There are no approved treatment options for acute ischemic stroke in the pediatric population. A case is presented of a 16-year-old boy with acute left-sided weakness who was transferred to our institution on the third day after onset of symptoms and after deterioration in his condition. He had right internal carotid artery occlusion beyond the origin of the ophthalmic artery. CT perfusion study showed a large area of penumbra in the right middle cerebral artery distribution. Recanalization was achieved with self-expanding stent placement and mechanical thrombectomy. Post procedure CT perfusion study showed resolution of the penumbra. At the 3 month follow-up, his modified Rankin Scale score was 1 and at 1 year it was 0. A subset of pediatric patients with acute ischemic stroke secondary to large intracranial arterial occlusion may be potential candidates for this treatment approach.
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Trials have shown the efficacy of intravenous thrombolysis (IVT) and intra-arterial thrombolysis (IAT) in adults with acute ischemic stroke.1 ,2 In some refractory cases, mechanical thrombectomy and stent assisted recanalization are being used for revascularization.3–6 However, no such treatment options are approved for pediatric ischemic stroke. We report our initial experience in performing delayed recanalization in a pediatric patient with acute ischemic stroke.
A 16-year-old boy with a history of Crohn's disease was brought to an outside institution after acute onset of left-sided weakness and slurred speech. A CT scan of head without contrast was normal. Due to partial improvement of his weakness after presentation and perhaps reluctance because of his age, IVT was not administered. The next day, his left-sided weakness worsened and he was eventually transferred to our center on hospital day 3 with a National Institutes of Health Stroke Scale (NIHSS) score of 11. CT scan with perfusion (CTP) displayed ischemic penumbra in the right middle cerebral artery (MCA) territory (figure 1A-D). The patient was then taken for emergent cerebral angiogram which revealed complete right internal carotid artery (ICA) occlusion at the supraclinoid segment. There was partial collateral flow to the right MCA from the left via a small anterior communicating artery and some leptomeningeal collateral supply from the posterior circulation (figure 2). After discussion of the potential risks and benefits of a late recanalization procedure, his parents opted for no endovascular intervention. He was admitted to the neurointensive care unit, and continued on a heparin drip, with a goal of a partial thromboplastin time of 50–60 s. He was administered a loading dose of clopidogrel 300 mg in addition to aspirin 325 mg. His blood pressure was artificially raised for a systolic blood pressure goal of 160–180 mmHg with aggressive intravenous normal saline. Unfortunately, the next day medical therapy failed, his condition worsened and his NIHSS score was 15. Repeat CTP continued to display a large area of penumbra in the right MCA territory (figure 1E-H). CT scan and MRI stroke protocol showed an area of core infarct in the right frontal lobe (figure 3). After consent from his parents, he was taken to the endovascular laboratory for intervention.
Under general anesthesia, vascular access was obtained in the left common femoral artery with a 5 F tapered micropuncture kit. A 6 F, 80 cm Cook shuttle sheath was coaxially brought up into the right common carotid artery over a 5 F Davis catheter. A 0.057 distal access catheter guide catheter (Concentric Medical Inc, Mountain View, California, USA) was then introduced into the Cook shuttle and advanced into the right ICA. Since intravenous heparin was temporarily stopped 1 h before vascular access, as part of the hospital protocol, interval doses of intravenous heparin were administered to maintain an activated clotting time of approximately 200 s for the duration of the procedure. The lesion was crossed using an 18 L Concentric microcatheter (Concentric Medical Inc) over a platinum wire. The microcatheter was exchanged for a 0.041 Penumbra catheter and the Penumbra Aspiration System was connected (Penumbra Inc, Alameda, California, USA). Thrombus aspiration was not successful. The system was then exchanged for a Wingspan 4.5×20 mm stent (Boston Scientific, Massachusetts, USA) which was then advanced into the distal M1 segment extending all the way to the ICA. The stent was deployed without incident. Post-stent deployment images showed residual clot in the MCA. Continued suction thrombectomy was performed using a combination of the distal access catheter and the Penumbra system. Following this there was TIMI 2 flow across the MCA and a decision was made to conclude the procedure (figure 2).
Hospital course and follow-up
After the procedure the patient was continued on aspirin, clopidogrel and intravenous heparin. Transesophageal echocardiography displayed an ill defined mobile echogenic density at the right ventricular outflow. However, repeat transesophageal echocardiography was negative for any intracardiac thrombus. CT scan of the head without contrast 3 days after the procedure displayed deep right frontal lobe, right basal ganglia and anterior limb of the right internal capsule hypodensities with sparing of more than two-thirds of the MCA territory. Postoperative CTP displayed resolution of the perfusion deficit (figure 1I-L). On discharge (day 10), his modified Rankin Scale (mRS) score was 3. After 3 months of follow-up, his mRS score improved to 1 and NIHSS score was 1. An extensive workup for thrombophillia in this patient was negative. Repeat cerebral angiogram after 3 months displayed no in-stent stenosis with TIMI 3 flow. At the 1 year follow-up he had only mild difficulty with left hand dexterity.
Our case differs from previously reported cases in the literature in that mechanical thrombectomy and stent assisted recanalization were performed more than 72 h after the onset of symptoms. Our case is also unique in terms of being a CT perfusion guided recanalization in a pediatric patient. Pediatric mortality from ischemic stroke is 5–10%, low compared with the adult population, but most survivors are left with persistent neurological and psychosocial deficits.7 To date, no randomized controlled trial has been performed to investigate the benefits of IVT, IAT or mechanical thrombolysis in pediatric stroke. One study reported a literature review of 17 children with ischemic stroke who underwent IVT (six patients), IAT (10 patients) or mechanical thrombolysis (one patient).8 Of 17 children, 16 survived and 12 (71%) had a good outcome (mRS 0 or 1). Only two patients had asymptomatic intracranial hemorrhage. Lai et al reported on the use of IAT and stenting for internal carotid dissection in a 12 year old with a successful outcome.9 Grunwald et al reported the use of mechanical thrombectomy in three children aged 7–16 years with complete recanalization and significant improvement in their NIHSS score.10 Irazuzta et al also reported successful use of IAT and mechanical thrombectomy in MCA occlusion with complete resolution of left hemiplegia in a 12-year-old child.7 The current American Heart Association guideline does not recommend tissue plasminogen activator use in young children other than in clinical trials.11
With CTP, it is possible to identify potentially salvageable ischemic tissue (penumbra) and separate this from irreversibly infracted tissue (core).12 In the adult population, several case series of treatment of acute ischemic stroke beyond 6 h have reported a good clinical outcome.5 ,6 ,13 ,14 In these case series, multimodal therapies with mechanical thrombectomy and stent assisted delayed recanalization were used in many patients. The rate of recanalization varies from 66% to 92% in these studies. Extended time window was based on salvageable ischemic tissue (penumbra) on CTP or perfusion diffusion mismatch on MRI.13 Diffusion weighted imaging–perfusion weighted imaging mismatch and diffusion weighted imaging reversibility are two MRI correlates that reflect the existence of the penumbra and the potential to salvage it through reperfusion, respectively.15–17 Our patient had potentially salvageable area of penumbra in right MCA distribution on CTP (figure 1) despite his late presentation. Most likely, due to collateral circulation (figure 2C–D), a large area of penumbra persisted late after his symptom onset.
Two FDA approved devices are available specifically for mechanical thrombectomy: the Merci retriever (Concentric Medical) and the Penumbra (Penumbra Inc). Both devices have shown safety and efficacy in the treatment of acute ischemic stroke within 8 h.3 ,18 Recanalization rates were 66% and 81%, respectively. The pilot study, SARIS (Stent Assisted Recanalization in acute Ischemic Stroke), evaluated the Wingspan stent for revascularization in patients who did not improve after IVT or who had a contraindication to IVT.19 It showed a high rate of recanalization (100%) with a symptomatic intracerebral hemorrhage rate of 5%. We have reported the use of delayed intracranial stenting in adults in acute and subacute stroke with a high rate of recanalization and good outcomes.5 ,6 In this case, we used the Penumbra system first, which was unsuccessful, and hence was followed by Wingspan stent assisted recanalization. The Penumbra system was used again for aspiration of residual clot with TIMI 2 recanalization. Post procedure CT perfusion showed normalization of mean transit time along with normal cerebral blood flow and cerebral blood volume, except in a small area of the deep frontal lobe and right basal ganglia.
In conclusion, a subset of patients, even in the pediatric age group, can be potential candidates for delayed endovascular intervention in acute ischemic stroke with guidance of CT perfusion or MRI diffusion/perfusion. Larger studies are needed to validate this approach in the pediatric population.
Dr Mahmoud Rayes helped with the figures in this manuscript.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was approved by the institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.