A nationwide study has shed new light on how to most effectively and safely treat Chiari malformation and syringomyelia, rare neurological diseases that impact both children and young adults.
In the first randomized controlled clinical trial for this condition conducted in the United States, a multi-center research team compared two surgical approaches most commonly used for treating this condition. According to the results, published today in the New England Journal of Medicine, the approaches showed no difference in complication rates and clinical outcomes, however, patients who underwent the more invasive procedure were less likely to need a second surgery and appeared to have greater improvement in their syringomyelia.
These insights are the culmination of more than 15 years of collaboration of more than 40 clinical centers and nearly half of all pediatric neurosurgeons in the country, making it the most widespread pediatric neurosurgical trial to date. The collaboration was led by David Limbrick , M.D., Ph.D., chair of the Department of Neurosurgery at Virginia Commonwealth University's School of Medicine and a neurosurgeon at Children's Hospital of Richmond at VCU .
"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," Limbrick said. "This study provides long-sought answers for the thousands of kids and their families who are impacted by this condition every year."
Evaluating treatments for Chiari malformation and syringomyelia
Chiari malformation is a neurological condition where the lowest part of the brain (cerebellum) protrudes into the spinal canal. Patients with this disease often experience throbbing headaches, shoulder and neck pain, balance problems and other symptoms. Chiari malformation is also associated with fluid accumulation in the spinal cord – a serious condition called syringomyelia – which leads to problems like numbness, spinal deformity, weakness and neurological disability.
Neurosurgeons typically treat Chiari malformation by combining two procedures, called posterior fossa decompression (PFD) and duraplasty. PFD involves removing the bone and soft tissue causing compression in the back of the skull, while duraplasty involves opening a protective layer of the brain, using a microscope to remove scar or other adhesions, and sewing in a dural tissue patch, which allows fluid from the brain to flow more freely into the spinal canal.
While the combination of these procedures has been used for more than 20 years, the invasive nature of the surgery carries a risk of complications. This has led some neurosurgeons to instead perform PFD without duraplasty, which is less invasive. However, it's unclear which surgical treatment is ultimately safer and more effective for improving a patient's symptoms and quality of life.
How researchers conducted this large-scale clinical trial
Because Chiari malformation is a rare neurological condition, impacting 1 out of 1,000 people, finding answers to these questions would be an impossible undertaking for one institution alone. This challenge led Limbrick to spearhead the Park-Reeves Syringomyelia Research Consortium , founded at his former institution, Washington University School of Medicine in St. Louis. The consortium began with two clinical centers in 2011 and grew to 43 centers by 2016, involving pediatric neurosurgeons from across North America.
"Despite caring for thousands of kids, any given pediatrician may only see these conditions once or twice in their whole career," Limbrick said. "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 and generalizable across the population."
For this trial, Limbrick and his colleagues aimed to identify which of the two surgical approaches minimized complications, provided the most relief from symptoms, effectively treated syringomyelia, and gave the highest quality of life for patients. The research team also partnered with advocacy groups to determine which clinical outcomes were the most important to patients, such as pain reduction and long-term spinal deformity, among other symptom improvements. While early work was supported through private philanthropy, the trial was funded through the Patient-Centered Outcomes Research Institute.
Conducted between 2016 and 2021 when Limbrick was at WashU Medicine, the trial involved 162 patients, aged 21 and younger, who were diagnosed with Chiari type 1 malformation and syringomyelia. For their treatment, participants underwent either PFD with duraplasty or PFD alone, depending on which center they received care.
Clinical trial results will help families make informed decisions about treatment
The data from the study showed that, for some patient outcomes, the two surgical approaches achieved similar results:
- The complication rate was not significantly different between the two procedures, suggesting that undergoing PFD alone does not reduce the risk of complications compared with PFD with duraplasty.
- Both procedures led to similar improvements in patient symptoms and quality of life.
However, the study did reveal two key differences between the treatment options:
- Patients who received PFD with duraplasty experienced a greater reduction in the size of their syrinx – the fluid-filled cyst that develops in the spinal cord – compared to those with just PFD (3.08mm vs. 1.21mm reduction).
- Patients who received PFD with duraplasty were also less likely to need a second surgery compared to those who received PFD alone (2.6% vs. 14.2%).
"Syrinx resolution is an important metric, because the number one reason people go back for second surgery is because the syrinx didn't respond," Limbrick said.
Limbrick and his colleagues say these findings mark an important step for giving patients and their families assurance that their providers have the most comprehensive, evidence-based information for treating this disease. The research milestone is also a testament to the life-changing impact of clinical innovations and discoveries led by the faculty at VCU School of Medicine and VCU Health.
"We have been trying to solve this issue for over three decades, and these study results will impact how every child in North America with Chiari and syringomyelia is treated," Limbrick said. "Before, when families would ask what the safest and most effective treatment was for their child, there was no data to answer that question. This study provides that answer."
