Inside Pediatrics, Neurology & Neurosurgery

Advanced Imaging Enables Complex Surgeries for Epilepsy

If you’re going to conduct surgery on the brains of children with severe epilepsy, you better know what type they have, where they have it, and how it affects function.  

That’s where functional imaging comes in, including single-photon emission computerized tomography (SPECT), functional MRI (fMRI), positron emission tomography (PET), and magnetoencephalography (MEG). Most neurosurgical centers have one or two; but Children’s of Alabama has them all.  

“This is important,” said pediatric neurosurgeon Jeffrey P. Blount, M.D., “because there is never perfect alignment between the studies.” With multiple studies, however, comes greater certainty about the brain regions the disease impacts, which provides greater certainty about which parts to remove during surgery. Agreement between the scans is called “concordance,” and it is the central concept in epilepsy localization, said Dr. Blount.  

Most patients who require epilepsy surgery also require an invasive monitoring system prior to surgery, said neurosurgeon Curtis J. Rozzelle, M.D. In the past, he explained, that required an open cranial exposure to place electrodes on the surface of the brain and, sometimes, within the brain. 

But with newer techniques, particularly stereoelectroencephalography (SEEG), a minimally invasive surgical procedure used to precisely find the areas of the brain where seizures originate, surgeons can place an array of depth electrodes without performing a craniotomy. Instead, each electrode is placed robotically through a tiny hole drilled in the skull using a robotic stereotactic approach. “That relies very heavily on high-resolution scans,” Dr. Rozelle said, including fusing CT and MRI images, to put the electrodes in without damaging a critical part of the brain. 

“Mostly what we’re trying to avoid is hitting blood vessels with the depth electrodes while getting an array of electrodes that will cover the area of interest,” Dr. Rozelle said. The functional imaging studies are critical in establishing the target zones. Plus, since MEG and fMRI are based on magnetic field fluctuations, the MEG images can be mapped onto the MRI scan in three dimensions. The older technique, in which electrodes were placed on the surface of the brain, only provided a two-dimensional image. 

The child spends several days with the implanted electrodes to capture data about the seizures, which a neurologist then analyzes to identify the exact area of the brain that requires treatment. That surgery itself also relies heavily on high-resolution imaging. A laser ablation, for instance, is performed in the MRI scanner. A larger-volume surgery that requires open resection also relies on imaging because the surgical target looks the same as the normal brain. “To help us ensure that we hit the target, we can map the neurologist analysis into a navigation system that directs us to the right area,” Dr. Rozzelle said. “That ensures that we remove the tissue we need to take out and keep everything else intact.” 

Neurosurgeons at Children’s perform about 50 cranial epilepsy procedures a year, of which about 30 require the invasive monitoring. 

“We are very fortunate to work in a center where we have so much high-quality functional imaging available on a single campus,” said Dr. Blount. 

Inside Pediatrics, Neurology & Neurosurgery

Addressing Post-Traumatic Syndrome Disease from Hydrocephalus

Hydrocephalus-Doctor-Brain-Scans-Resized-V2

Children’s of Alabama neurosurgeon Brandon Rocque, M.D.

It’s not surprising that kids with brain tumors and their parents experience a significant amount of stress and psychological distress during the acute post-diagnosis period. It even has a name: pediatric medical traumatic stress. As Children’s of Alabama neurosurgeon Brandon Rocque, M.D., studied this phenomenon a few years ago, it occurred to him that it would almost certainly apply to children with hydrocephalus. 

“We know that just encountering doctors or the medical system can be traumatic for children,” said Dr. Rocque. “For children, just coming to the hospital can be traumatic enough to trigger post-traumatic stress disorder,” or PTSD. 

Numerous factors contribute to stress, particularly the perceived threat to the child’s life. “Even if there isn’t a threat, the child perceives it as such,” Dr. Rocque said. Add to that separation from their parents, uncertainty about the outcome, and the unpredictability of a serious medical condition. “That describes hydrocephalus extremely well,” he said, because these children are treated with shunts that could become blocked at any time requiring additional medical interventions.  

Symptoms of shunt failure can vary widely. Some children simply have a mild headache; other patients can become extremely sick and be in danger of death within a couple of hours. By age 10, “the average child [with hydrocephalus] has had at least two shunt replacements. This is always hanging over the families,” Dr. Rocque said, putting them and their children at high risk for PTSD. 

To test his hypothesis, Dr. Rocque introduced a screening survey into the hydrocephalus clinic to screen for PTSD as well as anxiety, depression, fatigue and resilience. “We found that, overall, the kids with hydrocephalus are doing pretty well. But the parents are not doing so well,” he said. About one in five parents met the diagnostic criteria for PTSD based on their symptoms. More than half attributed it to their child’s condition.  

So why aren’t the kids as affected? One reason, Dr. Rocque said, is that the children don’t know anything different. They’ve lived their entire lives with the condition and the shunts. “But for parents, there was always something new and the risk that something bad is going to happen to their child,” he said.  

Not all the kids surveyed were fine, however. “Some had issues with PTSD, and those were the ones coming to the hospital more. Those whose shunts weren’t behaving well,” Dr. Rocque said. “We need to be aware that these kids have a higher risk for PTSD.”  

They also found that the children and their patients tested exhibited very little resilience, which can help protect against PTSD.  

A survey conducted in conjunction with the Hydrocephalus Association confirmed their findings.  

Dr. Rocque and his team are now working with the association to develop a program to help reduce the risk of PTSD in patients and their families and with a psychologist who is also the mother of an adult with hydrocephalus to develop a tool to help build resilience in patients and their families.  

“This is the first time anyone has really focused on the psychological comorbidities of this condition,” Dr. Rocque said. “I think it has the potential to have a big effect in our population.” 

Inside Pediatrics, Neurology & Neurosurgery

Exploring the Brain from the Inside Out

Pediatric neurointerventional radiology is a small but growing specialty, one increasingly in use given the growing number of endovascular procedures performed in children with neurovascular conditions. “It’s a niche specialty,” says Jesse Jones, M.D., Children’s of Alabama Chief of Neurointervention. “A lot of doctors don’t know about it—let alone patients.”  

Dr. Jones is part of the hospital’s vascular anomalies team, one of the largest pediatric vascular anomalies programs in the Southeast and the only one in Alabama. He works with an interdisciplinary team of experts specializing in the diagnosis, treatment and ongoing care of all vascular anomalies and is part of the team’s monthly clinic. 

On the adult side, neurointerventional radiologists spend a lot of time removing blood clots from stroke patients. But stroke is rarer in children. The hospital’s neurosurgeons and neurologists more often call on Dr. Jones to evaluate congenital anomalies, including vein of Galen malformation or arteriovenous malformations (AVM), as well as inflammatory disorders like vasculitis or obliterative vasculopathy. “It’s when a child presents with dangerous or unusual neurovascular findings and the team is trying to characterize it and plan future treatment that I come in,” he said. 

Dr. Jones, who completed a residency and two fellowships, uses minimally invasive techniques to diagnose and treat numerous neurovascular conditions, including stroke and AVM, but also aneurysms, and lympho-vascular proliferations of the head and neckThe beauty of his approach is that it helps avoid open incisions, reducing the risk of complications and enabling kids to go home sooner. 

His interest in pediatric medicine started with his grandfather, who was a pediatrician. “I looked up to the work he did treating children,” Dr. Jones said. “Working with adults can get frustrating because many conditions they have could have been avoided with lifestyle changes. But in children, they bear no responsibility.” 

Dr. Jones also knew he wanted to do something with the brain. “I’m fascinated with how the brain works,” he said. “It’s a miraculous organ and even after all these years of study still a bit of an enigma.” Being involved in a neuroscience-related field and interacting with other specialists who study the brain is intellectually stimulating, he said. “It’s the best of both worlds: I get to use my hands as an interventional radiologist and work with the brain too.” 

And, of course, work with children. 

Inside Pediatrics, Nephrology

Overflow at Children’s of Alabama’s Dialysis Unit

As the only pediatric dialysis unit in the state, Children’s of Alabama’s hemodialysis unit is used to being busy. But with COVID-19, “Our census has doubled,” said Children’s nephrologist Sahar Fathallah-Shaykh, M.D. One reason is that transplants were paused during the height of the pandemic, leaving many children who might have been able to stop dialysis forced to continue.  

Another reason is that more infants born with chronic kidney disease (CKD) are surviving because of new equipment capable of providing them dialysis. “We have seen many patients with CKD surviving who, just a few years ago, had no chance of surviving,” Dr. Fathallah-Shaykh said. Because these infants are so small, they must come to the hospital up to five times a week for the procedure, compared to three times a week for older children. Once infants are older, the team tries to transition them to peritoneal dialysis at home; but babies may have medical contraindications that require continuing on hemodialysis. 

The impact on the staff is significant, she said. “It’s a challenge.” Dialysis charge nurse Suzanne White, RN, ECP agrees. “It takes a lot of coordination to schedule treatments for 18 patients,” she said, particularly when treatment times last up to four hours. “Our days last 10 to 12 hours,” she said. 

One reason caring for infants on dialysis calls for intense attention, said Dr. Fathallah-Shayk, is that “nurses are at the bedside the entire time monitoring these babies. Babies move a lot, and if they move, the dialysis may not work as well.” The nurses console the babies, try to distract them and sometimes even hold them while they are dialyzed.  

The team includes a child life specialist who also tries to distract the infants during dialysis; social workers who support the families, including coordinating transportation and ensuring families keep their appointments; a dietician to help with nutrition and ensure proper growth; and a pharmacist to help with medications. “We all work as a team to make this happen,” Dr. Fathallah-Shayk said, “otherwise we couldn’t do it.”  

And, said White, “we have a good support system from the administration on down,” which helps avoid burnout. The unit also added more staff in anticipation of continued growth. “We are trying to coordinate their care to the best of our ability, troubleshoot and really communicate and work with each other,” she said. 

Inside Pediatrics, Nephrology

Welcoming the new PRISMAX Dialysis Machines to the PICU & CVICU

When you’re talking about continuous dialysis and plasmapheresis for sick kids, you want state-of-the-art technology. And that’s just what Children’s of Alabama got this year when hospital administrators approved a significant investment in the newest generation of the PRISMAX system for the Pediatric and Infant Center for Acute Nephrology (PICAN).  

The PICAN team is no stranger to these therapies; after all, the team has provided them for more than 500 children for over 10,000 days since 2013 in the pediatric, neonatal and cardiac intensive care units. In 2020, the newest PRISMAX became available, and Children’s became the first hospital in the state and one of the first children’s hospitals in the country to receive the new machines, said David Askenazi, M.D., who directs the PICAN. “We are very grateful to the hospital for making this available to us and our patients,” he said. “We know that patients will benefit.” 

But first, everyone had to be trained to use the new machines. While it sounds like replacing the old with the new should be a relatively simple switch, the staff required intense education. 

“The educational part of the rollout was very important,” said acute dialysis coordinator Daryl Ingram, RN, BSN, CDN. “We had to make sure the nurses and physicians were comfortable with them before they started using them on patients.” He was pleasantly surprised at how the entire team embraced the new technology and the groundbreaking opportunity the new machines offered, he said. 

One reason could be the improvements the new system brought. For instance, nurses no longer have to manually empty 5-liter effluent bags. “It definitely saves time,” said Suzanne Gurosky, RN, ECP, the dialysis charge nurse. She also touted the battery backup in the machines, which enables patients to ambulate and even do physical therapy while still connected. Another plus is the ability of the machines to decipher the cause for an alarm—because someone moved or jostled the fluids, or because there was a real issue going on. That helps avoid disruptive alarms and alarm fatigue. 

It does this through artificial intelligence, “so it understands what’s happening better than it used to,” said Dr. Askenazi.  

The new PRISMAX also sports improved safety features, such as correcting itself for fluid removal. In addition, it provides extensive data that can be integrated into the department’s quality-improvement initiatives. “We’re excited to dig into that information and incorporate it into our practice,” said Dr. Askenazi.  

After the training and the successful integration of the new PRISMAX machines into the unit, there was one more thing the team needed to do: name them. “We like to name our machines to help the kids feel more comfortable,” said Ingram. The winners were Rosie, Max, and Astro from the old “The Jetsons” cartoon, Johnny 5 from the movie “Short Circuit,” and C3PO from, of course, “Star Wars.” 

Inside Pediatrics, Nephrology

COVID-19 Infection May Leave Kids with Kidney Problems

Although children were far less likely to contract COVID-19 during the early days of the pandemic, they were affected. As of July 1, 2021, the American Academy of Pediatrics and the Children’s Hospital Association reported more than 4.04 million children had been diagnosed with COVID-19 in the United States; 50,439 in Alabama.1 Since the pandemic’s start, Children’s of Alabama has treated over 500 infants and children with COVID-19 and almost 100 with multisystem inflammatory syndrome (MIS-C), the long-term repercussions of which are just now emerging. 

Many affected children, like adults, have developed acute kidney injury (AKI) during hospitalization for severe disease, particularly children who have been hospitalized with MIS-C. One study of 152 children who had either acute COVID-19 or MIS-C found that AKI occurred in 10 percent of patients. These children had longer lengths of stay in the hospital and increased risk of other medical conditions.2 Another study of 52 patients with COVID-19 found that nearly 30 percent developed AKI.3 

“The jury is out on how much of that was due to severe illness versus how much the virus plays a direct role,” said Children’s nephrologist Erica C. Bjornstad, M.D. Some reports surmise that the virus is toxic to the kidney, but, Dr. Bjornstad said, more evidence is needed. Nonetheless, it appears that children who developed AKI while hospitalized need long-term follow-up as the long-term implications are not yet fully understood, she added. 

Thus, primary care physicians caring for these children after discharge should have a “high level of suspicion” if urine tests show high levels of protein, or children demonstrate new onset hypertension,” Dr. Bjornstad said. “They should look for COVID-19 as a culprit.” In fact, she suggests urine tests for all children who had COVID-19, even if they had a mild form of the disease, although no formal guidelines have been released. If the problem doesn’t resolve, the children should be referred to a nephrologist. “We don’t have a good handle if it goes away,” she said.  

“We’re still learning how this plays out since the pandemic is still not over,” Dr. Bjornstad said. Plus, “we don’t know what the fall holds with the Delta variant and as more people move indoors,” she added. 

Dr. Bjornstad and others at Children’s are involved with a large study that is mining an international registry of COVID-19 patients (children and adults) to tease out the effects on the kidney. Ideally, she would like to obtain funding to follow former patients for a prolonged period of time, “so we can keep learning and have data to support standard guidelines,” she said. 


1 Children and COVID-19: State-Level Data Report. American Academy of Pediatrics. July 1, 2021. Available at: https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/. Accessed July 7, 2021.

2 Basalely A, Gurusinghe S, Schneider J, et al. Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19. Clin Invest. 2021;100(1): 138-145

3 Knight, P.P., Deep, A. Save the kidneys in COVID-19. Pediatr Res (2020). https://doi.org/10.1038/s41390-020-01280-x

Inside Pediatrics, Neonatology

Bringing Evidence to Bear in the Use of Perioperative Antibiotics

Ninety percent of patients in the neonatal intensive care unit (NICU) at Children’s of Alabama will undergo a surgical procedure during their admission, putting them at risk of infections and other complications. Thus, the NICU team has been implementing performance improvement initiatives to improve outcomes, including focusing on pain control and standardizing handoffs before and after surgery. 

The most recent initiative targets perioperative antibiotic use. “The vast majority of surgical patients will require some type of antibiotic during the perioperative period,” said neonatologist Allison Black, M.D., “and we noticed there wasn’t any standard as to the dose or type of antibiotics used for each procedure.” 

That’s a problem, she said, because prolonged use of broad-spectrum antibiotics may be harmful. “It changes the infant’s gut flora, increases the risk for antibiotic-resistant infections, and may have toxicities,” she said. 

Thus, the NICU team, including physicians, nurse practitioners, and pharmacists, collaborated with the general surgeons and each surgical subspecialty to devise a solution. The surgeons collected evidence and then recommended an antibiotic as well as its dose and duration based on the specific procedure. The team used these recommendations and the evidence supporting them to create the NICU Perioperative Antibiotic Prophylaxis guidelines. 

“Now, unless there is a specific reason, all perioperative antibiotics are ordered based on these guidelines, and surgeons follow the protocol,” Dr. Black said. “It’s like clockwork.” The result is less use of prolonged empiric antibiotics and less confusion over which to use. Another advantage is less exposure to nephrotoxic drugs that can lead to acute kidney injury, she said. 

The unit’s two pharmacists ensure the protocol is followed. “Initially, it was difficult to break our decades-long habit of asking the surgeons which antibiotic they preferred and for how long after each surgical case,” said clinical pharmacist Sadie Stone, PharmD. “With the perioperative guidelines in place, we can initiate an evidence-based regimen quickly for our most common surgical procedures.”  

Since instituting the guidelines, the pharmacists have been collecting data and tracking guideline compliance. “We discuss each surgical plan with the nurse practitioner based on the guidelines when the patient returns from surgery,” said clinical pharmacist Emily Evans, PharmD. Each case is then retrospectively reviewed to determine if the procedure has an antimicrobial course included in the guidelines. If so, the actual antimicrobial course is screened against the guidelines for adherence. “These guidelines have expanded our antimicrobial stewardship role in the NICU,” she said. 

“The hope is that reduction in the use of antibiotics will decrease the need for central lines, which, in turn, also reduces the risk of infections and associated complications,” said Dr. Black. The team also tracks post-operative infection rates to ensure there is no increase. 

“This initiative again shows the improvement possible with multidisciplinary collaboration,” she said. 

Inside Pediatrics, Neonatology

Using Quality Improvement to Improve Maternal/Child Health

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Children’s of Alabama neonatologist Samuel Gentle, M.D.

Children’s of Alabama neonatologist Samuel Gentle, M.D., is passionate about the tiny babies he treats—and passionate in his belief that healthcare professionals like him can always do better. That’s why he helped start the Alabama Perinatal Quality Collaborative (ALPQC), a statewide initiative devoted to improving the quality of care for women and children. “Quality improvement is something I’ve been intrinsically drawn to,” he said. “I love the application of data science to a healthcare setting, allowing a confluence of providers to demonstrably show their efforts have impacted a patient population.”  

The collaborative’s first project in 2018 was improving birth certificate accuracy. This might sound small, but accurate vital statistics and birth data are critical ingredients to monitor population health—particularly that of women and children—solve public health problems at the local, state and federal levels; and make wise decisions about where to spend limited dollars.  

When the initiative started, just 70 percent of the 25 participating hospitals were submitting accurate birth certificates based on 11 key variables, with low reporting accuracy for individual variables such as antenatal corticosteroids, birth weight and maternal hypertension. After this quality improvement initiative, 95 percent of enrolled hospitals were submitting accurate birth certificates.  

The pandemic hit before the collaborative could launch its next project. Instead of shutting down, however, “we pivoted,” Dr. Gentle said, hosting webinars about COVID-19 and maternal and child health to share best practices from other hospitals and to “continue to evolve and learn from each other.” 

Finally, with the country returning to some version of normal, the ALPQC was ready to move on to one of its next projects: neonatal opioid withdrawal syndrome (NOWS).  “Alabama saw a 20 percent increase in overdose deaths in 2020 compared to 2019,” Dr. Gentle said. “This is a critical time to address many of the aims set forth by this initiative.” In 2016, NOWS affected 6.7 per 1,000 in-hospital births with overall hospitalization costs of $572.7 million.1 In Alabama that year, nearly 600 infants covered by Medicaid were diagnosed with NOWS, an increase of nearly 100 percent from 2010. 

Using the Institute of Health Improvement’s model for improving quality, the initiative focuses on developing and instituting standardized practices around NOWS, including reducing stigma, increasing the use of non-pharmacologic care, and providing structural support for mothers, including addiction services and medication for opioid use disorder.   

“The global aim is to optimize care for mothers and their newborns with NOWS,” Dr. Gentle said. More specifically, the ALPQC hopes to reduce length of stay and exposure to pharmacologic treatments by 20 percent; and ensure that 95 percent of families are discharged with a collaborative plan linking them to community services. The project will run in conjunction with a third ALPQC initiative to decrease rates of severe maternal morbidity associated with hypertensive disorders of pregnancy. The collaborative hopes to have results by the end of the year. 

Although the ALPQC is still gathering data, at least one hospital cut the length of stay in half for infants with NOWS, Dr. Gentle said. 

The success of such statewide improvement requires a broad group of stakeholders, he said. “This work would not be possible without our partnerships,” he added, which include the Alabama Hospital Association, the Alabama Department of Public Health and payers. He also highlighted ALPQC Program Director Evelyn Coronado-Guillaumet’s leadership, as well as the consortium of hospitals’ continued engagement. “The hospitals’ shared experience certainly accelerates the work,” he said.  

Asked what’s next on the agenda, Dr. Gentle said telecommunication-based training for neonatal resuscitation. 


1 Strahan AE, Guy GP, Bohm M, Frey M, Ko JY. Neonatal Abstinence Syndrome Incidence and Health Care Costs in the United States, 2016. JAMA Pediatr. 2020;174(2):200–202.

Inside Pediatrics, Neonatology

Focus on Feeding in the NICU

Infants in the neonatal intensive care unit (NICU) are at huge risk of problems with oral feeding, potentially requiring surgical intervention if they can’t take in the nutrition required for growth and healing.  

Historically, specialized occupational therapists evaluated and treated babies who had feeding issues at Children’s of Alabama. But today, they are joined by specialized speech therapists. 

“The addition of speech therapists with special interest in NICU patients gave us an additional caretaker with a different background and skill set,” said neonatologist Allison Black, M.D. “We took advantage of both disciplines and their specialized, yet different, training and teamed them to create the infant feeding team.” 

“The teamwork begins during the evaluation process, even performing some of the tests such as swallowing studies and fiberoptic endoscopic evaluations of swallowing together,” Dr. Black said. Having two therapists work together for these studies is a bonus, said Christy Moran, an occupational therapist who works on the feeding team.  

For instance, she said, it is quite challenging to perform a modified barium swallow on an infant. With two therapists, however, one positions the infant and serves as feeder, incorporating the techniques used to support oral feeding. The other therapist prepares the barium and watches the screen. “It is a much better study with two therapists working together, so each can focus completely on their part instead of splitting their attention between one or the other,” Moran said.  

The therapists then collaborate to form a feeding and therapy plan, which they share with the rest of the NICU team. The approach continues until the patient is discharged home. 

“The patient benefits because they get evaluated by different people at different times, both of whom are experts at feeding infants,” Dr. Black said. “This helps us get a clearer overall picture of what the infant is truly capable of since a baby’s interest in feeding can depend on the time of day and multiple other factors, all of which are constantly changing in the NICU.”  

Working as a team also enables greater support for families and caretakers, said speech-language pathologist Allie Gilbert. “Since we work so closely together, there is a rhythm to our discharge sessions,” she said, “and parents seem to appreciate having both disciplines reinforcing the same recommendations.” 

Dr. Black is now collecting data on the impact the team has on infant feeding. Anecdotally, however, she said she’s seen greater success at getting babies to take oral feeds more quickly since implementing the team concept.  

Hematology and Oncology, Inside Pediatrics

Bringing Groundbreaking Cancer Trials to Alabama Children

Left, Elizabeth Alva, M.D., and right, Katie Metrock, M.D.

Although there have been great strides in treating pediatric cancer, it remains the leading cause of death by disease among children. In addition, more than 95 percent of childhood cancer survivors have significant health-related issues because of the toxicity of current treatment options. Yet just 4 percent of government spending on cancer goes to pediatric cancer.1 

That’s why the Sunshine Project is so important. The project, part of the National Pediatric Cancer Foundation, brings together more than 20 children’s hospitals, including Children’s of Alabama, with the goal of streamlining the process required to bring new, less toxic, more effective pediatric oncology drugs to clinical practice. 

Children’s joined the consortium in 2020 and is already participating in several novel studies for some of the worst pediatric cancers. The ultimate goal is to “provide hope to families,” said Children’s oncologist Elizabeth Alva, M.D. 

One such trial is for patients newly diagnosed with metastatic fusion-positive rhabdomyosarcoma, which has a three-year, event-free survival rate of just 6 percent. “Traditionally, we inundate these patients with very intensive therapy,” said pediatric oncologist Katie Metrock, M.D., but outcomes are still dismal. Research has traditionally focused on intensifying that therapy, but sometimes that just leads to greater toxicity without improving outcomes, said Dr. Alva.  

This uniquely designed study, called the EVOLUTION trial, is based on evolutionary theories around adaptation and resistance. Patients will be enrolled into one of four arms based on shared decision-making between the family and clinicians—not randomization. The first arm is standard of care. The second arm is “first strike therapy,” which Dr. Alva compares to a “meteor hitting the Earth and killing all the dinosaurs.” This approach addresses the hypothesis that children relapse because once the chemo-sensitive cells are gone, a more resistant population emerges. “So the first-strike theory is to get rid of everything,” she said.  

A third arm focuses on maintenance, or a “second strike”: providing the standard of care until the patient is in remission and then switching to a less-intense maintenance therapy to keep those resistant cells at bay while restoring quality of life. 

The fourth arm provides adaptive therapy. This means starting with standard chemotherapy that starts and stops based on response and adaptive timing of therapy, with a goal of increased time to progression rather than complete remission.  

Children’sis also participating in a phase 2 study evaluating the use of digoxin, a decades-old drug typically used in patients with heart failure, for patients with recurrent/refractory medulloblastoma. The drug was identified as potentially beneficial in laboratory and animal studies. 

“It is exciting to think that there are well-known drugs that can be repurposed to help treat various cancers,” said Dr. Metrock. “Our hope is that the tumors will show response to digoxin, and it could potentially be added to other up-front regimens in the future.” While the drug is well tolerated in children,” she said, “we haven’t used it in this heavily pretreated population, so we need to see how our patients do with it.” 

Two other trials are exploring immunotherapy. One is testing the immunotherapy nivolumab in combination with azacitidine for children with recurrent, refractory osteosarcoma. The other is exploring a vaccine made from the patient’s own cancer cells designed to trigger the immune system to target the cancer for destruction in children with high-grade gliomas. Trials such as these are coordinated by the Clinical Trials Office at Children’s of Alabama, which was established in 2019 to increase access to new therapies for Alabama children, thanks to a lead gift from the Hugh Kaul Foundation.

Projects like the Sunshine Project are desperately needed, said Dr. Alva. “Unfortunately, pediatric cancer doesn’t get the same degree of funding as adult cancer. It’s rare, but when it strikes in a pediatric population, so many more years of life are lost.” 


1 National Pediatric Cancer Foundation. Facts about Childhood Cancer. Available at: https://nationalpcf.org/facts-about-childhood-cancer/