NIHSS Criteria for Alteplase Administration
There is no absolute NIHSS cutoff that excludes alteplase administration within 3 hours of symptom onset—even severe strokes (NIHSS >25) should receive treatment in this window due to proven benefit despite higher hemorrhage risk. 1
NIHSS Thresholds by Time Window
0-3 Hour Window
- No upper NIHSS limit exists for treatment eligibility 1
- Severe strokes (NIHSS >25) are explicitly indicated for treatment despite increased hemorrhagic transformation risk, as clinical benefit remains proven 1
- Minor strokes (low NIHSS) are also eligible, though benefit must be weighed against risks 1
- The European license historically listed "severe stroke (NIHSS >25)" as a contraindication, but this has been superseded by evidence showing benefit even in severe strokes when treated early 1
3-4.5 Hour Window
- NIHSS ≤25 is required for treatment eligibility in this extended window 1
- This cutoff was an exclusion criterion in the ECASS-III trial, which established efficacy in the 3-4.5 hour window 2
- Patients must also be ≤80 years old, without combined history of diabetes and prior stroke, not taking oral anticoagulants, and without imaging evidence of >1/3 MCA territory involvement 1
Beyond 4.5 Hours
- NIHSS criteria become less relevant as patient selection shifts to imaging-based criteria (CT/MRI perfusion mismatch or DWI-FLAIR mismatch) rather than clinical severity scores 3
- Treatment up to 9 hours requires demonstration of salvageable tissue on advanced imaging 3
Critical Nuances About Mild Strokes
Patients with minor or rapidly improving symptoms can benefit from alteplase and should not be automatically excluded 1. The 2018 AHA/ASA guidelines give a Class IIa recommendation (reasonable to administer) for mild strokes in the 3-4.5 hour window, noting that ECASS-III included only 128 patients with NIHSS 0-5 1. Registry data from SITS-ISTR and GWTG showed similar outcomes and hemorrhage rates for mild strokes treated in both time windows 1.
Common Pitfalls to Avoid
- Do not withhold alteplase from severe strokes (NIHSS >25) presenting within 3 hours—the European contraindication is outdated and contradicted by current evidence 1
- Do not dismiss patients with low NIHSS scores as "too mild"—disabling deficits can occur even with low scores (e.g., isolated aphasia, hemianopia) 1
- Do not apply the 3-4.5 hour exclusion criteria (NIHSS ≤25) to patients presenting within 3 hours—these are separate time windows with different eligibility requirements 1
- Remember that "rapidly improving" symptoms do not automatically exclude treatment—patients can still benefit if residual deficits remain potentially disabling 1
Dosing Regardless of NIHSS
The standard alteplase dose is 0.9 mg/kg (maximum 90 mg) given as 10% bolus over 1 minute, followed by 90% infusion over 60 minutes, regardless of stroke severity or NIHSS score 1