Seven hours after last seen at baseline, our child was significantly outside of the intravenous recombinant tissue plasminogen activator (IV r-tPA) therapeutic window. The recommended pediatric IV r-tPA window is 3–4.5 h after last known normal (9). However, he was deemed a suitable candidate for endovascular recanalization given the small core infarct and large penumbra. The patient was taken to the neuroendovascular suite and intubated. A 5 French (Fr) sheath was placed in the right common femoral artery and a 5 Fr 90 cm Envoy (Codman & Shurtleff, Inc., Raynham, MA, USA) was navigated into the distal cervical right internal carotid artery (ICA). Right ICA injections showed a right M1 segment MCA occlusion just distal to the origin of the right anterior temporal artery (Figures 2A,B). Successful mechanical thrombectomy was performed with a 3 mm × 20 mm Trevo retrievable stent device (Stryker Neurovascular, Fremont, CA, USA). Two passes with the Trevo were performed while under continuous aspiration through the base catheter during retraction of the retrievable stent. Thrombolysis in cerebral infarction (TICI) 3 right MCA recanalization was achieved within 1.5 h of completion of the MRI, for a total time between symptom onset to recanalization of 8.5 h. This procedure was complicated by thromboembolic occlusion of the A2 segment of the right anterior cerebral artery (Figure 2).

An urgent transesophageal echocardiogram confirmed bilateral severe atrial enlargement with normal ventricular size and function, with cardiac MRI confirming the diagnosis of restrictive cardiomyopathy and the absence of an intracardiac thrombus (Figure 2). A right ventricular endomyocardial biopsy showed cardiomyocyte hypertrophy with endocardial and superficial interstitial fibrosis.

Subsequently, anticoagulation with dabigatran was prescribed for secondary stroke prevention. Given his high risk for arrhythmia, an implantable cardiac defibrillator was placed. His hypercoagulable work-up was negative. Genetic testing revealed a missense mutation in the TNNI3 gene consistent with a primary restrictive cardiomyopathy (PRCM). Following the diagnosis of PRCM, a detailed history revealed frequent episodes of lip cyanosis when swimming or biking, which caused him to avoid physical exertion. This behavior had become progressively obvious to his relatives, who had attributed his inactivity to “being lazy.” On discharge, his examination was only notable for a left pronator drift (NIHSS 1), with a modified Rankin score of 1. Four months later, he underwent a successful heart transplant and at 1-year follow up, he continued to be without thromboembolic sequelae and neurologically stable.

Primary restrictive cardiomyopathy accounts for 2.5–5% of cardiomyopathies in children. It is characterized by biatrial enlargement, normal left ventricular wall thickness and atrioventricular valves, impaired ventricular filling with restrictive physiology, and preserved systolic function (18–21). Most commonly PRCM is idiopathic in nature (20, 22). Other etiologies involve genetic disorders, skeletal myopathies, and storage diseases (23, 24).

Arteriopathy is the most common cause of pediatric stroke. Our patient presented with congenital cardiomyopathy (CCM), which may herald a neglected diagnosis, yet typically occurs in 20–30% of children undergoing corrective surgery (25, 26). Children with CCM develop a procoagulant state owing to turbulent blood flow, a malfunctioning hemostasis cascade (27–32), abnormal fibrinolysis factors (30–33), and anomalous platelet count and function (28, 30, 34, 35).

Primary restrictive cardiomyopathy examination commonly reveals evidence of pulmonary hypertension and cor pulmonale, such as loud P2, gallop, distended jugular veins, hepatomegaly, and ascites (36–38). Abnormal EKG findings (right and/or left atrial enlargement, though ST segment depression and ST-T wave abnormalities) are present to varying extent in 98% of cases (36). Chest radiograph commonly shows cardiomegaly, particularly atrial enlargement, as well as pulmonary edema (36).

Up to 15% of children with PRCM present with arrhythmia (atrial flutter or atrial fibrillation), or conduction disorders (Mobitz 2 and third-degree AV block), or pre-excitation syndromes (e.g., Wolff–Parkinson–White syndrome) (38). Thereby, PRCM represents a known source of intracardiac thrombus formation due to blood stasis in the setting of severely dilated atrial chambers (18).

Although our patient did experience mild dyspnea on exertion, he did not exhibit other significant symptoms of cardiac decompensation, such as chest pain or syncope, and thus he remained undiagnosed until he developed symptoms secondary to his intracranial embolic stroke (36–38).

Primary restrictive cardiomyopathy is usually diagnosed by a combination of echocardiogram and cardiac catheterization, with the latter being the definitive test (18, 39–42). Elevation of biventricular end diastolic pressures in addition to pulmonary hypertension on cardiac catheterization is suggestive of PRCM (18, 39–42). Endomyocardial biopsy was non-diagnostic (18, 22, 43).

Adult acute arterial ischemic stroke management guidelines unequivocally support the use of IV r-tPA (44, 45), endovascular mechanical thrombectomy, or intra-arterial r-tPA administration (46, 47) in specific situations.

The Thrombolysis in Pediatric Stroke (TIPS) trial (9) and latest Royal College of Pediatrics and Child Health (RCPCH) recommendations (48) represent the current landmark in acute pediatric stroke. Pediatricians remain cautiously optimistic in the light of adult thrombolysis therapeutic success. Despite substantial differences in thrombolytic pharmacokinetics and dose–response (49, 50), IV r-tPA in children can be deemed safe through a focus on meticulous selection criteria (9, 51). A majority of childhood strokes are due to intracranial arteriopathy, wherein mechanical thrombectomy is questionable, owing to the inflamed and friable arterial walls (52). Conversely, cardio-embolic strokes represent an ideal correlate to adults that would benefit from mechanical intervention. However, the inability to use thrombo-aspiration devices due to small artery caliber and the consequent risk of thrombus fragmentation or migration may detract from enthusiasm.

While recent data have begun to unravel the detrimental effect of aging on collateral supply (53–55), pediatric collateral flow remains largely unexplored. Sparse reports compare pediatric stroke outcomes of similar NIHSS severity yet distinct collateral profiles treated with endovascular therapy (56). Nevertheless, the latest adult data support superior TICI scores (57–59) and functional outcomes (60–64) in patients undergoing recanalization in the setting of better collateral flow. Moreover, recanalization seems to carry fewer rates of hemorrhagic conversion post-instrumentation (57, 65, 66). At this time, the relationship of efficient pediatric cortical collaterals with diffusion/perfusion mismatch is incompletely understood. Unfavorable imaging does not render infarct progression an absolute certainty without treatment (67). Therefore, it would be intuitive to measure the recanalization benefit in clinical terms until radiological (i.e., angiographic) or parenchymal metrics are validated in children (68). In a field without studies controlled for intervention in the presence of good collaterals (69, 70), the preceding evidence informed the management of our patient.

With the aforementioned limitations to translate adult evidence to children in mind, we believe our case and others (71–77) provide hope and opportunity. Our child presented outside of the 4.5-h IV r-tPA window adopted by the TIPS trial methodology which represents the standard of practice in both children and adults. Additionally, the onset-puncture time was beyond our institutional guideline of 8 h yet within the current maximum advisory of 12 h by RCPCH. Nevertheless, the patient had a rich collateral supply, allowing for a small core infarct and large penumbra to be seen upon imaging, which led to our decision to intervene (Figure 1). Therefore, we pursued mechanical thrombectomy and salvaged a large ischemic brain area with a great impact on the child’s functional status. In terms of secondary prevention, we prescribed dabigatran which is a direct thrombin inhibitor that is independent of the variable antithrombin levels encountered in pediatrics and offers a favorable pharmacological profile (78). Primarily to avoid age-appropriate inconsistencies in daily intake, interactions with other medications, potential osteoporosis in long-term use of warfarin (79), and frequent laboratory monitoring (10, 80–82). Finally, our child underwent heart transplantation (18, 22, 39, 41, 42, 83, 84), which will prevent the occurrence of cardioembolic events.