Should a patient with a stroke and an Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) of less than 5 receive intravenous (IV) thrombolysis with tissue plasminogen activator (tPA) despite the EXTEND trial's findings?

ASPECTS <5 and IV tPA: The Evidence Does Not Support Routine Treatment

For patients with ASPECTS <5, IV thrombolysis with tPA should generally be withheld, as the decision must be based on clinical judgment of the treating physician in consultation with a stroke specialist, recognizing that extensive early infarction substantially increases hemorrhagic risk without clear benefit. 1

Guideline-Based Framework

The Canadian Stroke Best Practice Recommendations explicitly address this scenario:

• Patients with ASPECTS <6 fall into an uncertain treatment zone where the decision to treat or not treat with tPA "should be made based on the clinical judgment of the treating physician" rather than following a standard protocol 1

• ASPECTS ≥6 is the recommended threshold for identifying patients with small-to-moderate ischemic core who are appropriate candidates for IV tPA 1

• When uncertainty exists about treatment eligibility, urgent consultation with a stroke specialist within the institution or through telestroke services is mandated 1

Why ASPECTS <5 Is Problematic

The imaging threshold exists for critical reasons:

• Frank hypodensity on CT, particularly involving more than one-third of MCA territory, is a strong contraindication to treatment according to the American Heart Association 1

• ASPECTS <6 represents more extensive infarction with a larger ischemic core, which fundamentally changes the risk-benefit calculation 1

• The NINDS rtPA Stroke Study data showed a trend toward reduced mortality and increased benefit when baseline CT was favorable (ASPECTS >7), suggesting worse outcomes with more extensive early changes 2

The EXTEND Trial Context

While you reference the EXTEND trial suggesting otherwise, the established guidelines have not incorporated findings that would support routine tPA use in ASPECTS <5:

• Current evidence-based recommendations maintain the ASPECTS ≥6 threshold for standard treatment decisions 1

• The 2015 AHA/ASA guidelines and Canadian Best Practice Recommendations both specify that ASPECTS <6 requires individualized clinical judgment rather than routine treatment 1

Clinical Decision Algorithm for ASPECTS <5

When confronted with ASPECTS <5:

1. Immediately consult stroke neurology (on-site or via telestroke) as this is explicitly recommended for uncertain cases 1

2. Assess stroke severity using NIHSS - patients with severe strokes (NIHSS >15) may have different risk-benefit profiles than those with milder deficits 3

3. Verify time from symptom onset - the narrow 3-4.5 hour window becomes even more critical with unfavorable imaging 1, 4

4. Consider endovascular therapy instead - for large vessel occlusions, mechanical thrombectomy may be more appropriate than IV tPA in patients with extensive early changes 1

5. Document shared decision-making with patient/family regarding the uncertain benefit and increased hemorrhagic risk 1

Critical Hemorrhagic Risk Considerations

• Symptomatic intracranial hemorrhage occurs in 6.4% of tPA-treated patients versus 0.6% of placebo patients in standard populations 1, 5

• This risk increases substantially with protocol deviations, and extensive early ischemic changes represent a major risk factor 1

• The American Heart Association notes that frank hypointensity on CT is a strong contraindication, which ASPECTS <5 often represents 1

When Treatment Might Still Be Considered

In highly selected cases with ASPECTS <5, treatment might be considered if:

• Stroke severity is very high (NIHSS >15) where recanalization benefit may outweigh risks 3

• Large vessel occlusion is present and endovascular therapy is planned, with IV tPA as a bridge 1

• Stroke specialist consultation supports treatment after careful risk-benefit discussion 1

Common Pitfalls to Avoid

• Do not treat ASPECTS <5 routinely without stroke specialist input - this violates guideline recommendations 1

• Do not assume all patients with early ischemic changes will benefit - approximately one-third of patients initially deemed "too mild" or "improving" still end up dependent or dead, but this doesn't justify treating extensive infarcts 6

• Do not delay endovascular therapy consultation - mechanical thrombectomy may be more appropriate than IV tPA for these patients 1

• Do not fail to document the clinical reasoning when deviating from standard ASPECTS thresholds 1