Neurosurgery Institute leaders discuss innovations and their successes, and the need for much more work to be done

Two of CHOC’s leading pediatric neurosurgeons recently shared their insights on how innovation is helping to close the gap between clinical needs and the availability of pediatric devices, but how there is much more work to be done to get critically ill kids the treatments they need.

The webinar, “From Clinical Insight to Commercialization: Innovations That Can Transform Pediatric Healthcare,” featured Dr. Suresh N. Magge, CHOC CS Neurosurgery Division Chief, and co-director of CHOC’s Neuroscience Institute, and Dr. Michael G. Muhonen, the institute’s previous co-director.

Hosting the “OC LIFe (Lifesciences Innovators Forum)” on April 28, 2021 was Dr. Terence Sanger, a physician, engineer, and computational neuroscientist and vice president, chief scientific officer at CHOC, and vice chair of research for pediatrics at the UCI School of Medicine.

“As innovators, we should never be satisfied,” said Dr. Sanger, who specializes in movement disorders and who helped pioneer deep brain stimulation, which has yielded positive outcomes. “An innovative and collaborative approach is required so that pediatric patients can have access to the fit-for-purpose devices they need.”

Brain tumor treatments

Drs. Magge and Muhonen took turns discussing new neurosurgical technologies and opportunities for interventions.

Dr. Magge focused on new technology that has been used to treat brain tumors, which are a different breed compared to adult brain tumors. More often, Dr. Magge said, pediatric brain tumors are of a lower grade and can be treated.

“Many kids have gone on to live good lives thanks to innovation, research, and applying the technologies we have,” Dr. Magge said.

In one example, he detailed how microsurgical techniques have greatly aided in the removal of a craniopharyngioma, a benign tumor that usually arises in the base of the brain near the pituitary gland that can be dangerous or life threatening if not treated.

“If you can get the tumor out,” Dr. Magge said, “you can cure the patient. But it’s challenging because it’s in a deep part of the brain.” 

During the procedure, the neurosurgeon must locate some of the natural divides of the brain and separate them out to get to the tumor. Microsurgery allows the neurosurgeon to work between very narrow areas.

With a technology known as surgical navigation, neurosurgeons can pinpoint exactly where they are in the brain and get to very specific areas. Another technology is a powerful microscope that magnifies small areas of the brain. In addition, ultrasound and MRI within the operating room can tell you in surgery if there is any tumor left. 

“This is all thanks to innovation and technology that we are incorporating in surgery,” Dr. Magge said.

Dr. Magge then discussed medulloblastomas, one of the most common types of tumors neurosurgeons see in kids. Such large tumors grow in the lower back part of the brain — the cerebellum, which is involved in muscle coordination, balance, and movement.

Thirty years ago, Dr. Magge said, kids with medulloblastomas received high doses of radiation that left a lot of them with severe cognitive and hormonal deficits.

The treatment for medulloblastomas had evolved so that less radiation is used in the treatment. In addition, in the last decade, researchers have discovered that these tumors differ significantly based on their genetic makeup.

“These tumors have multiple genetic subtypes, and we can target them genetically with different types of treatments,” Dr. Magge explained.

He said innovation also has led to advances in the treatment of diffuse intrinsic pontine gliomas (DIGP), highly aggressive and difficult-to-treat brain tumors that grow in an area of the brainstem that controls many of the body’s most vital functions such as breathing, blood pressure, and heart rate.

The prognosis for DIPGs remains very poor because they are considered non-resectable tumors – ones that cannot be removed with surgery. Life expectancy is eight to 12 months after diagnosis.

“This is one of the toughest diagnoses we have to give to families because of the lack of good treatment options,” Dr. Magge said.

For years, biopsies were ruled out because they could cause significant side effects, and neurosurgeons saw no point in performing them since there were no treatments. Without biopsies, the tumor tissue could not be studied in a lab for potentially effective treatments. 

Technology has changed this is the last 10 years, Dr. Magge said, thanks to stereotactically guided needles that allow neurosurgeons to perform DIPG biopsies safely.

“We at CHOC and other pediatric hospitals have shown we can do this safely with minimum morbidity,” said Dr. Magge, who has participated in a large clinical trial regarding DIPG biopsies.

“With this technology, we can get tissue and genetically sequence these tumors and find out if there are certain mutations that are particularly amenable to certain treatments,” Dr. Magge said of this precision-medicine approach. 

“These are small steps along the path,” he added. “We have by no means found all the answers. We have so much farther to go, but I think we’re on the right track.” 

Closing the gap

Dr. Muhonen recalled one of the first patients he saw when he came to Orange County in 1995: a young girl with severe spasms in her legs. She couldn’t walk without assistance.

“We had to do something innovative,” Dr. Muhonen said.

He had injected baclofen, a muscle relaxer and antispasmodic agent, into the spinal column of an adult the year before, but never in a child. After receiving approval to do so, he implanted a device that allowed long-term injection of baclofen in the girl’s spinal cord. Six months later, she was able to walk and even run on her own.

In another example of innovation, Dr. Muhonen worked for five years on helping to develop a wireless sensor to measure pressure in the brain. The FDA approved the device for adults, but has yet to for children.

Most companies get medical devices approved for adults because it’s easier, because there’s a larger patient population, and there’s more money to be made. 

“The bulk of challenges associated with developing and accelerating pediatric medical devices is market-driven,” Dr. Muhonen said. “We want children to get the best possible care available, but the relative market size is small compared to adults, which is one reason some device makers avoid it.”

One of Dr. Muhonen’s chief interests is treating hydrocephalus, the buildup of fluid in the ventricles deep within the brain.

Innovation in this area has been a long time coming, he said, since the invention in the early 1950s of a shunt that drained fluid from the brain into the abdominal cavity. Many problems can occur with the shunt, such as spontaneously twisting up into a knot due to a child’s movement or calcifying and breaking apart after being in the body for a long time. Kids who received a shunt typically face more than 10 surgeries, Dr. Muhonen said.

“The holy grail for pediatric neurosurgeons is, can we create a ‘smart shunt?’” Dr. Muhonen said.

An ideal shunt, he said, could be programmed to drain a specific amount of water and measure pressure.

Dr. Muhonen said a derivative from cone snails is inspiring research into a new generation of painkillers for adults, but has yet to be approved for testing on kids.

Impediments to innovation

Dr. Sanger asked Drs. Magge and Muhonen about impediments to pediatric innovation. Ethically, he posited, shouldn’t new devices and other innovations be tested in adults first? 

“I don’t think there are any easy answers to this,” Dr. Magge said. “It’s difficult. You don’t just do a biopsy on a tumor that might help kids in the future. If you perform surgery on a child, there has to be some potential benefit to that child.”

Dr. Muhonen said children are the most vulnerable of society and thus are the worthiest of innovations in healthcare. 

Dr. Magge said he and others at CHOC have been looking at ways to inject dyes to paint brain tumors to more easily distinguish them from healthy brain tissue.

“Sometimes the tumor is obvious, sometimes it’s more challenging,” he said.  While dye injections have been used in adults, it is less commonly used in children.

Dr. Sanger mentioned “big effect sizes” resulting from innovation in pediatric medicine. 

“We’re used to the idea of statistical research involving a lot of patients,” he said. “But this is a different type of research. You take someone who has never walked before and now they’re running. You take someone who is going to die of a brain tumor and now they’re not. These are very big effect sizes.” 

“There are good reasons for the regulations we have,” Dr. Magge said. “That being said, that doesn’t mean we can’t innovate. And there are mechanisms for us to do that, and to do it safely.

“Our first motto is, ‘Do no harm,’” Dr. Magge continued. “I always tell residents to do the right thing and treat each patient as if they were your own child. Doing the right thing means asking the right questions. ‘How can we do this better?’ You can always learn from everything you do. At the end of every procedure, you critique it. You’re constantly learning. That’s what I always encourage.” 

Dr. Sanger closed the session by noting that clinical evidence should ideally be reflective of the spectrum of pediatric patients and the developmental differences that can impact the use and effectiveness of medical devices.

“This is a collaborative effort,” he added. “CHOC is working closely with the FDA’s new System of Hospitals for Innovation in Pediatrics – Medical Devices (SHIP-MD) Program, our academic partners, industry, entrepreneurs and the investor community to close the gaps. Also, we are now practicing medicine in a world immersed with data. Advances in computing and health information technology have given rise to new sources and types of biomedical data. Clinicians know real-world data will continue to emerge as a source of clinical evidence.”

The Presenting Sponsor of the webinar, “From Clinical Insight to Commercialization: Innovations That Can Transform Pediatric Healthcare,”  was Biocom California, which connects life science organizations to each other so they can collaborate and work smarter together. The CHOC Research Institute co-sponsored the hour-plus session.

The webinar was presented in partnership with SBDC @ UCI Beall Applied Innovation, a resource for any high-technology, high-growth, scalable venture from the community or the UCI ecosystem that needs help with business planning, business development and funding-readiness.

Learn more about CHOC’s Neurosciences Institute

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Three-stage DBS results in better outcomes for secondary dystonia

Due to the complexity of secondary dystonia and the brain’s potentially unpredictable response, deep brain stimulation (DBS) has seldom been used in the treatment of this disorder. However, a CHOC neuroscientist has developed a breakthrough method of DBS to treat secondary dystonia in pediatric patients.

Dr. Terence Sanger, pediatric neurologist and chief scientific officer at CHOC, has pioneered a new surgical approach in DBS for pediatric secondary dystonia. Patients undergo three procedures rather than two, nullifying the need for patients to be awake during DBS surgery. Not only does this save children from the potentially traumatic experience of being awoken during brain surgery, it leads to significantly better outcomes in secondary dystonia treatment, with a current success rate between 85% and 90%.

Dr. Terence Sanger, pediatric neurologist and chief scientific officer at CHOC

Unlike patients receiving DBS for other disorders, where results can be observed during surgery, a child with secondary dystonia may have concerns with movements or actions that can’t be addressed on the operating table. For example, a child with secondary dystonia may have difficulty walking, but the physician cannot test DBS’ effectiveness by waking the child and asking him or her to walk.

To overcome this obstacle, Dr. Sanger and his team first insert test electrodes into the patient’s brain. The initial procedure is followed by a week of surveillance and testing. After selecting which electrodes are most effective at treating the patient’s symptoms, the team places permanent electrodes followed by a third procedure to implant the stimulator. The week between the placement of test electrodes and the placement of permanent electrodes allows Dr. Sanger and his team to observe which electrodes are effective.

“The biggest benefit of the three-procedure method is we know where the wires need to be in the patient’s brain for the most effective treatment,” Dr. Sanger says. “By the time we get to the third surgery, we know exactly what’s going to happen. As an engineer, I’m a big believer in measuring twice and cutting once, and effectively, that’s what these three procedures allow us to do. Every child’s brain is different, so we have to learn about how each brain operates before we can perform a successful surgery.”

In addition to his revolutionary procedure for secondary dystonia, Dr. Sanger believes in the future of neuroscience at CHOC.

“At CHOC, our tagline for research is ‘Go beyond,’ and I’ve never seen that belief more exemplified than in the work I’ve seen at our Neuroscience Institute,” Dr. Sanger says. “We are not going to improve pediatric neurology care by doing what other hospitals do, but better. We are going to improve by doing something different, like we’ve done with DBS for secondary dystonia. It’s very exciting, and I believe we have the opportunity to make a huge difference.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the neurology/neurosurgery specialty.

USNWR Neurology and Neurosurgery award

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

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I’m a pediatric neurosurgeon. Here’s why I’m excited about the technology at our fingertips.

By Dr. Suresh Magge, medical director of neurosurgery at CHOC, and co-medical director of the CHOC Neuroscience Institute

Even as a child, I was fascinated with science, and it was ultimately the concept of using science and technology to help people that drew me to medicine. Today, I’m more excited and optimistic than ever about our ability as clinicians to provide best-in-class treatment to the patients we have the privilege to care for – particularly in a minimally invasive way.

While every effort is made for nonsurgical intervention, neurosurgery can often be the answer to saving or improving a child’s life. At CHOC, we are committed to creating a personalized treatment plan for each child, based on his or her needs.

When surgery is necessary, we strive to perform minimally invasive surgery whenever possible for the myriad benefits it brings our patients. Minimally invasive neurosurgery offers a smaller incision, less pain, minimal blood loss, shorter time spent in the operating room, shorter recovery time, shorter hospital stays and hidden scarring.

There are a number of tools that we use to make surgery less invasive. For example, we can use a small camera, called an endoscope, to look inside the brain without having to make a large incision. In some surgeries, we can use a specialized robot, called a ROSA robot, to allow for precise placement of catheters or electrodes, and to operate on tiny areas of the brain.

Here are four surgeries I’m excited about as a pediatric neurosurgeon. In each surgery, the child is asleep and does not feel any pain during surgery. 

  1. Endoscopic surgery — This option for many types of brain surgery allows the neurosurgeon to identify and treat conditions deep within the brain. A tube-like instrument with a camera is inserted into the brain through a small incision in the skull. In some cases, we can insert the tube through the nose and avoid making any incisions in the skull. This allows the neurosurgeon to have a clear picture of the tumor. Then, we use specialized surgical instruments to remove the tumor or damaged area. When possible, we use this technique for brain tumors, hydrocephalus, arachnoid cysts, craniosynostosis and skull base surgery. In treating craniosynostosis, endoscopic surgery can replace larger and more invasive surgeries but still achieve excellent outcomes.
  2. Responsive neurostimulation (RNS therapy) —The RNS system is similar to a heart pacemaker. By monitoring brain waves, it can detect seizure activity and then the system can respond to stop the seizure. What simultaneously amazes me and comforts families about this piece of technology is that patients can’t feel the device once it’s programmed. They don’t feel pain or anything unusual. Studies show RNS therapy reduces seizures and improves quality of life for most people who have used it.
  3. Deep brain stimulation This surgical treatment can offer lasting relief for many children who experience abnormal movements. CHOC offers DBS surgery for children with movement disorders of all degrees, including very complex cases. We are one of the only centers in the world to use a multiple stage approach that allows us to better target the correct areas of the brain, without the need to wake a child during surgery. DBS surgery at CHOC involves the placement of electrodes in the brain and wires that connect to a stimulator device implanted in the chest. The device is like a pacemaker; it sends impulses to the electrodes that tell the brain to stop or minimize uncontrolled movements throughout the body. Our specialized team places up to 12 electrodes, when needed, to target different areas of the brain to attain a good outcome. Surgeries take place in a state-of-the-art operating room at CHOC, which includes the latest navigation system for safer, more precise procedures and the ROSA 3D-mapping robotic system that aids surgeons in locating the exact areas to operate.
  4. Laser Interstitial Thermal Therapy (LITT) – Also known as laser ablation, this emerging technology provides pediatric patients with epilepsy and other conditions a range of benefits more traditional procedures can’t match and offers a potential solution for brain tumors that are hard to reach with traditional surgery. Instead of doing a craniotomy where a large incision is made to open up the skull, the neurosurgeon first makes a small hole in the skull just a few millimeters in a diameter. Then, under MRI visualization, the neurosurgeon can precisely position the laser probe and deliver heat to the specific area, which destroys the abnormal tissue. Laser ablation is especially useful in patients with tumors or seizure-generating abnormalities deep within the brain. Precision is essential in implanting the catheter, which guides the laser, since it allows the neurosurgeons to limit the thermal energy delivered to the tumor area only. Most LITT is minimally invasive and requires a short time in the operating room, and patients are often able to go home the next day.

Throughout my career, I’ve been fortunate to see firsthand how neurosurgery has advanced tremendously over the years, particularly through research and innovation.

I’ve had the privilege of studying and providing care at a number of institutions – Harvard, the National Institutes of Health, the University of Pennsylvania, Boston Children’s Hospital, and Children’s National Hospital (Washington, DC) — before coming to CHOC. At each of these institutions, it’s evident that through innovative technology and minimally invasive surgery, we as neurosurgeons can alleviate suffering and have a significant impact on the lives of children.

As a team here at CHOC, we always ask ourselves, “What is the best thing we can do for each child in the least invasive method, with the least amount of pain?” and then we try to do it in the most compassionate way possible.

It’s an exciting time in medicine, in part thanks to advances in technology — especially the pieces of technology that allow us to provide these minimally invasive surgical options that make a true impact on children and their families.

For more information about the CHOC Neuroscience Institute, click here.

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Wired for hope: deep brain stimulation for dystonia

Every morning when she awakes, Sydney Amato begins her daily battle with her body.

If she’s lucky, the 16-year-old will have gotten a handful of hours of uninterrupted sleep – dreaming, perhaps, of doing what most healthy kids her age take for granted:

Hanging out with friends. Going to school. Learning to drive.

Because of a neurological condition called dystonia, Sydney, who is in excellent cognitive health but speaks and walks with some difficulty, suffers from involuntary and near-constant contraction of muscles in her neck, arms, legs and trunk.

Sydney with her father, Louis

Her mind is unable to control the painful jerking that makes most of her body twist and go rigid, her muscles moving out of normal sequence.

Born a right-hander, she can feed herself with some struggle using her left hand. She wants to dress and put on makeup herself, but those normally simple tasks become lengthy ordeals.

“My body fights me all the time,” says Sydney, trying to distract herself in her hospital bed by watching an old episode of “Keeping Up with the Kardashians.” Listening to her favorite music – Ariana Grande, Lauren Daigle, Drake – can only temporarily transport Sydney away from her debilitating condition.

“She knows what she wants to do,” says her father, Louis. “But her body won’t let her.”

Specialists at CHOC are working hard to change that.

A first for CHOC

On Aug. 14, 2020, a team led by Dr. Terence Sanger, a physician, engineer, and computational neuroscientist who joined CHOC in January 2020 as its first chief scientific officer, and Dr. Joffre E. Olaya, CHOC’s functional restorative neurosurgeon, implanted several temporary electrodes into Sydney’s brain.

Dr. Terence Sanger, a physician, engineer, and computational neuroscientist and CHOC’s chief scientific officer

The surgery marked the first time a patient with a movement disorder at CHOC underwent a procedure called deep brain stimulation (DBS).

Working in perfect harmony as a team, Dr. Sanger and Dr. Olaya performed the first stage of a three-stage surgery on Sydney. As the surgeon, Dr. Olaya placed the leads following advice from Dr. Sanger, the neurologist, where they should go.

In the procedure, millimeter-thick electrodes were precisely positioned into the basal ganglia region of Sydney’s brain – about three inches deep. The surgery involved the use of the ROSA Robot, the same tool that has been used during brain surgery on epilepsy patients at CHOC since 2015.

Dr. Joffre E. Olaya, CHOC pediatric neurosurgeon

Considered one of the most advanced robotized surgical assistants, ROSA includes a computer system and a robotic arm. It’s a minimally invasive surgical tool that improves accuracy and significantly reduces surgery/anesthesia time.

The ROSA Robot helped with implanting and targeting the electrodes, and a portable operating-room CT scanner confirmed their position.

Turning down the volume

DBS is designed to ease Sydney’s condition by sending electrical currents to jam her malfunctioning brain signals.

Think of turning down the volume on your car radio.

“Nobody really understands the cause of dystonia,” Dr. Sanger explains, “but there’s probably too much electrical stimulation going on in the motor areas of the brain. We’re trying to calm down that extra noise.”

Although DBS dates to the 1960s, it wasn’t until the 1980s that the modern era of using it to treat adult patients with tremor and Parkinson’s disease began.

In 2000, Dr. Sanger, working with engineers, data scientists, neurosurgeons, and others, began implanting electrodes in pediatric patients.

Instead of the established method of placing the leads at predetermined sites and hoping they worked, Sanger and his team, just as they did in Sydney’s case, placed temporary leads to best assess where they should go permanently based on patient response.

In 2016, Dr. Sanger began honing DBS to treat children with dystonia. Before the surgery on Sydney, Dr. Sanger had performed DBS on 26 children using the same three-stage technique. He says 80 percent of those children have seen successful results.

Early signs

Sydney began showing symptoms of dystonia – tremors in her hands — when she was 5 ½ years old.

A year later, she was using a wheelchair. She had her first brain surgery at age 7.

Since then, “she’s been all over the U.S.” seeking the right treatment for her condition after several setbacks, says her father.

But her condition was not improving.

Early this year, a neurologist in Kansas City, Mo., recommended that Sydney see Dr. Sanger.

“I asked him, ‘If Sydney was your kid, where would you go?’ Louis Amato recalls. “He said, ‘Hands down, Dr. Sanger.’”

The COVID-19 pandemic pushed Sydney’s surgery to mid-August.

Sydney already had two electrodes in her brain that were only partially working when she came to CHOC in early August for surgery.

After two extensive run-throughs with their team, Dr. Sanger and Dr. Olaya, in a six-hour procedure that at one point had nearly 20 people in the operating room, implanted more electrodes to give her a total of nine.

On Thursday, Aug. 20, six days after Sydney’s surgery, Dr. Sanger stopped by her room at CHOC Hospital. The room was decorated in purple, Sydney’s favorite color.

Dr. Sanger greeted her as CHOC staff members, joined by members of Sanger Lab, which conducts research in pediatric movement disorders, prepared to have Sydney walk back and forth down a hallway while connected to electrical equipment programmed to record signals in her brain and muscles.

A thick coil of multicolored wires snaked from under a large white bandage covering Sydney’s head. Extending about 6 feet, the wires were plugged into specialized recording equipment controlled by Jennifer MacLean, a pediatric nurse practitioner whose job was to manipulate the strength of electrical charges affecting the four points of contact on each electrode.

The goal: determine which charges worked best and on which electrodes.

“It could have turned out that the DBS procedure made no difference,” Dr. Sanger says. “But we’ve seen a very good response in Sydney.”

For example, her once mostly useless right hand was working much better.

“It gives you goosebumps,” Louis Amato says.

After taking a bite of a veggie burger and sipping some water, Sydney started to walk.

Following her were seven CHOC and Sanger Lab specialists.

“Go nice and slowly,” Jennifer told Sydney. “You’re going too fast for us!”

Perhaps Sydney was anxious to get back to riding Tigger, a quarter horse, in her hometown of Carthage, Mo. She has been riding him for six months.

Sydney is eager to get back to riding her favorite horse, Tigger.

“Her balance isn’t bad on the horse,” says Louis Amato.

Sydney also loves to tan by her pool and swim.

What she wants most, however, is to be freed from her body so she can return to school and do what most teens enjoy.

“It’s stressful,” says her mother, Angie. “She has a lot of friends her age, but she can’t do a lot of the things they do. She has her days when she can get really upset.”

Now, however, working with Dr. Sanger, Dr. Olaya and the entire team at CHOC, the Amatos are more optimistic than ever.

“We’re hopeful that this is going to be a big life-changer for her,” Angie Amato says. “That would be the best thing that could ever happen – better than winning the lottery.”

‘The A Team’

After crunching numbers for a week to assess which of the nine electrodes proved to be the most effective based on how Sydney responded to varying degrees of electrical currents, Dr. Sanger and his team settled on four electrodes that were permanently used to treat her condition – three new ones, and one existing one.

The team performed this second surgery on Sydney in late August.

In the third and final surgery, successfully completed in early September, a rechargeable generator that powers the DBS leads was implanted in Sydney’s chest.

“As we get better and better at this,” says Dr. Sanger, “and as the technology progresses, we’ll be able to do this on kids who are less sick than Sydney.”

Dr. Sanger and Dr. Olaya are poised to dramatically improve the lives of many more patients like Sydney at CHOC.

“I’m really excited that we will be doing more of these procedures to help pediatric patients with movement disorders and significantly improve their quality of life,” says Dr. Olaya. “I look forward to continuing to provide this type of personalized care.”

Angie and Louis Amato say Sydney has never gotten this much special attention during her 11-year-plus medical journey.

“Here at CHOC,” Louis Amato says, “we feel like we’re with the A Team.”

Says Sydney: “I’ve never felt this much confidence and this good about treatment before.”

Learn more about deep brain stimulation (DBS) surgery at CHOC.