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 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

Dr. Mary Zupanc awarded prestigious Arnold P. Gold Humanism in Medicine Award

Dr. Mary Zupanc has achieved many superlatives over her long career in medicine; accolades and awards have followed.  But the co-medical director of the CHOC Neuroscience Institute and UCI professor of pediatrics and neurology considers the Arnold P. Gold Foundation Humanism in Medicine Award her highest honor of all.

Dr. Mary Zupanc, co-medical director of the CHOC Neuroscience Institute

The Child Neurology Society (CNS) has announced that Dr. Zupanc will receive this special distinction at their annual meeting in October 2021.  She is only the eighth individual to be thus honored in the 50-year history of the society, which represents the nation’s pediatric neurology subspecialists.

The Humanism in Medicine Award will be presented to Dr. Zupanc — who specializes in childhood epilepsy — for practicing “extraordinary and ongoing humanism” throughout her medical career. Included in the criteria noted by her peers are:

  • Compassion and empathy in the delivery of patient care
  • Respect for patients, families and co-workers
  • Cultural sensitivity in working with patients and family members of diverse backgrounds
  • Effective, empathetic communication and listening skills
  • Understanding of patients’ need for interpretation of complex medical diagnoses and treatments
  • Comprehension and respect for the patient viewpoint
  • Sensitivity to patients’ psychological well-being and patients’ and families’ emotional concerns
  • Ability to instill trust and confidence

“You may be the greatest scientist in the world, but if you don’t have empathy and compassion for patients and families, you can’t advance the field of medicine,” says Dr. Zupanc. “To me, as a clinician bringing science to the bedside – this is the ultimate award.”

This award also has personal meaning and sentiment for Dr. Zupanc, because as a faculty member at Columbia University, she and Dr. Gold – the award’s namesake – became good friends.

“Dr. Gold was one of the kindest, gentlest, most intelligent child neurologists I’ve ever known,” she says.  “He had a real compassion for children, and we just hit it off.”

Dr. Gold, who died in 2018 at the age of 92, frequently complimented Dr. Zupanc: “He went out of his way to tell me that I had taught him some things about epilepsy that he didn’t know,” she says. “I was sure that couldn’t be the case, since he was senior to me, with such knowledge and wisdom. But he insisted, and that was the kind of person he was; always offering encouragement and making people feel special.”

A trailblazer for both women and the epilepsy subspecialty

Dr. Zupanc has received many accolades over the years, including being the first woman to graduate top of class from UCLA Medical School, and at a time when women were just beginning to be have more representation in medicine.  She was later named one of 10 “outstanding young women in America.”  She has garnered many teaching awards from medical students and residents, and continues to be listed among the best doctors in America.

Dr. Zupanc is board-certified in four different medical specialty areas: pediatrics, neurology, neurophysiology and epilepsy. Her primary mentor, Dr. Raymond Chun, encouraged her to return to her home state of Wisconsin and become a child neurologist. Dr. Zupanc initially hesitated, but ultimately agreed, thinking it would simply be a good learning opportunity from her mentor. While there, she learned that pediatric epilepsy didn’t have many treatment options aside from a handful of drugs. However, there was exciting innovation with pediatric epilepsy surgery just starting to be performed in young children. 

“Epilepsy surgery in children was in its infancy at this time, and people thought we were crazy,” Dr. Zupanc says. “The advances we’ve made since then are astonishing. We can do things we’d never dreamed of before.”

Now, she says, she feels like Sherlock Holmes when she works with a new patient. Each child is different, and a physician must determine how to best help them in terms of their specific situation – medically, socioeconomically, culturally and religiously. It’s imperative to partner with families, listen to them and come to an agreement, Dr. Zupanc says.

A legacy that goes beyond awards

Throughout her career, Dr. Zupanc has been very active in the CNS and the Child Neurology Foundation, a parent/provider advocacy group linked to the CNS. A handful of her other legacy accomplishments include her work in infantile spasms and epilepsy surgery; transitioning care of pediatric patients to adult care; and, most recently, chairing the CNS relative value unit (RVU) task force, resulting in a seminal article about physician workload, compensation and burnout.  

As a clinical professor in academic medicine, she has continued to teach medical students, residents, fellows and colleagues, as well as mentor young faculty, especially women.

“Fifty percent of medical school classes are now women, but there is still a glass ceiling in terms of being leaders in our field,” she says. “We’ve come a long way, but the progress is slow. Having diversity, inclusion and equity in medicine makes the field better and stronger.”

Dr. Zupanc was recruited to CHOC 10 years ago to build the neurology division. She now considers her greatest accomplishment to be CHOC’s designation as a Level 4 Epilepsy Center – the highest level of specialization – providing “complex forms of intensive neurodiagnostic monitoring; extensive medical, neuropsychological and psychosocial treatment; and complete evaluation for epilepsy surgery, including intracranial electrodes and a broad range of surgical procedures for epilepsy.”

Since arriving at CHOC, she has grown the pediatric neurology division from four physician subspecialists to the present 16, specializing in areas such as epilepsy, sleep disturbances, movement disorders, concussion, stroke and autism. This growth has resulted in the reorganization and consolidation of the neurology division with the neurosurgery division, becoming today’s CHOC Neuroscience Institute. 

In working at CHOC, Dr. Zupanc has found inspiration from helping families who believe they have no hope. When they arrive here, she says, some feel as though their lives are falling apart; their child may have difficult-to-control epilepsy or is struggling developmentally. The quality of care they receive from CHOC is transformative and changes their lives, she says.

Medical outreach, both nationally and internationally

To only give honor to Dr. Zupanc’s academic and scientific accomplishments would be to miss a great part of what her life has been about, as reflected by the Humanism in Medicine Award. Throughout her medical career, she has continually been involved in family and community outreach and advocacy; actively participated in family support groups; and developed outreach programs for underserved communities.

Her passion and advocacy have even reached beyond national borders. She was a member of the board of directors of Physicians for Social Responsibility, the American section of the International Physicians for the Prevention of Nuclear War (IPPNW), when the group was awarded the Nobel Peace Prize in 1985. In that role, she traveled with an American delegation to the Soviet Union and met with like-minded Soviet physicians to share ideas for pulling their nations back from the brink of nuclear disaster.

More recently, Dr. Zupanc traveled to India, Armenia and Vietnam on missions of teaching and providing medical care in areas where doctors are rare and medical specialties often non-existent. Back home, her passion is family-centered care, and she is a regular guest speaker at family support groups.

“My patients and their families have taught me so much,” Dr. Zupanc says. “They’ve taught me humility, how to truly listen, to be open-minded and that deeply caring for the patient and family reaps great rewards.”

“One of the wonderful things about child neurology,” she explains, “is that you often embark on a decades-long journey with families.” She still receives letters and cards from patients she treated 30 years ago. “You transform a child’s life and a family’s life. That’s what this profession is all about, and why it has always been more than a job for me. It’s a calling.”

Learn more about the CHOC Neuroscience Institute.

The transition from child to adult care must start early with education, pediatric neurologist emphasizes

Navigating from child to young adult can be very challenging in the best of circumstances.

Add a chronic or rare medical condition to the journey, and the process can get very scary.

Teens with chronic conditions face a higher risk of non-adherence to taking their medication or even obtaining it when transitioning from a pediatric to adult primary care provider, medical experts say. And statistically, the chance of them having to be admitted into an ER or have surgery increases, as does the prospect of them dropping out of treatment – which could have fatal results.

Dr. Mary L. Zupanc, co-medical director of CHOC’s Neuroscience Institute and a pediatric neurologist who specializes in epilepsy and rare conditions, stressed in a recent webinar that she’s passionate about preventing patients transitioning to adult care from falling through the cracks.

Dr. Mary L. Zupanc, co-medical director of CHOC’s Neuroscience Institute

“We begin with introducing the concept of transitioning to adult care when our patients are 12 years old,” Dr. Zupanc said while speaking on a four-person panel hosted by Global Genes, an Aliso Viejo-based non-profit that advocates for the rare disease community.

The topic of the 50-minute discussion on Sept. 24, 2020 was “Navigating the Transition of Care for Young Adult Patients.”

In addition to her position at CHOC and as a faculty member at UC Irvine, Dr. Zupanc sits on the board of directors of the Child Neurology Foundation (CNF) in Minneapolis, Minn. On its website, the CNF details several resources about transitioning to adult care.

“We at CHOC have followed the CNF’s template to develop a formal transitioning program here,” Dr. Zupanc said.

Starting the conversation with families when a patient is 12 years old may seem too early, Dr. Zupanc said. But transitioning is a process that doesn’t have a one-size-fits-all solution, and it’s critical to start the discussion when patients are young.

The other panelists agreed. They were Dr. Leah Ratner, a fellow at Brigham and Women’s Hospital in Boston; Sneha Dave, 22, a student at Indiana University who since age 6 has lived with ulcerative colitis; and moderator Amy Ohmer, director of the International Children’s Advisory Network in Marietta, Ga., and the mother of two daughters, ages 17 and 19, who have chronic and rare conditions.

“I think it’s important to introduce the concept (of transitioning) early – to let the parents and patient know, ‘We’re not just going to throw you out,’” Dr. Zupanc said. “Rather, ‘We’re going to work with you so you can learn to self-manage your disease and your medications. And we’re going to go over your plan on a yearly or bi-annual basis.’”

Under the transitioning plan adopted by CHOC thanks to a grant, a healthcare transition program is initiated when patients turn 12 years of age.

Clinicians, social workers, and others continue to prepare their patients and their families for increased independence and management of their care, as well as to the adult model of care, Dr. Zupanc explained.

The actual transition to adult care varies from 18 to 22 years of age—often dependent on insurance—and ideally occurs in stages, as these young adults may have multiple subspecialists. Between the ages of 23 and 26 years, the young adults are integrated into adult care.

“It’s a partnership,” Dr. Zupanc said. “It takes a community.”

Sneha, the Indiana University student, said the transition must go slow because there are so many components to it, such as having to navigate health insurance.

“Young adults diagnosed with a condition at childhood tend not to be as prepared because their parents or guardians took care of everything and they had no ownership of their own care,” Sneha said.

When she was a freshman, Sneha founded the Health Advocacy Summit, which empowers young adults with chronic and rare diseases through advocacy events and programs. In August 2020, the organization hosted an international virtual summit.

“It’s a process,” Dr. Zupanc agreed of transitioning to adult care. “And I think it’s a process of self-empowerment. Most parents are used to taking care of everything. We try to empower our teenager and young adults as much as possible. Parents have to let go at some point, but it’s a process.”

The bulk of Dr. Zupanc’s patients have severe epilepsy that started in infancy. A high percentage also have intellectual disabilities.

“Sometimes they take a step forward and two steps back,” she said.

The path toward a successful transition to adult care begins with knowledge, she explained, followed by support, confidence and, finally, independence.

Dr. Zupanc noted that patients who leave CHOC are welcomed to stay in touch.

“As a pediatric provider for children with rare diseases,” she said, “I let my families and adolescents know that I have their backs and that I’m not going to let them fall into the abyss. If there are issues, I’m here to help them.”

November is epilepsy awareness month. To learn more about CHOC’s Comprehensive Epilepsy Program, click here.

Investigational Drug Study Leads to FDA Approval for Fenfluramine in Treatment for Dravet Syndrome

Children who experience seizures associated with Dravet syndrome have a new medication option, thanks to research at CHOC that helped gain the recent approval of the U.S. Food and Drug Administration (FDA).

Dravet syndrome is a sodium channelopathy that causes an intractable, difficult-to-control form of epilepsy beginning in the first year of life, as well as significant developmental and motor impairments. Many patients with this rare and severe type of epilepsy experience prolonged and unrelenting seizures and are at risk for SUDEP (sudden unexpected death in epilepsy).

Dravet syndrome is difficult to treat with the antiepileptic medications currently available in the United States, but the FDA has recently approved FINTEPLA® (fenfluramine) for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older. Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Neuroscience Institute, was a key investigator in one of the two international drug studies that led to U.S. FDA approval.

Dr. Mary Zupanc
Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Neuroscience Institute

“The drug we recently trialed, fenfluramine, showed a significant reduction in convulsive seizures and overall seizures, which helped improve the quality of life not only for patients with Dravet but for their families as well,” Dr. Zupanc said.

Study 1 trialed 0.2 mg/kg/day or 0.7 mg/kg/day. The patients on the higher dose had a 70% reduction relative to placebo in monthly convulsive seizure frequency. And 70% of the patients on the higher dose had at least a 50% reduction in their monthly convulsive seizures compared to 7.7% of patients on placebo. Patients on the lower dose of fenfluramine had a 31.7% reduction relative to placebo in monthly convulsive seizure frequency, and 34.2% of patients on the lower dose had at least a 50% reduction in their monthly convulsive seizures.

In addition to reducing the monthly convulsive seizure frequency in patients whose seizures were not adequately controlled on one or more antiepileptic drugs, most study patients responded to treatment with fenfluramine within three to four weeks, and the effects remained consistent over the treatment period. Dr. Zupanc remarked that fenfluramine’s effectiveness could be “life-changing” for patients with Dravet.

Fenfluramine — used on its own and also paired with phentermine in the popular weight-loss combination known as “fen-phen” — was withdrawn from the U.S. market in 1997 after reports of heart valve disease and continued findings of pulmonary hypertension. Due to these risks, subjects received frequent EKGs and echocardiograms throughout the investigational trial. No valve disease or hypertension was found, but a decrease in appetite and some observations of a minor increase in irritability were noted.

Dr. Zupanc is optimistic about fenfluramine’s application for Dravet, but advised that it is only part of an overall treatment plan. “If a physician has a patient with Dravet syndrome, I would make sure the patient gets referred to a Level 4 epilepsy program, the highest designation for epilepsy centers,” Dr. Zupanc said. “CHOC is a level 4 epilepsy center, which means we do investigational drug studies, vagus nerve stimulation, epilepsy surgery, ketogenic diet and provide a full-service epilepsy program with six epileptologists with board-certification in epilepsy. Because we have participated in these [investigational] studies, we are on the ground floor and know how to dose these drugs and adjust these medications.”

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.

5 things pediatricians should know about seizures

Seizures can bring up a lot of worries and unknowns, especially when it comes to children.

One percent of the population has epilepsy, which puts the estimated number of children with epilepsy in Orange County alone at about 7,500. It is estimated that one in five people will have a seizure at some point—whether it develops into epilepsy or not—making seizures a more common neurological condition than multiple sclerosis, Parkinson’s and Alzheimer’s disease combined.

There are many common misconceptions about seizures, even within the medical community. Dr. Mary Zupanc, pediatric neurologist and epileptologist and co-medical director of CHOC’s Neuroscience Institute, points to five important points pediatricians should consider when seeing a patient who has had one or more seizures.

Professional headshot of Dr. Mary Zupanc, Pediatric Epileptologist at CHOC Children's, in a while labcoat on a gray background.
Dr. Mary Zupanc, Pediatric Epileptologist at CHOC
  1. There should be zero tolerance for seizures.

    Seizures are considered epilepsy when a child has had two or more unprovoked seizures—seizures that are not tied to a different underlying condition.

    When epilepsy is diagnosed, treatment should be initiated early. Some families are reluctant to treat their child’s epilepsy, often fearful that antiepileptic medication is worse than epilepsy itself. They worry about the side effects — that it will cause their child to have cognitive impairments and slow them down. However, repeated seizures can translate into progressive injury to the brain, with a decline in cognitive abilities and frequent psychosocial co-morbidities, including anxiety and depression. Furthermore, even if seizures are infrequent, there is a loss of independence for children and adolescents. An example would be an adolescent’s inability to obtain his/her driver’s license.

  2. Epilepsy is progressive.

    “Brain cells that seizure together network together,” Dr. Zupanc says, forming neuronal circuitry that hardwires the brain for continued seizures. Over time, there can be brain cell loss, cognitive decline, and important psychosocial consequences. Furthermore, when seizures continue, there is increased risk among those with epilepsy of sudden, unexpected death or other progressive neurological issues over the subsequent 20-30 years.

  3. Encourage parents to act quickly.

    Recurrent unprovoked seizures is the definition of epilepsy. Epilepsy should be treated and not ignored, for the reasons outlined above. Approximately 60-70% of epilepsy can be completely controlled with antiepileptic medication. Thirty percent of patients with epilepsy have intractable seizures, i.e. a failure to control the seizures with antiepileptic medications. These patients require more comprehensive care, including an evaluation for epilepsy surgery — at a Level IV Epilepsy Center, which is a designated center given only to those centers who provide multidisciplinary care with cutting-edge technology. Some parents fear that epilepsy surgery will cause serious neurological deficits. Most epilepsy surgeries are highly successful without detrimental effects to cognitive or motor functions. With epilepsy surgery, the risk of a severe and permanent injury is under 1%, and the risk of a minor or temporary injury is under 5%. Compared to the risks associated with years of recurrent seizures, the risks of epilepsy surgery are much lower than the risks of continued epilepsy.  

    The effectiveness of epilepsy surgery decreases significantly over time, especially for children who have had epilepsy for seven or more years. In addition, the plasticity of younger brains allows a transfer of functions to other parts of the brain — something adult brains cannot do as readily, Dr. Zupanc says.

    Because of this, she strongly encourages epilepsy surgery early, not waiting until a child is older.

  4. Delay in seizure treatment affects long-term psychological health.

    The psycho-social components of seizures are oftentimes just as important as the physiological ones, says Dr. Zupanc. Depression and anxiety occur in 50- to 60% of children with epilepsy, and there is also a notable increase in suicidal risk.

    These effects are increased when families wait to pursue recommended surgery, she says. Later in life, the surgery may remove the seizures, but the psychological effects are already deeply embedded.

  5. Seizure history should affect your referral choice.

    “It is so important for pediatricians to know that if a child’s epilepsy has not come under complete control after trying two or more antiepileptic medications, he/she should be referred to a higher level of epilepsy care, specifically a Level III-IV Epilepsy Center, as designated by the National Association of Epilepsy Centers,” says Dr. Zupanc. If the child is a young baby, the referral is even more urgent. “If a baby continues to have seizures after just one drug, he/she needs a referral to a Level III-IV epilepsy center immediately.”

    The care plan should include pediatric epilepsy specialists, epilepsy-trained neurosurgeons, state of the art neuroimaging tools, nurse practitioners, pharmacists, dieticians, social workers and neuropsychologists.

    “At CHOC, we treat epilepsy with a multidisciplinary team approach,” says Dr. Zupanc. Additional diagnostic tests are usually necessary to diagnose the appropriate epilepsy syndrome, determine if epilepsy surgery is an option, and/or outline an individualized, optimal treatment plan.

    Furthermore, all of those involved in the child’s care hold a comprehensive epilepsy conference to discuss complex cases and lay out the best possible strategy for achieving a seizure-free outcome.

CHOC leaders observe International Women’s Day

As the world celebrates International Women’s Day, we turned to CHOC  physicians and nursing leaders for insight and words of encouragement to other women pursuing healthcare careers.

Melanie Patterson, vice president, patient care services, and chief nursing officerWhen beginning your career in medicine, don’t focus on one trophy. The fields of medicine and nursing have so many opportunities within them; be courageous and try new things. The most important aspect of leadership and of career success is to be kind. Remember to form your own opinion — go into every relationship with your eyes open and stop looking through others’ eyes; they don’t always have 20/20 vision.

Dr. Mary Zupanc, pediatric neurologist and epileptologist & co-medical director of the CHOC Neuroscience Institute

When I went to medical school, women were not encouraged, and it was hard. There were a lot of things that happened that made it very difficult, but medicine is truly one of the most gratifying professions you will ever have. Every patient is different. I believe that if you really and truly listen, a patient and their family will give you the diagnosis you’re searching for. Everyone’s story is so fascinating, and that makes our work like being a detective. Sometimes I feel like Sherlock Holmes searching for answers. Then once you do find an answer, you need to work with the family to make sure the treatment works for their lifestyle, culture and religion. That makes the work challenging, fun and meaningful.

The best piece of advice that I’ve ever received is to never apologize for excellence. Anyone would want their doctor to strive for excellence – and that goes for any profession.

Amy Waunch, nurse practitioner and trauma program managerNever underestimate your capabilities. Do not shy away from opportunities and always take on new challenges. Believe in yourself but don’t be afraid to ask for help. You may not have all of the answers all of the time, but you do have the ability to learn and grow.

Spot growth opportunities when they present themselves because they are the key learning opportunities. You will know because they make you uncomfortable and your initial impulse will be that you are not ready.

Dr. Azam Eghbal, medical director, radiologySince I was 7 years old, I wanted to be a doctor and becoming one has been the best decision of my life. As a female immigrant, I was told that I could never get to medical school, which, of course, motivated and challenged me even more to do so. The best advice I’ve gotten is don’t be discouraged about all your falls and obstacles. Think how you can succeed to get where you want to be.

Dr. Amber Leis, pediatric plastic surgeonMy advice for women pursuing a career in medicine is to trust yourself! Early on in your career, it’s easy to be overcome by feeling like you are not up to the task ahead of you. Your unique qualities will become your greatest strengths, so just keep chasing your passion.

I have great faith that if I stay true to my core principles, the right path will open in front of me. I try not to set specific goals for the future and instead I give my best to where I am. It keeps me focused on what I am doing now, and not distracted by trying to maneuver into some future place.

The best piece of career advice I’ve ever gotten has been, “You get to choose what kind of person you will be.”

Dr. Jasjit Singh, medical director, infection prevention & controlMy advice for women pursuing a career in medicine is to follow your passion! There are few other careers that offer the personal satisfaction and the intellectual rigor that medicine does. Find a good mentor early in your career. Later, make sure your practice partners have abilities that you respect, and the talent to make your shared time together meaningful.

I learned early on that delegation and time management are important, particularly if you want to balance a medical career and family. You can’t always do it all, and prioritization is tantamount to success in all the different spheres of your life.

One of the best pieces of advice that I got was from a mentor during fellowship, who told me, “It’s not enough to just be a good clinician.” He showed me the importance of asking good research questions and pursuing new knowledge. He also encouraged my love of teaching upcoming generations of pediatricians!

Dr. Katherine Williamson, pediatricianI love being a pediatrician. I help take care of kids every day and partner with their parents to help keep them healthy. To me, being successful is loving what you do, because then working hard and being motivated to do well doesn’t feel like work – it’s fulfilling a passion.

When asked to give advice, I always say these three things: be yourself, don’t rush, and follow your heart every step of the way. Be yourself, always. No matter how busy or loud life gets, never lose sight of you who you are and what you want to do.  Don’t be in a rush. Enjoy the journey because that is where you learn who you truly are. Lastly, follow your heart in every decision you make. When I look back on what got me to where I am in my career, I realize that it was not one or two big decisions that were the deciding factor, but instead it was a million little decisions along the way. And with each of those decisions I followed my heart and my passion.

Seizure-free after a rare epilepsy diagnosis

Thanks to the expertise of a CHOC epileptologist, a 12-year-old boy diagnosed with a rare type of epilepsy is seizure-free and has a bright future ahead – the significance of which is underscored in November, Epilepsy Awareness Month.

Gabriel Lucak had been a healthy, normally developing child until age 3, when he suddenly began experiencing seizures.

CHOC Children's Neuroscience Institute patient Gabriel Lucak poses by the ocean
CHOC Neuroscience Institute patient Gabriel Lucak

What began as a tonic-clonic seizure in May 2008 rapidly progressed to include myoclonic, atonic, and atypical absence seizures. On his worst days, Gabriel experienced up to 50 seizures a day.

“It was like living out a surreal nightmare,” said his mother, Nicole.

Gabriel was initially diagnosed with myoclonic-astatic epilepsy, also known as Doose syndrome. His seizures were difficult to control, and doctors attempted many different treatments, including eight months on a ketogenic diet. During this time, Gabriel was hospitalized numerous times to modify his medication and control his seizures.

Searching for answers

A low point for the Lucak family came about nine months after the seizures began. While hospitalized for respiratory syncytial virus, Gabriel’s seizures increased significantly. An electroencephalogram (EEG) recorded seizures occurring about once a minute and a slowing brain wave frequency. Magnetic resonance imaging (MRI) revealed decreased brain volume. Gabriel’s health was rapidly deteriorating.

Joe and Nicole desperately began looking elsewhere for help, and in March 2009 found a beacon nearly 1,400 miles away in Dr. Mary Zupanc, a pediatric neurologist and one of the nation’s leading epileptologists, who was then practicing in Wisconsin.

Under Dr. Zupanc’s care, Gabriel was placed on a new treatment program. He stopped following the ketogenic diet and began taking a new antiepileptic medication. He underwent a two-week long-term video EEG monitoring study, which revealed he was experiencing a fifth type of seizure – tonic – during sleep.

CHOC epileptologist Dr. Mary Zupanc holds a model of a human brain..
CHOC pediatric epileptologist Dr. Mary Zupanc

A new diagnosis

Dr. Zupanc then knew that Gabriel’s epilepsy had evolved into a more severe form called Lennox-Gastaut syndrome (LGS). This rare type of epilepsy is marked by seizures that are difficult to control, and typically persist through adulthood.

In addition, Dr. Zupanc diagnosed Gabriel with cerebral folate deficiency, a rare metabolic condition, following a spinal tap and extensive testing on his cerebral spinal fluid. He immediately began taking a folinic acid supplement and following a strict dairy-free diet.

Under this new treatment plan, Gabriel was seizure-free within two months. A second spinal tap showed a normal level of folate, and another MRI had normal results. The Lucaks were thrilled.

“Gabriel could have suffered severe brain damage, or he might not have survived at all,” Nicole said. “That’s how critical it was for us to have found Dr. Zupanc when we did.”

A bright future

Today, Gabriel is an intelligent, creative and artistic 12-year-old who dreams of being a paramedic when he grows up.

He remains under Dr. Zupanc’s care, traveling from San Diego to the CHOC Neuroscience Institute and its level 4 epilepsy center for appointments and annual long-term EEG monitoring.

Gabriel is also under the care of Dr. Jose Abdenur, chief of CHOC’s metabolics disorders division. Gabriel, his younger brother, Nolan, and his parents have all participated in several research studies involving genetic testing for both epilepsy and cerebral folate deficiency.

Recently, Gabriel was weaned off the antiepileptic medication and continues to be seizure-free.

“He has the opportunity to live a full life in good health, thanks to an amazing series of events that led to experienced doctors, correct diagnoses and effective treatment,” Nicole said.

Learn more about the CHOC Neuroscience Institute.

Infantile Spasms: What Pediatricians Should Know

Though seizures in children are always worrisome, pediatricians should be especially watchful for infantile spasms, a type of epilepsy that occurs in young infants typically between ages 3 and 8 months, a CHOC neurologist says.

These seizures should be considered a medical emergency due to the potentially devastating consequences on the developing brain, Dr. Mary Zupanc says. Many children with infantile spasms go on to develop other forms of epilepsy because a developing brain undergoing an epileptic storm essentially becomes programmed for ongoing seizures and cognitive/motor delays.

To that end, here’s what pediatricians should look for:

  • Infantile spasms often occur in clusters, with each spasm occurring every five to 10 seconds over a period of minutes ranging from three to 10 minutes or longer.
  • Though there is almost always a cluster of spasms in the morning when the child awakens from sleep, infantile spasms can occur at any time during the day or night.

Infantile spasms can be easily missed because they can mimic common symptoms and conditions such as sleep disturbances, gastroesophageal reflux, startle and shuddering attacks.

Diagnosis, treatment

If infantile spasms are suspected, a pediatrician should quickly refer the child to a pediatric neurologist. CHOC neurologists admit these children urgently for long-term video electroencephalogram (EEG) monitoring to confirm the diagnosis.

Infantile spasms are diagnosed on the basis of clinical spasms, in association with a markedly abnormal EEG showing a hypsarrhythmia pattern. A hypsarrhythmia pattern is characterized by very high amplitude electrical activity and multifocal areas of the brain demonstrating epileptic discharges.

High-dose adrenocorticotropic hormone, or ACTH, is CHOC neurologists’ first line of treatment for infantile spasms, per the American Academy of Neurology’s 2004 practice parameter. Vigabatrin (Sabril), the parameter states, is probably effective in the treatment of infantile spasms, especially in children with tuberous sclerosis and infantile spasms.

If started within four to six weeks of seizure onset therapy has better success at stopping spasms, eliminating the hypsarrhythmia pattern and improving developmental outcomes regardless of etiology.

The course of treatment is approximately six weeks. During this time, and for two to three months after the ACTH course, immunizations should not be administered. The effectiveness of ACTH may be as high as 85 percent, though a recent published study placed the efficacy at a slightly lower percentage, regardless of etiology.

Side effects, causes

Side effects of ACTH, a steroid, include high blood pressure, increased appetite and weight gain, increased sugar in the blood, temporary suppression of the immune system, and sometimes gastritis. All side effects are monitored during the time of the ACTH, and they disappear after the course of treatment.

Successful therapy is marked by two achievements: the cessation of the infantile spasms and the elimination of the hypsarrhythmia pattern. But because clinical spasms can be very subtle and the hypsarrhythmia pattern may sometimes only be seen during deep sleep, therapy’s success can only be confirmed through objective long-term video EEG monitoring.

The etiologies for infantile spasms can include:  tuberous sclerosis; cortical dysplasias; stroke; infection including meningitis and encephalitis; hypoxic-ischemic injury; trauma; or genetic conditions such as Down syndrome and metabolic disorders.

Dr. Mary Zupanc joins national pediatric neurology board of directors

A CHOC neurologist has been elected to the board of directors of a national pediatric neurology organization.

Dr. Mary Zupanc, Division Chief of pediatric  neurology at CHOC and director of the pediatric comprehensive epilepsy program, has been named councillor of the west for the Child Neurology Society, a nonprofit professional association of pediatric neurologists in the United States, Canada and worldwide.

CHOC Children's

“I’m thrilled for an opportunity to expand my work of advocacy for children with neurologic conditions at CHOC to a global level,” Dr. Zupanc said.

She begins her term in October 2016 at the organization’s annual meeting in Vancouver, Canada. The Child Neurology Society’s board of directors comprises councillors of the east, Midwest and west; a president; a past-president; and a secretary-treasurer.

“The Child Neurology Society is fortunate to be able to draw on such a deep pool of bright, capable, community-oriented leaders willing to offer their time and talent to help shape the future of child neurology through the Child Neurology Society,” the group said in its announcement.