All posts by CHOC Children's

NIH grant aims to locate high-frequency oscillations to reduce pediatric seizures

Epileptologists at the CHOC Neuroscience Institute and UC Irvine biomedical engineers have devised a novel approach to pinpoint precise targets for surgical resection or ablation as a means to control epileptic seizures in children. The approach uses densely spaced electrodes to map high-frequency oscillations (HFOs), which tend to be most prevalent in seizure-producing brain tissue. This research offers new hope for the approximately 50% of patients who still experience seizures after surgical intervention. It also has the potential to prevent unnecessary surgery.

HFOs recorded from electrodes inside the brain or on its surface help pediatric epilepsy specialists and neurosurgeons determine which brain regions should be removed or ablated during epilepsy surgery. Historically, most HFO research has not accounted for electrode size or the distance between electrodes when analyzing the use of HFOs to identify diseased brain tissue, believing these recording characteristics to be irrelevant. This new approach challenges that notion and seeks to improve identification of seizure-generating tissue through multi-scale recordings. Additionally, mapping brain function with this high-density electrode array allows more targeted surgeries, enabling resection or ablation with less post-operative morbidity and functional deficits.

The research is being conducted courtesy of a $1.8 million grant from the NIH National Institute of Neurological Disorders and Stroke. Awarded to UC Irvine’s Dr. Beth Lopour, the five-year R01 grant aims to develop and validate computerized tools that would improve identification of the seizure onset zone. Pediatric epileptologists and neurosurgeons at the CHOC Neuroscience Institute are collaborating with UCI biomedical engineers on the research.

Recording signals from the brain

HFOs hold the key to CHOC’s ongoing research. When a pediatric patient does not respond to seizure medication, electrodes are often implanted into the brain or onto its surface to monitor abnormal electrical activity and capture seizures. The neurologist then uses the collected data to determine surgical candidacy.

Standard intracranial grid electrodes are spaced 10 millimeters apart, from center to center. In this study, on the other hand, researchers utilize a high-density grid with electrodes spaced only 3 millimeters apart. They hypothesize that closer electrodes will lead to a greater amount of diagnostic information and an enhanced ability to pinpoint the source of seizures.

With this enhanced capability, neurologists have already seen preliminary success. Early data was submitted as part of the NIH grant application, according to Dr. Joffre Olaya, pediatric neurosurgeon at CHOC, and one patient recently received a successful resection. The team hopes to enroll 35 patients with pediatric epilepsy in the study.

Reducing deficits and avoiding unnecessary surgery

“We review a lot of data before concluding someone is a surgical candidate,” Dr. Olaya says. “Based on pre-op workup, we focus our evaluation on a certain area of the brain to narrow down the source of seizures. We hope this study will help us narrow our focus even more, so we can diagnose troubling areas with greater precision.”

When the area of surgical focus is housed within structures in the brain that govern critical functions, providers must consider the risks and benefits of surgery over any potential deficit. Being able to precisely locate a troublesome area helps physicians determine and reduce potential risks with greater exactitude. As a result, physicians and patients are better prepared to make educated treatment decisions.

“We believe that our novel techniques will help to identify patients who would not significantly benefit from surgical removal of brain tissue and therefore allow them to avoid unnecessary and ultimately unsuccessful operations,” says Dr. Daniel Shrey, pediatric neurologist and epileptologist at CHOC. “In instances where no seizures or an insufficient number of seizures are captured during intracranial monitoring to make a clinical decision about surgery, we hope that including HFO data will give us sufficient confidence to pursue surgery, when appropriate.”

Expanding the scope of epilepsy knowledge

By collecting novel data from patients with epilepsy, CHOC pediatric neurologists are adding to the collective knowledge of the disorder. Their hope is that the medical world will gain new tools for diagnosing and treating one of the most common childhood neurologic disorders.

“We’re fortunate to have such a wonderful collaboration with UC Irvine,” Dr. Olaya says. “This is truly a team effort, and it’s exciting to have the opportunity to do this important project together — one that increases our ability to provide patients with freedom from their seizures.”

Learn more about the CHOC Neuroscience Institute.

New tool for craniosynostosis treatment highlights Neuroscience Institute’s push to advance care

For pediatric neurosurgeon, Dr. Suresh Magge and his colleagues in the CHOC Neuroscience Institute, Christmas this year arrived in late June.

That’s when a 3D camera system was installed in the neurosurgery clinic that will significantly advance CHOC’s mission to treat craniosynostosis, says Dr. Magge, PSF neurosurgery division chief for CHOC and co-medical director of the Neuroscience Institute.

Craniosynostosis, which affects 1 in every 2,000 infants, causes an infant’s skull to fuse early, creating an irregular skull shape, and can lead to increased pressure on the brain as a child matures. This can lead to headaches, vision problems, and cognitive issues. 

The 3D motion-capture camera can, in seconds, capture a comprehensive array of images that will allow CHOC neurosurgeons to better analyze and measure in detail a child’s head. This, in turn, will allow them to enhance research in craniosynostosis and design the best possible treatments.

Dr. Suresh Magge, neurosurgery medical director
Dr. Suresh Magge, neurosurgery medical director

“This really makes a difference,” says Dr. Magge, noting that traditional 2D photos and measurements “only go so far.”

“This new camera allows us to get data quickly and safely,” Dr. Magge says.

CHOC recently had its first craniosynostosis patient imaged by the 3D camera.

A push to greatness

The new camera is a critical step in Dr. Magge’s push to advance the path of the Neuroscience Institute in becoming a world-class destination for neurological care.

Dr. Magge was recruited to CHOC last October after an 11-year tenure at Children’s National Hospital in Washington, D.C., where he started the medical center’s neurosurgery fellowship training program and was the director of medical student education in pediatric neurosurgery.

During his time at Children’s National, Dr. Magge started the region’s first minimally invasive craniosynostosis program. He has brought this surgery to CHOC as well.

The neurosurgery division also includes Dr. Michael Muhonen, Dr. William Loudon, and Dr. Joffre Olaya.

For the last several decades, the go-to surgery to treat craniosynostosis has been an open surgical correction called calvarial reconstruction. For this surgery, doctors must wait until the child is 6-12 months of age and perform a large surgery that involves opening the scalp, taking apart the entire skull, then putting it back together.

“It’s a good surgery, and most kids do well, but we have newer techniques that are less invasive,” Dr. Magge says. The open calvarial reconstruction surgery generally takes 4-6 hours and requires a hospital stay of 3-5 days, as well as a blood transfusion during surgery. 

Unlocking the skull

The minimally invasive procedure Dr. Magge learned during his fellowship at Boston Children’s Hospital involves using an endoscope with a camera attached to its tip.

After making one or two small incisions, Dr. Magge goes under the scalp and then under the skull, using the endoscope to separate the skull from the underlying tissue. He then cuts out a piece of bone — 1 to 2 centimeters in width – to “unlock” the skull.

This surgery only takes about an hour, and most children don’t need a blood transfusion and can go home the next day. After surgery, they wear a molding helmet that helps to reshape the skull. This minimally invasive surgery is generally done by 3-4 months of age (earlier than the open surgery).

“The data shows this surgery works very well,” says Dr. Magge, who has given many presentations and written multiple papers about this procedure.

The aesthetic results have been shown to be excellent in many papers, Dr. Magge says. What still needs to be verified by research are the long-term cognitive outcomes of patients after either the open or minimally invasive surgery.

To that end, Dr. Magge launched a study about two years ago involving patients from multiple hospitals that looks at children five years after surgery. Dr. Magge plans to enroll patients from CHOC in the study.

He estimates the study will be completed in about two years. 

Working with plastic surgeon Dr. Raj Vyas, Dr. Magge says CHOC offers comprehensive cranio-facial services. 

Dr. Raj Vyas
Dr. Raj Vyas

“To be comprehensive,” he says, “you have to offer traditional surgery as well as minimally invasive surgery.” 

Part of the funding for the new 3D camera came from a CSO grant established by CHOC Vice President for Research and Chief Scientific Officer Dr. Terence Sanger, a physician, engineer, and computational neuroscientist who also is vice chair of research for pediatrics at the UCI School of Medicine.

Dr. Terence Sanger
Dr. Terence Sanger

The 3D camera arrives as significant infrastructure changes are underway at the Neuroscience Institute: CHOC recently opened its new state-of-the-art outpatient center, establishing a clinical hub for caregivers to serve patients and families in a centralized location. Additionally, plans are underway to expand the hospital’s inpatient neuroscience unit.

“CHOC has been very supportive of the Neuroscience Institute,” Dr. Magge says. “I’m very excited.”

Learn more about the CHOC Neuroscience Institute.

LITT: Prolonging life, limiting complications in recurrent medulloblastoma

CHOC’s multidisciplinary team used laser interstitial thermal therapy (LITT) — one of several minimally invasive treatments shaping the present and future of pediatric neuro-oncology and pediatric neurosurgery — to treat recurrent medulloblastoma in a young patient as an alternative to standard-of-care surgical resection. A year after the procedure, the patient showed significant reduction in tumor size and enhancement.

“Up to 30% of patients have recurrence of medulloblastoma,” says Dr. Chenue Abongwa, pediatric neuro-oncologist at the Hyundai Cancer Institute at CHOC. “In those situations, less than 25% survive, which is a challenge because we are always looking for ways to improve treatment for patients with recurrent disease who have undergone extensive treatment and are dealing with complications of treatment.”

The benefits of laser ablation

While the outlook for medulloblastoma is bleak — survival rates have stagnated in the last two decades, while survivors tend to have poor quality of life — LITT holds out hope for both prolonged survival and improved outcomes. The procedure is still relatively rare, but increasingly, clinicians are turning to LITT to treat certain recurrent medulloblastomas and similar malignancies. Ideal candidates include patients with small — a circumference of 3 centimeters or less — focal lesions situated deep in the brain for whom resection via craniotomy is not optimal or desirable.

“With LITT, we make a small, 5-millimeter incision and stereotactically insert a probe to the location of the lesion,” says Dr. Joffre Olaya, pediatric neurosurgeon at the CHOC Neuroscience Institute. “We use a laser to ablate the tumor under direct MRI visualization. Ablating the tumor is comparable to resecting it, but without having to perform a craniotomy.”

A robotic stereotactic assistance device allows pediatric neurosurgeons to precisely target tumors without damaging surrounding brain tissue or vasculature. Typically, the surgeon will conduct a concurrent biopsy of the tumor.

“Our patients have tolerated LITT quite well,” Dr. Olaya says. “Most return home the day after the procedure and have minimal pain. Recovery is much quicker than with a standard craniotomy.”

Dr. Olaya also values the flexibility that LITT affords.

“LITT does not eliminate the option of standard resection,” he says. “If a tumor continues to grow or spread after a patient undergoes LITT, we can always go back and perform a standard craniotomy.”

LITT for a patient with recurrent medulloblastoma and posterior fossa syndrome

Dr. Abongwa and Dr. Olaya were part of a multidisciplinary team that used LITT to treat an 11-year-old patient who developed posterior fossa syndrome after undergoing initial medulloblastoma treatment — consisting of gross total resection followed by chemotherapy and radiation therapy — years earlier and had a recurrence of the brain tumor.

“This case is an excellent illustration of when we can use laser ablation,” Dr. Abongwa says. “The patient had undergone standard treatment for medulloblastoma at age 5, developed significant complications as a result, then had a recurrence. Surgery was not a good option because the family was worried about the patient’s quality of life and the potential for more problems after another craniotomy.”

As with all pediatric brain tumor cases at CHOC, the case was presented to the biweekly neuro-oncology tumor board comprised of pediatric neurosurgeons, pediatric neuroradiologists, a pediatric neuro-oncologist, pediatric neurologists and pediatric endocrinologists. The group discussed the patient’s case and determined LITT would be appropriate.

“We evaluated the patient based on their situation and found that LITT would be a good option to help us control the tumor locally without increasing the chances of the patient experiencing problems related to treatment,” Dr. Abongwa says. “The patient tolerated the treatment well.”

After undergoing LITT, the patient began receiving standard chemotherapy treatment for tumor control. That regimen continues, but after a year of surveillance, no signs of tumor recurrence have emerged.

“LITT offers a less invasive method that may serve as an adjunct in treating recurrent tumors, or, potentially, as palliation,” Dr. Olaya says. “Some patients have recurrent tumors that cause symptoms, but we may not want to put them through an initial major surgery. From a palliative standpoint, LITT may help improve their quality of life and extend life in these situations without having to put these children through a craniotomy.” 

Growing applications

Clinicians need more long-term follow-up data for patients treated with LITT. That is why CHOC is participating in Laser Ablation of Abnormal Neurological Tissue Using Robotic Neuroblate System (LAANTERN), a prospective, multicenter registry that collects safety, quality of life, and outcomes and survival data on up to 1,000 patients for up to five years. This data will help clinicians better understand the efficacy of LITT compared with standard treatment.

Recent research supports the use of LITT to treat newly diagnosed tumors, such as low-grade gliomas, according to Dr. Abongwa, but data from large clinical trials are necessary to justify widespread adoption. In the meantime, CHOC continues to seek ways to enhance patient care.

“CHOC is dynamic,” Dr. Abongwa says. “We are always trying to improve the care of children by offering standard treatments and new, innovative therapies that can improve the chance of a cure.” 

Learn more about the Neuro-oncology Treatment Program.

Bien, gracias a Dios: Childhood Cancer Awareness Month

By Dr. Rishi Chavan, pediatric stem cell transplanter and oncologist at CHOC 

Not too long ago we had a patient; a child who underwent stem cell transplant for relapsed acute myeloid leukemia. Their donor was a sibling who lived in Mexico, and we had them travel here to have their bone marrow harvested prior to their transplant. The transplant was challenging as the patient had developed an infection in their lungs prior to transplant. We had to treat the infection first while doing bridging chemotherapy to ensure sustained remission because the transplant would temporarily wipe out their immune system. Now, they are more than a year post transplant and happily back with family in Mexico. They still visit us to ensure sustained remission and long-term follow up.

This patient was one of our sweetest. Not only were they extremely polite, but despite their pain while undergoing chemotherapy, they were always very grateful.

We often ask patients, “How are you doing today?”

This patient always responded, “Bien, gracias a Dios” or “Good, thank God.”

September is Childhood Cancer Awareness Month. As the motto goes: “No one fights cancer alone.” At Hyundai Cancer Institute at CHOC, we truly live this motto everyday as it takes a village. We have an amazing army of nurses, child life specialists, pharmacists, experienced advanced practitioners, occupational and physical therapists, nutritionists, music therapists, social services experts, chaplain, care coordinators, medical interpreters, research coordinators, quality mangers, laboratory and blood bank staff, radiology technicians, schedulers, front desk staff, environmental support staff, volunteers and many who are tirelessly working behind the scenes closely with multiple subspecialties of physicians to help families care for their loved ones. Their only hope is to ensure that the child receives the best possible treatments as guided by the amalgamation of recent research advances and years of evidence based clinical experience.  

Cancer often starts with a few cells in the body choosing to misbehave while its misery extends well beyond the patient to their extended family. What inspires us to do what we do is our patients and their families. We can never really have a bad day as there are always families whom we know very intimately going through difficult times. We can also never even have a bad hair day – most of our patients lose their hair while getting chemotherapy and radiation.

Amongst these untiring days are also teary-eyed moments of joy when we watch our patients ring the bell to complete their last chemotherapy, transition to a long-term survival clinic, get married or graduate college. Apart from these sparks, what propels cancer care is the ongoing research — which is one of the most collaborative effort in almost all of science. Childhood cancer researchers are a very close-knit community where most physicians are eager to collaborate and work together to help advance overall survival while safeguarding quality of life and minimizing long term side-effects of treatments. At the Cancer Institute, we are a part of major clinical research consortia with access to multiple national and international phase 1 and 2 clinical trials with most physicians leading their own investigator-initiated trials to help advance various aspects of childhood cancer care.

As our patients and families continue to push through their multiple hardships and smile beyond the pain, we all are greatly enthused and feel sincerely grateful to be a part of their stories. Lastly, in case you were wondering how we all were doing amidst the crazy COVID-19 pandemic:

Bien, gracias a Dios!  

Learn more about the Hyundai Cancer Institute at CHOC. 

Virtual Pediatric Lecture Series: Inguinoscrotal Swelling

CHOC’s virtual lecture series continues with a lesson on Inguinoscrotal Swelling.

This online presentation will be held on Thursday, Sept. 23 from 12:30 to 1:30 p.m. and is designed for general pediatricians, family practitioners and other healthcare providers.

Dr. Saeed Awan, a and thoracic surgeon at CHOC, will cover the following topics:

  • Understanding the anatomy of pediatric hernias and hydroceles
  • Understanding the pathophysiology of pediatric hernias and hydroceles
  • Differentiating between the hydrocele and hernia
  • Techniques for reducing incarcerated hernias
  • When and how make repairs
Dr. Saeed Awan
Dr. Saeed Awan

This virtual lecture is part of a series provided by CHOC that aims to bring the latest, most relevant news to community providers. You can register here.

CHOC is accredited by the California Medical Association (CMA) to provide continuing medical education for physicians and has designated this live activity for a maximum of one AMA PRA Category 1 Credit™. Continuing Medical Education is also acceptable for meeting RN continuing education requirements, as long as the course is Category 1, and has been taken within the appropriate time frames.

Please contact CHOC Business Development at 714-509-4291 or with any questions.

AAP publishes statement strongly discouraging off-label use of the COVID-19 vaccine for children under 12

With the recent approval of the Pfizer-BioNTech COVID-19 vaccine for ages 16 and older finalized by the U.S. Food and Drug Administration (FDA), clinicians are now able to legally administer the COVID-19 vaccine off-label to children 11 years and younger who are ineligible for an authorized vaccine.

However, in its recent statement, the American Academy of Pediatrics (AAP) strongly discouraged this practice.

With many differences in dose calculations and schedules between adults and children, Dr. Yvonne Maldonado, chair of the AAP Committee on Infectious Diseases, urges against the administration of the vaccine to children under 12 years based on experiences with the vaccine in older patients.

AAP President Dr. Lee Savio Beers advises clinicians to wait for the data from the clinical trials for the COVID-19 vaccine in children ages 11 years old and younger.

While the FDA is still considering full approval of the COVID-19 vaccine for ages 12-15, it is still available under emergency use authorization for this age group. The AAP strongly recommends all eligible adolescents to be vaccinated as soon as possible.

The AAP is also calling on the FDA to work aggressively to authorize a vaccine for ages 11 years and younger. With the delta variant spreading rapidly among unvaccinated people, as of Aug. 19, the AAP reported 180,000 new cases of COVID-19 among children and adolescents. Increasing the vaccination rates amongst those who are eligible now is important to protect children while the clinical trials are still underway.

Read the AAP’s full statement here.

Three-stage DBS results in better outcomes for secondary dystonia

Due to the complexity of secondary dystonia and the brain’s potentially unpredictable response, deep brain stimulation (DBS) has seldom been used in the treatment of this disorder. However, a CHOC neuroscientist has developed a breakthrough method of DBS to treat secondary dystonia in pediatric patients.

Dr. Terence Sanger, pediatric neurologist and chief scientific officer at CHOC, has pioneered a new surgical approach in DBS for pediatric secondary dystonia. Patients undergo three procedures rather than two, nullifying the need for patients to be awake during DBS surgery. Not only does this save children from the potentially traumatic experience of being awoken during brain surgery, it leads to significantly better outcomes in secondary dystonia treatment, with a current success rate between 85% and 90%.

Dr. Terence Sanger, pediatric neurologist and chief scientific officer at CHOC

Unlike patients receiving DBS for other disorders, where results can be observed during surgery, a child with secondary dystonia may have concerns with movements or actions that can’t be addressed on the operating table. For example, a child with secondary dystonia may have difficulty walking, but the physician cannot test DBS’ effectiveness by waking the child and asking him or her to walk.

To overcome this obstacle, Dr. Sanger and his team first insert test electrodes into the patient’s brain. The initial procedure is followed by a week of surveillance and testing. After selecting which electrodes are most effective at treating the patient’s symptoms, the team places permanent electrodes followed by a third procedure to implant the stimulator. The week between the placement of test electrodes and the placement of permanent electrodes allows Dr. Sanger and his team to observe which electrodes are effective.

“The biggest benefit of the three-procedure method is we know where the wires need to be in the patient’s brain for the most effective treatment,” Dr. Sanger says. “By the time we get to the third surgery, we know exactly what’s going to happen. As an engineer, I’m a big believer in measuring twice and cutting once, and effectively, that’s what these three procedures allow us to do. Every child’s brain is different, so we have to learn about how each brain operates before we can perform a successful surgery.”

In addition to his revolutionary procedure for secondary dystonia, Dr. Sanger believes in the future of neuroscience at CHOC.

“At CHOC, our tagline for research is ‘Go beyond,’ and I’ve never seen that belief more exemplified than in the work I’ve seen at our Neuroscience Institute,” Dr. Sanger says. “We are not going to improve pediatric neurology care by doing what other hospitals do, but better. We are going to improve by doing something different, like we’ve done with DBS for secondary dystonia. It’s very exciting, and I believe we have the opportunity to make a huge difference.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the neurology/neurosurgery specialty.

USNWR Neurology and Neurosurgery award

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

CHOC awarded $2.3-million grant to study how toxic stress and unpredictability in the early environment affects neurodevelopment

The state of California has awarded CHOC, in partnership with UC Irvine and Chapman University, a $2.3-million grant to screen patients for adverse childhood experiences (ACEs) and childhood unpredictability to assess how such high-stress events affect the brain and put kids at increased risk of later developing physical and mental illnesses.

In a novel aspect of the study, researchers also will determine if there are epigenetic markers on the DNA that predict whether any given child will be more adversely affected than another.

The team is among four awardees statewide that have been given a total of $9 million to assess which children are most vulnerable to the effects of ACEs and unpredictability in the home environment, and to design medical care to improve the outcomes for this particular group of patients – a model known as “precision medicine,” which eschews a one-therapy-fits-all approach to healthcare.

“The whole concept here is that kids who grow up in environments with frequent exposures to toxic levels of stress can have all kinds of internal things happen in their bodies related to prolonged or extensive stress hormone response – their brains can develop differently, and when they become adults, research has shown that they have a higher risk of developing medical conditions such as heart disease, asthma and cancer,  among other physical diseases, as well as mental disorders,” says Dr. Charles Golden, a co-investigator on the study and executive medical director of the CHOC Primary Care Network (PCN).

Dr. Charles Golden, executive medical director of the CHOC Primary Care Network (PCN)

The California Governor’s Office of Planning & Research, in partnership with the Office of the California Surgeon General, awarded the three-year research project as part of the California Initiative to Advance Precision Medicine (CIAPM). The other three recipients were Children’s Hospital Los Angeles, University of California, San Francisco, and Loma Linda University.

The CHOC-UCI-Chapman research project begins in July 2021, with screening expected to start in CHOC PCN clinics by November 2021. Lead principal investigator on the project is Dr. Tallie Baram, Bren Distinguished Professor and director of the Conte Center at UCI. The National Institute of Mental Health-funded Conte Center also addresses how early-life experiences influence the brain and contribute to mental illnesses.

Results of the study are expected by the end of 2024, says Laura Glynn, PhD, a Professor of Psychology and Associate Dean for Research at Chapman University and one of the principal investigators on the study.

CHOC’s PCN has been screening its Medi-Cal patient population for ACEs since February 2020, and expanded such screening – using a tool called PEARLS, for Pediatric ACEs and Related Life Events Screener – to all patients in November 2020, Dr. Golden says.

The 17-question PEARLS tool screens for such experiences as a parent being jailed, the prevalence of alcohol or drug abuse in the household, and whether the child has been a victim of violence in his or her neighborhood, in the community at large, or at school.

“This existing infrastructure at CHOC was a very important part of the application for this grant,” Glynn says.

The CHOC-UCI-Chapman study, “Using Precision Medicine to Tackle Impacts of Adverse and Unpredictable Experiences on Children’s Neurodevelopment,” will dig deeper than standard PEARLS screening.

The children will be asked an additional five questions to assess exposure to unpredictability in the social, emotional, and physical domains. Such questions are an attempt by researchers to develop an instrument that will predict this population of kids’ resilience to, or risk of developing, physical or mental illnesses. Children from low socioeconomic and racial/ethnic minority communities are at greater risk of exposure to ACEs.

“This study will involve looking at whether routine, or lack of routine, in a child’s life contribute as an ACE,” Dr. Golden explains. “In other words, do they eat dinner every night at 6 p.m., do they have a routine bedtime, do they have a stable household versus a family with no routine or little structure.”

Such factors of unpredictability potentially are amenable to intervention, Glynn notes.

Emerging evidence from experiments with rodents show that fragmented or unpredictable maternal signals influence the maturation of systems governing emotional and cognitive function in the developing brain. In preclinical work led by Dr. Baram, the group has shown that rats exhibited diminished memory function when exposed to unpredictable maternal signals early in life, as well as anhedonia (reduced ability to experience pleasure) beginning in adolescence.

Also, as part of the study, DNA swabs will be performed on a cohort of 120 children who experience high levels of ACEs to determine if genetic expression patterns indicate a vulnerability to chaos and unpredictability in their lives. The team also will be examining whether epigenetics – the process of how genes may be altered based on environmental events – may play a role in the development of ACE-related medical conditions.

“We think potentially we can look at these epigenetic profiles to predict neurodevelopmental outcomes,” Glynn says.

Dr. Michael Weiss, vice president of population health at CHOC and a primary investigator on the study, says such information may make it easier for doctors to identify a child who has a genetic predisposition to experiencing a bad outcome from being exposed to ACEs – thus leading to targeted interventions to kids who need them the most.

“This project is a great demonstration of a collaboration between CHOC and UCI and Chapman University involving primary care research,” Dr. Weiss says.

Other CHOC researchers who will participate in the research project are Dr. Dan Cooper, who treats kids with lung conditions at CHOC and who serves as director of UC Irvine’s Institute for Clinical & Translational Science; Dr. Candice Taylor Lucas, co-director of LEAD-ABC (Leadership Education to Advance Diversity–African, Black and Caribbean) at UCI/CHOC; Louis Ehwerhemuepa, PhD, a senior data scientist; and Dr. Mary Zupanc, co-medical director of the Neuroscience Institute.

CHOC leads first ED study on adverse childhood experiences and prevalence of food and housing insecurity

In the only known hospital research project of its kind in the United States, CHOC’s Emergency Department is leading a study on how food and housing insecurity impacts children’s health and environment.

The project, being conducted in collaboration with departments at UC Irvine and Chapman University, involves surveying 7,000 CHOC ED patients by September 2021, with results expected by the end of the year, says Dr. Theodore Heyming, medical director of emergency medicine at CHOC and chief architect of the effort.

Dr. Theodore Heyming, medical director of emergency medicine at CHOC

The study, which to date already has enrolled some 2,500 CHOC patients, will assess ACEs, also known as adverse childhood experiences. Most ACEs studies conducted to date by other hospitals have been limited to the primary care setting. Since July 2020, CHOC’s ED has been screening for ACEs with particular attention to the following three areas: abuse, neglect, and/or household challenges. 

“To my knowledge, we’re the only pediatric hospital that has this kind of health research project implemented in an emergency department,” Dr. Heyming says. And that makes sense, he adds.

“People don’t usually think of an emergency room as a primary care setting,” Dr. Heyming says. “However, the opposite actually is true. A lot of patients use the ER as their primary care. EDs also have the ability to potentially intervene on patients even to a greater extent than in the primary care setting, given the availability of experienced social workers.”

The potential benefits of the study, which involves questioning patients in more depth than standard ACEs screenings, are numerous, as detailed in an abstract that Dr. Heyming and his collaborators have submitted to the American Public Health Association (APHA), a Washington, D.C.-based organization for public health professionals.

For example, ED-based research has yet to investigate the extent to which neighborhood-level factors such as fast-food accessibility and a lack of healthy food options contribute to poor pediatric health outcomes.

The CHOC-led study aims to identify such neighborhood-level factors and generate valuable information that could be leveraged for public policy and advocacy efforts to improve pediatric health. That, in turn, could lead to a reduction of ED overutilization and associated healthcare costs.

Disadvantaged kids hit hardest

Food and housing insecurity disproportionately impact children in disadvantaged communities, studies show.

And children living in so-called “food swamps” — areas with an abundance of fast-food restaurants, pharmacies and discount stores that sell cheap but unhealthy food — as well as “food deserts,” areas that lack affordable food that is fresh and nutritious, are more at risk of obesity, diabetes and other adverse health conditions, as well as mental and behavioral issues and trauma, the paper explains.

The study of 7,000 CHOC ED patients comes on the heels of a smaller CHOC ED study on the prevalence of ACEs in patients that was conducted between July 2020 and February 2021. Twenty-four CHOC ED doctors were certified in state-run ACEs modules and 1,861 patients participated – the biggest cross-sectional survey that CHOC has done to date, according to Dr. Heyming.

About 20 percent of respondents in that smaller-scale survey reported at least one ACE or more — a percentage consistent with national numbers, Dr. Heyming says. In addition, the survey found that the prevalence of food insecurity among CHOC patients is about 15 percent. 

Now, in partnering with Chapman University and UCI, CHOC is digging deeper into the prevalence of food and housing insecurity with its study of 7,000 patients — and the potential neighborhood-level factors that contribute to such insecurity.

Dr. Jason Douglas, an assistant professor of public health at Chapman University, specializes in investigating social and environmental determinants of public health disparities that disproportionately impact the Black and Latinx communities. 

Dr. Douglas, who has extensive experience connecting social and environmental factors to public health disparities in Los Angeles County as well as Northern California, New York and Jamaica, will use data from the 7,000 survey respondents to analyze neighborhood-level factors that contribute to poor pediatric health.

“The goal is to identify factors that are affecting community health and well-being and inform public policies to improve health in underserved communities,” Dr. Douglas says. “To be able to identify adverse childhood experiences and food and housing security within the clinical context and use that data to garner a better understanding of how social and environmental factors may be exacerbating health disparities will allow us to develop a more holistic understanding of the deleterious impacts of these challenges on children’s lives.”

At UCI, Dr. Victor Cisneros, an emergency medicine clinical instructor and current research fellow in population health and social emergency medicine, will lead a team of investigators who will participate in follow-up phone calls with the CHOC ED survey respondents. The follow-up interviews will be conducted three and six weeks after respondents complete the survey.

“These follow-up interviews are important to assess if interventions given in the ED are effective, and if not, what barriers our patients are facing,” Dr. Cisneros says.

All CHOC ED patients up to 18 years of age and their parents or guardians qualify as potential participants in the survey, which is available in English and Spanish. The survey includes 16 questions that take about 5 to 10 minutes to complete on iPads provided by CHOC.

Patients identified as experiencing food and/or housing insecurity are directed to passive food and housing resource materials in the form of informational pamphlets and flyers.

“We’re going to potentially be able to leverage this data to help cities and the county to make informed policy changes,” Dr. Heyming says. 

“Obtaining this information will not only be great for Orange County,” he adds. “I think we’ll be able to point to the fact that pediatric EDs are a great place to conduct these screenings because there’s a high incidence of either adverse childhood experiences or food or housing insecurity.”

Dr. Heyming says pediatric EDs in the future would be able to provide patients more active resources such as gift and food cards.

Dr. Douglas says the study ideally will serve as a model for pediatric and other emergency departments across the country.

The bottom line, Dr. Cisneros says, is getting people resources they need – for example, food that restaurants now dispose of that can be “recycled.”

The ED, he says, is a perfect microcosm of the community.

“One of the beauties of this study,” Dr. Cisneros says, “is we’ll be able to identify people with housing and food insecurity and be able to refer these people to the appropriate tailored resources. In addition, we will be able to further quantify what obstacles our patients face both at the individual and community level.”

Batten disease patients highlight CHOC’s growing reputation as a destination for kids with rare conditions

In the yard of his home just outside Boise, Idaho, Ely Bowman loves to toss balls and play with Bobo, the family Goldendoodle. He also loves the trampoline.

“If you were to come over and just watch him,” says his mother, Bekah, “you would not believe me if I told you he was blind.”

Ely, who turns 8 in July, lost his sight when he was 6 due to the rare neurological disorder CLN2 disease, one of the most common forms of a group of inherited disorders known as Batten disease.

Kids with CLN2 disease are missing an enzyme that chews up waste products in the brain. This lack of a cellular “Pac Man” to gobble up the bad stuff eventually leads to the destruction of neurons, resulting in blindness, loss of ability to speak or move, dementia, and death – usually by the teens.

There is no cure for CLN2 disease. But thanks to genetic scientists, neurosurgeons and nurses at CHOC, there is hope for delaying progression of the disease – one that claimed the life of Ely’s older brother, Titus, at age 6 in September 2016 before a cutting-edge therapy became available at CHOC six months later.

Ely Bowman and his older brother, Titus. Both were diagnosed with Batten disease. Titus passed away in 2016 at age 6.

The therapy, Brineura, is a medication that treats the brain via a port under the scalp with a synthetic form of the missing enzyme. CLN2 patients come to CHOC every two weeks for the four-hour infusion to keep the drug working effectively.

Largest infusion center in country

CHOC since has grown into the largest Brineura infusion center in the country and the second largest in the world. Kids from all over the United States have come to CHOC for Brineura treatment since it first was offered in March 2017 following a three-year effort by Dr. Raymond Wang to get the green light for CHOC to become the second infusion site in the U.S.

Dr. Raymond Wang, director of the multidisciplinary lysosomal storage disorder program at CHOC

“When a family has a child with a rare disease,” Dr. Wang says, “and if the South Pole were the only place that was offering treatment, the family would find a way to get there. Those are the lengths that a rare disease family would go to help their child.”

CHOC now has treated 13 Brineura patients, the latest being 3-year-old Max Burnham, whose parents having been making the trek to Orange every two weeks from their home in the Bay Area since Max’s first infusion on Feb. 8, 2021.

CHOC’s Brineura program underscores its growing reputation as a destination for kids with rare diseases.

Recently, CHOC specialists started treating a 3-month-old with Hurler syndrome, another serious and neurodegenerative condition. The family drove across the country because CHOC is the only site in the world that has a clinical trial of gene therapy for their son’s condition.

Because the family will be staying at CHOC for at least through April 2021, a team of three study coordinators — Nina Movsesyan, Harriet Chang, and Ingrid Channa – helped the family get settled in at an Airbnb in Irvine.

“Our case managers and financial coordinators were crucial in getting the infant’s weekly enzyme therapy approved within a week’s time, and our excellent nurse practitioner, Rebecca Sponberg, asked purchasing to procure the enzyme drug for the baby on two days’ notice,” notes Dr. Wang, a metabolic specialist and director of CHOC’s Campbell Foundation of Caring Multidisciplinary Lysosomal Storage Disorder Program.

Dr. Wang says CHOC became an active site for the RGX-111 gene therapy after treating a child from a family in Indio in 2019. Another 14-year-old girl from West Virginia has received the same treatment.

“All of these cases wouldn’t be possible without the awesome teamwork from team members, who all are dedicated to the mission of CHOC,” says Dr. Wang. “I think it’s pretty remarkable that people from all over the country are coming here for clinical care and research studies because of our expertise and what we offer them: hope for their beloved children.”

A true team effort

For the Brineura infusions, which are administered by pediatric neurosurgeon Dr. Joffre Olaya, CHOC metabolic specialists work closely with providers in CHOC’s Neuroscience Institute.

Dr. Joffre Olaya, pediatric neurosurgeon at CHOC

Susan See is nurse manager of CHOC Hospital’s neuroscience unit, where the patients receive their infusion and stay for care afterward.

“We quickly put together a comprehensive program that really treats the patient and family not just medically, but also from an emotional support standpoint,” she says.

Batten disease especially is terribly cruel because its symptoms typically hit just as parents are starting to enjoy their child reaching several developmental and cognitive milestones such as walking and talking.

Untreated, the disease eventually takes all that away.

“What makes them who they are gets rapidly erased,” says Dr. Wang. “As a practitioner, it’s hard. I’m trying to imagine being in the shoes of a parent knowing this is going to happen to their child.”

For Bekah Bowman and her husband, Daniel, the diagnosis for Titus and, two months later, Ely, was like being on a high diving board and being shoved off and belly flopping into the water.

“We had to learn what little control we have in life,” Bekah says.

The Bowmans worked closely with Dr. Wang to get the Brineura clinical trial launched at CHOC.

“When we met Dr. Wang,” Bekah says, “he told us: ‘We don’t have the answers for you right now, but I want you to know we’re going to keep fighting and we’re not going to give up.’”

Brineura families form tight bonds with their team at CHOC, which includes eight nurses who have been trained to care for them: Allison Cubacub, Genevieve Romano-Valera, Anh Nguyen, Melissa Rodriguez, Kendall Galbraith, Annsue Truong, Monica Hernandez and Trisha Stockton.

Some families, including the Bowmans, have moved on from the program at CHOC when Brineura infusions became available near their hometowns. The Bowmans returned to their native Idaho outside Boise in October 2018. Leaving CHOC was difficult.

“That was one of the hardest goodbyes we had to say,” Bekah says.

All Brineura patients receive the transfusions on the same day – something unique to CHOC, See says.

“We learn what is unique about each patient and we become very close to them,” she adds. “It really reminds us why we said yes to nursing. What we thrive on is being able to care for families.”

Quick to action

Laura Millener, the mother of Max, CHOC’s latest Brineura patient, says she selected CHOC for Max’s condition, diagnosed in January 2021, because he needed to be treated right away. She first spoke to Dr. Wang on Jan. 11, and Max got his first infusion less than a month later.

“You could just tell how much he cares about his patients,” Laura says of Dr. Wang.

Max Burnham had his first infusion at CHOC on Feb. 8, 2021

Says Dr. Wang, who has three children ages 10 to 18: “I count [my patients and my families] as my extended family, and I want the best for all of them.”

Laura and her husband, Matthew, a C-5 pilot in the U.S. Air Force, will be relocating to Quantico Marine Base in Virginia this summer from Pleasantville, Calif. Max, who has a 6-year-old sister, Ella, will continue his Brineura infusions at Children’s National Hospital in Washington, D.C.

“I don’t want to leave CHOC,” Laura says. “CHOC has done such an amazing job of making this easier on us. I am so grateful for the team.”

Dr. Wang says the Brineura infusions have made it possible for the patients to maintain meaningful interactions with their parents and siblings – despite having such conditions as, in Ely’s case, blindness.

Ultimately, the goal is for CHOC to be considered for a gene therapy clinical trial aimed at giving brain cells the ability to produce the missing enzyme by itself so Batten disease patients wouldn’t have to receive infusions every two weeks. Dr. Wang says such a trial could happen this fall.

“If there’s anything in my power I can do to help these families,” says Dr. Wang, “I’m going to try to make it happen.”

Learn more about CHOC’s robust metabolic disorders program.