Regional Pediatric Acute Stroke Protocol
Initial Experience During 3 Years and 13 Recanalization Treatments in Children
Background and Purpose—To evaluate hyperacute management of pediatric arterial ischemic stroke, setting up dedicated management pathways is the first recommended step to prove the feasibility and safety of such treatments. A regional pediatric stroke alert protocol including 2 centers in the Paris-Ile-de-France area, France, was established.
Methods—Consecutive pediatric patients (28 days–18 years) with confirmed arterial ischemic stroke who had acute recanalization treatment (intravenous r-tPA [recombinant tissue-type plasminogen activator], endovascular procedure, or both) according to the regional pediatric stroke alert were retrospectively reviewed during a 40-month period.
Results—Thirteen children, aged 3.7 to 16.6 years, had recanalization treatment. Median time from onset to magnetic resonance imaging was 165 minutes (150–300); 9 out of 13 had large-vessel occlusion. Intravenous r-tPA was used in 11 out of 13 patients, with median time from onset to treatment of 240 minutes (178–270). Endovascular procedure was performed in patients time-out for intravenous r-tPA (n=2) or after intravenous r-tPA inefficiency (n=2). No intracranial or peripheral bleeding was reported. One patient died of malignant stroke; outcome was favorable in 11 out of 12 survivors (modified Rankin Scale score 0–2).
Conclusions—Hyperacute recanalization treatment in pediatric stroke, relying on common protocols and adult/pediatric ward collaboration, is feasible. Larger systematic case collection is encouraged.
Stroke management in adults relies on high-grade evidence-based recommendations, concerning fast-track stroke management, stroke unit implementation, and acute stroke recanalization treatments, that is, intravenous (IV) thrombolysis and endovascular procedures.1 In contrast, pediatric arterial ischemic stroke (AIS) acute management relies on experts’ recommendations.2
As it is much less frequent than in adults,3 recognition of stroke is often delayed in children. Consequently, acute-phase trials are difficult to set up and perform. The phase I multicentric international prospective trial TIPS (Thrombolysis in Pediatric Stroke) was prematurely stopped because of poor enrollment.4 Finally, investigators recommended that next step would be to make recanalization treatments feasible, through improving healthcare organization.5
In the Paris-Ile-de-France region (pediatric population of 2.3 million), France, 2 tertiary care centers joined in a regional network with a pediatric stroke alert protocol (online-only Data Supplement). The protocol, which was adapted to children from international recommendations6 and a posteriori comparable to the most recently published ones,5 was established by a multidisciplinary working group involving pediatric and adult specialists. Brain magnetic resonance imaging (MRI) and collaborative decision-making process were considered mandatory for recanalization treatment decision because of frequent stroke mimics in children. To favor regulation before hospital arrival, regional prehospital and in-hospital emergency departments were informed.
Herein, we report the first pediatric recanalization treatments this organization permitted.
A retrospective multicentric study included consecutive pediatric patients aged 28 days to 18 years with confirmed AIS who had acute recanalization treatment, that is, IV r-TPA (recombinant tissue-type plasminogen activator), endovascular procedure, or both, in one of the centers affiliated to the regional Paris-Ile-de-France pediatric stroke alert protocol between February 2012 and June 2015.
Patients’ information and clinical and radiological stroke characteristics were collected.
These treatments included IV r-tPA, intra-arterial r-tPA, mechanical thrombectomy, or a combination. Bridging therapy was defined as IV-rtPA immediately followed by endovascular procedure, whereas rescue therapy was defined as endovascular procedure after inefficiency of IV r-tPA, that is, persistent occlusion without clinical improvement.
Protocol Functioning Indicators
These included time from symptom onset to MRI and time from symptom onset to beginning of first treatment, either IV or intra-arterial. Intrahospital functioning was evaluated through time from patient’s arrival to beginning of first treatment (door-to-needle).
A brain MRI–magnetic resonance angiography was performed 24 hours after treatment. Good recanalization was defined as thrombolysis in cerebral infarction (TICI) grade 2b-3 for patients who had an endovascular procedure or an arterial occlusive lesion (AOL) magnetic resonance angiography score=3 for patients who did not. Partial recanalization was defined as TICI=1-2a or AOL=2. No recanalization was defined as TICI=0 or AOL=1.7 Symptomatic or radiological peripheral or brain hemorrhage was noted. Clinical outcome evaluation used the modified Rankin Scale (mRS) score at hospital discharge.
This evaluation used mRS score at 3-month follow-up and the type of academic curriculum at 1-year follow-up.
Clinical and radiological scores (ie, NIHSS, mRS, TICI, and AOL) were either prospectively calculated or retrospectively estimated from chart data, using usual adult scales. As samples were small, description of variables used median and range. Comparison between groups used Mann–Whitney nonparametric test, with significant P<0.05.
The research was conducted according to the principles of the Declaration of Helsinki.
From February 2012 to June 2015, 13 patients, 7 boys and 6 girls, median age 11.8 years (3.7–16.6 years), received recanalization treatment for hyperacute AIS within the regional pediatric stroke alert protocol. Ten were treated in center A and 3 in center B.
See the Table.
Predominant clinical presentations comprised acute hemiplegia/hemiparesis and language disorder. Median NIHSS score was 10 (1–21). Most strokes involved the middle cerebral artery territory (n=11/13); 2 children had posterior circulation stroke. Large-vessel occlusion was demonstrated in 9 patients. Main stroke mechanism was cerebral/cervical arteriopathy (n=8).
Eleven children received IV r-tPA with a median time from onset to treatment of 240 minutes (178–270). Four patients underwent endovascular procedure, alone in 2 patients who were out of the time window for IV r-tPA (ie, with time from onset to treatment of >4 hours and 30 minutes, patients 1 and 7), and following IV r-tPA in 2 patients: 1 rescue therapy (patient 4) and 1 bridging therapy (patient 11). Two patients (patients 3 and 7) had recanalization treatment although they were past the time limit according to significant diffusion–perfusion mismatch and slight fluid attenuated inversion recovery hyperintensity.
Protocol Functioning Indicators
Median time from onset to MRI was 165 minutes (150–300 minutes). Patients managed in pediatric wards (n=8) were significantly younger, and their door-to-needle delay was longer than patients managed in adult stroke units: median age 6.5 years (3.7–12 years) and 14.2 years (13.7–16.6 years), respectively (P=0.016), and median door-to-needle time 165 minutes (125-210 minutes) and 59 minutes (50-160 minutes), respectively (P=0.005).
No intracranial or peripheral bleeding was reported after treatment. Recanalization was good in 6 out of 9 children with initial large-vessel occlusion. At discharge, median mRS score was 3 (0–6). We report an early death secondary to malignant stroke, without radiological evidence of intracranial hemorrhage.
Among the 12 survivors, 11 had favorable outcome (mRS score=0–2) at 3-month follow-up; all children had returned to school at 1-year follow-up, with regular schooling (n=7), regular schooling with dedicated assistance (n=2), or adapted schooling (n=3). Outcome did not correlate with the quality of radiological recanalization nor with initial stroke extent.
This experience of 13 recanalization treatments is the first report of consecutive pediatric cases treated with the same protocol through a common organization. It illustrates the feasibility of fast-track management and interventional therapy in hyperacute pediatric stroke in the European setting, although most publications originate from the United States.
Moreover, in situations where randomized control trial is not feasible,4 systematic data collection gives valuable information. Large multicentric data collections may be limited by heterogeneity and lack of exhaustivity. For example, the IPSS report (International Pediatric Stroke Study) on thrombolysis8 concerned an 8-year period, with 18 children treated in 13 centers located in different countries. Focusing on fewer centers with common protocols may overcome this limitation. National or international registries are encouraged, as small samples cannot reach enough statistical power to provide relevant data about treatment safety and efficacy.
A short survey within our centers estimated that only one fifth of the children entering the stroke alert pathway had acute AIS. Because we estimated from the national health insurance information system data3 that 16 to 26 non-neonatal pediatric AIS occurred yearly in the Ile-de-France region during the study period, we could expect 80 to 130 children entering the stroke alert protocol per year, a goal which is still not reached at present. Nevertheless, recanalization treatments represented 16% to 25% of estimated regional pediatric AIS during the study period, which is an unexpectedly high proportion. These findings suggest to setup exhaustive data collection and to focus the training on pediatric wards.
Hyperacute recanalization treatment of pediatric stroke using common protocols is feasible. Reports of consecutive cases are interesting in this setting and can provide valuable information. Pediatric stroke recanalization treatment registries are strongly encouraged.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.117.016591/-/DC1.
- Received October 5, 2016.
- Revision received April 22, 2017.
- Accepted April 26, 2017.
- © 2017 American Heart Association, Inc.
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