The results, now published in the New England Journal of Medicine, will guide surgeons and families in the treatment of these conditions.
Chiari malformation – a condition in which the lowest part of the brain, the cerebellum, protrudes through the back of the skull – is identified in up to 1% of MRI scans.
“Fortunately, neurological diseases in children are uncommon, but when it is your child who is affected, it doesn’t matter how rare a disease is. It is the most important thing in your life,” said David Limbrick, M.D., Ph.D., pediatric neurosurgeon at Children’s Hospital of Richmond at VCU and professor and chair of the Department of Neurosurgery at Virginia Commonwealth University School of Medicine.
With these families in mind, Limbrick has made it his life’s work to research, treat and cure rare conditions of the brain and spine, making him a natural fit to lead the largest pediatric neurosurgical trial to date, and the only randomized control trial in pediatric Chiari malformation. The results have just been published in the New England Journal of Medicine.
What is Chiari malformation?
The lowest part of the brain is called the cerebellum, and the lowest parts of the cerebellum are the tonsils. In Chiari malformation, the tonsils protrude through the back of the skull and into the spinal canal, causing headaches, balance problems and other challenging symptoms.
A frequent result of Chiari malformation is interruption of the fluid flow from the head to the spine. This can cause fluid to accumulate in the spinal cord – a condition called syringomyelia – and lead to problems like numbness and tingling in the hands or feet, spinal deformity, weakness and neurological disability.
Treatment options for Chiari malformation and syringomyelia
Surgeons address Chiari malformation with two primary treatment approaches. One procedure, posterior fossa decompression (PFD), involves removing the bone and soft tissue causing compression in the back of the skull. The second option, PFD with duraplasty, begins the same way and adds a more invasive step of opening a protective layer of the brain, using a microscope to release scarring and adhesions at the intersection of the cerebellum, brainstem and spinal cord, and sewing a dural tissue patch, allowing even more room for fluid to flow.
“At any given center, we don’t see enough patients with these conditions to determine which surgical treatment is best,” Limbrick said. “Despite caring for thousands of kids, any given pediatrician may only see these conditions once or twice in their whole career. Because these conditions are rare, and they can happen anywhere, having a multi-center research study allows us to collect data on enough patients to make information statistically valid.”
The benefits of this wide-reaching clinical trial
The study was conducted across more than 40 centers and involved nearly half of all pediatric neurosurgeons in the country. In total, 162 patients with both Chiari and syringomyelia were enrolled.
“We partnered with patient advocacy groups in this space and then we went to a funding agency called the Patient Centered Outcomes Research Institute and said, ‘We’d like to address the most controversial question in this field, which is how do we best treat these patients.’ And the trial was funded, so that’s how it came about — with the support of clinicians, professional organizations and patients themselves,” he added.
The trial focused not just on surgical outcomes, like complications and follow-up surgeries, but also quality of life and symptom resolution, measures that patients and families care most about. Limbrick led the team of researchers as they studied the intersection of this information in pursuit of an answer.
“The advantage of conducting a trial for a rare disease across such a large cohort of institutions is that you not only acquire the sample size needed to make important statistical conclusions, but the results will also be broadly generalizable. It’s a better representation of how that particular problem manifests across North America, in this case, and what treatment outcomes you can expect across many different providers,” Limbrick explained.
For example, it can be difficult to convey all the subtleties experienced by a single surgeon studying a particular problem with their patients. In large clinical trials with multiple providers in hospitals in different areas, there’s confidence that the results will be relevant, no matter where a child is being treated or by whom.
What the study means for families facing these rare, complex conditions
Going into this clinical trial, researchers originally thought that the complication rate would be higher for the more invasive procedure (PFD with duraplasty). To their surprise, the data showed no difference. Differences in clinical and quality of life improvements also did not appear to be different between the two procedures.
However, there were two notable contrasts. Researchers found that children went back for a second surgery at a significantly higher rate after having the less invasive procedure, meaning patients would return to the operating room for the more invasive surgery. The other variance was in the resolution of syringomyelia, which appeared to respond better to the more invasive procedure.
“This is the randomized control trial that’s been requested by experts in the field for years – and it will impact how every child in North America with Chiari and syringomyelia is treated,” Limbrick said.
When asked what he wants families to know, Limbrick said, “If you have a child with Chiari and syringomyelia, we can offer safe and effective care. I know it’s a scary and emotional time, but we now have a pathway forward for you and your child.”