Multi-Focus Seizures Complicate Surgical Treatment for Pediatric Epilepsy Case

During Celeste’s pregnancy, an ultrasound showed that her baby had heart abnormalities. Once baby Jaylynn was born, further diagnostic evaluation confirmed she had tuberous sclerosis complex (TSC), a disorder that causes growths in multiple organs, including the heart, brain, kidneys and lungs. TSC is a genetic disorder, and patients with this condition are known to have a high seizure burden.

In the days after her birth, the right side of Jaylynn’s body seemed to twitch, and Celeste’s instincts told her Jaylynn was having seizures. Celeste mentioned this to her nurse at the hospital where Jaylynn was born, but her worries were dismissed. After being sent home, Celeste called CHOC Children’s and met with Dr. Lily Tran, a pediatric epileptologist at CHOC’s level 4 pediatric epilepsy center.

Over the next three years, Jaylynn tried several different treatment options, including medications, ketogenic diet and steroid treatment. Most treatments followed the same pattern: the seizures would stop for a few months, but then come back stronger than before. She regressed significantly in terms of development, no longer made eye contact, could not sit up even with support and was lethargic all day due to the high seizure burden. She started losing weight and had to have a G-tube placed for adequate nutrition. Her medication regimen was at high doses to control seizures, which led to side effects, such as vomiting and lethargy, which impacted her quality of life significantly. Her days consisted of seizures, vomiting and sleep. At that point, Celeste said her family was simply trying to survive.

“Jaylynn’s refractory case of epilepsy was quite complex because we couldn’t pinpoint where her seizures were coming from based on Phase I surface EEG monitoring,” says Dr. Tran. “We used several different imaging techniques to locate the focus of her seizures, including a virtual reality simulation program. Through these tests and Phase II invasive EEG monitoring, we found her seizures were coming from the left side of her brain, but on this one side, we then found the seizures were coming from three distinct areas. Her case was discussed extensively at our comprehensive epilepsy surgery conference, but there was no clear-cut answer and consensus on what to do next. Each approach had various pros and cons, and each option had questions and concerns. As a team, we constantly asked ourselves, ‘What’s best for Jaylynn?’ when considering these treatment options. Mom was updated at every step of the way so she could make the most informed decision for her daughter.”

Because the seizure focus came from three different areas in the left hemisphere, it was not reasonable to resect these regions separately without significantly more post-operative side effects. Dr. Tran elected to proceed with a functional hemispherectomy to give Jaylynn the best outcome for seizure control and to turn her quality of life around. The procedure essentially “quieted down” the electrical activity in the left side of her brain.

“For Jaylynn, I used everything I learned in fellowship, consulted with other colleagues and leveraged the tools we have at CHOC — such as our ability to perform invasive surgery and our research capabilities — to determine the best course of treatment for this complex epilepsy case. When you have a multidisciplinary team like ours that includes a dedicated neurosurgeon, neuroradiologists, neuropsychologists, educated nurses, EEG technologists, epilepsy pharmacists, social workers and parent champions who work cohesively together, it helps make the patient’s journey a little bit easier.”

Today, Jaylynn is seizure-free and on fewer medications. She is now laughing and smiling, more interactive, enrolled in school and even got to visit Disney World.

“What makes CHOC different from similar centers, I think, is our focus on the patient journey and how we value the quality of life for each patient,” says Dr. Tran. “We treat every child and their family as a whole unit. When you come to CHOC, you’re not just our patient. You truly become part of our family.”

Our Care and Commitment to Children Has Been Recognized

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

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

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.

Leading-edge biomarker research aids in infantile spasms management

The CHOC Children’s Neuroscience Institute has partnered with the Pediatric Epilepsy Research Consortium (PERC) to advance treatment for infantile spasms.

PERC is a national consortium inclusive of more than 54 epilepsy programs, with 25 centers collaborating on infantile spasms research.

“PERC’s inception 10 years ago was born out of the American Epilepsy Society and a select team of specialists interested in building a wider network and infrastructure for large-scale clinical trials. Many diseases, like infantile spasms, are rare, and collaboration within PERC offers a wider patient pool for researching such uncommon conditions,” says Dr. Daniel Shrey, pediatric epileptologist at CHOC.

Dr. Daniel Shrey, Pediatric Epileptologist at CHOC Children's
Dr. Daniel Shrey, pediatric epileptologist at CHOC Children’s

Dr. Shrey was recently selected to lead PERC’s infantile spasms sub-group. In his new role, he is coordinating efforts between over a dozen pediatric epilepsy centers to catalyze multi-centered research on infantile spasms, a devastating type of epilepsy that typically begins in the first year of life.

Much of the current research on infantile spasms focuses on the visual analysis of a patient’s EEG, whereas Dr. Shrey’s research uses a computational approach. His research uses various mathematical tools to analyze neural data and identify new biomarkers of disease. Most of this work is done in collaboration with Dr. Beth Lopour, assistant professor of biomedical engineering, who leads the Laboratory of Computation and Translational Neuroscience at the University of California, Irvine.

“A novel biomarker we are studying is functional connectivity — measuring how activity in one part of the brain impacts another. We use characteristics of the brain network to predict how patients are likely to respond to treatment, compared to visual measures alone,” Dr. Lopour says.

She and her students develop computer code and perform data analysis for their research.

“This approach removes human interpretation and natural biases to instead focus on the data to make clinical decisions,” Dr. Shrey says.

Biomarkers also advance research by beginning to tell researchers how a disease responds to treatment and evolves over time. Discovering and validating a biomarker opens the possibility for a future clinical trial for patients with rare diseases.

The PERC infantile spasms group combines specialists in biomarker research, genetics, RNA genetics and brain inflammation, among others. In the future, the epilepsy field will look to quantitative approaches to guide clinical decision-making, ultimately improving the lives of children with epilepsy.

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 Children’s
  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.

Seizure-free after a rare epilepsy diagnosis

Thanks to the expertise of a CHOC Children’s 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 Children’s 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 Children’s 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 Children’s 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 Children’s Neuroscience Institute.