By Nidhi Ravishankar & Arpita Lakhotia.
The Save ChildS study1 is the first retrospective, multicenter cohort study that analyzed databases from 27 stroke centers in the United States and Europe suggesting comparable safety data for endovascular thrombectomy (EVT) in all pediatric patients (< 18 years of age) compared with those presented by randomized-controlled clinical trials performed in the adult population. A follow-up post hoc analysis in Stroke2 suggested positive neurological outcomes regardless of any specific EVT device technique or device selection. The authors of this study found that there was no association between the stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Thus, there was a reassurance for clinicians that it is safe and important to offer thrombectomy in eligible children presenting with acute ischemic stroke due to large vessel occlusion regardless of technique or device selection. These studies were a benchmark of reassurance for clinicians who opt for the EVT technique for children presenting with acute ischemic stroke due to large vessel occlusion.
It is our privilege to invite Dr. Peter Sporns, who spearheaded both studies, as our guest, to speak more about the study and the practice of endovascular management in pediatric stroke.
In what ways does this study differ from previous systematic reviews and meta analyses published on endovascular thrombectomy in pediatric acute ischemic stroke?
Previously, the use of endovascular thrombectomy in the pediatric population with arterial ischemic stroke due to large vessel occlusion has only been presented in scarce case reports and case-series, raising inevitably questions on the efficacy and predominantly on the safety of using the relatively large endovascular devices in children. The Save ChildS Study was the first large retrospective, multicenter cohort study suggesting comparable safety data for EVT in children <18 years of age compared with those presented by randomized-controlled clinical trials performed in the adult population.
The SAVE CHILDS registry spans 18 years. How did the number of thrombectomies performed per year change over that time frame? How has the overall treatment of pediatric patients with endovascular thrombectomy changed over time?
Even though the timespan of the Save ChildS Study is over 18 years, a gradual increase of the number of thrombectomies was observed after publication of the randomized trials in adults in 2015. Before 2015, only 7 of the 73 included patients underwent EVT with first-generation thrombectomy devices like coil/or braided retrievers. After 2015 the annual number of included cases was on average ~15 per year, reaching its maximum in 2018 with 24 included children.
Why do you think outcomes in the younger children were poorer than the older children in the SAVE CHILDs study?
This is an interesting question. For the analysis we created 3 age groups of children (0-6 years, 7-12 y and 13-18 y). Indeed, when looking at the PSOM, pedNIHSS and pedmRS, outcomes in the youngest children were worse compared to the other age groups. Of note, only 11 of the 73 children were 0-6 years, so this may be biased. The frequency of peri-/postinterventional complications was not significantly higher in younger children but the only symptomatic intracerebral hemorrhage in the whole study cohort occurred in a child in this age group and one child died after the stroke. If 2 of 11 children have such poor outcomes it will of course influence the results. To draw definite conclusions on a possible lower age limit of EVT it seems to early and higher quality evidence is needed.
Was there anything that was surprising or striking to you from results of the study?
For me, as a neurointerventionist also performing adult thrombectomies, it was not surprising that EVT, which has made a huge impact on adult stroke care, would also work in children. Especially in older children, there would be no obvious reasons why this method should not work as it does in adults. A little surprising for me was that the rate of successful recanalization was even higher in children than in the randomized trials in adults. On the other hand, even in adults, recanalization rates have improved since publication of the first trials in 2015, which is probably explained by greater technical experience of the treating neurointerventionists and further improvements of the used devices. The lack of arteriosclerotic changes and arterial elongation in children in my opinion also contributes to a higher rate of successful catheterization of the intracranial arteries.
Based on the paper, thrombectomy in childhood stroke appears to be safe. With this data, what other barriers do you see in making endovascular thrombectomy a standard of care in pediatric stroke management?
As we know children with arterial ischemic stroke often present late due to various reasons like an unawareness of the possibility of a stroke in children and a large spectrum of stroke mimics. Therefore, increasing the time-window of eligibility for EVT offers a great potential to increase the total number of children with hyperacute stroke receiving a treatment. First studies have investigated the use of advanced imaging for selection of children in the extended time window. Indeed, there is evidence that when vascular imaging demonstrates a vessel occlusion and perfusion–diffusion imaging demonstrates salvageable brain tissue, the time since onset of symptoms (which is often not precisely known) seems of little additional prognostic value.
What do you feel are 2 take home points for readers of this paper?
First of all, the Save ChildS Study shows that endovascular thrombectomy is safe in children presenting with arterial ischemic stroke due to large arterial occlusion. It also shows that some questions remain:
- How can we identify which patients will not benefit from hyperacute reperfusion therapies?
- Is there a lower age limit for EVT?
- What are the actual risks of EVT in children with underlying arteriopathies and do they outweigh the benefits?
Although stroke has been long recognized as one of the leading causes of mortality in the adult population, approximately 2 to 8 per 100 000 children per year suffer from this rare clinical event that can lead to potentially severe negative outcomes and long-term social and functional disabilities3 ,4. While management modalities in childhood stroke differs between centers and individual cases, in 2019, the American Heart Association Stroke Council and Council on Cardiovascular and Stroke Nursing suggested that consideration of endovascular therapies be limited to children with persistent disabling neurological deficits (pediatric National Institutes of Health Stroke Scale [NIHSS] score ≥6 at the time of intervention or higher if DAWN trial criteria are being applied), radiographically confirmed large vessel occlusions, and larger children because of size-based limitations on contrast dye and radiation exposure5. While the benefits of EVT in pediatric stroke relies heavily on the techniques used to gain positive outcomes in the adult population, studies in the recent past have shown that EVT is likely a safe modality which confers high rates of favorable functional outcomes6-8.
Here, we continue our discussion with Dr. Sporns about the advancements in management for pediatric stroke.
In your opinion, what recent developments have made the biggest impact on the treatment of pediatric acute ischemic stroke?
The development of regional pediatric stroke networks, education of paramedics and pediatric emergency physicians leading to a more rapid diagnostic workup and also the greater use of rapid MRIs as the first imaging modality have already and will continue to increase access to reperfusion therapies. This has already and will continue to help children getting treated with hyperacute therapies – or if a stroke mimic is detected the adequate alternative therapy.
There is a shift in adult stroke management from time-based criteria for intervention to imaging-based criteria for intervention. Do you anticipate a similar shift in pediatric stroke care?
Yes! As not only an interventional but also diagnostic neuroradiologist I am convinced that neuroimaging will play a crucial role in determining the actual “tissue clock” for every child instead of applying a fixed “time clock” for all patients. There are so many factors influencing individual tissue fate like collaterals, degree of occlusion/stenosis, etiology, thrombus histology, just to name a few.
How do you envision the advancement of endovascular management for pediatric stroke care in the coming 5 to 10 years?
As pointed out above, there are several open questions that need to be addressed to tailor individual approaches for every child and select the children that will benefit from endovascular thrombectomy. The ongoing Save ChildS Pro prospective cohort study will hopefully help to further define these selection criteria and generally provide a higher-level evidence for the use of EVT in children. Thereby, in my opinion more centers will gain confidence to offer hyperacute therapies like thrombectomy to children with arterial ischemic stroke while the indications for EVT will expand to include more children.
Peter Sporns, MD, MHBA Bio: Dr. Peter Sporns is an attending interventional neuroradiologist and assistant professor at the University of Basel, Switzerland. He has been a member of the International Pediatric Stroke Society (IPSS) since 2019 and co-chairs the IPSO Communications Committee.
- Sporns PB, Strater R, Minnerup J, et al. Feasibility, Safety, and Outcome of Endovascular Recanalization in Childhood Stroke: The Save ChildS Study. JAMA Neurol 2020;77(1):25-34. doi: 10.1001/jamaneurol.2019.3403 [published Online First: 2019/10/15]. PMID: 31609380
- Sporns PB, Straeter R, Minnerup J, et al. Does Device Selection Impact Recanalization Rate and Neurological Outcome?: An Analysis of the Save ChildS Study. Stroke 2020;51(4):1182-89. doi: 10.1161/STROKEAHA.119.028221 [published Online First: 2020/03/03]. PMID: 32114927
- Mallick AA, Ganesan V, Kirkham FJ, et al. Childhood arterial ischaemic stroke incidence, presenting features, and risk factors: a prospective population-based study. Lancet Neurol 2014;13(1):35-43. doi: 10.1016/S1474-4422(13)70290-4 [published Online First: 2013/12/07]. PMID: 24304598
- Goldenberg NA, Bernard TJ, Fullerton HJ, et al. Antithrombotic treatments, outcomes, and prognostic factors in acute childhood-onset arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 2009;8(12):1120-7. doi: 10.1016/S1474-4422(09)70241-8 [published Online First: 2009/10/06]. PMID: 19801204
- Ferriero DM, Fullerton HJ, Bernard TJ, et al. Management of Stroke in Neonates and Children: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke 2019;50(3):e51-e96. doi: 10.1161/STR.0000000000000183 [published Online First: 2019/01/29]. PMID: 30686119
- Dicpinigaitis AJ, Gandhi CD, Pisapia J, et al. Endovascular Thrombectomy for Pediatric Acute Ischemic Stroke. Stroke 2022;53(5):1530-39. doi: 10.1161/STROKEAHA.121.036361 [published Online First: 2022/03/12]. PMID: 35272483
- Wilson JL, Eriksson CO, Williams CN. Endovascular Therapy in Pediatric Stroke: Utilization, Patient Characteristics, and Outcomes. Pediatr Neurol 2017;69:87-92 e2. doi: 10.1016/j.pediatrneurol.2017.01.013 [published Online First: 2017/02/25]. PMID: 28233666
- van Es A, Hunfeld MAW, van den Wijngaard I, et al. Endovascular Treatment for Acute Ischemic Stroke in Children: Experience From the MR CLEAN Registry. Stroke 2021;52(3):781-88. doi: 10.1161/STROKEAHA.120.030210 [published Online First: 2021/02/23]. PMID: 33617341
Nidhi Ravishankar, MD
University of Louisville
Dr. Nidhi Ravishankar is currently a PGY1 Pediatric Neurology resident at the University of Louisville. Her interests include pediatric NICU, pediatric and adult stroke and pediatric and adult neurointervention
Arpita Lakhotia, MD
University of Louisville / Norton Children's Medical Group
Dr. Lakhotia is originally from India and completed medical school at Dr. Sampurnanand Medical College at Jodhpur in India. After medical school she moved to the United States to pursue residency in Pediatrics and fellowship in Child Neurology at Rainbow Babies and Children’s Hospital in Cleveland Ohio. She is now an Assistant Professor of Child Neurology at University of Louisville and Norton Children’s Medical Group. She has special interest in pediatric stroke and medical education.