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.

Multidisciplinary Approach to Pediatric Cancer Treatment Benefits an Underserved Young Adult Population

As one of the most robust adolescent and young adult (AYA) pediatric cancer programs in the nation, CHOC’s AYA program offers more than comprehensive oncology care to an underserved teen and young adult population — it’s a model for other AYA programs in the country to build upon.

“In the last 15 years or so, we’ve realized there is a huge survival gap in the AYA population, everyone from the age of 15 to 39 years old, whereas over the past 30 to 40 years, we’ve seen significant survival gains in pediatric patients and older adults,” says Dr. Jamie Frediani, pediatric oncologist at the Hyundai Cancer Institute at CHOC. “The AYA population has had very few survival gains, and we believe this is because of a multitude of reasons. They are much less likely to enroll in clinical trials or have access to clinical trials, they do not have the same access to novel new experimental treatments that can improve their survival, their tumor biology is likely different and then there’s a whole host of psychosocial reasons. AYA patients really are their own unique population, and the AYA program at CHOC aims to address that survival gap and to address it from a multipronged approach.”

The multipronged CHOC AYA program focuses on education, research and psychosocial support to increase survivorship within the AYA population.

“Our patients really want to know more about their disease,” Dr. Frediani says. “They want to know more about how their condition impacts their lives whether they’re in treatment or survivorship, such as fertility and sexual education, for example. Our team of experts have education nights with patients to talk about any topics they want to discuss. We have peer mentorship so patients can talk through the highs and lows they experience with someone who’d been through the same thing they’re going through.”

From a research standpoint, Dr. Frediani says the goals of the program are getting more of the AYA patients into clinical trials, knowing where the clinical trial enrollment gap exists and building relationships with adult counterparts to find the best hospitals where AYA patients can be treated.

“We know pediatric diseases do better if a patient is treated at a pediatric hospital. Finding where these patients will do best and forming those relationships to get the most appropriate care is critical. It’s also about finding everything else they need — the supportive medicine, other drugs and different dosing, clinical trials and research projects.”

Addressing AYA patients’ psychosocial needs is the third prong of CHOC’s AYA program.

“I’m a firm believer that multidisciplinary psychosocial supports plays a huge role,” Dr. Frediani says. “Mental health plays a significant role in the treatment of our AYA patients, and I have to believe that affects their outcomes. AYA patients are at a critical juncture in their lives where they’re trying to seek independence. A lot of them are having kids, getting married, starting new jobs, going to college — all these critical life transitions are happening. When you put cancer on top of that, the natural order of this time in their lives is completely disrupted. Social workers, child life specialists, psychologists, case managers, music therapists — all of our resources help our patients know we truly understand their feelings and needs and are here to help them in every way we can.”

CHOC’s AYA program was developed around 2014 and was one of the only AYA programs in the nation to offer such a comprehensive range of services. Dr. Frediani notes that while some AYA programs in the United States today have a heavier focus on treatment, nurse navigation and clinical trials, others are more support-group focused. CHOC is unique because its program is a hybrid of both.

“Our AYA program has a depth that most programs do not. We have this very robust psychosocial support and clinical trial programming around ours. I think we are unique in the amount of resources we provide for our AYA patients. Addressing cancer from our multipronged approach with a multidisciplinary team ends up being so important.”

The strength of CHOC’s AYA program is rooted in the institution’s values and commitment to providing comprehensive cancer care.

“CHOC comes from a community-based model of medicine,” Dr. Frediani says. “We value the bedside relationships with patients, spending time with them and taking care of not just their medical disease, but everything else around it. I see that across our team, from our nurses to our physicians to our social workers to our child life specialists. Everyone is here to stand with our AYA patients and to help them live whatever life they want to live, in whatever way that means. Other physicians should know CHOC wants to help their AYA patients in any way we can, from offering second opinions to helping with fertility preservation to checking on the availability of a clinical trial. I want to make sure there’s not a person in this age range who goes without these critical resources, without knowing this program is here for them.”

Our Care and Commitment to Children Has Been Recognized

CHOC 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 cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.

Silk Biomaterial Research Advances Urologic Treatment Capabilities

The Urology Center at CHOC Children’s is collaborating with Joshua Mauney, PhD, associate professor of urology/biomedical engineering and Jerry D. Choate Presidential Chair in Urology Tissue Engineering in the University of California, Irvine Urology Department, who focuses his research on tissue engineering with the development of silk biomaterials for the repair of visceral hollow organs. Dr. Mauney has a productive basic science laboratory with NIH grant funding and was previously a staff scientist in the Department of Urology at Boston Children’s Hospital and associate professor of surgery at Harvard Medical School.

“The overall goal is the creation of clinically useful scaffold configurations for hollow organ regeneration by engineering materials which fulfill structural and mechanical requirements of native tissues as well as present microenvironmental cues necessary for host tissue integration and defect consolidation,” said Dr. Mauney.

3D matrix designs using silk biomaterials can be used to restore function related to injury or fibrotic disease. Silk scaffolds offer advantages over non-biomaterial implants for human bladder augmentation and can support bladder storage, voiding function and defect correction.

“The addition of Dr. Mauney allows the CHOC team to focus on the reconstruction of bladders and organs using his 3D matrix designs to offer options for children born with missing or abnormal parts of their urinary tract,” said Dr. Antoine “Tony” Khoury, chief of pediatric urology.

Dr. Tony Khoury, chief of pediatric urology at CHOC
Dr. Tony Khoury, chief of pediatric urology at CHOC

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 urology specialty.

US News and World Report, Urology

Learn now CHOC’s urology care, ongoing treatment and surgical interventions preserve childhood for children in Orange County, Calif., and beyond.

Clinical Trials Continue the Advancement of Pediatric Oncology Treatment

Children, adolescents and young adults with cancers that do not respond to traditional treatments continue to find new treatment options because of CHOC’s extensive efforts and active engagement in clinical trial research.

The Hyundai Cancer Institute at CHOC Children’s is a member of the Children’s Oncology Group (COG) and one of only 21 elite facilities in North America and three in California that has received a prestigious Phase 1 clinical trial designation to offer COG’s investigational, potentially promising and innovative clinical trials. COG is the most experienced organization in the world when it comes to the research and development of new therapeutics for children and adolescents with cancer.

“I’ve witnessed the dramatic progress made in the survival of our pediatric patients because of clinical trials,” says Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s. “Clinical trials are the mortar behind our successes here at CHOC.”

Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s
Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s

CHOC currently offers more than 140 clinical trials in varying phases, including multiple pharmaceutical industry-sponsored clinical trials. Besides membership in COG, CHOC is also a member of the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium (TACL), which offers novel treatments in Phase 1 studies for childhood leukemia and lymphoma; the Lymphoma consortium; and the UC Children, Adolescent and Young Adults Cancer Consortium, which includes all of the University of California pediatric oncology programs.

Among the research at CHOC is an upcoming clinical trial for the treatment of diffuse intrinsic pontine glioma (DIPG), a highly aggressive and one of the most difficult-to-treat childhood tumors.

“We are in the process of opening and initiating this clinical trial which, in my opinion, will be extremely important for patients in the future,” Dr. Kirov says. “DIPG is a brainstem tumor which is universally deadly, and very few patients survive more than a year, or even six months. CHOC, the Dana-Farber Cancer Institute in Boston and Lurie Children’s Hospital in Chicago are the only three sites where this new study will be offered. This study will explore a new vaccine for the treatment of DIPG in combination with checkpoint inhibitors. We’re hoping this study will be open in the next several months to offer hope to patients with this disease.”

While clinical research is fundamental to advancing pediatric oncology treatments, Dr. Kirov said the trials themselves are only part of CHOC’s comprehensive approach to helping children and young adults survive cancer.

“These cutting-edge medications and products we are testing, including new targeting agents, monoclonal antibodies and various types of small molecules and vaccines, for example, require an extremely strong supportive and clinical research infrastructure, which CHOC can offer,” says Dr. Kirov. “Our highly educated clinical research coordinators, physicians-scientists, nurses, educators, pharmacists, and other professionals, along with our unparalleled supportive services for both patients and their families, such as social workers, psychologists, child life specialists, palliative care experts and spiritual services, make our patients’ experiences at CHOC unique, and I think this is why CHOC truly stands out. In fact, many patients who come to CHOC for Phase 1 studies express their desire to stay here even after the study is completed, which really speaks very highly of CHOC and the continuum of care and support we provide to young patients and their families.”

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 cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.

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 Children’s 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 Children’s 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 Children’s
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 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.