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2017: A banner year for innovation at Children’s National

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In 2017, clinicians and research faculty working at Children’s National Health System published more than 850 research articles about a wide array of topics. A multidisciplinary Children’s Research Institute review group selected the top 10 articles for the calendar year considering, among other factors, work published in high-impact academic journals.

“This year’s honorees showcase how our multidisciplinary institutes serve as vehicles to bring together Children’s specialists in cross-cutting research and clinical collaborations,” says Mark L. Batshaw, M.D., Physician-in-Chief and Chief Academic Officer at Children’s National. “We’re honored that the National Institutes of Health and other funders have provided millions in awards that help to ensure that these important research projects continue.”

The published papers explain research that includes using imaging to describe the topography of the developing brains of infants with congenital heart disease, how high levels of iron may contribute to neural tube defects and using an incisionless surgery method to successfully treat osteoid osteoma. The top 10 Children’s papers:

Read the complete list.

Dr. Batshaw’s announcement comes on the eve of Research and Education Week 2018 at Children’s National, a weeklong event that begins April 16, 2018. This year’s theme, “Diversity powers innovation,” underscores the cross-cutting nature of Children’s research that aims to transform pediatric care.

William Gaillard

Putting childhood epilepsy in the spotlight at American Epilepsy Society Meeting

William Gaillard

“We aim to build the evidence base for treatments that are effective specifically for children with epilepsy,” says William D. Gaillard, M.D., chief of Child Neurology, Epilepsy and Neurophysiology, and director of the Comprehensive Pediatric Epilepsy Program.

While epilepsy affects people of all ages, the unique way it manifests in infants, children and adolescents can be attributed in part to the complexities of the growing and developing brain. Researchers from the Children’s National Comprehensive Pediatric Epilepsy Program brought their expertise on the challenges of understanding and treating epilepsy in children to the recent American Epilepsy Society Annual Meeting, the largest professional gathering on epilepsy in the world.

“We aim to build the evidence base for treatments that are effective specifically for children with epilepsy,” says William D. Gaillard, M.D., chief of Child Neurology, Epilepsy and Neurophysiology, and director of the Comprehensive Pediatric Epilepsy Program. “We have learned much from studies in adult populations but technologies like functional MRI allow us to get in-depth understanding, often in non-invasive ways, of precisely how epilepsy is impacting a child.”

Dr. Gaillard was also recently elected to serve as the Second Vice President of the American Epilepsy Society. “The AES is the largest multidisciplinary professional and scientific society dedicated to the understanding, treatment and eradication of epilepsy and associated disorders, and I am honored to serve as the new Second Vice President,” he said.

The team’s presentations and poster sessions focused on several key areas in pediatric epilepsy:

Better ways to see, measure and quantify activity and changes in the brain for children with epilepsy before, during and after surgery

  • Novel applications of fMRI for children with epilepsy
    • Evaluation of an fMRI tool that tracks verbal and visual memory in children with epilepsy – one of the first to capture memory functions in this population of children using noninvasive fMRI;
    • Early study of the use of “resting-state” fMRI to map language skills before epilepsy surgery – an important first step toward noninvasively evaluating children who are too young or neurologically impaired to follow tasks in traditional MRI studies;
  • A study of whether intraoperative MRI, i.e. imaging during neurosurgery, allows for more complete removal of abnormal brain tissue associated with focal cortical dysplasia in children, which is a common cause of intractable epilepsy;
  • A preliminary case review of existing data to see if arterial spin labeling MRI, which measures blood flow to the brain, has potential to identify blood flow changes in specific locations of the brain where seizures occur;
  • An analysis of language laterality – the dominant side of the brain controlling language –  questioning the true reasons that the brains of children with epilepsy have differences in the hemisphere that predominantly controls language;
  • A review of some common assessments of language and working memory that are used pre- and post-operatively to gauge the impacts of pediatric epilepsy surgery. The study found that using multiple assessments, and studying results individually rather than as a group average, resulted in a more complete picture of the outcomes of surgery on these areas of brain function;
  • A preliminary study examining whether continuous EEG monitoring of neonates with hypoxic ischemic encephalopathy, or lack of oxygen to the brain, can be a reliable predictor of neurodevelopmental outcomes while the infant is undergoing therapeutic hypothermia.

“In order to expand our understanding of causes, impacts and outcomes, the range of research is broad given the complexity of epilepsym,” says Madison M. Berl, Ph.D. “This is the only way we can contribute to the goal of providing our colleagues and the families they serve with better resources to make informed decisions about how best to assess and treat pediatric epilepsy.”

The molecular, genetic and biological factors that contribute to onset and severity of pediatric epilepsy

  • A retrospective study of young patients with malformations in cortical development that are important causes of childhood epilepsy;
  • Investigation of a simple saliva test to effectively identify the presence of two common viral infections, human herpesvirus-6B and Epstein-Barr virus, that may be contributors to onset of epilepsy in otherwise normally functioning brains;
  • A preliminary review of the possible relationship between febrile infection-related epilepsy syndrome and the co-occurrence of another neuro-inflammatory condition – hemophagocytic lymphohistiocytosis.

Madison Berl, Ph.D., director of research in the Division of Pediatric Neuropsychology, and a pediatric neuropsychologist in the Comprehensive Pediatric Epilepsy Program, adds, “In order to expand our understanding of causes, impacts and outcomes, the range of research is broad given the complexity of epilepsy. This is the only way we can contribute to the goal of providing our colleagues and the families they serve with better resources to make informed decisions about how best to assess and treat pediatric epilepsy.”

Oluigbo and Myseros neurosurgery

Working miracles to control seizures and preserve brain power in newborns

Oluigbo and Myseros neurosurgery

In the spring of 2017, a multidisciplinary team applied an innovative approach to help preserve function in the working right hemisphere of a baby who experienced her first seizure hours after birth.

When orderly early fetal brain development is disturbed in one half of the brain, infants can be born with hemimegalencephaly—a rare occurrence—that results in one of the brain’s two hemispheres being oversized, heavy and malformed. This brain malformation arises early in the fetal period of life, is not inherited and is associated with seizures early in life.

Children with hemimegalencephaly can develop horrible seizures within the first hours or days of life. According to published research, every month these infants experience uncontrolled seizures correlates to a steep decline in IQ.

Because these types of seizures do not respond to multiple anti-seizure medications—medicines which may also cause worrisome side effects of their own in neonates—care teams attempt to schedule surgery as soon as feasible to remove or disconnect the hemisphere triggering the damaging seizures. “The ‘bad’ brain does not sustain any function and it interferes with the ‘good’ brain doing what it needs to do,” says William D. Gaillard, M.D., chief of Children’s division of Epilepsy and Neurophysiology and chief of Neurology.

Hemispherectomy is intricate surgery on an organ that is softer than normal and crisscrossed with a tangle of blood vessels that supply the damaged hemisphere with blood. Because of the risks of life-threatening blood loss in very young infants, the dramatic surgery is usually not performed until babies are at least 3 months old and weigh at least 10 pounds.

The challenge: The vulnerable babies who most need relief, infants who have been seizing since early life, are too young for the operation.

Neurosurgeons have clamped the carotid artery that supplies blood to the brain to minimize blood loss when the hemisphere is surgically removed. Dr. Gaillard says knowledge of that approach led the team to think: What if we use embolization—blocking blood supply to targeted locations in the brain—to achieve the same effect?  The plan effectively destroys the malformed brain from within, neutralizing its ability to cause the seizures.

“It was eye-opening for us to think about actually inflicting brain injury as a way of treating something in the brain that was causing seizures. That is really novel in itself: We’re thinking out of the box in applying existing techniques in a different age group. The conventional thinking with newborns is to let them be; their seizures don’t look that bad,” says Taeun Chang, M.D., director of Children’s Neonatal Neurology and Neonatal Neurocritical Care Program.

“We have evidence to suggest this is a safe and effective way of avoiding recurrent seizures and minimizing the need to give these infants potentially toxic medications so early in life. Ultimately, this helps a select group of babies who need the surgery to get to the point of being old enough to have it—all the while, sparing the healthy part of their brain,” Dr. Gaillard adds.

Darcy hemimegalencephaly

Once the embolization ended Darcy’s most severe seizures, the little girl could make eye contact, started smiling, and then graduated from smiling to full laughs. In weekly physical therapy, the infant works on tummy time, head control and ensuring her eyes track.

In the spring of 2017, the multidisciplinary team applied the innovative approach to help preserve function in the working right hemisphere of a baby named Darcy Murphy. Darcy experienced her first seizure hours after she was born, and when she arrived at Children’s National had been in and out of two different emergency rooms in another state for the first few weeks of her life.

The team explained to the Murphy family that Darcy was on multiple medications, but her seizures continued unabated. The options included inducing a coma, sending Darcy home despite ongoing seizures or minimally invasive embolization.

“We would not have even posed this if we were not confident in our ability to do the procedure and deal with potential complications,” Dr. Chang says.

“Oh my gosh, as a parent you know what you’re doing is permanent,” says Rachel Murphy, 29, Darcy’s mom said of the decisions that she and husband Ryan, 33, faced for the youngest of their three children. “What if it’s not the right decision? What if in a week they come out with a new procedure you could have done? We were horrified all the time. The nice part with this procedure is the reward is apparent very quickly, and it just gets better. You don’t have to wait two years to know you made the right decision. You can see half a brain is better than the whole thing for this specific child.”

Once the embolization ended Darcy’s most severe seizures, the little girl could initiate and maintain eye contact with family members, started smiling and then graduated from smiling to full laughs. In weekly physical therapy, the infant works on tummy time, head control and ensuring her eyes track.

Children’s multidisciplinary care team includes experts in newborn intensive care (neonatologists) to aggressively manage seizures in the traditional fashion as they occur and to monitor vital signs; a neonatal neurologist/neurointensivist at the bedside and in the Angio suite monitoring Darcy’s brain activity; a neonatal epileptologist; a surgical epilepsy team; an interventional neuroradiologist; neurosurgeons to perform the delicate functional hemispherectomy to remove any residual brain tissue from the bad hemisphere; and physical therapists working to help Darcy achieve maximum function after surgery.

“We were just like one unit in the sense of being able to provide coherent, comprehensive care. It’s about blood pressure management, breathing, electrolytes, making sure everything is right for going to the operating room,” Dr. Chang explains. “Darcy’s case highlights the ways in which Children’s National is different and offers personalized care that is superior to other centers.”

The team, which recently published a case report of two previous serial embolizations followed by hemispherectomy, plans follow-up papers describing EEG manifestations during an acute stroke in a newborn, advice to the field on best practices for the embolization and using cooling to control the planned brain injury during embolization hemispherectomy.

Revised Nov. 7, 2017

Related resources

Chima Oluigbo

A novel way to treat intractable epilepsy caused by hemimegalencephaly

Chima Oluigbo

A multidisciplinary team led by Chima Oluigbo, M.D., F.R.C.S.C., pioneered a novel technique to preserve newborns’ healthy brain tissue, buying time until the infants became old enough to undergo a hemispherectomy.

What’s known

Hemimegalencephaly is an extremely rare birth defect in which one side of the brain grows larger than the other. This anomaly typically leads to severe, recurrent seizures that can be difficult to control solely with medications. While the seizures themselves are detrimental to the developing brain, the amount of medications used to reduce seizure frequency often come with significant side effects and have the potential to hamper brain growth. Hemispherectomy, a radical surgery in which one half of the brain is removed, is often the most successful way to treat severe and intractable epilepsy. However, this surgery can be challenging to perform successfully in very young babies.

What’s new

In this case report, the Children’s National Health System Epilepsy Team led by Chima Oluigbo, M.D., F.R.C.S.C., a pediatric neurosurgeon; Tammy N. Tsuchida, M.D., PhD., a pediatric surgical epileptologist; Monica Pearl, M.D., a pediatric interventional neuroradiologist; Taeun Chang, M.D., a neonatal neurointensivist; and the neonatal intensive care team explored the possibility of using minimally invasive surgery to cut off the blood supply to the brain hemisphere responsible for generating seizures in newborns with hemimegalencephaly. This procedure, they reasoned, could buy time for babies to mature and become more resilient to withstand the future hemispherectomy while also lessening the damage caused by uncontrolled, recurrent seizures. The case report focused on the first two patients with hemimegalencephaly who had sequential procedures to gradually restrict blood flow to the affected brain hemisphere within their first few weeks of life, followed by hemispherectomies at a few months of age. This novel approach significantly lessened their seizures until hemispherectomy, allowing these children to continue to grow and develop seizure-free.

Questions for future research

Q: Which patients are best suited for this surgical procedure?
Q: How can surgeons reduce the risk of excessive blood loss during hemispherectomy caused by the growth of additional blood vessels after flow through the brain’s major vessels has been blocked?
Q: What are the long-term outcomes for infants who undergo these procedures?

Source: “ ‘Endovascular embolic hemispherectomy’: A strategy for the initial management of catastrophic holohemispheric epilepsy in the neonate.” Oluigbo, C., M.S. Pearl, T.N. Tsuchida, T. Chang, C.-Y. Ho and W. D. Gaillard. Published by Child’s Nervous System October 29, 2016.