Article In Brief
Evidence from a study of children who had stroke found the safety profile for the use of endovascular recanalization in those with acute, large-vessel occlusion was similar to findings from studies of adult stroke patients. The data support off-label thrombectomy for pediatric stroke.
Pediatric stroke patients undergoing endovascular thrombectomy appear to have mostly favorable neurologic outcomes with low complication rates, a new multicenter retrospective review indicated.
The findings lend support to performing mechanical recanalization for childhood stroke even though prospective randomized clinical trials have investigated its use only in adults, the authors reported in the Save ChildS study published online October 14 in JAMA Neurology.
After reviewing the databases from 27 stroke centers in Europe and the United States, the researchers concluded that “endovascular recanalization appeared to be safe with positive outcomes in a real-world setting.” The overall “proportion of successful recanalization” totaled 87 percent.
Several sizeable randomized clinical trials in adults have demonstrated the safety and efficacy of thrombectomy for large intracranial vessel occlusions. However, other than small case series, the potential for this intervention in children had not yet been examined systematically, the study's authors noted.
“Etiologies are very different in children and adults,” said lead author Peter B. Sporns, MD, MHBA, assistant professor of radiology/neuroradiology at University Hospital Muenster in Muenster, Germany. “Results from adult trials cannot be extrapolated to pediatric populations,” Dr. Sporns told Neurology Today.
Few children experience this emergency, posing challenges to researchers in designing randomized clinical trials. Arterial ischemic stroke rarely occurs in childhood, but when it strikes two to eight of 100,000 children per year, it can inflict severe disabilities with long-term social and financial consequences. Standard of care relies on supportive medical management tailored to the underlying etiology of arterial ischemic stroke. Thrombolytic and endovascular therapy is “only recommended as a last resort,” the authors noted.
Dr. Sporns expects the findings to have implications for current treatment guidelines. “Endovascular recanalization will become first-line therapy in children with acute ischemic stroke due to large-vessel occlusion,” he said. “The main message is that endovascular thrombectomy in children can be performed with a similar safety profile and recanalization rate as in adults. Therefore, all physicians should keep this in mind and refer their patients to highly specialized neurointerventional centers.”
Meanwhile, Dr. Sporns emphasized the need for pediatric stroke centers worldwide to contribute data to the Save ChildS Pro registry, which he is launching in 2020. “We hope that this registry will provide the highest level of evidence for the use of endovascular thrombectomy in children with large intracranial arterial occlusion,” he said.
Study Design, Findings
From January 1, 2000 to December 31, 2018, researchers analyzed data for all pediatric patients (<18 years) with ischemic stroke who underwent endovascular recanalization at 27 participating stroke centers. The researchers initially had contacted 42 tertiary stroke centers, but 15 of those centers (36 percent) did not treat any pediatric patients with this technique.
The total cohort at 27 centers consisted of 73 children, with a median age of 11.3 years. Sixty-three children (86 percent) had treatment for anterior circulation occlusion and 10 patients (14 percent) received intervention for posterior circulation occlusion; 16 patients (22 percent) underwent intravenous thrombolysis concomitantly. Median follow-up was 16 months.
The primary outcome was a decline on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score from admission day; the score ranges from 0 for no deficit to 34 for maximum deficit.
Secondary clinical outcomes, measured on the modified Rankin scale (mRS)—where 0 (for no deficit) to 6 (death)—at six and 24 months, evaluated the rate of complications.
The researchers reported improvements in neurologic outcome, with a median PedNIHSS score of 14.0 at admission and 4.0 at day seven. Median mRS score was 1.0 at six months and at 24 months. One patient developed postinterventional bleeding and four patients exhibited transient peri-interventional vasospasm.
To facilitate interpretation of the results in a broader context, investigators compared long-term outcomes in their Save ChildS study to available data from the HERMES meta-analysis trials of adults. They extracted data from intervention arms of seven published HERMES trials.
The proportion of symptomatic intracerebral hemorrhage events in Save ChildS was 1.37 compared with 2.79 in the HERMES meta-analysis.
“This is a very optimistic time for pediatric stroke because these techniques of mechanical recanalization are so powerful in adults,” said Christine Fox, MD, MAS, co-author of an editorial published concurrently in JAMA Neurology and associate professor of neurology and director of the Pediatric Stroke and Cerebrovascular Disease Center at the University of California, San Francisco.
While she was enthusiastic about the investigation of recanalization in children, Dr. Fox and her co-author advised caution in interpreting long-term outcome measures from the Save ChildS research.
“Stroke recovery is heterogeneous in children at various stages of brain development, and the natural history of recovery may be good even in the absence of recanalization,” they wrote.
For instance, they pointed out that while only 4 percent of children in the Swiss Neuropediatric Stroke Registry underwent thrombolysis, about half experienced good outcomes without functional deficits. In addition, despite the positive two-year outcomes in the Save ChildS study, selection bias may have affected the results due to data missing for more than one-third of subjects.
More complete data were available for earlier outcomes, but this may not represent “the full picture,” considering that disabilities in children could emerge over time.
“Cognitive and language deficits may initially go unrecognized in a toddler but become apparent as skills required for success in school grow increasingly complex,” the editorialists noted.
Furthermore, there are drawbacks to using published studies for comparison purposes. The modified Rankin scales may not accurately reflect outcomes in the youngest children in the Save ChildS study. In addition, outcomes in different studies may not be measured in parallel ways: For example, in the Save ChildS study, the outcomes were evaluated at discharge and at 180 days, compared to at 90 days in the HERMES trials, rendering the comparisons questionable.
However, Dr. Fox stressed the significance of the Save ChildS research. Childhood stroke is “difficult to study because it's a relatively uncommon event,” she acknowledged. Parents and pediatricians may not recognize symptoms swiftly after onset and within the four-and-a-half-hour treatment window. Bringing together experts across related fields would advance knowledge of stroke mechanisms and recovery with the aim of prevention and better outcomes, Dr. Fox told Neurology Today.
Those with a common interest in childhood cerebrovascular disease—from physicians and surgeons to nurses, psychologists, therapists, and scientists—can share their insights through professional groups, she said. Among them is the International Pediatric Stroke Organization, founded in February 2019.
“To really understand how to best treat children who have a stroke, we need to continue to collaborate broadly across a number of different disciplines,” said Dr. Fox, who often consults with neurointerventional radiologists, neurosurgeons, physiatrists, and hematologists.
“If publication of the Save ChildS study raises awareness of pediatric stroke, the heightened attention would be a positive step toward encouraging the design of improved protocols to streamline diagnosis and deliver time-sensitive treatment,” said David Y. Huang, MD, PhD, FAHA, FAAN, FANA, professor and chief of the division of stroke and vascular neurology at the University of North Carolina at Chapel Hill.
“It's heartening because some data is better than the absence of data,” Dr. Huang said, allowing neurologists to feel more confident in recommending endovascular thrombectomy to parents of sick children now that there is data supporting the safety of the procedure. Furthermore, “in the absence of alternatives, most parents would agree to it,” he added.
In rural areas without a large stroke center in relatively close proximity, it is important to consider lowering the threshold for suspecting a stroke and prompting physicians to seek outside input sooner rather than later, Dr. Huang said.
Even in an era of advanced emergency medical services and improved public awareness of stroke, few pediatric patients arrive at hospitals within the optimal treatment window, said Dana D. Cummings, MD, PhD, associate professor of pediatrics and director of the pediatric stroke program at the University of Pittsburgh Medical Center's Children's Hospital of Pittsburgh.
“My hat is off to the centers that provided thrombectomy for these patients at the early time frame in the study, but that's going to be hard to replicate in most settings,” said Dr. Cummings, who would like to see a study looking at outcomes in children who present more than 4.5 hours after stroke onset and undergo mechanical recanalization.
“As the editorial commentators noted, there may be more neuroplasticity in kids, which complicates the interpretation of outcomes, he said. “You wouldn't want to have a stroke at any age, but if you have a stroke at age three, you probably have maximal plasticity for recovery.”
The editorial also addressed special considerations for performing thrombectomy in children. It should ideally be undertaken by neurointerventional radiologists skilled in both pediatric endovascular procedures and stroke embolectomy to “guide selection of devices appropriate for the smaller cerebrovasculature in children.” However, “as stent retriever devices have been developed for embolectomy of more distal cerebral arteries, size may become less of a barrier in experienced hands. Caution remains advisable even early after stroke, particularly in young or small patients,” the authors wrote.
Planning for a neurointerventional procedure in a child is inherently different, and most adult cases are handled at hospitals with minimal or no pediatric experience.
“Clinicians with only adult experience shouldn't feel a sense of obligation to undertake pediatric cases based on this study alone,” said Heather Fullerton, MD, MAS, professor and chief of the division of child neurology and medical director of the Pediatric Brain Center in the Benioff Children's Hospital at the University of California, San Francisco.
“I am aware of complications anecdotally that haven't been reported in medical literature,” she said, citing the tendency to publish successful cases. “Nonetheless, the Save ChildS study is a great contribution to this field. It's the first large series on children who have received hyperacute therapy for stroke since all of these new thrombectomy trials really changed standard of care in adults.”
To make additional strides in treating childhood stroke, rigorous prospective studies are needed. “That's the only way we're going to get really reliable safety data,” Dr. Fullerton said.
Dr. Sporns, Fox, and Fullerton had no competing interests. Dr. Cummings has received fees as a consultant on pediatric cerebrovascular disorders from the Vaccine Injury Compensation Program. Dr. Huang has received honoraria for service on a data safety and monitoring boards for Cerenova, LLC and ReNeuron.