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.

Boy, 9, showing great progress after deep brain stimulation procedure at CHOC

Ryder Montano is the third and youngest CHOC patient with a movement disorder to undergo a procedure called deep brain stimulation (DBS), which is designed to ease involuntary movements by sending electrical currents that jam malfunctioning brain signals. CHOC treated its first DBS patient in late 2020.

Ryder is also among CHOC’s dramatic DBS success stories.

The procedure is being championed by DBS pioneer Dr. Terence Sanger, a physician, engineer, and computational neuroscientist and vice president, chief scientific officer at CHOC, and vice chair of research for pediatrics at the UCI School of Medicine. The DBS team also includes Dr. Joffre E. Olaya, CHOC’s functional restorative neurosurgeon, who implants the electrodes, as well as collaborating partner Dr. Mark Liker, a neurosurgeon at CHLA.

In January 2021, Ryder underwent surgery at CHOC to replace four electrodes in his brain that help ease the severity of a movement disorder, post-pump chorea, that he developed after he had open-heart surgery at age 2 ½. Since those four electrodes were replaced, he has shown remarkable improvement, Ashley says.

“It’s just incredible and mind-blowing that this is happening because of DBS,” she says.

Ashley says Ryder’s clinical team at CHOC had expectations that were lower than what the outcome turned out to be. They thought his condition would worsen before it got better.

But in February 2021, for a post-op appointment, Ryder walked into Dr. Sanger’s office for the first time by himself. He also stood on a scale and sat in a chair without assistance.

Ryder was diagnosed with Williams Syndrome and a heart defect at age 2. After undergoing open-heart surgery, he developed post-pump chorea, which causes involuntary twitching or writhing.

Now, Ryder also can walk independently, feed himself, and sit down and watch a movie. He is limited verbally and uses an AAC (augmentative and alternative communication)device to say simple things. 

“I’m so happy to see how well Ryder is doing,” Dr. Olaya says. “This procedure has tremendously improved his quality of life.”

Answers at age 2

Ryder was born full term on Sept. 29, 2011. He had a heart murmur, but his mother, Ashley, didn’t get a lot of answers from Ryder’s cardiologist until their son was 2. That’s when doctors at another hospital determined that Ryder had been born with supravalvar aortic stenosis (SVAS) and Williams Syndrome.

SVAS, a heart defect that develops before birth, is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body.

Williams Syndrome is a rare genetic condition that affects many parts of the body. It is caused by missing more than 25 genes from a specific area of chromosome 7. Williams Syndrome can cause mild to moderate intellectual disabilities, unique personality traits, distinctive facial features, as well as heart and blood vessel problems.

Ryder’s Williams Syndrome led to him undergoing open-heart surgery at 2 ½, which in turn led to post-pump chorea, which causes involuntary twitching or writhing.

“He was walking and talking and drinking from a cup prior to surgery,” Ashley recalls. “He woke up one day and wasn’t able to sit up or hold his head up or make eye contact. He made weird movements. I first thought it was withdrawal symptoms from the medications he took for the surgery.”

Ryder first saw Dr. Sanger in 2016 at CHLA (Dr. Sanger came to CHOC in March 2020). Ryder’s first DBS surgery was in 2017, the same year he got four permanent electrodes. One of the leads got entwined with a growing bone, which prompted the January 2021 surgery to replace all four electrodes.

The perfect team for Ryder

Ashley and her husband, Al, are determined to provide Ryder with the best quality of life possible. His DBS treatment at CHOC, they say, has made a huge difference.

“Ryder and Dr. Sanger were a perfect match,” Ashley says. “I’m very thankful for DBS and Dr. Sanger. I feel he thinks outside of the box. There are so many other neurologists who think, ‘Oh, let’s just load (the patient) up with medication.’ But Dr. Sanger wants to get at the root of the problem and fix it.”

Ryder loves to go to the beach and on nature walks. At the beach, he will roll into the shallow waters on a stroller with large, fat wheels.

Dr. Olaya stressed the importance of teamwork in treating Ryder and other DBS patients at CHOC.

“We are so fortunate to have the resources and the team here at CHOC to offer DBS treatment to patients with moving disorders,” he says. “Jennifer MacLean, Ryder’s nurse practitioner, is very involved with his care and treating other DBS patients as well. It’s not just one person. It really is the nurses, the OR staff – it’s a lot of people collaborating.”

“I’m so thankful for everybody at CHOC,” Ashley says. “I just feel that without the entire team, none of this would be possible for Ryder or for really anybody. It makes me so happy to know we’ve not only improved Ryder’s life so much, but we’re helping improve other kids’ lives, too. Dr. Sanger goes the extra mile and it’s so amazing to think, yes, that’s our doctor.”

Ashley says Ryder has worked very hard to get to where he is today.

“We’ve all worked hard together to get to this place and give Ryder the validation to show him how much we realize how hard he’s been working,” she says. “I know it’s defeating for a kid who understands but can’t communicate well, but he’s working very hard.”

Learn more about CHOC’s Neuroscience Institute.

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.

CHOC telehealth visits continue at a rapid pace

As the world surpasses the one-year anniversary of the COVID-19 pandemic, the resulting rapid rise of telehealth continues to propel forward in 2021, with CHOC patients consistently reporting a 90-plus percent satisfaction rate in surveys, hospital officials say.

Virtual visits with a CHOC provider via a smart phone, tablet, or computer not only are here to stay, but are expected to continue growing at a rapid pace – not just in Orange and surrounding counties, but nationally and globally.

The rapid growth and acceptance of telehealth is a definite sign that consumers want easier access, convenience, and comfort as they seek medical care,” says Dr. Michael Weiss, vice president of population health. “CHOC is committed to providing the highest quality and service to fulfill these needs.”

Kathleen Lear’s son, Matthew, 18, was diagnosed with intractable epilepsy when he was 6 and the last 12 years have been a non-stop roller-coaster, she says.

In mid-February 2021, Matthew became the first epilepsy patient at CHOC to undergo a procedure called Deep Brain Stimulation (DBS), in which electrodes were placed in his brain to help reduce his seizures by sending electrical currents to jam his malfunctioning brain signals. In another first, CHOC recently conducted DBS on a patient with the movement order dystonia.

Kathleen and Matthew recently have had neurology and hematology telehealth visits with Dr. Joffre Olaya and Dr. Mary Zupanc, as well as a consultation with Dr. Antonio Arrieta and Dr. Loan Hsieh.

“I think it was amazing that we even could have a virtual neurology visit,” Kathleen says. “The doctors were able to assess a lot by watching Matthew walk and run and touch his finger to his nose.”

Kathleen says the telehealth session was especially helpful because her husband is working from home during the pandemic and he, too, could participate.

“It was really nice,” she says.

Growth projections

According to Fortune Business Insights, the global telehealth market size was valued at $61.4 billion in 2019 and is projected to reach $559.52 billion by 2027, exhibiting a compound annual growth rate (CAGR) of 25.5 percent during the forecast period.

The U.S. telehealth market size was valued at $9.5 billion in 2020, up a whopping 80 percent over 2019, and is expected to exhibit a CAGR of 29 percent between 2020 and 2025, according to market research firm Arizton.

Quick pivot

At CHOC, a lot of teamwork was necessary for the quick pivot that began in the early days of the pandemic, says Lisa Stofko, CHOC’s telehealth manager.

“There is a difference between a two-way video and telehealth,” Lisa says. “We are committed to making telehealth a seamless experience for both patients and providers, and ensuring that it replicates the safe, quality care patients are used to receiving in person.”

The information services department, Lisa says, worked feverishly to get technology set up so clinicians could use video conference software that came with extra layers of protection that allowed them to safely consult with patients virtually.

Training videos were delivered to more than 700 providers so they could replicate the in-person visit as closely as possible, Lisa says. And a 20-member steering committee was established from key stakeholders from across CHOC’s health system — including administrative executives and physicians — to further improve the telehealth experience and capabilities at CHOC.

In December 2020, Dr. Robert Hillyard, CHOC neonatologist, and Dr. Kenneth Grant, CHOC pediatric gastroenterologist, began serving as co-medical directors of CHOC’s telehealth program, while each retaining existing clinical responsibilities.

Some statistics

Dr. Weiss tracks telehealth visits daily.

From March 2020 through April 2020, CHOC telehealth visits zoomed to 14,457, from 2,233 prior to the pandemic, he says.

Since the pandemic began through early February 2021, CHOC telehealth visits totaled 95,757. The average number of telehealth visits per month during COVID-19 have remained in the 8,500 range.

Telehealth visits at CHOC have grown dramatically in both primary and specialty care.

In January 2021, the most visits (370) in CHOC’s Primary Care network were recorded at Orange Primary Care, followed by Pediatric and Adult Medicine (338), Clinica Para Ninos (286), Breathmobile (176), Los Alamitos Pediatrics (149) and Boys and Girls Clinic Santa Ana (92).

In January 2021, the most visits (1,498) in CHOC’s Specialty Care network were recorded at Providence Speech and Hearing Center, followed by endocrinology (1,017), mental health (991), gastroenterology (893), neurology (481), pulmonary (450), the Thompson Autism Center (407), and outpatient rehabilitation (301).

Kathleen says she looks forward to continuing Matthew’s treatment at CHOC – in person when possible, and virtually, too. She finds telehealth visits especially useful when doctors want to go over test results.

“There’s definitely a time and a place for it,” Kathleen says. “And I just feel so privileged to have CHOC so close to us.”

Learn more about telehealth at CHOC

MRI-Guided Laser Ablation with Stereotactic Assistance Targets Epilepsy, Tumors

Laser interstitial thermal therapy (LITT), or laser ablation, is among the latest advancements in minimally invasive neurosurgery, allowing surgeons to reach difficult areas of the brain — and offering less risk to patients at the same time.

“Instead of performing a craniotomy, which entails making a large incision and opening up the skull, we place a probe through a small hole in the skull a few millimeters in diameter,” says Dr. Joffre Olaya, pediatric neurosurgeon at CHOC. “Then, under MRI visualization, we deliver heat to the specific area, which destroys the abnormal tissue. Laser ablation is especially useful in patients with small seizure foci or tumors, particularly if they are deep.”

Dr. Joffre Olaya, pediatric neurosurgeon at CHOC

The benefits this minimally invasive approach provides to patients are especially welcoming. “For a craniotomy, patients will be in the hospital for three to five days, in the ICU most likely for a day or two, and they’ll experience discomfort from the skin and muscles on the head,” Dr. Olaya says. “With laser ablation, patients typically go home within a day or two and recover pretty quickly. They also experience less blood loss, pain and side effects overall. Also, laser ablation doesn’t prevent patients from having another procedure. If the tumor is still growing or the seizures are still continuing after ablation, I can go back and perform another laser ablation or a craniotomy.”

To increase surgical precision and accuracy when ablating brain tumors, deep lesions and tissue in the brain where seizures occur, Dr. Olaya employs a ROSA™ (robotic stereotactic assistance) robot.

“We obtain preoperative imaging studies and load those into the ROSA system, which allows us to plan the entry point and trajectory so we can precisely place the laser. This precision helps us to not only locate and effectively ablate our target, but avoid hitting blood vessels or causing unintended damage to surrounding tissues,” Dr. Olaya says. “We were the first pediatric center on the West Coast to have this technology. We use ROSA for multiple conditions, including patients with epilepsy and oncology patients with tumors.”

ROSA’s precision also helps minimize some risks commonly associated with surgery. “ROSA is an amazing tool that yields many benefits for our patients, including less time under anesthesia in the operating room,” Dr. Olaya says. “It also reduces blood loss and risk of infections.”

Although CHOC is at the forefront utilizing the latest technologies to best treat its patients in a minimally invasive manner when possible, Dr. Olaya says CHOC’s team approach to patient care is what sets it apart from other centers in the region.

“I’m really excited that CHOC is investing in this newer technology and it’s available here to provide to our patients, but our team mentality and how well we work together is crucial. Our epileptologists, radiologists, neuropsychologists, all of us really work well together as a team to identify the best candidates for this technology and to provide the best outcomes for our patients.”

Our Care and Commitment to Children Has Been Recognized

CHOC 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.

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

Wired for hope: deep brain stimulation for dystonia

Every morning when she awakes, Sydney Amato begins her daily battle with her body.

If she’s lucky, the 16-year-old will have gotten a handful of hours of uninterrupted sleep – dreaming, perhaps, of doing what most healthy kids her age take for granted:

Hanging out with friends. Going to school. Learning to drive.

Because of a neurological condition called dystonia, Sydney, who is in excellent cognitive health but speaks and walks with some difficulty, suffers from involuntary and near-constant contraction of muscles in her neck, arms, legs and trunk.

Sydney with her father, Louis

Her mind is unable to control the painful jerking that makes most of her body twist and go rigid, her muscles moving out of normal sequence.

Born a right-hander, she can feed herself with some struggle using her left hand. She wants to dress and put on makeup herself, but those normally simple tasks become lengthy ordeals.

“My body fights me all the time,” says Sydney, trying to distract herself in her hospital bed by watching an old episode of “Keeping Up with the Kardashians.” Listening to her favorite music – Ariana Grande, Lauren Daigle, Drake – can only temporarily transport Sydney away from her debilitating condition.

“She knows what she wants to do,” says her father, Louis. “But her body won’t let her.”

Specialists at CHOC are working hard to change that.

A first for CHOC

On Aug. 14, 2020, a team led by Dr. Terence Sanger, a physician, engineer, and computational neuroscientist who joined CHOC in January 2020 as its first chief scientific officer, and Dr. Joffre E. Olaya, CHOC’s functional restorative neurosurgeon, implanted several temporary electrodes into Sydney’s brain.

Dr. Terence Sanger, a physician, engineer, and computational neuroscientist and CHOC’s chief scientific officer

The surgery marked the first time a patient with a movement disorder at CHOC underwent a procedure called deep brain stimulation (DBS).

Working in perfect harmony as a team, Dr. Sanger and Dr. Olaya performed the first stage of a three-stage surgery on Sydney. As the surgeon, Dr. Olaya placed the leads following advice from Dr. Sanger, the neurologist, where they should go.

In the procedure, millimeter-thick electrodes were precisely positioned into the basal ganglia region of Sydney’s brain – about three inches deep. The surgery involved the use of the ROSA Robot, the same tool that has been used during brain surgery on epilepsy patients at CHOC since 2015.

Dr. Joffre E. Olaya, CHOC pediatric neurosurgeon

Considered one of the most advanced robotized surgical assistants, ROSA includes a computer system and a robotic arm. It’s a minimally invasive surgical tool that improves accuracy and significantly reduces surgery/anesthesia time.

The ROSA Robot helped with implanting and targeting the electrodes, and a portable operating-room CT scanner confirmed their position.

Turning down the volume

DBS is designed to ease Sydney’s condition by sending electrical currents to jam her malfunctioning brain signals.

Think of turning down the volume on your car radio.

“Nobody really understands the cause of dystonia,” Dr. Sanger explains, “but there’s probably too much electrical stimulation going on in the motor areas of the brain. We’re trying to calm down that extra noise.”

Although DBS dates to the 1960s, it wasn’t until the 1980s that the modern era of using it to treat adult patients with tremor and Parkinson’s disease began.

In 2000, Dr. Sanger, working with engineers, data scientists, neurosurgeons, and others, began implanting electrodes in pediatric patients.

Instead of the established method of placing the leads at predetermined sites and hoping they worked, Sanger and his team, just as they did in Sydney’s case, placed temporary leads to best assess where they should go permanently based on patient response.

In 2016, Dr. Sanger began honing DBS to treat children with dystonia. Before the surgery on Sydney, Dr. Sanger had performed DBS on 26 children using the same three-stage technique. He says 80 percent of those children have seen successful results.

Early signs

Sydney began showing symptoms of dystonia – tremors in her hands — when she was 5 ½ years old.

A year later, she was using a wheelchair. She had her first brain surgery at age 7.

Since then, “she’s been all over the U.S.” seeking the right treatment for her condition after several setbacks, says her father.

But her condition was not improving.

Early this year, a neurologist in Kansas City, Mo., recommended that Sydney see Dr. Sanger.

“I asked him, ‘If Sydney was your kid, where would you go?’ Louis Amato recalls. “He said, ‘Hands down, Dr. Sanger.’”

The COVID-19 pandemic pushed Sydney’s surgery to mid-August.

Sydney already had two electrodes in her brain that were only partially working when she came to CHOC in early August for surgery.

After two extensive run-throughs with their team, Dr. Sanger and Dr. Olaya, in a six-hour procedure that at one point had nearly 20 people in the operating room, implanted more electrodes to give her a total of nine.

On Thursday, Aug. 20, six days after Sydney’s surgery, Dr. Sanger stopped by her room at CHOC Hospital. The room was decorated in purple, Sydney’s favorite color.

Dr. Sanger greeted her as CHOC staff members, joined by members of Sanger Lab, which conducts research in pediatric movement disorders, prepared to have Sydney walk back and forth down a hallway while connected to electrical equipment programmed to record signals in her brain and muscles.

A thick coil of multicolored wires snaked from under a large white bandage covering Sydney’s head. Extending about 6 feet, the wires were plugged into specialized recording equipment controlled by Jennifer MacLean, a pediatric nurse practitioner whose job was to manipulate the strength of electrical charges affecting the four points of contact on each electrode.

The goal: determine which charges worked best and on which electrodes.

“It could have turned out that the DBS procedure made no difference,” Dr. Sanger says. “But we’ve seen a very good response in Sydney.”

For example, her once mostly useless right hand was working much better.

“It gives you goosebumps,” Louis Amato says.

After taking a bite of a veggie burger and sipping some water, Sydney started to walk.

Following her were seven CHOC and Sanger Lab specialists.

“Go nice and slowly,” Jennifer told Sydney. “You’re going too fast for us!”

Perhaps Sydney was anxious to get back to riding Tigger, a quarter horse, in her hometown of Carthage, Mo. She has been riding him for six months.

Sydney is eager to get back to riding her favorite horse, Tigger.

“Her balance isn’t bad on the horse,” says Louis Amato.

Sydney also loves to tan by her pool and swim.

What she wants most, however, is to be freed from her body so she can return to school and do what most teens enjoy.

“It’s stressful,” says her mother, Angie. “She has a lot of friends her age, but she can’t do a lot of the things they do. She has her days when she can get really upset.”

Now, however, working with Dr. Sanger, Dr. Olaya and the entire team at CHOC, the Amatos are more optimistic than ever.

“We’re hopeful that this is going to be a big life-changer for her,” Angie Amato says. “That would be the best thing that could ever happen – better than winning the lottery.”

‘The A Team’

After crunching numbers for a week to assess which of the nine electrodes proved to be the most effective based on how Sydney responded to varying degrees of electrical currents, Dr. Sanger and his team settled on four electrodes that were permanently used to treat her condition – three new ones, and one existing one.

The team performed this second surgery on Sydney in late August.

In the third and final surgery, successfully completed in early September, a rechargeable generator that powers the DBS leads was implanted in Sydney’s chest.

“As we get better and better at this,” says Dr. Sanger, “and as the technology progresses, we’ll be able to do this on kids who are less sick than Sydney.”

Dr. Sanger and Dr. Olaya are poised to dramatically improve the lives of many more patients like Sydney at CHOC.

“I’m really excited that we will be doing more of these procedures to help pediatric patients with movement disorders and significantly improve their quality of life,” says Dr. Olaya. “I look forward to continuing to provide this type of personalized care.”

Angie and Louis Amato say Sydney has never gotten this much special attention during her 11-year-plus medical journey.

“Here at CHOC,” Louis Amato says, “we feel like we’re with the A Team.”

Says Sydney: “I’ve never felt this much confidence and this good about treatment before.”

Learn more about deep brain stimulation (DBS) surgery at CHOC.

From the Nursing Frontline of the Batten Disease Battle

When the neuroscience unit nurses at CHOC Hospital discovered that teen patient Maya loved to crack people up, they knew a joke book would be the perfect gift.

Compared to the life-changing treatment Maya is receiving at CHOC Hospital, a book is a very small token. But as partners in this journey, CHOC nurses say it’s the very least they can do.

Maya is among nine patients receiving a novel treatment for CLN2 disease, or late infantile Batten disease at CHOC. The group comes every two weeks for an infusion of Brineura, a drug that replaces a deficient enzyme.

The CHOC team has just celebrated the second anniversary of the first infusion, having clocked more than 300 procedures in the last 24 months. Since CHOC began offering the treatment in spring 2017, the number of patients has more than doubled, says Dr. Raymond Wang, a pediatric metabolic specialist and the program’s medical director.

Dr. Raymond Wang, medical director, and Susan See, Neuroscience nurse manager
Dr. Raymond Wang, medical director of the Batten disease treatment program, and Susan See, neuroscience unit nurse manager

Among the handful of institutions nationwide offering the treatment, CHOC’s program is the largest.

Despite the juggling act of placing patients, made especially tough during high wintertime patient census, CHOC nursing leadership has helped ensure these patients have never missed a procedure.

Nurses play an integral role in the procedure, assisting pediatric neurosurgeon Dr. Joffre Olaya in inserting a needle through the skin of the patient’s skull and into an Ommaya reservoir implanted beneath the flesh to reach the fluid surrounding the brain.

The procedure is conducted inside the patient’s room on CHOC’s neuroscience floor. During the procedure and afterward as they monitor the patients, the nursing team is in frequent, close contact with the children – and their parents.

“Because of this, we know how some parents take their coffee, which brand of diapers they prefer, and how the families gather to talk after treatments,” says Alison Cubacub, a clinical nurse II in CHOC’s neuroscience unit.

They also know how life-changing the treatment is for families.

Before Brineura clinical trials and its ultimate approval by the U.S. Food and Drug Administration, this small group of patients and their families endured a long odyssey of poring over Internet pages, making endless phone calls, and traveling the country in hopes of finding treatment for the devastating diagnosis that is Batten disease.

The rare and fatal neurologic condition typically begins with language delays and seizures before age 3, and rapidly progresses to dementia, blindness, loss of the ability to walk and talk, and death in childhood.

But Brineura has shown to slow the disease’s progression. Over a three-year period, patients treated during clinical trials showed no advancement of the disease, which was radically different from the disorder’s natural course. The medication improves quality of life and buys patients critical time as researchers continue to search for a cure.

Before, Southern California patients traveled every 10 days from their homes to Columbus, Ohio, to receive treatment as part of a clinical trial. Aside from the inconvenience, the process split apart families. But now, they need only drive a few miles to CHOC for a few hours of treatment.

And while it can’t compare to the relief felt by patients and families, CHOC’s neuroscience nursing team is invigorated by the professional growth that’s been afforded to them as a result of CHOC offering the treatment.

“The science and research that went into developing this treatment is fascinating,” says Melissa Rodriguez, RN, BSN, CPN, a clinical nurse III in CHOC’s neuroscience unit. “To assist in its administration, we participated in an in-depth study that included literature about the procedure and the condition, as well as extensive training in the sterile procedure required to infuse the medication.”

ROSA Robot Assists in CHOC Patient’s Successful Epilepsy Surgery

Five-year-old Ian Higginbotham recently enjoyed his best summer yet.  He experienced his first family vacation. He learned to swim and ride a bike. He got himself ready for kindergarten.  These are milestones most kids and parents, alike, eagerly welcome.  But there was a time when Ian’s parents weren’t certain their son, who was born seemingly healthy, would enjoy such happy pastimes.

Ian began talking and walking in his sleep as a toddler.  When the episodes, including night terrors, increased in frequency and severity, his mom Lisa made an appointment with the pediatrician.  One day, Lisa knew something just wasn’t right and didn’t want to wait for the appointment to get Ian checked out.  She and her husband Derek took him to the Julia and George Argyros Emergency Department at CHOC Hospital.  To her surprise, doctors diagnosed her son with epilepsy.    Ian’s “sleepwalking” and “night terrors” were actually seizures.

The family was referred to CHOC’s comprehensive epilepsy program.  A national leader in pediatric epilepsy care, CHOC’s comprehensive epilepsy program offers cutting-edge diagnostics, innovative medical approaches and advanced surgical interventions.  CHOC was the first children’s hospital in the state to be named a Level 4 epilepsy center by the National Association of Epilepsy Centers, signifying the highest-level medical and surgical evaluation and treatment for patients with complex epilepsy.

CHOC Children's

Ian’s neurologist Dr. Andrew Mower suspected he was experiencing complex partial seizures, which was confirmed by video EEG monitoring.  Complex partial seizures start in a small area of the temporal or frontal lobe of the brain, and quickly involve the areas of the brain affecting alertness and awareness.  The pattern of Ian’s seizures suggested they were originating from the right frontal lobe.  Dr. Mower knew Ian and his family were in for a tough journey.

“I really don’t think the general public understands the impact epilepsy has on a child and his family.  Its effects are multifaceted and extensive.  Our team’s goal is to reduce or eliminate our patients’ seizures, helping improve their quality of life,” explains Dr. Mower, who placed Ian on a series of medications.

The medications reduced Ian’s seizures, but did not control them.  Dr. Mower was concerned about the seizures affecting Ian’s development, and presented his case to the epilepsy team.   The multidisciplinary team agreed Ian was a candidate for epilepsy surgery.  For children who fail at least two medications, surgery may be considered early in treatment versus as a last resort.  Surgery can result in an improvement in seizure control, quality of life, and prevent permanent brain damage.  Ian’s surgery was going to be performed by CHOC neurosurgeon Dr. Joffre Olaya.

While the thought of surgery was frightening to Lisa and her husband, they were confident in the team and comforted to know their son was going to benefit from innovative technology, like the ROSA™ Robot. Considered one of the most advanced robotized surgical assistants, ROSA includes a computer system and a robotic arm.  The computer system offers 3D brain mapping to aid surgeons in locating the exact areas they need to reach and planning the best surgical paths.  The robotic arm is a minimally invasive surgical tool that improves accuracy and significantly reduces surgery/anesthesia time.

Dr. Olaya used ROSA to accurately place electrodes in the area of Ian’s brain suspected to be the source of his seizures.  By using the robot, Dr. Olaya avoided performing a craniotomy.

“ROSA is an amazing tool that yields many benefits for our patients, including less time under anesthesia in the operating room.  It reduces blood loss and risk of infections.  Patients tend to recover faster than they would if they had craniotomy,” says Dr. Olaya.

Lisa was amazed at the outcome. “I couldn’t believe how great Ian looked after the placements of the electrodes with ROSA.  He wasn’t in any pain, there was no swelling.  It was wonderful!”

She and her husband were also amazed at how well Ian did following his epilepsy surgery.

“We got our boy back,” says Lisa. “There were no more side effects from medication and, more importantly, no more seizures!  He started developing again and doing all the things a child his age should do.”

Ian’s care team isn’t surprised by his recovery.

“Children are resilient, and their brains are no different.  In fact, the plasticity of a young brain allows it to adapt to changes and heal more easily than an adult brain,” explains Dr. Mower.

Learning to ride a bike and swim were among the first of many milestones Ian quickly reached following surgery.  He enjoys playing with his younger brother and his friends.  And, whether inspired by his experience with ROSA or not, Ian loves robots.