What Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) would preclude thrombolysis with alteplase (tissue plasminogen activator) in a patient with acute ischemic stroke outside the 4.5 hour window?

ASPECTS Threshold for Thrombolysis Outside the 4.5-Hour Window

An ASPECTS score <6 should generally preclude thrombolysis with alteplase outside the 4.5-hour window, as lower scores are associated with increased risk of intracranial hemorrhage and poor functional outcomes without clear benefit. 1, 2

Evidence-Based Threshold

The most robust guideline evidence establishes ASPECTS ≥6 as a requirement for extended window treatment:

• The 2015 AHA/ASA guidelines explicitly require ASPECTS ≥6 for endovascular therapy within 6 hours, and this threshold has been adopted for patient selection in extended window thrombolysis protocols 1
• Current guidelines recommend ASPECTS ≥6 when considering alteplase beyond 4.5 hours with perfusion imaging selection 2, 3
• The 2020 JACC guidelines note that even patients with ASPECTS <6 can benefit from endovascular thrombectomy, but this does not extend to thrombolysis alone, where hemorrhage risk is the primary concern 1

Supporting Research Evidence

Recent high-quality trials provide critical context:

• The 2023 study on low ASPECTS patients (≤5) found that bridging thrombolysis was associated with very poor functional outcomes (OR 2.22) and significantly increased symptomatic intracranial hemorrhage (17.8% vs 6.4% for direct thrombectomy, OR 3.44) 4
• The 2025 HOPE trial, which demonstrated benefit of alteplase at 4.5-24 hours, required salvageable brain tissue on perfusion imaging, implicitly excluding patients with extensive early ischemic changes 5
• The 2025 EXPECTS trial for posterior circulation strokes specifically excluded patients with "extensive early hypodensity on computed tomography" 6

Practical Algorithm for Extended Window Decision-Making

When considering thrombolysis outside 4.5 hours:

1. Calculate ASPECTS score on baseline non-contrast CT - scores range from 0-10, with 1 point subtracted for each region showing early ischemic changes 1, 2

2. If ASPECTS <6: Do not proceed with thrombolysis - the hemorrhage risk outweighs potential benefit, particularly in the extended window 4, 2

3. If ASPECTS ≥6: Proceed with advanced imaging (CT or MRI perfusion) to confirm salvageable tissue and core/perfusion mismatch 2, 3, 5

4. Confirm no large vessel occlusion requiring thrombectomy - if LVO is present, proceed directly to mechanical thrombectomy rather than thrombolysis 3

Critical Caveats

Within the standard 3-hour window, the ASPECTS threshold is less stringent - the 2007 Stroke guidelines note that early ischemic changes >1/3 MCA territory were not independently associated with adverse outcomes when treatment occurred within 3 hours 1. However, this permissiveness does not extend beyond 4.5 hours.

For posterior circulation strokes, use the pc-ASPECTS (posterior circulation ASPECTS) - the 2024 ESO/ESMINT guidelines suggest pc-ASPECTS ≥8 for basilar artery occlusion treatment, though this is based on observational data 1

The relationship between ASPECTS and outcome is continuous - while ASPECTS ≥6 is the established threshold, lower scores within the 6-10 range still confer progressively better outcomes 7. An ASPECTS of 6 is the minimum acceptable, not the ideal.

Hemorrhage risk increases substantially with lower ASPECTS - the symptomatic intracranial hemorrhage rate in low ASPECTS patients receiving thrombolysis approaches 17-18%, compared to 2-4% in typical populations 4, 8