Intravenous tenecteplase thrombolysis and endovascular bridging intra-arterial tirofiban injection therapy in a pediatric case of acute ischemic stroke

Abstract

Background

Acute ischemic stroke (AIS) in pediatric patients is a significant contributor to neurological impairment and long-term disability. Due to the absence of specific pediatric treatment guidelines, management strategies are frequently adapted from adult protocols. This report details the application of intravenous tenecteplase thrombolysis, endovascular bridging therapy, and tirofiban in treating a pediatric case of AIS.

Case description

A pediatric patient presented with AIS involving the left limb, lasting 2.5 h. The stroke occurred during physical activity without loss of consciousness or seizures. Head magnetic resonance imaging (MRI) combined with clinical manifestations confirmed the diagnosis of acute cerebral infarction. Intravenous thrombolytic therapy using tenecteplase was initiated in the ultra-early phase of infarction. Subsequent cerebral angiography revealed occlusion of the superior trunk of the right middle cerebral artery. Three-dimensional rotational imaging identified multiple aneurysms at its bifurcation. A targeted intra-arterial injection of tirofiban (6 mL) was administered to stabilize plaque and enhance blood flow. The patient underwent 11 days of antiplatelet therapy and supportive care. At the 90-day postoperative follow-up, notable recovery of limb function was observed.

Conclusions

Pediatric AIS exhibits variable clinical manifestations, requiring head MRI for definitive diagnosis. Early initiation of intravenous thrombolysis with tenecteplase, combined with targeted intra-arterial tirofiban injection, demonstrates potential as a safe and effective therapeutic approach in pediatric ischemic stroke management.

Introduction

Stroke remains a major cause of disability and mortality globally, characterized by high recurrence rate and significant disease burden. Pediatric acute ischemic stroke (AIS), affecting children aged 1 month to 18 years, results from disrupted blood supply to the brain, leading to hypoxic brain tissue necrosis and subsequent neurological dysfunction. Studies indicate that the incidence of pediatric AIS ranges from 0.6 to 7.9 per100 000, with a mortality rate of 3.0–4.7% [1, 2]. While the incidence and mortality rates are lower in children compared to adults, AIS remains a significant cause of neurological impairment and lifelong disability in pediatric populations [3]. Pediatric AIS is associated with high rates of disability, elevated mortality, and poor long-term prognosis, if not treated in a timely and effective manner [4]. Significantly different from adults, common etiologies and risk factors of AIS in children include vascular lesions (arterial dissection, focal cerebral arteriopathy, vascular malformation, systemic vasculitis, primary central nervous system vasculitis), cardiac abnormalities (congenital heart disease, especially cyanotic congenital heart disease, myocarditis, endocarditis, cardiac tumor disease, arrhythmia, cardiomyopathy, and artificial valve implantation after cardiac surgery), hematological abnormalities (sickle cell anemia, leukemia, polycythemia, thrombocytosis, thrombotic thrombocytopenic purpura, antiphospholipid syndrome, coagulation disorders such as protein C and protein S deficiency, antithrombin III activity reduction, coagulation factor V mutation, etc., methylenetetrahydrofolate reductase deficiency, hyperlipoproteinemia, severe dehydration, iron deficiency anemia), infections [virus, Mycoplasma pneumoniae, bacteria, Toxoplasma, tuberculosis, human immunodeficiency virus (HIV), Leptospira, and fungi], head and neck trauma, and genetic diseases (Fabry disease, Menkes disease, adenosine deaminase 2 deficiency, homocystinuria, urea cycle disorders, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) [5–9]. The incidence of these factors varies with different study populations, and congenital and genetically related etiologies are more prominent in children [10]. Currently, there are no established treatment guidelines specifically tailored for pediatric AIS and management often relies on adapting protocols designed for adults. Reperfusion therapy during the acute phase presents considerable challenges in pediatric cases. For adult ischemic stroke, there is relevant evidence and guidelines supporting the use of tenecteplase (TNK) and tirofiban. However, there are no related studies on pediatric patients. This article aims to provide some experience in the treatment of large vessel occlusion in children with TNK and tirofiban by presenting the diagnosis and treatment of a pediatric AIS case involving intravenous thrombolysis with TNK followed by endovascular bridging intra-arterial tirofiban injection therapy as off-label use initiated 2.5 h after symptom onset.

Medical records

A 12-year-old female pediatric patient, 175 cm tall and weighing 80 kg, presented to the emergency department of Hulunbuir People’s Hospital at 18:45 on April 7, 2024 with complaints of acute onset of speech impairment and left limb weakness that lasted 4 h. The patient experienced a sudden onset of symptoms during physical activity resulting in a fall where she did not experience any injuries. Clinical examination revealed left limb weakness, facial asymmetry, and slurred speech. Initial head computed tomography (CT) at a local hospital ruled out cerebral hemorrhage, but persistent symptoms prompted referral to Hulunbuir People’s Hospital. Upon admission, the vital signs were stable: body temperature 36.8 ℃, respiratory rate 16 breaths/min, pulse 80 beats/min, and blood pressure 125/75 mmHg. The patient was alert but exhibited anarthria, a flattened left nasolabial fold, decreased muscle strength in the left upper and lower extremities, diminished pinprick sensation on the left side of the face and limbs, and a positive Babinski sign on the left side. This study was conducted with approval from the Ethics Committee of The People’s Hospital of Hulunbuir (Approval Number: 2025-SYY-TG-09), written informed consent was obtained from the participant’s legal guardians.

The National Institutes of Health Stroke Scale (NIHSS) score, used by approximation in the absence of a validated pediatric score, was 11 and the Modified Rankin Scale (mRS) score was 4, indicating significant neurological impairment. The diagnosis was consistent with pediatric AIS with large vessel occlusion (LVO). She had no notable past medical history, including surgery, trauma, or relevant family genetic conditions. Emergency head magnetic resonance imaging (MRI) revealed a new cerebral infarction in the right basal ganglia and lateral paraventricular regions, as well as abnormal signals in the lumen of the M1 segment and distal portion of the right middle cerebral artery, suggesting thrombosis (Figs. 1, 2 and 3). During the interventional procedure, attempts were made to aspirate the thrombus, but the thrombus could not be successfully aspirated. Angiography revealed small aneurysm-like dilatations with stenosis, as shown in the three-dimensional reconstructed vascular image in Fig. 3d. After attempting intra-arterial administration of tirofiban, revascularization was achieved. Follow-up angiography demonstrated revascularization, although stenosis still persisted. Continuous intravenous tirofiban was then administered to prevent thrombus formation following endothelial injury.

Fig. 1.

Head MRI showing abnormal signal in right basal ganglia on diffusion weighted imaging and abnormal signal in right basal ganglia on fluid attenuated inversion recovery. The upper panels (a-d) of head MRI DWI (upper row) show abnormal signals in the right basal ganglia region. The corresponding lower panels (a-d) of T2 Flair also demonstrate abnormal signals in the right basal ganglia region

Fig. 2.

MRI displaying abnormal signals in the M1 middle and distal segments of the right middle cerebral artery. TOF-MRA images (a-b) reveal intraluminal abnormal signals (thrombus) in the mid and distal segments of the right middle cerebral artery (M1)

Fig. 3.

Intraoperative digital subtraction angiography. Intraoperative DSA (a-c) shows segmental occlusion of the superior trunk of the right middle cerebral artery. Panel d (3D rotational DSA) demonstrates multiple aneurysms at the bifurcation of the right middle cerebral artery, along with segmental stenosis and occlusion of the superior trunk of the right middle cerebral artery

On admission, electrocardiogram (ECG) was normal, finger-stick blood glucose was 5.25 mmol/L, and blood tests revealed an elevated white blood cell count of 14.05 × 10⁹/L. Electrolyte, liver function, kidney function, and coagulation profiles were within normal limits. Based on the 2023 Chinese Guidelines for the Diagnosis and Treatment of Cerebrovascular Diseases for adults, a diagnosis of cerebral infarction was confirmed. Intravenous thrombolysis and endovascular bridging therapy were deemed appropriate, with no evident contraindications. After obtaining informed consent from the child’s family, intravenous thrombolysis with 22.5 mg of TNK (calculated as 90 kg * 2.5 mg/kg) was administrated at 19:25 (door-to-needle time (DNT) time: 40 min).

Subsequently, under local anesthesia a right femoral artery puncture was performed and an 8 F vascular sheath was inserted. However, difficultly in advancing the Loach guidewire suggested the possibility of vascular malformation or narrow blood vessels, a common challenge in pediatric patients. Due to these difficulties, the approach was switched to the radial artery of the right upper limb. Successful radial artery puncture was achieved at 20:10 (door-to-puncture time (DPT): 85 min) and a 6.5 F vascular sheath was placed. During the procedure, there was a vascular spasm which was subsequently managed with nitroglycerin. A 6.5 F guiding catheter and a 260 cm super-stiff Loach guidewire were inserted through the vascular sheath. Angiography imaging revealed segmental occlusion of the superior trunk of the right middle cerebral artery. Additionally, three-dimensional rotational imaging identified multiple aneurysms at the bifurcation of the right middle cerebral artery.

A 5 F intermediate catheter was positioned in the proximal segment of the right middle cerebral artery and negative pressure aspiration was performed. However, subsequent angiography still indicated persistent segmental occlusion with minimal improvement in anterograde blood flow. To address this, bolus injection of 6 mL of tirofiban was administered intra-arterially at the rate of 1 mL/min. Re-examination of the angiography demonstrated satisfactory imaging of the right middle cerebral artery with the superior trunk achieving a modified thrombolysis in cerebral infraction (mTICI) grade of 2b for forward blood flow. Considering the child’s age, the anticipated further development of blood vessels and the requirement for long-term antiplatelet therapy post-surgery, stent placement was deemed unnecessary after a discussion with the family. After a 20 min observation period, follow-up imaging confirmed good perfusion in the right internal carotid artery and middle cerebral artery. The NIHSS score remained at 11 points 30 min post-procedure.

The patient was subsequently transferred to the intensive care unit of the Department of Neurology, for continuous monitoring of ECG, blood pressure, and blood oxygen saturation. According to the “Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023,” the target blood pressure should be controlled within 180/105 mmHg. For patients undergoing mechanical thrombectomy: In patients with large vessel occlusion who are undergoing mechanical thrombectomy (with or without intravenous thrombolysis), it is recommended to control blood pressure below 180/105 mmHg before endovascular treatment, with systolic blood pressure controlled between 140 and 160 mmHg during the procedure. For patients with complete vessel recanalization after the procedure, maintaining postoperative systolic blood pressure below 140 mmHg may be reasonable, but not lower than 120 mmHg [11, 12]. The child does not have a history of hypertension, and the blood pressure generally fluctuates around 120/70 mmHg. Postoperatively, tirofiban infusion was maintained at the rate of 8 mL/h. A follow-up head CT performed 24 h postoperatively revealed cerebral infarction in the right basal ganglia region without evidence of hemorrhage. Clinically, the patient demonstrated improvement in limb weakness, was alert, and could respond accurately to questions, though anarthria and a shallow left nasolabial fold persisted. Neurological examination revealed proximal left upper limb muscle strength at grade 2, left hand-grip strength at grade 1, and left lower limb muscle strength at grade 2, while right limb muscle strength remained at grade 5.

A positive pathological sign was observed in the left lower limb and the NIHSS score improved to 8 points. The tirofiban infusion rate was reduced to 6 mL/h, with a total maintenance duration of 48 h. Four hours prior to the discontinuation of tirofiban treatment, the patient was initiated on a combination of aspirin (100 mg) and clopidogrel (75 mg) administered orally, once daily for 21 days. Additional therapy, included intravenous butylphthalide (25 mg twice daily) and ligustrazine (120 mg once daily) for symptomatic rehydration and supportive care. During follow-up, the child’s condition remained stable.

Ultrasound assessments revealed normal findings: cardiac color Doppler ultrasound revealed no structural or functional abnormalities, transcranial Doppler ultrasound bubble test was negative, and carotid artery, subclavian artery and abdominal organ ultrasounds were normal. Laboratory investigations also yielded normal results: tests for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and syphilis antibody were negative; cardiac enzymes thyroid function and coagulation profiles were within normal ranges; blood lipid levels, homocysteine, and serum uric acid were also within normal ranges. Notably, cardiolipin IgM was mildly elevated at 22.84 IU/mL (reference value < 20), lupus anticoagulant screening and other autoimmune-related tests were negative. Diagnostic criteria specifically for pediatric antiphospholipid syndrome (APS) have not yet been established, and the diagnosis of pediatric APS currently follows the adult APS criteria [13, 14]. Among the laboratory criteria, the patient exhibited positive IgG and/or IgM aCL at intermediate to high titers (≥ 2 times), persisting for at least 6 weeks. The patient’s IgM anticardiolipin level was 22.84 IU/ml (reference value < 20), which did not reach the intermediate-high titer (≥ 40 IU/ml) threshold, necessitating further observation and retesting of the indicators.

Based on the patient’s clinical history, physical examination, and auxiliary test results, this case of AIS was classified as “other etiological type” according to the Trial of Org 10,172 in Acute Stroke Treatment criteria.

During the subsequent week of treatment, the patient showed significant recovery, with resolution of anarthria and improvement in left limb muscle strength to grade 4. The patient was discharged on April 18, 2024, with an NIHSS score of 4 and an mRS score of 3. At the 90-day follow-up, the patient demonstrated further improvement with an mRS score of 2, indicating a favorable recovery trajectory.

Discussion

Pediatric AIS is a significant cause of mortality and long-term disability in children [15]. The principle that “time is brain” is particularly relevant in pediatric cases, as the developing brain is highly vulnerable to ischemic injury, and long-term outcomes can differ substantially from those observed in adults. While the pediatric nervous system demonstrates a remarkable degree of plasticity, studies indicate that approximately two-thirds of children with AIS experience persistent sequelae, including permanent disabilities. Management of pediatric AIS remains challenging due to the absence of standardized diagnostic and therapeutic guidelines. Current approaches, such as intravenous thrombolysis, mechanical thrombectomy, and antiplatelet therapy are primarily adapted from adult protocols and present significant limitations in pediatric applications. The inability to restore perfusion to ischemic brain tissue in a timely manner often results in poor functional outcomes. Consequently, survivors of pediatric AIS frequently face lifelong disabilities, posing a considerable socioeconomic burden on individuals, families, and healthcare systems [3].

It is worth noting that the patient in this case is a 12-year-old child weighing 80 kg, which meets the criteria for pediatric obesity. Obesity itself is one of the risk factors for atherosclerotic cerebrovascular disease, and it cannot be ruled out that it may be related to the patient’s condition. Given the potential impact of obesity on vascular health, it is recommended that weight management be considered as part of the post-discharge care plan to mitigate this risk factor.

In adults, reperfusion therapy encompassing intravenous thrombolysis and endovascular interventions has significantly reduced disability and mortality rates associated with ischemic stroke, fundamentally transforming patient outcomes. The efficacy of these treatments is supported by robust clinical evidence from numerous large-scale randomized controlled trials. However, for pediatric AIS, evidence supporting the use of intra-arterial recombinant tissue plasminogen activator (rt-PA) and endovascular therapy remains limited. This disparity arises from differences in stroke etiology, patient age, treatment duration, stroke severity, and imaging findings between pediatric and adult populations. Despite the limited high-quality evidence, the use of reperfusion therapy in pediatric AIS has been increasingly documented in international case reports and studies. These reports have contributed to the development of preliminary guidelines regarding eligibility and exclusion criteria for acute stroke interventions in children. Such advancements have enabled certain pediatric patients to access treatment options beyond conventional methods minimizing complications. Research indicates that in pediatric AIS, administering thrombolytic therapy within 4.5 h of symptom onset achieves a high success rate significantly improving clinical outcomes while maintaining a low risk of symptomatic intracranial hemorrhage [16]. However, logistical and clinical challenges often hinder the delivery of vascular reperfusion therapy within the six-hour window for pediatric patients. The developing brain in children possesses remarkable compensatory, plasticity, and repair capacities which differentiates their response to ischemic injury from that of adults. Consequently, the use of intravenous tissue plasminogen activator (t-PA) in pediatric patients (< 12 years of age) is generally discouraged outside of controlled clinical trials or rigorous research frameworks [17, 18]. For adolescents aged 12 years or older thrombolytic therapy may be considered if AIS diagnosis is firmly established through clinical presentation, physical examination, and neuroimaging. In these cases, t-PA administration should strictly adhere to the established adult guidelines regarding time windows and eligibility criteria [5].

Numerous studies on intravenous thrombolysis with TNK t-PA for the treatment of AIS, including TAAIS, ATTEST, NOR-TEST, EXTEND-IA TNK, and AcT, have explored the efficacy of intravenous thrombolysis employing recombinant human TNK. These studies collectively suggest that TNK is non-inferior to rt-PA and may offer a safer alternative. Unlike rt-PA, TNK is administered as a single intravenous injection, offering a more convenient and rapid treatment method, particularly advantageous in transporting patients or managing those with LVO. TNK has demonstrated the potential to achieve thrombolysis to femoral artery puncture enhancing its utility in emergency care. For adults with AIS combined with LVO, who are candidates for bridging thrombectomy, TNK at a dose of 0.25 mg/kg significantly improves reperfusion rate and shortens arterial puncture times compared with standard-dose rt-PA when administered within 4.5 h of symptom onset. This has led to a level II recommendation with level B evidence for its use in this setting [19]. Despite its promising results in adults there is no evidence supporting its utilization in pediatric AIS.

In April 2023, Wilson JL et al. distributed an online survey to members of the International Pediatric Stroke Organization. The majority of pediatric stroke neurologists who responded to the survey reported that they would be willing to consider using TNK in children. However, data on the use of TNK in children, provider experience, and the readiness of pediatric hospitals are limited [20]. In 2025, Sun LR et al. prospectively collected safety data on the management of TNK in children. According to statistics from the International Pediatric Stroke Study and the Pediatric Neurocritical Care Research Group, 11 children received TNK between February 2023 and January 2024. Among them, 10 were adolescents (aged 13–17 years) and 1 was between the ages of 5 and 12 years. TNK was administered outside the hospital in 7 cases. Ultimately, 8 cases were diagnosed with stroke, and 3 cases were mimics of stroke. During follow-up, no significant safety issues or intracranial hemorrhages related to TNK were reported. Preliminary data suggest that TNK may be safe for pediatric arterial ischemic stroke. However, strategically designed prospective studies are still needed to further clarify the safety, optimal dosing, and efficacy of TNK in acute pediatric stroke [21].

Currently, there are no similar pediatric acute ischemic stroke cases reported using tirofiban. However, in 2023, Wang H et al. reported a favorable outcome in a 5-year-old child with acute thrombosis in the left atrial septum treated with a GPIIa/IIIb agent [22]. The most commonly used GPIIb/IIIa receptor antagonist (GPIIb/IIIa inhibitor, GPI) in China is tirofiban, while other GPIs are still required to be imported. Regarding the use of GPI as a salvage therapy during endovascular treatment of intracranial aneurysms, a meta-analysis comprising 23 studies showed that compared with the use of thrombolytic drugs, the use of GPI significantly reduced the incidence of perioperative stroke/bleeding and long-term mortality, with a trend towards increased vessel recanalization rates. Among different GPIs, tirofiban or eptifibatide had higher recanalization rates than abciximab [23]. Moreover, tirofiban was the only GPI available in our hospital at that time, and it was relatively inexpensive.

Most pediatric aneurysms are located in the anterior circulation, with the ophthalmic segment of the internal carotid artery being the most common site. Intracranial aneurysms in children may exhibit different developmental trends: some cases show stable aneurysm size, and some may even shrink, rather than all cases presenting a continuous enlargement trend. Studies have shown that the size of intracranial aneurysms in children is inversely proportional to their growth rate [24]. It is recommended to perform the first imaging follow-up at 3 to 6 months, followed by at least one follow-up per year [25]. Due to the potential plasticity of children’s blood vessels, partial recanalization was achieved after local application of tirofiban. Moreover, considering the need for long-term oral antiplatelet therapy after stent placement, it is suggested to carefully evaluate the necessity of invasive treatment after elective follow-up for the child.

The ISUIA (International Study of Unruptured Intracranial Aneurysms) follow-up results showed that for patients with aneurysms located in the anterior circulation, with a diameter of less than 7 mm and no history of subarachnoid hemorrhage (SAH), the rupture rate within 5 years is almost zero [26]. The role of tirofiban in preventing and salvage treatment of thromboembolic complications during endovascular embolization of intracranial aneurysms has also been preliminarily confirmed [27–34]. Considering the comprehensive analysis, the risk of aneurysm rupture in the child at that time was extremely low, and the vessel was not recanalized. Therefore, the emergency decision was made to apply tirofiban locally through the artery.

In recent years, an increasing number of case reports from both China and other countries have suggested that thrombolysis and endovascular thrombectomy can significantly improve clinical outcomes in pediatric patients with ischemic stroke [35–38]. Endovascular therapy may be a viable option for select pediatric patients who meet the diagnostic and treatment criteria established for adult stroke management, particularly in cases of ischemic stroke caused by LVO confirmed via imaging within six hours of symptom onset. However, due to differences in pathophysiology between children and adults, as well as absence of robust, high-quality randomized controlled trials, the risk-benefit profile of endovascular therapy in the pediatric population remains uncertain.

The favorable prognosis observed in this pediatric case may be attributed to timely revascularization during the ultra-acute phase of the stroke. Currently there are no established guidelines or dosing recommendations for the use of TNK in pediatric stroke treatment. The potential risk of intracerebral hemorrhage complications associated with TNK in children remains unclear and the optimal dose to ensure both safety and efficacy is yet to be determined. Consequently, maintaining a lower dose is a reasonable approach to minimize the risk of hemorrhagic complications. Treatment strategies for pediatric stroke should be tailored to the individual clinical scenario. Previous studies have reported that some children were treated with reduced doses of rt-PA and urokinase compared to adults, while others received adult-equivalent doses without experiencing hemorrhagic complications. In this case, the pediatric patient was administered TNK at a dose of 0.25 mg/kg intravenously, equivalent to the adult dosing recommendation. The treatment yielded favorable clinical outcomes without adverse events, including bleeding.

Stroke recurrence remains a significant challenge in China, with data from the China National Stroke Registry indicating a one-year recurrence rate of 14.7% for patients with ischemic stroke, rising to 28.8% in those with complications [39]. Early-stage reperfusion therapy particularly intravenous thrombolysis within 4.5 h of symptom onset is considered the standard of care [40]. The addition of antiplatelet therapy to thrombolysis has been shown to reduce the risk of re-occlusion [41]. Traditionally, aspirin alone or in combination with clopidogrel has been administered as part of dual antiplatelet therapy (DAPT) 24 h post-thrombolysis. However, pooled analysis of Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events and Platelet-Oriented Inhibition in New Tia and Minor Ischemic Stroke studies revealed that stroke recurrence still occurs in 6.3% of patients receiving DAPT therapy [42]. Clinical deterioration, defined as an increase in the NIHSS score ≥ 4 points, has been reported in approximately 11.8% of patients following intravenous thrombolysis, with 82% of these cases associated with persistent occlusion or re-occlusion [43]. In recent years, there has been increasing evidence to support the use of tirofiban as an adjuvant therapy for endovascular treatment of atherosclerotic cardiovascular and cerebrovascular diseases, including ischemic stroke and intracranial aneurysm. The 2018 Chinese Guidelines for Endovascular Treatment of Acute Ischemic Stroke and the 2019 Chinese Guidelines for the Clinical Management of Cerebrovascular Diseases (Excerpted Edition) – Clinical Management of Ischemic Cerebrovascular Disease highlight the safety and efficacy of perioperative tirofiban administration in bridging therapy or endovascular treatment for ischemic stroke [40, 41, 43].

Tirofiban exerts its antiplatelet effects by selectively inhibiting the GPIIb/IIIa receptor, the final pathway of platelet aggregation. This mechanism allows for rapid and direct inhibition of platelet aggregation. Clinical evidence has increasingly supported the efficacy of tirofiban in patients undergoing endovascular therapy for acute coronary syndrome, ischemic stroke, and intracranial aneurysms. Studies have demonstrated the safety and efficacy of adjunctive tirofiban administration following intravenous thrombolysis [44–46], or during endovascular therapy for AIS [43, 47].

Furthermore, tirofiban has shown promise in preventing and managing thromboembolic complications during endovascular embolization of intracranial aneurysms [29, 33, 48–52]. Intravenous tirofiban administered within 24 h of AIS onset has been associated with significant reductions in early neurological deterioration without increasing the risk of intracranial or systemic hemorrhage [39]. However, these findings are derived exclusively from studies conducted in adult populations with no corresponding data available for pediatric patients. Despite the absence of controlled trials, extensive literature supports the safety of anticoagulation and antiplatelet therapies including triofiban in pediatric stroke cases [33, 50–56].

Although there is limited evidence, current studies have not identified an increased risk of bleeding associated with the administration of anticoagulation and antiplatelet aggregation drugs in pediatric stroke patients. These therapies are considered safe in pediatric patients. In this case no adverse reactions such as bleeding were observed following the administration of tirofiban. During the procedure, multiple aneurysms were detected in the right middle cerebral artery and no significant emboli were identified. Tirofiban was administered specifically to prevent excessive thrombus formation that could result from vascular intimal injury caused by aspiration. The treatment was well-tolerated with no complications such as thrombocytopenia or bleeding reported.

The 12-year-old in this case, presenting with superior trunk segment occlusion of the middle cerebral artery accompanied by aneurysms sought medical attention 2.5 h after symptom onset, met the adult criteria for intravenous thrombolysis and endovascular bridging therapy. To minimize the duration of vascular occlusion and achieve vascular recanalization, intravenous thrombolysis with TNK was administered followed by endovascular bridging therapy. During the procedure, multiple aneurysms in the right middle cerebral artery were identified, though no thrombus was detected.

A bolus injection of tirofiban was administered intra-arterially followed by continuous infusion. The DNT time was 40 min and the DPT was 85 min. Post-surgery the mTICI grade was 2b with no observed complications. The NIHSS and mRS score of the patient improved significantly over the course of treatment and recovery. Before reperfusion therapy, the NIHSS score was 11 and mRS score was 4. At discharge, the NIHSS score improved to 4 and mRS score improved to 3. At the 90-day follow-up, the patient achieved further functional recovery with an mRS score of 2.

This study involved only one pediatric AIS patient, limiting generalizability and precluding statistical analysis. The 90-day follow-up is insufficient to fully assess long-term outcomes. Treatment protocols were adapted from adult guidelines and may not be fully applicable to children. Imaging and diagnostic techniques have limitations in pediatric applications, and data collection may be incomplete. Urgent treatment decisions might have compromised comprehensive assessments. Future research should validate these findings in larger cohorts and conduct more rigorous randomized controlled clinical trials with long-term follow-up.

Conclusions

In conclusion, the prognosis for pediatric AIS remains challenging, yet intravenous thrombolysis, endovascular intervention, and antiplatelet therapy have demonstrated feasibility and therapeutic potential. Although, the current understanding of thrombolytic therapy in pediatric AIS is limited, existing reports indicate that such interventions may also benefit pediatric patients. Establishing dedicated stroke centers equipped for thrombolysis, thrombectomy, and subsequent maintenance therapy is essential for improving outcomes. Further research is necessary to optimize the dosage, safety, and efficacy of thrombolytic pediatric patients with acute stroke. Additionally, accumulating clinical experience and evidence on the use of endovascular bridging therapy in this population is critical for advancing treatment strategies. Furthermore, there is an urgent need for international pediatric stroke registries to formulate guidelines for pediatric thrombolytic therapy, endovascular bridging, and subsequent antithrombotic treatment, as well as to propose the development of pediatric treatment decision algorithms for AIS with large vessel occlusion (LVO). This article aims to contribute foundational knowledge for future studies focusing on diagnosis and treatment of pediatric AIS.

Abbreviations

AIS

Acute ischemic stroke

TNK

Recombinant human TNK tissue-type fibrinogen activator

LVO

Large vessel occlusion

NIHSS

National Institute of Health Stroke Scale

mRS

Modified Rankin Scale

rt-PA

Recombinant Tissue Plasminogen Activator

TAAIS

Comparison of tenecteplase with alteplase for the early treatment of ischaemic stroke in the Melbourne Mobile Stroke Unit (TASTE-A): a phase 2, randomized, open-label trial

ATTEST

Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomized, open-label, blinded endpoint study

NOR-TEST

Tenecteplase- tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion

EXTEND-IA TNK

Tenecteplase versus alteplase before thrombectomy for ischemic stroke

AcT

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicenter, open-label, registry- linked, randomized, controlled, non-inferiority trial

RCT

Randomized Controlled Trial

CNSR

China National Stroke Registry

CHANCE

Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events

POINT

The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke

DNT

Door to Needle Time

DPT

Door-to-puncture time

mTICI

modified Thrombolysis in Cerebral Infarction

TOAST

Trial of Org 10172 in Acute Stroke Treatment

Authors’ contributions

Ying Zhang: Conceptualization, Data curation, Formal Analysis, Software, Writing – original draft, Writing – review & editing. Chang-Xing Jiang: Data curation, Formal Analysis.Hong-Gang Wang: Conceptualization, Data curation.Hao-Ran Gao: Formal Analysis, Software.Dan Li: Data curation, Formal Analysis.Lei Zhao: Data curation, Formal Analysis.Li-Hong Gao: Conceptualization, Writing – review & editing. All authors read and approved the final draft.

Funding

No external funding was received to conduct this study.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted with approval from the Ethics Committee of The People’s Hospital of Hulunbuir (Approval Number: 2025-SYY-TG-09). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from the participant’s legal guardians.

Consent for publication

The patient guardians signed a document of informed consent.

Competing interests

The authors declare no competing interests.