Neurology & Neurosurgery

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For fifth year in a row, Children’s National Hospital nationally ranked a top 10 children’s hospital

US News badges

Children’s National Hospital in Washington, D.C., was ranked in the top 10 nationally in the U.S. News & World Report 2021-22 Best Children’s Hospitals annual rankings. This marks the fifth straight year Children’s National has made the Honor Roll 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 fifth year in a row.

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

“It is always spectacular to be named one of the nation’s best children’s hospitals, but this year more than ever,” says Kurt Newman, M.D., president and CEO of Children’s National. “Every member of our organization helped us achieve this level of excellence, and they did it while sacrificing so much in order to help our country respond to and recover from the COVID-19 pandemic.”

“When choosing a hospital for a sick child, many parents want specialized expertise, convenience and caring medical professionals,” said Ben Harder, chief of health analysis and managing editor at U.S. News. “The Best Children’s Hospitals rankings have always highlighted hospitals that excel in specialized care. As the pandemic continues to affect travel, finding high-quality care close to home has never been more important.”

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 surgerygastroenterology and gastro-intestinal surgery, and urology.

blue and pink chalk transgender symbol

New study looks at potential predictors of mental health in transgender adolescents

blue and pink chalk transgender symbol

Autism and autism-related traits, common in transgender populations, are associated with greater mental health burden in transgender adolescents, according to a new study published in the Journal of Clinical Child and Adolescent Psychology.

Autism and autism-related traits, common in transgender populations, are associated with greater mental health burden in transgender adolescents, according to a new study published in the Journal of Clinical Child and Adolescent Psychology.

The study, led by John Strang, Psy.D., director of the Gender and Autism Program (GAP) at Children’s National Hospital, found that autistic transgender adolescents experienced significantly greater emotional distress compared to both autistic cisgender and non-autistic transgender adolescents.

The research team notes that given the mental health risks transgender youth often face, characterization of attributes that predispose certain gender-diverse youth to mental health challenges may be useful in clinical settings. For example, this information may be helpful in screening transgender young people to identify those who may benefit from specific supports, such as accommodations for organization and planning skills (executive function skills) which are needed to navigate the multiple steps of gender transition.

“To date, the primary focus of transgender youth mental health research has been environmental drivers of wellbeing and distress. Specifically, rejection and stigma are established predictors of poorer mental health in transgender adolescents,” Dr. Strang said. “This current study takes a new direction by examining cognitive and neurodevelopmental factors as additional potential predictors of emotional distress in transgender youth.”

In addition to well-established LGBT stigma-related predictors of transgender youth mental health challenges, this study found cognitive and autism-related factors associated with increased transgender youth distress. Specifically, problems with executive function and the impact of executive function problems on a young person navigating their gender transition were associated with greater suicidality. Social symptoms of autism and executive function problems impacting gender transition were associated with greater emotional internalizing symptoms.

More than 90 adolescents ages 13 through 21 were part of the study. Participants were evenly divided between autistic-transgender, autistic-cisgender and non-autistic-transgender groups. Thirteen transgender adolescents were found to be at the margin of autism spectrum disorder (ASD) diagnosis and included within a larger “broad-ASD” grouping for analyses. To evaluate the groups psychologically and neuropsychologically, the study included comprehensive gold-standard assessment of autism and autistic symptoms for all participants as well as evaluation of mental health, IQ, gender dysphoria, LGBT-related perceived stigma, executive function planning skills, and executive function-related barriers to achieving gender transition.

Children’s National GAP is the first clinical and research initiative founded to address the needs of the many transgender youth who are autistic, or more broadly, neurodiverse. Findings from this current study and the growing body of research on co-occurring autism and gender diversity help inform the GAP’s evaluation and support programs for neurodiverse gender diverse youth.

Roger Packer

All about neurology: Upcoming conferences led by Roger Packer, M.D.

Roger Packer

Roger Packer, M.D., senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital, will speak at a series of symposiums in the next couple of months.

Most recently, he presented on pediatric brain tumor trials at a webinar hosted by the American Brain Tumor Association titled “Clinical Trials – Paving the Way Forward.” In case you missed it, you can watch it here.

For details on more upcoming presentations, see below:

On Friday, May 14, Dr. Packer will speak at the Cure Search for Children’s Cancer’s ‘Blurred Lines: Therapeutic vs. Research-only Biopsies,’ a session highlighting technologies, including liquid biopsies and single-cell sequencing, that have the potential to allow researchers to collect more data while decreasing the amount of tissue needed from solid tumor biopsies.

On Friday, May 28, he will give a virtual keynote address at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology during their “Pediatric oncology, hematology and immunology in 21st century: From research to clinical practice” online presentation. Dr. Packer will co-chair the session on central nervous system tumors and present on “CNS tumors: Major advances in neuro-oncology in last 10 years.”

And at the50th Golden Anniversary Meeting of the Child Neurology Society, taking place September 29 to October 2, Dr. Packer will lead a symposium on new therapies for childhood medulloblastoma — the most common malignant brain tumor in children. Here, he will receive a recognition during the society’s annual gala honoring the “Founders of Child Neurology,” for his contribution in a new book in which Dr. Packer has a chapter outlining the history of child neurologists in the field of pediatric neuro-oncology.

PAS Logo

Children’s National participants share their expertise at PAS meeting

PAS Logo

The 2021 Pediatric Academic Societies (PAS) Virtual meeting hosted live-streamed events, on-demand sessions with live Q+A, a virtual exhibit hall, poster presentations and networking events that attracted pediatricians and healthcare providers worldwide. Among the physician-scientists, there were over 20 Children’s National Hospital-affiliated participants at this year’s meeting, adding to the conversation of pediatric research in specialty and sub-specialty areas.

Children’s National experts covered a range of topics, including heart disease, neurology, abnormal glycemia in newborns and antibiotic use in hospitalized children.

The “Neurological Implications of Abnormal Glycemia in Neonatal Encephalopathy and Prematurity” was a hot topic symposium presented by a panel of experts, including Sudeepta Basu, M.B.B.S., M.S., neonatologist at Children’s National.

The experts addressed the importance of recognizing early blood glucose disturbances in newborns with encephalopathy following birth asphyxia and its likely impact on brain injury and long-term outcomes. Although whole body cooling for newborns with encephalopathy after birth asphyxia is now standard of care in most advanced centers like Children’s National, many newborns still die or have neurological impairments. Dr. Basu emphasized on the need of continued advances in newer therapies and optimizing intensive care support for these vulnerable newborns immediately after birth. Dr. Basu’s presentation focused on the association of not only low blood glucose (hypoglycemia) but also high blood glucose (hyperglycemia) with abnormal motor, visual and intellectual outcomes in surviving newborns.

“Recognizing the problem is the first step for further advancement,” Dr. Basu said. “The scientific community needs to recognize the importance of early glucose status as an early marker for disease severity and risk of brain injury.” To sum up, Dr. Basu drew attention to recent newborn resuscitation guidelines from the International Liaison Committee on Resuscitation (ILCOR), which recommends close monitoring of blood glucose levels and optimizing supportive care to maintain it within normal range. Dedicated clinical trials are the need of the hour to guide what are “normal” glucose levels in newborns with encephalopathy and what treatment options are most beneficial.

Rana F. Hamdy, M.D., M.P.H., M.S.C.E., director of the Children’s National Antimicrobial Stewardship Program, delved into the increased number of children receiving care for acute conditions – like acute respiratory tract infections – from urgent care centers and direct-to-consumer (DTC) telemedicine companies during her session “Implementing Antibiotic Stewardship in Telemedicine and Urgent Care Settings.”

Telemedicine, in this case, refers to DTC telemedicine companies—not to be confused with the telemedicine established with primary care providers, like the services provided by Children’s National.

There has been little research focused on promoting good antibiotic stewardship in urgent care settings that tend to overprescribe antibiotics compared to a primary care setting. In addition to her work focusing on improving antimicrobial use within Children’s National, Dr. Hamdy has led collaborative quality improvement work nationally in both the pediatric urgent care and DTC telemedicine settings.

“What we’ve learned from our work with the DTC telemedicine setting is that leadership commitment coming from the company is a necessary core element,” Dr. Hamdy said. “There may be unique opportunities in the telemedicine setting to employ the home-grown computer systems for antimicrobial stewardship interventions, for example, incorporating clinical decision support or feedback reports into the electronic health record systems or displaying a commitment letter in the virtual waiting room.”

In the urgent care setting, Dr. Hamdy’s team recruited approximately 150 pediatric urgent care providers to participate in the national quality improvement initiative. Communication training modules for pediatric urgent care providers with scripted language for target infectious conditions — acute otitis media, pharyngitis and otitis media with effusion — were among the successful intervention approaches that led to improved appropriate antibiotic prescribing practices, according to her team’s findings.

“Understanding the prescribing practices in the urgent care setting is important to knowing where and how to focus on target conditions and to be able to support with education and resources,” Dr. Hamdy said. “And understanding the perceived barriers to judicious antibiotic prescribing can help to identify the highest yield interventions.”

This also reflects the approach taken by the outpatient antibiotic stewardship team at the Children’s National Goldberg Center, led by Ariella Slovin, M.D., primary care pediatrics provider at Children’s National Hospital. Dr. Slovin’s oral abstract entitled “Antibiotic Prescribing Via Telemedicine in the Time of COVID-19,” examined the effect that a shift to telemedicine due to the COVID-19 pandemic had on antibiotic use for acute respiratory tract infections. Overall, her team found a decrease in the proportion of acute respiratory tract infections prescribed antibiotics and concluded that the shift to telemedicine did not adversely affect judicious antibiotic prescribing for acute respiratory tract infections.

Other participants from Children’s National included: Taeun Chang, M.D.; Yuan-Chiao Lu, Ph.D.; Chidiogo Anyigbo, M.D., M.P.H.; Panagiotis Kratimenos, M.D.; Sudeepta Basu, M.B.B.S., M.S.; Ashraf Harahsheh, M.D., F.A.C.C., F.A.A.P.; Rana F. Hamdy, M.D., M.P.H., M.S.C.E.; John Idso, M.D.; Michael Shoykhet, M.D., Ph.D.; Monika Goyal, M.D.; Ioannis Koutroulis, M.D., Ph.D., M.B.A.; Josepheen De Asis-Cruz, M.D., Ph.D.; Asad Bandealy, M.D., M.P.H.; Priti Bhansali, M.D.; Sabah Iqbal, M.D.; Kavita Parikh, M.D.; Shilpa Patel, M.D.; Cara Lichtenstein, M.D.

To view the PAS phase I mini session list and the various areas of expertise at Children’s National, visit: https://innovationdistrict.childrensnational.org/childrens-national-hospital-at-the-2021-pediatric-academic-societies-meeting/

The PAS virtual conference phase II starts on Monday, May 10 and it goes through Friday, June 4. Those interested in attending may still register for phase II here: http://2021.pas-meeting.org/registration/

Magnetic resonance angiography (MRI) of vessel in the brain

A new framework helps guide safe pediatric diagnostic cerebral angiography

Magnetic resonance angiography (MRI) of vessel in the brain

Although many practitioners perform cerebral angiograms in children, these practitioners have varying levels of prior neuroangiography training and experience.

The Society of Neurointerventional Surgery (SNIS) Pediatric Committee published practice guidelines for pediatric diagnostic cerebral angiography (DCA) in a recent report. Monica Pearl, M.D., director of Neurointerventional Radiology Program at Children’s National Hospital, and other experts developed a framework within the report to ensure that DCA is performed safely in children. The findings detailed specific procedural considerations as well as peri-procedural evaluation and care.

“Diagnostic cerebral angiography has a low complication rate and maintaining this safety profile in children is an expectation for all practitioners performing this procedure,” Dr. Pearl said. “This is predicated on supplementing prior training and experience with a sustained, consistent volume of pediatric cases while paying special attention to the important nuances described in the findings.”

Although many practitioners perform cerebral angiograms in children, these practitioners have varying levels of prior neuroangiography training and experience. Dr. Pearl and experts suggest that a consistent volume of pediatric cases, modifications in device sizes, medication dosing, radiation protocols and technique are necessary to maintain the expected favorable safety profile. The recommendations also include referral to a higher-volume pediatric center or practitioner for those operators who infrequently perform cerebral angiography in children.

“Patient families and referring providers should seek practitioners with ample pediatric neuroangiography experience,” Dr. Pearl advised. “We provide this level of care and experience here at Children’s National.”

As the senior author for this paper, Dr. Pearl led this effort and shaped the task force recommendations providing critical input based on her current and prior pediatric neuroangiography experience. She and her team continue to serve as the leading advocates for the safety of cerebral neuroangiography procedures in children.

Blood Clot or thrombus

Endovascular therapy for acute stroke in children

Blood Clot or thrombus

Endovascular therapies for acute childhood stroke remain controversial and little evidence exists to determine the minimum age and size cut-off for thrombectomy in children. In a recent study published in the Journal of NeuroInterventional Surgery, Monica S. Pearl, M.D., director of Neurointerventional Radiology Program at Children’s National Hospital, and other experts found an increasing number of reports suggesting the feasibility of thrombectomy in at least some children by experienced operators.

When compared with adults, technical modifications may be necessary in children owing to differences in vessel sizes, tolerance of blood loss, safety of contrast and radiation exposure, and differing stroke etiologies. Dr. Pearl and experts reviewed critical considerations for neurologists and neurointerventionalists when treating pediatric stroke with endovascular therapies.

Additional study authors from Children’s National include: Dana Harrar, M.D., Ph.D., and Carlos Castillo Pinto, M.D., F.A.A.P.

Read the full study in the Journal of NeuroInterventional Surgery.

Neuronal network with electrical activity

New robotic platform at Children’s National aids adult epilepsy patient

Neuronal network with electrical activity

Epilepsy specialists at Children’s National Hospital are working collaboratively with their colleagues at George Washington University Hospital (GWU) to deliver advanced epilepsy surgical care to some adult patients by using cutting-edge surgical technologies available at Children’s National.

Epilepsy specialists at Children’s National Hospital are working collaboratively with their colleagues at George Washington University Hospital (GWU) to deliver advanced epilepsy surgical care to some adult patients by using cutting-edge surgical technologies available at Children’s National.

The need for this collaboration has risen because of the availability and experience of the Children’s National team in minimally invasive epilepsy surgery techniques, which require the use of advanced neurosurgical robots and laser ablation technologies. Children’s National has been a leader in this area of advanced epilepsy care.

Years after being diagnosed with epilepsy, an adult patient was referred to Children’s National Hospital for epilepsy surgery, where doctors have been using a robot-assisted stereotactic system called ROSA ONE Brain.

Doctors were having difficulties locating the origin of the seizures. The brain MRI did not show any abnormalities. Using stereo electroencephalography (SEEG) assisted by the robot, the joint Children’s National and GWU team were able to confirm the origin of the seizures.

“In this procedure we use a robot to implant a number of wires into specific areas of the brain where we suspect the seizures could be coming from,” said Chima Oluigbo, M.D., pediatric epilepsy neurosurgeon at Children’s National.

Children’s National is one of the few centers to have this technology available and has been using it since 2016. Up to date, Children’s National has done over 40 SEEG cases where doctors deal with more complicated cases with patients who have seizures and it is hard to pinpoint the seizure’s origin in the brain.

“The surgical procedures performed in adults are what we perform in children,” said William D. Gaillard, M.D., chief of the Divisions of Child Neurology, Epilepsy and Neurophysiology at Children’s National. Children’s National is one of the oldest pediatric epilepsy surgery centers in the country.

“The wires are 1.1 mm in diameter and the technology allows us to place these wires in the brain in such a way that it avoids hurting the patient while being able to conduct the procedure repeatedly and precisely,” Dr. Oluigbo added.

The risk with placing wires in brain is that there are many blood vessels. Doctors must be precise because if there is any mistake it can cause one of the vessels to bleed and thus, cause a stroke. Using robotic placement of SEEG wires minimizes these risks.

Once they identified where the seizures came from, Dr. Oluigbo and the epilepsy team scheduled a second surgery using laser ablation to destroy the area causing the seizures.

First, the robot scanned the patient’s brain (just like an iPhone scans the face, enabling ID recognition) while combining the brain MRI scan. Then, the doctors used a laser beam to heat the tissue area that needed to be removed by the absorbed laser energy and evaporated the target.

“It is a one-time procedure that has few side effects, such as less bleeding and less risk of infection with shorter recovery time at the hospital,” Dr. Gaillard said. “It is a little safer than other procedures and more cost-effective.”

Following the procedure, the patient was discharged back to the care of their adult GWU epileptologist, with whom the team at Children’s National worked closely with while caring for the patient. “It is wonderful to be in a position to partner with our adult-care hospitals to provide a full spectrum of care for patients, even those that have graduated from pediatric care,” concluded Dr. Oluigbo.

Sickle-Cell-Blood-Cells

Treating neurocognitive difficulties in children with sickle cell disease

Sickle-Cell-Blood-Cells

An adaptive cognitive training program could help treat attention and working memory difficulties in children with sickle cell disease (SCD), a new study published in the of Journal of Pediatric Psychology shows.

An adaptive cognitive training program could help treat attention and working memory difficulties in children with sickle cell disease (SCD), a new study published in the of Journal of Pediatric Psychology shows.

These neurocognitive difficulties have practical implications for the 100,000 individuals in the U.S. with SCD, as 20-40% of youth with SCD repeat a grade in school and fewer than half of adults with SCD are employed. Interventions to prevent and treat neurocognitive difficulties caused by SCD have the potential to significantly improve academic outcomes, vocational attainment and quality of life.

The study, led by Steven Hardy, Ph.D., director of Psychology and Patient Care Services at the Center for Cancer and Blood Disorders at Children’s National Hospital, examined a promising approach using an adaptive cognitive training program (known as Cogmed Working Memory Training) that patients complete at home on an iPad.

Using a randomized controlled trial design, children were asked to complete Cogmed training sessions 3 to 5 times per week for about 30 minutes at a time until they completed 25 sessions. The Cogmed program involves game-like working memory exercises that adapt to the user’s performance, gradually becoming more challenging over time as performance improves. The team found that patients with sickle cell disease (SCD) who completed the cognitive training intervention showed significant improvement in visual working memory compared to a waitlist group that used Cogmed after the waiting period. Treatment effects were especially notable for patients who completed a training “dose” of 10 sessions.

“Patients who completed at least 10 cognitive training sessions showed improved visual working memory, verbal short-term memory and math fluency,” Dr. Hardy said.

SCD increases risk for neurocognitive difficulties because of cerebrovascular complications (such as overt strokes and silent cerebral infarcts) and underlying disease characteristics (such as chronic anemia). Neurocognitive effects of SCD most commonly involve problems with attention, working memory and other executive functions.

“This study demonstrates that digital working memory training is an effective approach to treating neurocognitive deficits in youth with sickle cell disease,” Dr. Hardy added. “We also found that benefits of the training extend to tasks that involve short-term verbal memory and math performance when patients are able to stick with the program and complete at least 10 training sessions. These benefits could have a real impact on daily living, making it easier to remember and follow directions in school and at home, organize tasks or solve math problems that require remembering information for short periods of time.”

To date, there have been few efforts to test interventions that address the neurocognitive issues experienced by many individuals with SCD. These findings show that abilities are modifiable and that a non-pharmacological treatment exists.

The Comprehensive Sickle Cell Disease Program at Children’s National is a leader in pediatric SCD research and clinical innovation. This study was funded by a grant from the Doris Duke Charitable Foundation, which was the only Innovations in Clinical Research Award ever awarded to a psychologist (out of 31 grants totaling over $15 million), since the award established a focus on sickle cell disease in 2009.

doctor examining pregnant woman

Low parental socioeconomic status alters brain development in unborn babies

doctor examining pregnant woman

A first-of-its-kind study with 144 pregnant women finds that socioeconomic status (SES) has an impact in the womb, altering several key regions in the developing fetal brain as well as cortical features.

Maternal socioeconomic status impacts babies even before birth, emphasizing the need for policy interventions to support the wellbeing of pregnant women, according to newly published research from Children’s National Hospital.

A first-of-its-kind study with 144 pregnant women finds that socioeconomic status (SES) has an impact in the womb, altering several key regions in the developing fetal brain as well as cortical features. Parental occupation and education levels encompassing populations with lower SES hinder early brain development, potentially affecting neural, social-emotional and cognitive function later in the infant’s life.

Having a clear understanding of early brain development can also help policymakers identify intervention approaches such as educational assistance and occupational training to support and optimize the well-being of people with low SES since they face multiple psychological and physical stressors that can influence childhood brain development, Lu et al. note in the study published in JAMA Network Open.

“While there has been extensive research about the interplay between socioeconomic status and brain development, until now little has been known about the exact time when brain development is altered in people at high-risk for poor developmental outcomes,” said Catherine Limperopoulos, Ph.D., director of the Developing Brain Institute and senior author. “There are many reasons why these children can be vulnerable, including high rates of maternal prenatal depression and anxiety. Later in life, these children may experience conduct disorders and impaired neurocognitive functions needed to acquire knowledge, which is the base to thrive in school, work or life.”

The findings suggest that fetuses carried by women with low socioeconomic backgrounds had decreased regional brain growth and accelerated brain gyrification and surface folding patterns on the brain. This observation in lower SES populations may in part be explained by elevated parental stress and may be associated with neuropsychiatric disorders and mental illness later in life.

In contrast, fetuses carried by women with higher education levels, occupation and SES scores showed an increased white matter, cerebellar and brainstem volume during the prenatal period, and lower gyrification index and sulcal depth in the parietal, temporal and occipital lobes of the brain. These critical prenatal brain growth and development processes lay the foundation for normal brain function, which ready the infant for life outside the womb, enabling them to attain key developmental milestones after birth, including walking, talking, learning and social skills.

There is also a knowledge gap in the association between socioeconomic status and fetal cortical folding — when the brain undergoes structural changes to create sulcal and gyral regions. The study’s findings of accelerated gyrification in low SES adds to the scientific record, helping inform future research, Limperopoulos added.

The Children’s National research team gathered data from 144 healthy women at 24 to 40 weeks gestation with uncomplicated pregnancies. To establish the parameters for socioeconomic status, which included occupation and education in lieu of family income, parents completed a questionnaire at the time of each brain magnetic resonance imaging (MRI) visit. The researchers used MRI to measure fetal brain volumes, including cortical gray matter, white matter, deep gray matter, cerebellum and brain stem. Out of the 144 participants, the scientists scanned 40 brain fetuses twice during the pregnancy, and the rest were scanned once. The 3-dimensional computational brain models among healthy fetuses helped determine fetal brain cortical folding.

Potential proximal risk factors like maternal distress were also measured in the study using a questionnaire accounting for 60% of the participants but, according to the limited data available, there was no significant association with low and high socioeconomic status nor brain volume and cortical features.

Authors in the study from Children’s National include: Yuan-Chiao Lu, Ph.D., Kushal Kapse, M.S., Nicole Andersen, B.A., Jessica Quistorff, M.P.H., Catherine Lopez, M.S., Andrea Fry, B.S., Jenhao Cheng, Ph.D., Nickie Andescavage, M.D., Yao Wu, Ph.D., Kristina Espinosa, Psy.D., Gilbert Vezina, M.D., Adre du Plessis, M.D., and Catherine Limperopoulos, Ph.D.

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.

illustration of brain with stem cells

Innovative phase 1 trial to protect brains of infants with CHD during and after surgery

A novel phase 1 trial looking at how best to optimize brain development of babies with congenital heart disease (CHD) is currently underway at Children’s National Hospital.

Children with CHD sometimes demonstrate delay in the development of cognitive and motor skills. This can be a result of multiple factors including altered prenatal oxygen delivery, brain blood flow and genetic factors associated with surgery including exposure to cardiopulmonary bypass, also known as the heart lung machine.

This phase 1 trial is the first to deliver mesenchymal stromal cells from bone marrow manufactured in a lab (BM-MSC) into infants already undergoing cardiac surgery via cardiopulmonary bypass. The hypothesis is that by directly infusing the MSCs into the blood flow to the brain, more MSCs quickly and efficiently reach the subventricular zone and other areas of the brain that are prone to inflammation. The trial is open to eligible patients ages newborn to six months of age.


Learn more in this overview video.

The trial is part of a $2.5 million, three-year grant from the National Institutes of Health (NIH) led by Richard Jonas, M.D.Catherine Bollard, M.B.Ch.B., M.D., and Nobuyuki Ishibashi, M.D.. The project involves collaboration between the Prenatal Cardiology program of Children’s National Heart Institute, the Center for Cancer and Immunology Research, the Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

“NIH supported studies in our laboratory have shown that MSC therapy may be extremely helpful in improving brain development in animal models after cardiac surgery,” says Dr. Ishibashi. “MSC infusion can help reduce inflammation including prolonged microglia activation that can occur during surgery that involves the heart lung machine.”

Staff from the Cellular Therapy Laboratory, led by director Patrick Hanley, Ph.D., manufactured the BM-MSC at the Center for Cancer and Immunology Research, led by Dr. Bollard.

The phase 1 safety study will set the stage for a phase 2 effectiveness trial of this highly innovative MSC treatment aimed at reducing brain damage, minimizing neurodevelopmental disabilities and improving the postoperative course in children with CHD. The resulting improvement in developmental outcome and lessened behavioral impairment will be of enormous benefit to individuals with CHD.

For more information about this new treatment, contact the clinical research team: Gil Wernovsky, M.D., Shriprasad Deshpande, M.D., Maria Fortiz.

MRI of the patient's head close-up

Early versus late MRI in newborn brain injury

MRI of the patient's head close-up

A single magnetic resonance imaging (MRI) performed in the first week after birth is adequate to assess brain injury and offer prognostic information in newborn infants with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia, according to a new study published in The Journal of Pediatrics.

A collaborative team of neonatology, neurology and neuroradiology experts from Children’s National Hospital that included Gilbert Vezina, M.D., Taeun Chang, M.D., and An N. Massaro, M.D., came together to evaluate the agreement in brain injury findings between early and late MRI in newborn infants with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. The team then compared the ability of early versus late MRI to predict early neurodevelopmental outcomes.

This was a prospective longitudinal study of 49 patients with HIE who underwent therapeutic hypothermia and had MRI performed at both <7 and ≥7 days of age. MRIs were reviewed by an experienced neuroradiologist and assigned brain injury severity scores according to established systems. Scores for early and late MRIs were assessed for agreement using the kappa statistic. The ability of early and late MRI scores to predict death or developmental delay at 15-30 months of age was assessed by logistic regression analyses.

The results of the study found agreement between the early and late MRI was substantial to near perfect (k>0.75, p<0.001) across MRI scoring systems. In cases of discrepant scoring, early MRI was more likely to identify severe injury when compared with late MRI. Early MRI scores were more consistently predictive of adverse outcomes compared with late MRI.

Read the full study in The Journal of Pediatrics.

structure of EGFR

Study suggests EGFR inhibition reverses alterations induced by hypoxia

structure of EGFR

The study suggests that specific molecular responses modulated by EGFR (seen here) may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

Hypoxic (HX) encephalopathy is a major cause of death and neurodevelopmental disability in newborns. While it is known that decreased oxygen and energy failure in the brain lead to neuronal cell death, the cellular and molecular mechanisms of HX-induced neuronal and glial cell damage are still largely undefined.

Panagiotis Kratimenos, M.D., and colleagues from the Center for Neuroscience Research at the Children’s National Research Institute, discovered increased expression of activated-epidermal growth factor receptor (EGFR) in affected cortical areas of neonates with HX and decided to further investigate the functional role of EGFR-related signaling pathways in the cellular and molecular changes induced by HX in the cerebral cortex.

The researchers found that HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation and reversed HX-induced astrogliosis.

The researchers also performed, for the first time, high-throughput transcriptomic analysis of the cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in brain injury. Their results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

This study defines many new exciting avenues of scientific exploration to further elucidate the beneficial impact of EGFR blockade on perinatal brain injury at the cellular and molecular levels. This analysis could potentially result in the identification of new therapeutic targets associated with EGFR signaling in the developing mammalian brain that are linked with specific long-term abnormalities caused by perinatal brain injury.

Children’s National researchers who contributed to this study include Panagiotis Kratimenos, M.D., Ioannis Koutroulis, M.D., Ph.D., M.B.A., Susan Knoblach, Ph.D., Payal Banerjee, Surajit Bhattacharya, Ph.D., Maria Almira-Suarez, M.D., and Vittorio Gallo, Ph.D.

Read the full article in iScience.

newborn

Predicting risk for infantile spasms after acute symptomatic neonatal seizures

newborn

Infantile spasms (IS) is a severe epilepsy in early childhood. Early treatment of IS provides the best chance of seizure remission and favorable developmental outcome.

Taeun Chang, M.D., director of the Neonatal Neurology and Neurocritical Care Program at Children’s National Hospital, participated in a study with other national pediatric experts which aimed to develop a prediction rule to accurately predict which neonates with acute symptomatic seizures will develop IS.

The group of researchers found that multiple potential predictors were associated with IS, including Apgar scores, EEG features, seizure characteristics, MRI abnormalities and clinical status at hospital discharge. The final model born from this work included three risk factors: (a) severely abnormal EEG or ≥3 days with seizures recorded on EEG, (b) deep gray or brainstem injury on MRI and (c) abnormal tone on discharge exam.

The significance of these findings is that IS risk after acute symptomatic neonatal seizures can be stratified using commonly available clinical data. No child without risk factors, vs >50% of those with all three factors, developed IS. This risk prediction rule may be valuable for clinical counseling as well as for selecting participants for clinical trials to prevent post‐neonatal epilepsy. This tailored approach may lead to earlier diagnosis and treatment and improve outcomes for a devastating early life epilepsy.

Read the full study in Epilepsia.

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.

Lee Beers

Lee Beers, M.D., F.A.A.P, begins term as AAP president

Lee Beers

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
  • Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
  • Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.

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.”