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brain network illustration

$2.5M to protect the brain from metabolic insult

brain network illustration

The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, which makes this organ particularly vulnerable to changes in metabolism.

More than 30 million Americans have diabetes, with the vast majority having Type 2 disease. Characterized by insulin resistance and persistently high blood sugar levels, poorly controlled Type 2 diabetes has a host of well-recognized complications: compared with the general population, a greatly increased risk of kidney disease, vision loss, heart attacks and strokes and lower limb amputations.

But more recently, says Nathan A. Smith, MS, Ph.D., a principal investigator in Children’s National Research Institute’s Center for Neuroscience Research, another consequence has become increasingly apparent. With increasing insulin resistance comes cognitive damage, a factor that contributes significantly to dementia diagnoses as patients age.

The brain comprises only 2% of the body’s volume, but it uses more than 20% of its energy, Smith explains – which makes this organ particularly vulnerable to changes in metabolism. Type 2 diabetes and even prediabetic changes in glucose metabolism inflict damage upon this organ in mechanisms with dangerous synergy, he adds. Insulin resistance itself stresses brain cells, slowly depriving them of fuel. As blood sugar rises, it also increases inflammation and blocks nitric oxide, which together narrow the brain’s blood vessels while also increasing blood viscosity.

When the brain’s neurons slowly starve, they become increasingly inefficient at doing their job, eventually succumbing to this deprivation. These hits don’t just affect individual cells, Smith adds. They also affect connectivity that spans across the brain, neural networks that are a major focus of his research.

While it’s well established that Type 2 diabetes significantly boosts the risk of cognitive decline, Smith says, it’s been unclear whether this process might be halted or even reversed. It’s this question that forms the basis of a collaborative Frontiers grant, $2.5 million from the National Science Foundation split between his laboratory; the lead institution, Stony Brook University; and Massachusetts General Hospital/Harvard Medical School.

Smith and colleagues at the three institutions are testing whether changing the brain’s fuel source from glucose to ketones – byproducts from fat metabolism – could potentially save neurons and neural networks over time. Ketones already have shown promise for decades in treating some types of epilepsy, a disease that sometimes stems from an imbalance in neuronal excitation and inhibition. When some patients start on a ketogenic diet – an extreme version of a popular fat-based diet – many can significantly decrease or even stop their seizures, bringing their misfiring brain cells back to health.

Principal Investigator Smith and his laboratory at the Children’s National Research Institute are using experimental models to test whether ketones could protect the brain against the ravages of insulin resistance. They’re looking specifically at interneurons, the inhibitory cells of the brain and the most energy demanding. The team is using a technique known as patch clamping to determine how either insulin resistance or insulin resistance in the presence of ketones affect these cells’ ability to fire.

They’re also looking at how calcium ions migrate in and out of the cells’ membranes, a necessary prerequisite for neurons’ electrical activity. Finally, they’re evaluating whether these potential changes to the cells’ electrophysiological properties in turn change how different parts of the brain communicate with each other, potentially restructuring the networks that are vital to every action this organ performs.

Colleagues at Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and Harvard Medical School, led by Principal Investigator Eva-Maria Ratai, Ph.D.,  will perform parallel work in human subjects. They will use imaging to determine how these two fuel types, glucose or ketones, affect how the brain uses energy and produces the communication molecules known as neurotransmitters. They’re also investigating how these factors might affect the stability of neural networks using techniques that investigate the performance of these networks both while study subjects are at rest and performing a task.

Finally, colleagues at the Laufer Center for Physical and Quantitative Biology at Stony Brook University, led by Principal Investigator Lilianne R. Mujica-Parodi, Ph.D., will use results generated at the other two institutions to construct computational models that can accurately predict how the brain will behave under metabolic stress: how it copes when deprived of fuel and whether it might be able to retain healthy function when its cells receive ketones instead of glucose.

Collectively, Smith says, these results could help retain brain function even under glucose restraints. (For this, the research team owes a special thanks to Mujica-Parodi, who assembled the group to answer this important question, thus underscoring the importance of team science, he adds.)

“By supplying an alternate fuel source, we may eventually be able to preserve the brain even in the face of insulin resistance,” Smith says.

Andrea Gropman

$5M in federal funding to help patients with urea cycle disorders

Andrea Gropman

Andrea L. Gropman, M.D.: We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.

An international research consortium co-led by Andrea L. Gropman, M.D., at Children’s National Hospital has received $5 million in federal funding as part of an overall effort to better understand rare diseases and accelerate potential treatments to patients.

Urea cycle disorder, one such rare disease, is a hiccup in a series of biochemical reactions that transform nitrogen into a non-toxic compound, urea. The six enzymes and two carrier/transport molecules that accomplish this essential task reside primarily in the liver and, to a lesser degree, in other organs.

The majority of patients have the recessive form of the disorder, meaning it has skipped a generation. These kids inherit one copy of an abnormal gene from each parent, while the parents themselves were not affected, says Dr. Gropman, chief of the Division of Neurodevelopmental Pediatrics and Neurogenetics at Children’s National. Another more common version of the disease is carried on the X chromosome and affects boys more seriously that girls, given that boys have only one X chromosome.

Regardless of the type of urea cycle disorder, when the urea cycle breaks down, nitrogen converts into toxic ammonia that builds up in the body (hyperammonemia), particularly in the brain. As a result, the person may feel lethargic; if the ammonia in the bloodstream reaches the brain in high concentrations, the person can experience seizures, behavior changes and lapse into a coma.

Improvements in clinical care and the advent of effective medicines have transformed this once deadly disease into a more manageable chronic ailment.

“It’s gratifying that patients diagnosed with urea cycle disorder now are surviving, growing up, becoming young adults and starting families themselves. Twenty to 30 years ago, this never would have seemed conceivable,” Dr. Gropman says. “We have collected many years of longitudinal clinical data, but with this new funding now we can answer questions about these diseases that are meaningful on a day-to-day basis for patients with urea cycle disorders.”

In early October 2019, the National Institutes of Health (NIH) awarded the Urea Cycle Disorders Consortium for which Dr. Gropman is co-principal investigator a five-year grant. This is the fourth time that the international Consortium of physicians, scientists, neuropsychologists, nurses, genetic counselors and researchers has received NIH funding to study this group of conditions.

Dr. Gropman says the current urea cycle research program builds on a sturdy foundation built by previous principal investigators Mendel Tuchman, M.D., and Mark Batshaw, M.D., also funded by the NIH. While previous rounds of NIH funding powered research about patients’ long-term survival prospects and cognitive dysfunction, this next phase of research will explore patients’ long-term health.

Among the topics they will study:

Long-term organ damage. Magnetic resonance elastrography (MRE) is a state-of-the-art imaging technique that combines the sharp images from MRI with a visual map that shows body tissue stiffness. The research team will use MRE to look for early changes in the liver – before patients show any symptoms – that could be associated with long-term health impacts. Their aim is spot the earliest signs of potential liver dysfunction in order to intervene before the patient develops liver fibrosis.

Academic achievement. The research team will examine gaps in academic achievement for patients who appear to be underperforming to determine what is triggering the discrepancy between their potential and actual scholastics. If they uncover issues such as learning difficulties or mental health concerns like anxiety, there are opportunities to intervene to boost academic achievement.

“And if we find many of the patients meet the criteria for depression or anxiety disorders, there are potential opportunities to intervene.  It’s tricky: We need to balance their existing medications with any new ones to ensure that we don’t increase their hyperammonemia risk,” Dr. Gropman explains.

Neurologic complications. The researchers will tap continuous, bedside electroencephalogram, which measures the brain’s electrical activity, to detect silent seizures and otherwise undetectable changes in the brain in an effort to stave off epilepsy, a brain disorder that causes seizures.

“This is really the first time we will examine babies’ brains,” she adds. “Our previous imaging studies looked at kids and adults who were 6 years and older. Now, we’re lowering that age range down to infants. By tracking such images over time, the field has described the trajectory of what normal brain development should look like. We can use that as a background and comparison point.”

In the future, newborns may be screened for urea cycle disorder shortly after birth. Because it is not possible to diagnose it in the womb in cases where there is no family history, the team aims to better counsel families contemplating pregnancy about their possible risks.

Research described in this post was underwritten by the NIH through its Rare Diseases Clinical Research Network.

Bella when she was sick

Preserving brain function by purposely inducing strokes

Bella when she was sick

Born to young parents, no prenatal testing had suggested any problems with Bella’s brain. But just a few hours after birth, Bella suffered her first seizure – one of many that would follow in the ensuing days. After brain imaging, her doctors in Iowa diagnosed her with hemimegalencephaly.

Strokes are neurologically devastating events, cutting off life-sustaining oxygen to regions of the brain. If these brain tissues are deprived of oxygen long enough, they die, leading to critical loss of function – and sometimes loss of life.

“As physicians, we’re taught to prevent or treat stroke. We’re never taught to inflict it,” says Taeun Chang, M.D., director of the Neonatal Neurology and Neonatal Neurocritical Care Program at Children’s National Hospital.

That’s why a treatment developed at Children’s National for a rare brain condition called hemimegalencephaly is so surprising, Dr. Chang explains. By inflicting controlled, targeted strokes, Children’s National physician-researchers have treated five newborns born with intractable seizures due to hemimegalencephaly before they’re eligible for epilepsy surgery, the standard of care. In the four surviving infants, the procedures drastically reduced or completely relieved the infants of hemimegalencephaly’s characteristic, uncontrollable seizures.

The most recent patient to receive this life-changing procedure is Bella, a 13-month-old from Iowa whose treatment at Children’s National began within her second week of life. Born to young parents, no prenatal testing had suggested any problems with Bella’s brain. But just a few hours after birth, Bella suffered her first seizure – one of many that would follow in the ensuing days. After brain imaging, her doctors in Iowa diagnosed her with hemimegalencephaly.

A congenital condition occurring in just a handful of children born worldwide each year, hemimegalencephaly is marked by one brain hemisphere growing strikingly larger and dysplastic than the other, Dr. Chang explains. This abnormal half of the brain is highly vascularized, rippled with blood vessels needed to support the seizing brain. The most conspicuous symptoms of hemimegalencephaly are the numerous seizures that it causes, sometimes several in the course of an hour, which also may prevent the normal half of the brain from developing and learning.

Prior studies suggest early surgery achieves better developmental outcomes with one study reporting as much as a drop of 10-20 IQ points with every month delay in epilepsy surgery.

The standard treatment for unilateral megalencephaly is a dramatic procedure called a hemispherectomy, in which surgeons remove and disconnect the affected half of the brain, allowing the remaining half to take over its neurological duties. However, Dr. Chang says, implementing this procedure in infants younger than 3 months of age is highly dangerous.  Excessive, potentially fatal blood loss is likely in infants younger than 3 months who have a highly vascularized brain in the setting of an immature coagulation system. That leaves their doctors with no choice but to wait until these infants are at least 3 months old, when they are more likely to survive the surgery.

However, five years ago, Dr. Chang and her colleagues came up with a different idea when a newborn continued to have several seizures per hour despite multiple IV seizure medications: Because strokes cause irreversible tissue death, it might be possible to effectively incapacitate the enlarged hemisphere from within by inflicting a stroke on purpose. At the very least, this “functional embolization” might buy time for a traditional hemispherectomy, and slow or halt ongoing brain damage until the infants are able to withstand surgery. Ideally, this procedure may be all some children need, knocking out the offending hemisphere completely so they’d never need a hemispherectomy, which has late complications, such as hydrocephalus.

A pediatrician friend of Bella’s paternal grandparents read a story on Children’s National website about Darcy, another baby who’d received functional embolization a year earlier and was doing well. She contacted Dr. Chang to see if the procedure would be appropriate for Bella.

Within days, Bella and her family headed to Washington, D.C., to prepare for functional embolization herself. Within the first weeks of life, Bella underwent three separate procedures, each three to four hours long. Under real-time fluoroscopic and angiographic guidance, interventional neuroradiologist Monica Pearl, M.D., threaded a micro-catheter up from the baby’s femoral artery through the complex network of blood vessels all the way to her brain. There, in targeted branches of her cerebral arteries, Dr. Pearl strategically placed liquid embolic agent to obstruct blood flow to the abnormal half of Bella’s brain.

Immediately after the first procedure, the team had to contend with the same consequences that come after any stroke: brain swelling that can cause bleeding and herniation, complicated further by the already enlarged hemisphere of Bella’s brain. Using neuroprotective strategies learned from treating hundreds of brain-injured newborns, the neonatal neurocritical care team and the neonatal intensive care unit (NICU) minimized the brain swelling and protected the normal half of the brain by tightly controlling the brain temperature, her sugar and electrolyte levels, her blood pressure and coagulation system.

As the brain tissue in the oversized hemisphere died, so did the seizures that had plagued Bella since birth. She has not had a seizure since she left Children’s National more than one year ago. Her adoptive parents report that Bella is hitting many of the typical developmental milestones for her age: She’s getting ready to walk, blowing kisses and saying a few words. Physical, speech and occupational therapy will keep her moving in the right direction, Dr. Chang says.

“We believe that Children’s National is the only place in the world that’s treating newborns in this way to preserve their futures,” Dr. Chang says. “We’re privileged to be able to care for Bella and other kids with this rare condition.”

Bella’s transfer and successful procedures required the support and collective efforts of many within the hospital organization including William D. Gaillard, M.D., and his surgical epilepsy team; interventional neuroradiology with Dr. Monica Pearl; Neurosurgery; Neonatology and the NICU; social work; and even approval from Robin Steinhorn, M.D., senior vice president of the Center for Hospital-Based Specialties, and David Wessel, M.D., executive vice president and Chief Medical Officer.

“While obvious credit goes to the medical team who saved Bella’s future and the neonatal intensive care nurses who provided exceptional, intensive, one-on-one care, Bella’s team of supporters extend to all levels within our hospital,” Dr. Chang adds.

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Bella's brain scan

Born with hemimegalencephaly, Bella now has a bright future

bella's brain scans

Bella was born with a rare condition (hemimegalencephaly) in which one half of the brain developed abnormally, causing seizures. The textbook approach is to let babies grow big enough for a dramatic surgery. But Bella’s left hemisphere was triggering so many seizures each hour that waiting would mean her life would be defined by severe disability. Children’s National Hospital is believed to be the only center in the world that calms these seizures through controlled strokes.

Procedure one occurred five days after Bella came to Children’s National Hospital from Iowa, when she was 13 days old. The team first optimized control of her seizures and obtained special magnetic resonance images to plan their approach. They glued up the branches of the left posterior cerebral artery and branches of the left middle cerebral artery. Bella had a tiny bleed that was controlled immediately in the angio suite and afterwards in the Children’s National neonatal intensive care unit.

Procedure two occurred 10 days later when Bella was 23 days old. The team waited until brain swelling had subsided and brain tissue loss had occurred from the first procedure. This time, they glued up the remaining branches of the left posterior cerebral artery and some branches of the left anterior cerebral artery.

The third and final procedure was done nine days later when Bella was 29 days old.  This time the team glued and coiled, placing little wire coils where it was unsafe to use glue, getting at the remaining small and numerous branches that remained of the left anterior cerebral artery.

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banner year

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

banner year

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 epilepsy,” 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.