Adjuvant Therapies for Ischemic Cerebrovascular Disease in Children

Medical

• Initial antithrombotic therapy: The vast majority of children who present with ischemic stroke do not require endovascular treatment or open surgery and are instead managed medically. The most recent scientific statement on the management of pediatric ischemic stroke, published in 2019 by the AHA Stroke Council and Council on Cardiovascular and Stroke Nursing, recommends initial treatment with either an antiplatelet (aspirin) or an anticoagulant (low molecular weight or unfractionated heparin) medication; the latter is preferred for stroke due to suspected thrombophilic or cardiac etiologies, but anticoagulation therapy is contraindicated in the presence of a very large infarct or severe bleeding diathesis (62). For pediatric ischemic stroke in general, it remains unclear whether antiplatelet or anticoagulant therapy is superior.
• Longer term antithrombotic therapy: The AHA Stroke Council and Council on Cardiovascular and Stroke Nursing recommend at least 2 years of antiplatelet (aspirin) or anticoagulant (heparin or warfarin) therapy, depending on the stroke etiology (62). The optimal duration of long-term antithrombotic therapy is unclear.
• IV tPA or TNK: In children who present with ischemic stroke, IV tPA may be considered at the adult dose of 0.9 mg/kg within 4.5 hours of stroke onset (56). Importantly, however, there are no trials addressing the use of IV tPA in children presenting with ischemic stroke, as the TIPS study was forced to close due to failure to recruit enough patients (61). For IV TNK, the adult dose is usually 0.25 mg/kg with a maximum dose of 25 mg (251,252).
• Inflammatory etiologies: Patients with pediatric ischemic stroke of a suspected inflammatory etiology, such as vasculitis, may require an extensive workup in coordination with rheumatologists and/or immunologists to determine whether secondary stroke prevention strategies are indicated. It should be noted, however, that use of anti-inflammatory or immunomodulatory drugs for secondary stroke prevention is controversial (62,132).
• Evaluation for cardiac etiologies: Children presenting with ischemic stroke are generally screened for cardiac etiologies via TTE with bubble to assess for PFO and via inpatient telemetry, ECG, and/or Holter monitor to assess for arrhythmia (62,203). Although cardiac surgery consultation may be considered for PFO closure, reports have found no benefit to closure versus standard medical therapy, so surgical intervention in this setting remains highly controversial (253).
• Considerations for sickle cell hemoglobinopathy: Initial management of pediatric ischemic stroke in patients with HbSS should include hydration, correction of hypoxemia and hypotension, and evaluation for HbSS moyamoya syndrome; consider regular blood transfusions (with a target of hemoglobin S <30%) for secondary stroke prevention (62).

Other

Considerations for Craniocervical Arterial Dissection

Patients with craniocervical arterial dissection are managed medically in most cases, although endovascular treatment may be considered in cases refractory to medical therapy.

• Medical management: Antiplatelet therapy with aspirin is routinely used in the initial management of patients with craniocervical arterial dissection who present with pediatric ischemic stroke. Although it is recommended, the role of anticoagulation therapy is controversial (62,89).
• Serial imaging and screening for connective tissue disorders: Longer term (at least 1 year) serial imaging and screening for connective tissue disorders is recommended for patients with craniocervical arterial dissection (62).
• Endovascular therapy: Stenting and intra-arterial thrombolytics are sometimes used in the treatment of craniocervical arterial dissection refractory to medical therapy (88-90).

Considerations for CVST

Treatment in cases of CVST depends on several factors, including patient age, presence of comorbidities, and disease severity. Medical management is often sufficient, although endovascular treatment is considered in some cases.

• Treatment of neonates: For CVST in neonates, seizure control, hydration, serial imaging, and correction of anemia is crucial. Underlying infections may need to be treated, and anticoagulation (heparin or warfarin) may be considered, especially if there is evidence of thrombus propagation on serial imaging (62).
• Treatment of older children: For CVST in older children, initial measures should include fever control, hydration, anemia correction, seizure control, HOB elevation, and anticoagulation (heparin, or warfarin) therapy (62).
• Monitoring for disease severity and consideration of endovascular treatment: Serial imaging and examination for signs of elevated ICP are also important, and endovascular intervention (which includes mechanical thrombectomy and local thrombolysis) may be considered when clinical deterioration with a high risk of mortality is observed (62,254,255).