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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.

 

Dr. Bornhorst talks with her patient Maddox Gibson,

A melanoma drug shows promise for NF1 plexiforms

Dr. Bornhorst talks with her patient Maddox Gibson,

Dr. Bornhorst talks with her patient Maddox Gibson, who is part of the compassionate use trial of selumentinib for which she serves as site principal investigator.

A class of drugs originally approved for stopping tumor growth in adult cancers including melanoma and small cell lung cancer may be the key to treating plexiform neurofibromas in neurofibromatosis type 1 (NF1), too. If effective, doctors will finally have a treatment to offer for children with complicated plexiform neurofibromas that can’t be removed via surgery.

These drugs, including selumentinib, work by inhibiting the activity of the mitogen-activated protein kinase enzymes MEK1 and MEK2. The enzymes have a direct impact on the activity of the cellular signaling pathway MAPK/ERK, which can be overactive some cancers.

Ongoing pre-clinical studies made possible by national and international neurofibromatosis research collaborations demonstrated that this same pathway is overactive in children with NF1 who have plexiform neurofibromas. The compelling findings from these studies set the stage for clinical trials to test the safety and efficacy of selumetinib and other MEK inhibitors as a therapy for pediatric NF1 patients with inoperable plexiform neurofibromas.

At Children’s National, these studies are run by clinicians such as Miriam Bornhorst, M.D., clinical director of the Gilbert Family Neurofibromatosis Institute and Aerang Kim, M.D., Ph.D. Children’s is one of only four sites in the United States to participate in a National Institutes of Health-led clinical trial to study the use of selumetinib in NF1. Dr. Kim is the site principal investigator and Dr. Bornhorst serves as co-principal investigator on phase 2 of the trial.

“Any time we find a medication that works with NF1, we’re excited, especially because for so many years, we didn’t have any of these options for these families,” Dr. Bornhorst says. “We’re offering something these families have never had before – a treatment that may stop growth and maybe even keep these tumors from returning. It means we’re doing more than managing symptoms – we’re really treating them.”

NF1 affects a relatively small number of people, particularly children. However, researchers and clinicians who are dedicated to the condition have banded together via collaborations and consortia to fuel research and development of new therapies across multiple institutions in the U.S. and abroad.

“Patients come to see me who’ve been at our clinic for years and I’ll talk about MEK inhibitors, and they are just shocked to hear there may be a new option,” Dr. Bornhorst says.

The NIH trial continues to collect data at four U.S. centers, with the ultimate goal of submitting the results for FDA review. Additional data is also collected from patients who didn’t qualify for the trial but who received the drug for compassionate use, an effort led by Dr. Bornhorst. The information collected from that compassionate use trial also helps investigators make the case to broaden the eligibility criteria for future trials.

“The medications are showing that they work,” Dr. Bornhorst notes. “Now we need to determine how to identify the patients who we know will need these therapies.”

To meet that need, other studies, led by both Dr. Bornhorst and Dr. Kim, seek radiographic and blood biomarkers that will identify children with NF1 who are more likely to develop plexiform neurofibromas, and whose plexiforms may progress to something malignant.

Pediatric Neurology Update Attendees

Pediatric neurologists get a primer on the state of ASD research and care

Pediatric Neurology Update Attendees

Neurologists who attended the 2019 Pediatric Neurology Update received a broad look at autism spectrum disorders, ranging from biology to clinical care and advocacy.

Autism spectrum disorders (ASD) took center stage for the afternoon sessions of the annual Pediatric Neurology Update in April. The meeting, hosted by the Center for Neuroscience and Behavioral Medicine at Children’s National Health System, brings together 150-plus pediatric neurologists each year to discuss critical research and clinical care of pediatric neurological conditions.

Led by the Center for Autism Spectrum Disorders Director Lauren Kenworthy, Ph.D., the afternoon’s slate of presentations sought to give broad perspective of the current state of ASD research and treatment best practices.

“We know that the brain is different in autism, but many times we continue to define autism by behavioral traits,” Dr. Kenworthy told the crowd in her introduction. “Sitting between the brain and behavior often is cognition – how do you understand your world and interpret it?”

The afternoon’s presentations were organized to provide the audience with a clear picture of many facets of ASD research and treatment. Highlights included:

  • Joshua Corbin, Ph.D., director of the Center for Neuroscience Research, offered “New Insights into the Neurobiologic Underpinnings of Autism,” which mapped out some of the biological mechanisms of autism.
  • Adelaide Robb, M.D., and Dr. Kenworthy presented current clinical care outlines, with Dr. Robb focusing on pharmacological therapies and Dr. Kenworthy sharing successful strategies to improve executive functioning and day to day task management for school-aged children.

Attendees also received a taste of two current “hot topics” in autism research and care:

  • Kevin Pelphrey, Ph.D., presented recent findings on “Gender Differences in Autism Spectrum Disorders: Girls with Autism” calling attention to the fact that the current diagnostic standards may not capture some female-associated phenotypes of ASD.
  • Julia Bascom of the Autistic Self Advocacy Network brought the autistic person’s point of view to the table via her presentation: “Autism: Society and Government Challenges and Solutions,” which focused on her organization’s efforts to improve inclusivity in advocacy and research, which she sums up as, “Nothing about us without us.”

The session concluded with a real-world focused “Autism-Friendly Hospital Roundtable,” of six panelists from the clinical, advocacy, community and technology fields, who are all involved in hands-on practices to improve medical experiences for autistic children and adults.

  • CASD’s Yetta Myrick talked about her work to engage families of autistic children in discussions of research and clinical care programs, including the start of CASD’s first-ever Stakeholder Advisory Board.
  • Julia Bascom talked about some of the less-often discussed challenges for many autistic people who seek medical services.
  • Kathleen Atmore, Psy.D., and Eileen Walters, MSN, RN, CPN, provided an overview of Beyond the Spectrum, the clinical service at Children’s National that coaches providers and families in techniques to reduce the stress of routine medical visits for patients with autism and other developmental disabilities.
  • Amy Kratchman, director of the LEND Family Collaboration at Children’s Hospital of Philadelphia, talked about some of the autism-friendly strategies underway at her institution.
  • Michael O’Neil, JD, MBA, founder and CEO of the GetWell Network, Inc., previewed how GetWell and Children’s National are partnering on a new tool that harnesses app technology to bring better information to autistic children and their families after a new autism diagnosis.
  • Vijay Ravindran, CEO and co-founder at Floreo, demonstrated how it might be possible to reduce stress and create a calm peaceful autism-friendly environment even in the busiest of waiting rooms, by allowing the patient to escape via virtual reality.

The roundtable showcased how Children’s National and other health care institutions are using evidence-based strategies to improve medical care experiences for autistic people and their families. Ideally any provider, including pediatric neurologists, who cares for people from the autism community, can incorporate any or all of these strategies as a way to meet the unique needs of this patient population.

The content was so timely and relevant to the audience that many attendees stayed past the official end of the meeting to continue discussing best practices with the panelists and each other.

Roger Packer

From discovery to ‘no excuses’ in neuro-oncology

For more than three decades, the world’s pre-eminent scientists and clinicians in pediatric neuro-oncology have convened the International Symposium on Pediatric Neuro-oncology every two years. Their goal is to advance the care and treatment of pediatric brain and central nervous system tumors by connecting across disciplines to share research findings and discuss the latest treatment approaches.

This year for the first time, representatives from parent advocacy groups and patient support foundations were also invited to attend the traditionally scientific meeting. Their inclusion allowed care providers and scientific investigators to make sure the voices of patients and families, and their needs, are heard.

Roger J. Packer, M.D., senior vice president of the Center for Neuroscience and Behavioral Medicine at Children’s National Health System, served as international organizing committee chair this year. He was chair and organizer of the very first symposium, held in 1986, and has led additional sessions over the years.

Dr. Packer had the honor of giving the opening keynote address to more than 1,200 participants in Denver this year. He used his lecture to highlight some of the amazing knowledge leaps made in the last decade in understanding the molecular makeup and genetics behind brain and spinal cord tumors.

“We’ve made more discoveries in these areas in the last 10 years than we made in the 50 years before that. It’s been a phenomenal decade for discovery,” he notes.  “But the fact remains we have not yet been able to translate all of this knowledge into more effective therapies for most children with brain and central nervous system cord tumors.”

Dr. Packer says progress made in managing and treating childhood low grade gliomas is one example of how care should move forward for other tumor types. The unique genetic and molecular makeup of low grade gliomas, which are the single most common form of childhood low grade tumor, has allowed clinicians to begin moving away from surgeries, radiation therapy and chemotherapy toward less neurotoxic treatments targeted at the specific molecular properties of the tumor itself.

“Although the chemotherapy protocol we began for low-grade gliomas 30 years ago works well and is still the standard of care today, the new molecular approaches we and others have tested will hopefully replace it soon and result in even better outcomes,” he adds.

Medulloblastoma, the most common form of malignant brain tumor, is one area Dr. Packer notes could stand to benefit from therapies with less impact on a child’s quality of life. The current treatment protocol used for this childhood tumor also remains the same as the one that Dr. Packer helped develop more than 30 years ago.

“Our protocol is effective, and we’ve moved survival from 50 percent to 80 percent for these types of tumors using this approach, but it’s time to determine how best to move toward effective molecularly targeted therapies that would allow us to reduce the neurotoxic treatments necessary to treat these tumors.”

“We have to move from our decade of discovery to a decade of no excuses where we are able to use what we’ve learned to improve the care of all childhood brain and spinal cord tumors,” he says.

Dr. Packer says the key is to avoid getting paralyzed by the mountain of molecular data that is available and really focus on the specific information needed to make treatments more precise.

One promising new approach is the use of immunotherapy for pediatric brain and spinal cord tumors. Children’s National and colleagues from across the U.S. are at the forefront of developing these therapies to control tumor growth, and presented several related studies at ISPNO:

There were also several poster session presentations where Dr. Hwang, Lindsey Kilburn, M.D., Brian Rood, M.D., and others from the Children’s National team shared findings related to the potential and the challenges of molecular targeted therapies, especially immunotherapies. The team at Children’s also presented data related to new findings about how to reverse neurologic and neurocognitive deficits that often result from these conditions, including some that for years were thought to be irreversible, such as vision deficits.

Dr. Packer notes that many of the newest clinical trials both in the U.S. and internationally have the potential to kick start this decade of “no excuses.”

“We’ve made great progress, but we haven’t yet been able to take full advantage of the knowledge we’ve amassed. To do it, we all have to work together as a community nationally and internationally to change the paradigms of how we treat these children and make meaningful advances.”

Roger Packer high fives patient Olivia Enos

Kids’ resilience pushes neurologist to seek better therapies

Roger Packer high fives patient Olivia Enos

“I get strength from kids and families, strength like that shown by Nick and his family,” answered Roger Packer, M.D., when Quicken Loans owner Dan Gilbert asked how he copes with the stress of seeing children struggling with brain tumors and other neurological problems every day.

Dr. Packer, senior vice president of the Center for Neuroscience and Behavioral Health at Children’s National Health System, joined Mr. Gilbert and his son, Nick, who was treated for neurofibromatosis at Children’s National, for a panel discussion at the recent Crain’s Health Care Heroes event. The discussion focused on Nick Gilbert, now a college student, and how he has stayed positive while undergoing intense treatments for neurofibromatosis since he was 15 months old.

Dr. Packer met Nick at age 10, when he first came to Children’s National for its world-renowned expertise in neurofibromatosis research and care. After their experiences, the Gilberts generously supported the creation of the Gilbert Family Neurofibromatosis Institute at Children’s National Health System to continue research into new and innovative treatments for the disorder.

Mr. Gilbert credits Dr. Packer with taking on difficult cases and having a positive impact on both Nick and himself. “When other doctors give up on patients, he intervenes with magic and saves lives.”

The reason, according to Dr. Packer, is that kids like Nick “don’t want to give up.” Thankfully, he notes, better tools to treat diseases like cancer and neurofibromatosis have finally arrived. “There are remarkable advances that were not possible five years ago,” he said.

The full session at the Health Care Heroes event was featured in Crain’s Detroit Business.