Table 5

Summary of PICO questions, evidence-based recommendations, and expert consensus statements

Topic/PICO question	Evidence-based recommendation	Expert consensus statement
Mothership PICO 1: For large vessel occlusion acute ischemic stroke (≤4.5 hours of symptom onset) patients directly admitted to a thrombectomy-capable center and eligible for both treatments, does mechanical thrombectomy alone compared with intravenous thrombolysis plus mechanical thrombectomy lead to: a non-inferior proportion of patients with good outcome (mRS 0–2) at 90 days? non-inferior or better results on other efficacy outcomes (whole range of the mRS; mRS 0–1; successful reperfusion)? a reduction in the risk of adverse events (mortality at 90 days, sICH, any ICH)? a reduction in key time metrics?	For patients directly admitted to a thrombectomy-capable center for an acute ischemic stroke (≤4.5 hours of symptom onset) with anterior circulation large vessel occlusion and who are eligible for both treatments, we recommend intravenous thrombolysis plus mechanical thrombectomy over mechanical thrombectomy alone. Both treatments should be performed as early as possible after hospital arrival. Mechanical thrombectomy should not prevent the initiation of intravenous thrombolysis and intravenous thrombolysis should not delay mechanical thrombectomy. Quality of evidence: Moderate ⊕⊕⊕ Strength of recommendation: Strong ↑↑	For patients directly admitted to a thrombectomy-capable center within 4.5 hours of symptom recognition after wake-up ischemic stroke caused by anterior circulation large vessel occlusion, we suggest intravenous thrombolysis plus mechanical thrombectomy over mechanical thrombectomy alone in selected patients. The selection criteria for IVT and MT for patients with wake-up stroke are detailed in the corresponding European Guidelines.5 23 Notably, eligibility imaging criteria for IVT include DWI-FLAIR mismatch or perfusion core/penumbra mismatch. Perfusion core/penumbra mismatch: Infarct core volume <70 mL and critically hypoperfused^† volume/infarct core volume >1.2 and mismatch volume >10 mL **rCBF <30% (CT perfusion) or ADC <620 µm²/s (diffusion MRI) ^†Tmax >6 s (perfusion CT or perfusion MRI)
Drip-and-ship PICO 2: For large vessel occlusion acute ischemic stroke (≤4.5 hours of symptom onset) patients admitted to a non-thrombectomy-capable center and eligible for both treatments, does mechanical thrombectomy alone compared with intravenous thrombolysis plus mechanical thrombectomy lead to: a non-inferior proportion of patients with good outcome (mRS 0–2) at 90 days? non-inferior or better results on other efficacy outcomes (whole range of the mRS; mRS 0–1; successful reperfusion)? a reduction in the risk of adverse events (mortality at 90 days, sICH, any ICH)? a reduction in key time metrics?	For patients admitted to a non-thrombectomy-capable center for an acute ischemic stroke (≤4.5 hours of symptom onset) with anterior circulation large vessel occlusion and who are eligible for both treatments, we recommend intravenous thrombolysis followed by rapid transfer to a center with thrombectomy facilities over omitting intravenous thrombolysis and transfer to a center with thrombectomy facilities. Intravenous thrombolysis should not delay the transfer to a center with thrombectomy facilities. Quality of evidence: Low ⊕⊕ Strength of recommendation: Strong ↑↑	For patients admitted to a non-thrombectomy-capable center within 4.5 hours of symptom recognition after wake-up ischemic stroke caused by anterior circulation large vessel occlusion, we suggest intravenous thrombolysis plus mechanical thrombectomy over mechanical thrombectomy alone in selected patients. The selected criteria for IVT and MT for patients with wake-up stroke are detailed in the corresponding European guidelines.5 23 Notably, eligibility imaging criteria for IVT include DWI-FLAIR mismatch or perfusion core/penumbra mismatch. Perfusion core/penumbra mismatch: Infarct core volume <70 mL and critically hypoperfused^† volume/infarct core volume >1.2 and mismatch volume >10 mL **rCBF <30% (CT perfusion) or ADC <620 µm²/s (diffusion MRI) ^†Tmax >6 s (perfusion CT or perfusion MRI)

ADC, apparent diffusion coefficient ; CT, computed tomography; DWI-FLAIR, diffusion weighted imaging-fluid attenuated inversion recovery; ICH, intracranial hemorrhage; IVT, intravenous thrombolysis with alteplase; MRI, magnetic resonance imaging; mRS, modified Rankin Scale; MT, mechanical thrombectomy; PICO, Population, Intervention, Comparator, Outcome; rCBF, relative cerebral blood flow; sICH, symptomatic intracranial hemorrhage.