro-cognition.

Dr. Smith has just secured a new $600,000 grant from the Department of Defense Army Research Laboratory to pursue cutting-edge experimental approaches to examine the role of astrocytes in Ca2+-dependent microglia modulation of synaptic activity. This project will enhance our understanding of neuronal excitability and cognition, and define a new role for microglia in these processes.

“Glia cells play an important role in modulating synaptic function via Ca2+-dependent mechanisms,” says Dr. Smith. “It’s time for these cells to receive recognition as active participants, rather than passive contributors, in fundamental neural processes.”

Dr. Smith and his laboratory at Children’s National Research Institute are using novel experimental models to study the dynamics underlying Ca2+-mediated microglia process extension and retraction to further our understanding of how microglia, astrocytes and neurons interact in the healthy brain.

“Completion of the proposed studies has the potential to redefine the role(s) of microglia in higher brain functions and highlight the significant contribution of these cells,” Dr. Smith says. “Most importantly, elucidating the mechanisms that underlie glial cell modulation of neural circuits will not only further our understanding of normal brain function but also open new avenues to developing more accurate computational models of neural circuits.”

Dr. Nathan Smith

Dr. Smith and his laboratory at Children’s National Research Institute are using novel experimental models to study the dynamics underlying Ca2+-mediated microglia process extension and retraction to further our understanding of how microglia, astrocytes and neurons interact in the healthy brain.

Microglia are the resident immune cells of the central nervous system that have highly dynamic processes that continuously survey the brain’s microenvironment, making contact with both neurons and astrocytes. However, because of our inability to directly monitor Ca2+ activity in microglia, very little is known about the intracellular Ca2+ dynamics in resting microglia and their role in surveillance and modulation of synaptic activity.

Dr. Smith’s research team and his use of cutting-edge technology are a perfect match with the Army’s new modernization priorities. Dr. Smith’s research program and the new Army’s initiatives will greatly benefit from each other and ultimately contribute to a better understanding of the human brain.

“This research will help address a major gap in our understanding of the roles that glial cells play in regulating the computations of the nervous system through their interactions with neurons, which could also inspire a new class of artificial neural network architectures,” said Dr. Frederick Gregory, program manager, Army Research Office, an element of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory.

The grant will begin on July 1, 2020, and will last over three years. Dr. Smith’s research is also supported by other grants, including awards from the NIH and the National Science Foundation.

“As Dr. Smith’s mentor, the ultimate joy for a mentor is to see his mentees follow their dreams and be recognized for their accomplishments,” said Vittorio Gallo, Ph.D., Chief Research Officer at Children’s National Hospital. “I couldn’t be prouder of Nathan, and I am fully confident that this new research grant will help him continue to grow an exceptional research program.”

Drs. Oluigbo and Myseros

Spotlight on Children’s National Hospital Neurosurgery

Drs. Oluigbo and Myseros

Our neurosurgery team is among the most experienced in the nation. We have performed thousands of surgeries and are dedicated to giving the best possible care. The Children’s National Hospital Division of Neurosurgery consistently ranks among the country’s top programs according to U.S. News & World Report.

Patients travel to us from all over the world because we have the resources and expertise necessary to care for their neurological conditions through multidisciplinary programs such as:

  • Spine Disorders
  • Deep Brain Stimulation Program
  • Neuro Intensive Care Unit (Neuro ICU)
  • Neuro-ophthalmology
  • Spina Bifida Program
  • Brain and Spinal Cord Tumors
  • Craniofacial Disorders
  • Chiari Malformations
  • Epilepsy
  • Brachial Plexus Injury
  • Spasticity Program
  • Neurovascular diseases such as AVM’s and Moyamoya

Minimally invasive surgery

The Children’s National Hospital Division of Neurosurgery is among the first in the country to develop new techniques and adopt the latest technologies that make minimally invasive neurosurgery possible by utilizing state of the art equipment and developing new techniques, including:

  • ROSA surgical robot / SEEG placement
  • Surgical Theater with virtual reality visualization
  • Visualase® magnetic resonance imaging (MRI)-guided laser ablation
  • 5T intra-operative MRI (iMRI)
  • Deep brain stimulation
  • Neuropace epilepsy control

Advanced treatment and cutting edge research

Children’s National is involved in cutting edge scientific research offering new hope for our patients and new methods of treatment. Our doctors have developed some of the most advanced treatments and clinics for our patients including:

  • Multidisciplinary skull base neurosurgery program
  • Participating in the 1st generation of genetic modulation trials
  • CAR T-Cell Therapy research
  • Ehlers-Danlos syndrome (EDS) /Hypermobility Program
  • Pseudotumor Cerebri Multidisciplinary panel
  • Leader in open and endoscopic craniosynostosis surgery

Ranked No. 5 in the nation

U.S. News & World Report ranks our neurosurgery program number five in the nation, reflecting our commitment to excellence in care for our patients and families.

Level 1 surgery verification

Children’s National is one of only 12 children’s hospitals in the country to attain Level 1 Surgery Verification from the American College of Surgeons.

doctor performing neurosurgery

Successful outcomes

Children with rare and medically complex conditions, such as brain tumors, craniofacial disorders, Chiari malformations, vascular disorders and brachial plexus palsy, to name a few, achieve exceptional outcomes at Children’s National. Our patients experience fewer complications, go home sooner and maintain long-term symptom relief.

Specialized expertise

Our entire team is dedicated to meeting your child’s unique needs. Our Neuro-Intensive Care Unit nurses recognize signs of pain and complications your child may not be able to explain.

Pioneering new treatments

Children’s National is at the forefront of new device-based treatments that not only fix neurologic problems, but also restore brain function. We are one of the few pediatric programs in the country offering dedicated pediatric deep brain stimulation, which uses a pacemaker-like device to significantly reduce the burden of movement disorders and difficult-to-control epilepsy, as well as Neuropace implantation to help with seizures in eloquent areas of the brain.

Training the next generation of top neurosurgeons

We are proudly training the next generation of pediatric neurosurgeons through residency programs and fellowships in conjunction with several area medical schools.

covers of books edited by Children's National faculty

We wrote the book

Children’s National Hospital is proud to have a number of faculty members who literally wrote the books on pediatric cardiology, neonatology, neurology and pulmonology. These texts, edited by experts Gil Wernovsky, M.D., Gordon Avery, M.D., Ricardo Munoz, M.D., Anastassios Koumbourlis, M.D., MPH, Robert Keating, M.D. and Roger Packer, M.D., have become the definitive references for medical students everywhere.

Through these books, generations of children worldwide will benefit from the expertise at Children’s National:

  • Anderson’s Pediatric Cardiology. Wernovsky, G., Anderson, R.H., Kumar, K., Mussatto, K.A., Redington, A.N., Tweddell, J.S., Tretter, J.T. (Eds.). (2019). Philadelphia, PA: Elsevier Publishing.
  • Avery’s Neonatology: Pathophysiology and Management of the Newborn. MacDonald, M.G., and Seshia, M.M.K. (Eds.) (2015). Philadelphia, PA: Lippincott Williams & Wilkins.
  • Critical Care of Children with Heart Disease: Basic Medical and Surgical Concepts. Munoz, R.A., More, V.O., da Cruz, E.M., Vetterly, C.G., da Silva, J.P. (Eds.). (2010) London, UK: Springer-Verlag London Ltd.
  • Diagnostic Tests in Pediatric Pulmonology. Davis, S.D., Koumbourlis, A.C., and Eber, E. (Eds.). (2015) London, UK: Springer-Verlag London Ltd.
  • Pulmonary Complications of Non-Pulmonary Pediatric Koumbourlis, A.C., and Nevin, M. (Eds.). (2018) London, UK: Springer-Verlag London Ltd.
  • Tumors of the Pediatric Central Nervous system. Keating, R.F., Goodrich, J.T., and Packer, R.J. (Eds.). (2013) New York, NY: Thieme Medical Publishers.

covers of books edited by Children's National faculty

William Gaillard

William D. Gaillard, M.D., elected president of the American Epilepsy Society

William Gaillard

“The AES, is one of the oldest neurological professional organizations in the country dedicated to the scientific investigation, exchange of clinical information and eradication of epilepsy and associated disorders, and I’m honored to serve as the new president,” Dr. Gaillard said.

In early December 2019, William D. Gaillard, M.D., chief of the Divisions of Child Neurology, Epilepsy and Neurophysiology at Children’s National Hospital, began his term as president of the American Epilepsy Society (AES) at the annual meeting in Baltimore. The AES is a medical and scientific society with over 4,000 members consisting of clinicians, scientists investigating basic and clinical aspects of epilepsy, and other professionals interested in seizure disorders.

“The AES, is one of the oldest neurological professional organizations in the country dedicated to the scientific investigation, exchange of clinical information and eradication of epilepsy and associated disorders, and I’m honored to serve as the new president,” Dr. Gaillard said.

Dr. Gaillard’s clinical research focuses on the use of advanced imaging to investigate the effect of childhood epilepsy on brain structure and function with an emphasis on cognitive systems. His group also develops and implements imaging strategies to improve epilepsy outcomes.

In addition, Dr. Gaillard, an active participant in AES activities, has served as treasurer and as chair of the Clinical Investigator Workshop and Pediatric Content Committees. He also serves as an associate editor for the journal Epilepsy Research, and as a regular reviewer on AES and Epilepsy Foundation study sections.

As division chief of Child Neurology, Epilepsy and Neurophysiology, Dr. Gaillard directs a team of pediatric specialists who see thousands of patients each year. Dr. Gaillard has worked throughout his career to care for children and young adults with epilepsy from the onset of seizures through novel therapeutic interventions, medication trials and, when appropriate, surgery. Treatment options at Children’s National addresses the full range of the condition, including problems of difficult-to-control epilepsy. Additionally, treatment includes the concurrent social, education and emotional issues faced by children with the condition and their families.

His academic appointments include Professor of Pediatrics and Neurology at George Washington University, Professor of Neurology at Georgetown University, and Professor (adjunct), Hearing and Speech, University of Maryland, College Park.

Epilepsy infographic

At a glance: Comprehensive Pediatric Epilepsy Program

Epilepsy is one of the most common neurological conditions that lasts a lifetime, and, in extreme cases, can lead to death. It affects one out of every 26 people across their lifetime, and 8% of children will have a seizure before leaving childhood. One in 10 children with epilepsy is a candidate for surgery.

Children’s National has one of the largest and most experienced multidisciplinary epilepsy programs in the country with a range of programs specializing in new onset epilepsy, the ketogenic diet, intractable epilepsy, neuroinflammation, neurogenetics, epilepsy surgery, epileptic encephalopathy and more.

The Children’s National epilepsy program is continuously working to improve care for patients through clinical innovation, growing our team and expanding access in locations throughout the region.

Epilepsy infographic

To refer a patient or learn more about our program, call 202-476-3611 or visit ChildrensNational.org/Epilepsy.

a necrotic muscle fiber with Duchenne’s Muscular Dystrophy

Children’s National Hospital to host 30th Annual Pediatric Neurology Update

a necrotic muscle fiber with Duchenne’s Muscular Dystrophy

The Children’s National Hospital’s Center for Neuroscience and Behavioral Medicine is proud to host the 30th Annual Pediatric Neurology Update course.

This year’s course will feature two critical areas in pediatric neuroscience: neuromuscular diseases with a special emphasis on the scientific, medical, ethical and financial implications of the new molecular genetic therapies for pediatric neuromuscular disease (including Werdnig- Hoffmann and Duchenne’s Muscular Dystrophy) and advances in neurocritical care.

We invite you to join us for presentations from renowned experts in the field during this full-day, CME accredited event on April 2, 2020.

For more information and to register, visit ChildrensNational.org/NeurologyUpdate.