New Data May Support Off-Label Thrombectomy in Pediatric Stroke

October 17, 2019

Further evidence that mechanical thrombectomy is safe and feasible in childhood stroke has come from a new registry study, which investigators suggest, "may support the use of off-label thrombectomy in childhood stroke in the absence of high-level evidence."

"This is by far the biggest database so far of endovascular thrombectomy treatment in pediatric stroke," lead author, Peter Sporns, MD, University Hospital of Münster, Germany, told Medscape Medical News.

"Our study raises awareness of endovascular therapy for children with stroke and gives us a lot more data on this than we've had before. We expect that our results will impact current treatment guidelines and that endovascular recanalization will become first-line therapy in children with acute ischemic stroke due to large vessel occlusion."

Sporns also said the findings have immediate clinical implications.

"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."

The study was published online October 14 in JAMA Neurology.

Safety in Kids Uncertain

Childhood arterial ischemic stroke is a rare clinical event with an estimated incidence of 2 to 8 per 100,000 children per year, but can result in severe disability with long-term social and financial effects.

While endovascular treatment has been shown to be safe and effective for acute ischemic strokes caused by large intracranial vessel occlusions in adults, its safety and effectiveness in children is unknown with only data from small case series available.

To date, supportive medical management specific to the underlying etiology of acute ischemic stroke is considered the standard of care in pediatric patients and thrombolytic and endovascular therapy are only recommended as a last resort due to a lack of level-A evidence.

Randomized trials in pediatric stroke patients have proven difficult and may never reach equipoise in the setting of evidence for a strong treatment effect in adults, the researchers note.

The current study evaluated real-world experience with thrombectomy in pediatric patients with stroke with large-vessel occlusion from 27 stroke centers in Europe and the United States.

The registry study included 73 children with a median age of 11.3 years. Of these, 63 children received treatment for anterior circulation occlusion, and 10 patients received treatment for posterior circulation occlusion; 16 patients received concomitant intravenous thrombolysis.

Most (82%) of the thrombectomy devices used were currently available stent retrievers, with 4 × 20 mm the most frequently chosen size. Aspiration catheters were used as the first-line approach in seven patients.

Results showed that neurologic outcome improved from a median PedNIHSS score of 14.0 at admission to 4.0 at day 7. The median modified Rankin scale score was 1.0 at 6 months and 1.0 at 24 months.

In terms of safety, one patient (1%) developed a postinterventional bleeding complication and three patients (4%) had a malignant infarction followed by decompressive hemicraniectomy.

In addition, four patients (5%) developed transient peri-interventional vasospasm, which resolved after administration of nimodipine and without any clinical sequelae.

One patient with a preexisting heart anomaly died of cardiac arrest after complete recanalization of the occlusion. No vascular complications, such as arterial dissection, periprocedural thrombosis, or puncture site complications were reported.

The proportion of symptomatic intracerebral hemorrhage events was 1.37 compared with 2.79 in the HERMES meta-analysis of trials of endovascular therapy in adults.

Key Findings

The authors note the main findings of the retrospective, multicenter cohort study show endovascular thrombectomy in pediatric patients with ischemic stroke and large-vessel occlusion is feasible, since most patients underwent successful recanalization.

Secondly, complication rates were low in children undergoing mechanical recanalization treatment and long-term neurologic outcomes were good in most patients. In addition, short-term improvement determined by PedNIHSS score was comparable with the short-term improvement of NIHSS in adult trials.

Endovascular intervention for pediatric stroke is used judiciously.

The cause of stroke in children is more often due to an underlying inflammatory arteriopathy, which may increase the risk of bleeding complications during endovascular procedures owing to vessel fragility.

"Inflammatory arteriopathy is more common in pediatric stroke than in adult stroke and this obviously causes concerns about damaging the vessel further with any intervention. But we didn't see any problems with endovascular intervention in the seven patients with arteriopathy treated with endovascular therapy in this registry," Sporns said.

"This is a small number and we still have to be cautious, but there was no hint of worse outcomes or more complications in this group, which is encouraging," he said.

Subgroup analysis by age showed worse outcomes in younger patients (age 0 - 6 years).

"Although the statistical significance of these findings is questionable, the data suggest that successful endovascular recanalization in younger children aged 0 to 6 years may be futile more frequently and should be performed only after careful consideration of all risks and potential benefits," the researchers write.

While stroke in children is rare and not often encountered by emergency physicians, strokes in the large vessels — which are those suitable for endovascular treatment — are easier to diagnose as these patients are usually severely affected with aphasia and hemiparesis, said Sporns.

"Also the great advancement of endovascular therapy for adult stroke in recent years has raised general awareness of stroke among ER doctors even in children," he added.

Sporns further noted that in adults, endovascular therapy can now be used up to 24 hours after stroke onset in selected patients with suitable imaging.

"We only had one or two late patients in our registry, so we cannot recommend endovascular therapy for this group on the basis of our study," he said.

However, he still believes that based on the adult data, it will be used in late pediatric patients.

"If there is a large vessel occlusion and the patient is very severely affected and has the right imaging for late endovascular treatment — a small area of brain infarct and a large area that may be salvageable — then I don't think we can just do nothing."

The researchers are now building up a prospective registry of endovascular therapy in children, which will collect data on pediatric stroke patients potentially eligible for endovascular thrombectomy and compare those treated with endovascular therapy with those not receiving such treatment.

"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 and are happy if pediatric stroke centers will join our registry," Sporns said.

Some Unanswered Questions

In an accompanying editorial, Christine Fox, MD, University of California, San Francisco, and Nomazulu Dlamini, MBBS, The Hospital for Sick Children, Toronto, Ontario, Canada, note that the study begins to address the knowledge gap in hyperacute stroke therapy studies in children.

However, they add the safety concerns about use of endovascular therapy in children with focal cerebral arteriopathy remain unanswered due to the small number of such patients in the study.

The editorialists also urge caution on the interpretation of long-term outcome measures in study.

"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 write.

They also point out that 2-year outcomes were missing for more than one third of the children, and although earlier outcomes were more complete, they may not provide the full picture as deficits may emerge over time in children.

"Given differences in the interpretation of outcome instruments and timing of outcome measures in the Save ChildS study compared with the HERMES trials, comparisons between these studies are of questionable value," they conclude.

Sporns, Fox, and Dlamini have disclosed no relevant financial relationships. The remaining study co-authors report owning patents related to thrombectomy.

JAMA Neurol. Published online October 14, 2019. Abstract, Editorial

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