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Inside Pediatrics, Neurology & Neurosurgery

Epilepsy Transition Clinic Helps Adolescents Move to Adult Care 

At right, Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics. At left is epilepsy specialist Quynh Vo, M.D., of the University of Alabama at Birmingham.

At right, Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics. At left is epilepsy specialist Quynh Vo, M.D., of the University of Alabama at Birmingham.

Adolescents are not known for self-discipline. Yet that’s exactly what teens with epilepsy need in order to avoid seizure triggers, like lack of sleep and alcohol consumption. They also must be vigilant about taking their medication. However, as young people become young adults and start to manage their care independently, “these are the hardest things to do,” said Children’s of Alabama pediatric neurologist Kathryn Lalor, M.D. 

Which is why young adulthood carries a high risk of recurrent seizures, particularly as epilepsy patients transition from pediatric to adult neurology. “Many of these patients have had epilepsy for a long time, and they’ve been diagnosed and cared for by the same neurologist for a long time. It can be very scary and disconcerting to change that, especially as you’re coping with so many other things,” Dr. Lalor said. 

Then there are the difficulties on the medical side, such as electronic medical record systems that don’t talk to each other, making transitioning between providers difficult. “We were hearing from our adult colleagues that they just didn’t have the information they needed,” Dr. Lalor said. “It was like starting over with the medical history.” 

Which is why Dr. Lalor and her team started one of the first epilepsy transition clinics in the country. “We really wanted to improve the process from a logistical and informational perspective but also help guide these patients through the process.” That’s particularly important given the impact of epilepsy on daily life. “It affects school, being able to drive, your job,” she said. “And we really wanted to be a place where we could help young adults gain their footing in their life.” 

Now when the pediatric neurologist refers the patient to the adult provider, they gather all the pertinent data and meet together with the patient. 

The young person also completes a transition-readiness assessment questionnaire, a validated tool specifically for epilepsy, to determine how ready they are to independently manage their disease. “And if there are any places where they’re still behind, still not doing things quite on their own, we set ‘homework’ goals for them for the next visit,” said Dr. Lalor. Clinic staff follow patients until they are fully managing their own care or until the staff feels they’re stable and ready to transition, at which point most patients continue with epilepsy specialist Quynh Vo, M.D., of the University of Alabama at Birmingham. 

The clinic is so busy that in December 2021, staff added a second day a month. The next step, Dr. Lalor said, is to implement national guidelines that recommend beginning transition at age 12 and add case management and social workers to the team.  

Inside Pediatrics, Neurology & Neurosurgery

License Plates and Safer Schools: Advocacy in Action in Epilepsy 

Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

Kathryn Lalor, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

When you think about epilepsy and Children’s of Alabama, you think about the epilepsy clinic, groundbreaking research, and state-of-the-art treatments and surgeries. You probably don’t think about license plates and training school staff to give life-saving emergency treatments. Yet that’s just what the pediatric neurology division has been doing as part of its advocacy efforts in the epilepsy field.  

Together with the Epilepsy Foundation AlabamaChildren’s of Alabama pediatric neurologists Monisha Goyal, M.D., Kathryn Lalor, M.D., and other staff designed the first epilepsy license plate in the country. The state approved the “Help End Epilepsy” car tag in March 2020, but it couldn’t be produced until at least 1,000 people committed to buying it. The team hit that milestone in 2021 thanks to the help of a generous donation that made the first 1,000 tags free.

“That was a big, big deal,” Dr. Lalor said. Each plate costs $50, $41.25 of which goes to the pediatric epilepsy program at Children’s. “We want to use some of that money to help educate future epilepsy specialists,” she said, citing a shortage of specialists in the region. In fact, while Children’s has a fellowship slot in epilepsy, it hasn’t had the funding to fill it.

The second major advocacy effort in 2021 revolved around improving the school environment for children with epilepsy by training school personnel other than nurses to administer seizure-rescue medications. That’s important for the 7,500 Alabama students with epilepsy. If there isn’t a nurse nearby, they can’t participate in activities like sports and field trips. Yet just 70 to 75 percent of Alabama public schools have access to a nurse, often sharing that nurse among several schools. 

Dr. Lalor and her colleagues, along with the Epilepsy Foundation Alabama, lobbied state legislators to pass the Seizure Safe Schools Act, including testifying in front of the House and Senate committees.  

It wasn’t as easy as they expected it to be, with opposition coming from the school nurses association and some legislators concerned that allowing non-medical volunteers to administer emergency medicine would hinder efforts to hire more nurses. That was never the intention, Dr. Lalor said. “We would love for school nurses to be everywhere,” she said. “The school systems just can’t afford that.” And there’s a national shortage of school nurses. Nonetheless, the legislature added an amendment to the act calling for more efforts to put school nurses in every school. “We fully support this,” said Dr. Lalor. “This is crucial for the safety of students.” 

A statewide task force composed of Epilepsy Foundation and Children’s representatives, school nurses, and public health officials is working to implement the new law and hopes to roll out education in early spring 2022. 

Inside Pediatrics, Neurology & Neurosurgery

Stopping Tics in Their Tracks 

Emily Gantz, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

Emily Gantz, M.D., is a pediatric neurologist at Children’s of Alabama and an assistant professor in the Division of Neurology in the University of Alabama at Birmingham Department of Pediatrics.

The hallmark of Tourette syndrome is an array of tics, ranging from eye blinking and rolling to head and neck movements to verbal sounds. “It’s like feeling that you need to cough in a meeting, so you try to suppress it. But the more you try not to cough, the bigger the itch gets, so you just have to cough,” said Children’s of Alabama pediatric neurologist Emily Gantz, D.O. “Then [Tourette syndrome patients’] brains learn that when they do the movement or make the sounds, the urge goes away, and they feel better.” 

Those tics, however, can lead to bullying, academic issues, and social isolation. But just a few hours spent with the occupational therapists and neurologists at the Comprehensive Behavioral Intervention for Tics, or CBIT, clinic at Children’s of Alabama, can be lifechanging. 

The multidisciplinary program began in 2010. Since then, thousands of children have passed through, and 95 percent have significantly reduced or eliminated their tics. “It’s very doable,” said Jan Rowe, M.D., OT, who started the clinic“While it is hard work, the kids see it as a very easy way to manage their tics.” 

The children first meet with Dr. Gantz or Pediatric Neurology Director Leon S. Dure IV, M.D., who makes or confirms a diagnosis of Tourette syndrome, tic disorder, or other functional movement disorder. Then patients spend about one hour a week for eight weeks with a CBIT-trained occupational therapist in the clinic, where they learn competing responses to interrupt the tics, which minimizes and/or extinguishes them. 

For instance, someone with a head or neck tic, such as flipping their head back, is taught to push their head straight back, like leaning into a headrest. “When you do that, your chin automatically comes down just a bit and the front neck muscles are activated, which holds the head still,” Dr. Rowe said. An eye-rolling tic might be managed by looking down and out. And shoulder shrugs can be headed off by pushing and holding the shoulders down with the arms against the sides. 

“Having a competing response or strategy to block the tic allows the child to do something instead of just trying to suppress it, which takes a tremendous amount of physical and mental energy,” Dr. Rowe said. “This therapy can be really life-changing for these kids, especially those facing teasing or bullying in school or in their social life,” she said. And it only takes a handful of sessions. 

The clinic has been particularly busy the past 18 months with a pandemic-related phenomenon called “TikTok tics.” It primarily affects teenage girls with no previous history of tics. Time spent watching people with Tourette syndrome on the social media platform TikTok, combined with anxiety and stress, seem to trigger abnormal vocalizations and movements. 

The problem is global, Dr. Rowe said. Girls come into the clinic with a diagnosis of Tourette syndrome from their primary care clinician, but it’s clear something else is going on since they didn’t have the tics before, something Dr. Gantz confirms during a Zoom visit. The teens are invited into the CBIT program but must also work with a therapist to deal with their anxiety, stress, or trauma. “Let’s face it, these kids have had tremendous loss in the past two years,” Dr. Rowe said. “Many of them are on overload.”  

Dr. Rowe, who has tics herself, has been running the clinic for 12 years. “I just absolutely love it,” she said. “It is so life-changing.” 

Inside Pediatrics, Neurology & Neurosurgery

Pioneering Surgery Spares Parents and Infants from Helmets

The Cleft and Craniofacial Center at Children’s of Alabama is one of the busiest in the country, with some of the most experienced physicians and support staff. From cleft palate to craniosynostosis (a condition in which the skull fuses too early) and complex tumor surgeries, the center draws patients from the entire Southeast region and beyond. It is a truly multidisciplinary group with neurologists, neurosurgeons, plastic surgeons, and a craniofacial pediatrician. 

It also offers state-of-the art therapies, including a new type of endoscopic surgery for craniosynostosis in infants as young as three months that is only performed in a few centers in the U.S. “The typical procedure is an endoscopic release of the craniosynostosis followed by post-operative helmet therapy,” said neurosurgeon James M. Johnston, M.D. “Helmet therapy works well, but kids have to wear it for 23 hours a day, and that can be a lot of work for families, especially when they live far from Birmingham,” he said. In addition, the Alabama Medicaid program, which covers most of these children, does not pay for the helmets, which can cost thousands of dollars (and children often need more than one). This puts tremendous financial strain on many families.  

So Dr. Johnston, joined by neurosurgeon Curtis J. Rozzelle, M.D., and plastic surgeons Rene’ P. Myers, M.D., and John Grant, M.D., brought spring-mediated cranioplasty, which was developed at Wake Forest University, to Children’s. It starts with the same endoscopic craniectomy used for children who would require helmets. Only in this procedure, the plastic surgeon steps in and inserts custom-made springs into the bony defect created by the surgery. The springs work to expand the skull over several months to correct the abnormal head shape and ensure appropriate cranial volume for brain growth. A few months later, the plastic surgeon removes the springs during a same-day surgery.  

“What’s nice is that there’s no need for a helmet,” Dr. Johnston said. Plus, studies show the procedure is just as safe and effective as cranioplasties requiring helmets.1 It’s also covered by all health insurance. “So, we’re able to do it for all children,” he said.  

A similar procedure using cranial distractors like those used to lengthen femurs is used for skull expansion, explained Dr. Grant. This technology is used in older children who need more intracranial volume but who are beyond the age at which the skull can form new bone to fill in surgically created soft spots. By “stretching” the bones of the skull more slowly, he said, the child’s body adjusts by making bone to fill in the growing gap. 

Regardless of the procedure used, early referrals are critical for these babies, said Dr. Rozzelle. “If we can see them by 2 months of age, that gives us plenty of time to get whatever preoperative assessments we need and get them on the schedule so that either the spring or endoscopic craniectomy with subsequent molding helmet is a viable option,” he said. Older babies cannot be treated endoscopically and require standard open surgery, which may lead to more blood loss and longer hospital stays.2 

Yet the craniofacial clinic still sometimes sees babies 6 months or older who never received a diagnosis or whose pediatrician didn’t refer them to Children’s. “That’s frustrating,” Dr. Rozzelle said. 

Nonetheless, said Dr. Myers, “Since we are comfortable with all of the techniques, we can tailor a plan to the individual child. No one is exactly the same.” 


1 Arko L, Swanson JW, Fierst TM, et al. Spring-mediated sagittal craniosynostosis treatment at the Children’s Hospital of Philadelphia: technical notes and literature review. Neurosurg Focus. 2015 May;38(5):E7

2 Hashim PW, Patel A, Yang JF, et al. The effects of whole-vault cranioplasty versus strip craniectomy on long-term neuropsychological outcomes in sagittal craniosynostosis. Plast Reconstr Surg 134:491–501, 2014.

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, Neurology & Neurosurgery

Pediatric Neurosurgeon Launches Interactive Website Fostering Global Collaboration

Having partnered over the years with neurosurgeons in Vietnam and Ghana, James Johnston, Jr., M.D., a pediatric neurosurgeon at Children’s of Alabama and the University of Alabama at Birmingham (UAB), knew many in his field who craved this type of global collaboration but didn’t know where to start. That’s why he co-founded an interactive website designed to bring specialists and organizations together to improve the care of surgical patients worldwide.

Known as InterSurgeon (https://intersurgeon.org), the effort is the joint vision of Johnston and British pediatric neurosurgeon William Harkness, M.D., who focused on the stark fact that 80% of the world’s population lacks access to safe, timely and affordable surgical care. The pair, with support from multiple international organizations and Dean Vickers at the University of Alabama at Birmingham (UAB), raised funds to build InterSurgeon to help fill this void. It matches surgeons from disparate locations to not only collaborate, but form a supportive global community of like-minded professionals.

Initially launched with pediatric neurosurgeons in mind, InterSurgeon now also includes members from many other surgical specialties. The free service empowers surgeons, anesthesiologists, allied health professionals and equipment providers to partner on training, education and clinical care as well as share equipment and other resources.

“We’ve tried to create a stand-alone nexus for all players in global surgery to be able to join with others to better collaborate,” said Johnston, also an associate professor of pediatric neurosurgery at UAB.

“The World Health Organization passed a resolution in 2016 that put new emphasis on global surgery training as a major priority for global health,” he said. “We focus so much on infectious diseases, but what’s ended up happening is that the annual morbidity and mortality from surgery worldwide dwarfs all of that. It’s stunning.”

Key partnerships between InterSurgeon and other organizations over the past several years have driven opportunities for collaboration as well as access to surgical education with specialized technology. In addition to the United Nations Institute for Training and Research (UNITAR), partners include the G4 Alliance, which advocates for increased access to safe surgical care; and Ohana One, which has sent “smart glasses” loaded with augmented reality software from Birmingham-based HelpLightning to various sites around the world. This enabled mentor surgeons in developed healthcare systems to virtually interact in real time with mentees performing surgery for training purposes.

 With procedural competence integral to the specialty, surgery requires “a certain amount of infrastructure, and a lot of that has lagged worldwide,” Johnston noted. “But even in places with equipment, the quality of surgical training is not always as good as it could be.”

 With more than 600 members in 95 countries and growing, InterSurgeon aims to “shore up” that gap.            

“It’s a very difficult problem, and no one thing will solve it,” Johnston said. “But in surgery, it’s very important to connect experts and institutions with learners to bring them up to speed and improve the quality of the surgery they’re doing.”     

Inside Pediatrics, Neurology & Neurosurgery

Probing the Molecular Underpinnings of Undiagnosed Muscle Disorders

The Jerry Lewis fundraising telethons of yore educated many people about myopathies, the most famous of which – muscular dystrophy – highlights the often-progressive and disabling muscle weakness afflicting these children. But up to 10% of myopathy cases seen by Michael Lopez, M.D., Ph.D., a Children’s of Alabama pediatric neuromuscular physician-scientist, are undiagnosable, despite comprehensive evaluation.

This dilemma has driven Lopez, also an assistant professor of pediatric neurology at the University of Alabama at Birmingham (UAB), to collaborate with colleagues to use whole genome and RNA-Seq sequencing to potentially solve such cases. Lopez has enrolled 10 patients and their families into innovative clinical research aiming to reveal the molecular basis of undiagnosed myopathies in hopes of offering affected patients a prognosis and steering them toward effective treatments.

“In a small sliver of patients, I’m convinced they have a myopathy but am unable to refine their diagnosis and give clarity on what type,” Lopez explained. “In that group of kids, in which I’m pretty sure the cause is genetic and everything else is ruled out, we end up in this diagnostic odyssey.”

To tackle this problem, Lopez joined with UAB’s Liz Worthey, Ph.D., director of the Center for Genomic Data Sciences, and Matthew Alexander, Ph.D., an assistant professor of pediatric neurology. Using simple blood draws from parents and children and next-generation gene sequencing techniques, the trio hope to identify new genes responsible for muscle disorders or previously unreported variants of uncertain significance, dubbed VUS, in genes already known to cause myopathies. These mutations can be inserted into animal models to build evidence that a specific VUS triggers the condition.

“This allows us to get a snapshot of all the mutations possible in the genome, not excluding places that turn genes on and off,” Lopez said. “Data can help us support or refute a disease-causing mechanism for the VUS.”

Lopez is well aware the project won’t produce quick answers, and participating families also understand the findings may not benefit them personally.

“But it is possible to come back with a molecular diagnosis,” he said. “If we find something that’s already well-understood, that would offer them some treatment options if they’re already available.”

 Longer-term, Lopez hopes the research will point toward targeted treatments for these muscle disorders, some of which might be derived by repurposing old drugs in “off-the-shelf libraries.”            

“Treatment is just one goal, a second is resolving the diagnosis and solving the case,” he said. “That’s a huge burden relieved for both family and patient. And another piece is the science – to improve our understanding of how these diseases occur and how the muscle functions.”

Hematology and Oncology, Inside Pediatrics, Neurology & Neurosurgery

Children’s of Alabama Launches Second Groundbreaking Trial of Viral Treatment for Brain Tumors

Children’s of Alabama and the University of Alabama at Birmingham are leading studies using a genetically re-engineered herpes virus to treat pediatric high-grade gliomas.

“A uniformly dismal prognosis.” That’s how Children’s of Alabama neurosurgeon James M. Johnston, Jr., M.D., describes what children with recurrent malignant brain tumors face, with an average lifespan of six months given a lack of effective treatments.

Now Johnston, in collaboration with Greg Friedman, M.D., associate professor of pediatric oncology and director of Developmental Therapeutics at Children’s, is leading groundbreaking studies designed to shift that trajectory. The team recently completed a Phase 1 immunotherapy clinical trial of genetically re-engineered herpes virus G207 to treat pediatric high-grade gliomas. Their work builds on adult research on the viral treatment pioneered by James Markert, M.D., MPH, who chairs the Department of Neurosurgery at the University of Alabama at Birmingham (UAB), as well as Friedman’s laboratory work, which showed the virus was more effective against pediatric brain tumors than adult tumors.

In the past three years, 11 patients with high-grade gliomas have traveled to Children’s from throughout the country, Mexico and Canada to participate in the study. They receive special screening to pinpoint the tumor location, which is then biopsied. Johnston then places three to four catheters in the tumor. The next day, Friedman and his team infuse the genetically-modified virus into the brain through the catheters.

“We think the virus works by directly killing the tumor cells,” Johnston said, as well as activating the immune system to destroy any remaining cells. “Brain tumors have a way to hide from the immune system by making themselves immunologically ‘cold,’” he explained. The herpes virus turns a “cold” tumor into a “hot” tumor and generates the immune response. Indeed, months after the surgery tests show that immune cells have infiltrated the tumor and continue killing tumor cells.

The initial phase 1 trial in patients with high-grade gliomas was designed to demonstrate safety and wasn’t powered to show efficacy. Nonetheless, Johnston said, “our median survival was significantly longer than the historical six months,” with several children now long-term responders.

In late December 2019, the team received a three-year, $750,000 R01 grant from the U.S. Food and Drug Administration for a Phase 1 trial in malignant cerebellar brain tumors, which may be even more sensitive to the virotherapy than the gliomas. At the same time, they are submitting grants for a Phase 2 multicenter trial of the virus therapy for recurrent malignant supratentorial tumors.

Johnston stresses that the research is a team effort, involving basic scientists, oncologists, surgeons, nurses and intensivists. “It’s an ‘all-hands-on-deck’ kind of thing,” he said.