NIHSS Score Eligibility for Alteplase in Acute Ischemic Stroke
There is no absolute NIHSS score cutoff that excludes patients from alteplase treatment—eligibility depends on the time window and specific clinical context rather than a single NIHSS threshold. 1, 2
Time-Based NIHSS Considerations
0-3 Hour Window
- No upper NIHSS limit exists for treatment within 3 hours, including patients with severe strokes (NIHSS >25), despite historically being listed as a contraindication in older European guidelines 1
- The American Heart Association recommends alteplase for severe strokes when treated early, acknowledging higher hemorrhage risk but proven benefit 1
- No lower NIHSS limit either—even patients with NIHSS 0-2 can receive alteplase if symptoms are potentially disabling, though evidence remains uncertain (Class IIb recommendation) 3
- Minor strokes (NIHSS 0-5) with nondisabling symptoms may be treated, but the PRISMS trial showed no benefit over aspirin (78.2% vs 81.5% favorable outcome), with 3.2% symptomatic ICH risk in the alteplase group 4
3-4.5 Hour Window
- NIHSS ≤25 is recommended for the extended window, along with additional exclusion criteria: age ≤80 years, no diabetes plus prior stroke combination, not on oral anticoagulants, and <1/3 MCA territory involvement on imaging 1
- This represents a practical upper limit rather than an absolute contraindication—the restriction reflects increased risk without proven benefit in this delayed timeframe 1
- The SITS-ISTR study demonstrated safety in 664 patients treated at 3-4.5 hours with similar outcomes to the 0-3 hour cohort (symptomatic ICH 2.2% vs 1.6%, p=0.24) 5
Beyond 4.5 Hours
- NIHSS score becomes irrelevant—patient selection shifts entirely to imaging-based criteria (perfusion mismatch or DWI-FLAIR mismatch) rather than clinical severity scores 1
- Treatment up to 9 hours requires demonstration of salvageable tissue on advanced imaging 1
Critical Nuances by Stroke Severity
Severe Strokes (NIHSS >25)
- Historically contraindicated but now accepted within 3 hours based on evidence showing benefit despite higher hemorrhage risk 6, 1
- The ATLANTIS trial excluded very severe strokes and showed no benefit at 3-5 hours, with 11% mortality in treated patients 7
- In one Chinese cohort, patients with NIHSS >25 had 80% mortality, suggesting careful patient selection is warranted even within approved windows 8
Mild Strokes (NIHSS 0-5)
- The key distinction is "disabling" vs "nondisabling" deficits, not the NIHSS number itself 3, 4
- For nondisabling symptoms, dual antiplatelet therapy (aspirin + clopidogrel for 21 days) is a reasonable alternative (Class IIa) 3
- Patients with NIHSS 0-2 who received alteplase had better outcomes than NIHSS 3-5 (81.3% vs 48.7% excellent outcome) without increased hemorrhage risk, though this may reflect baseline severity rather than treatment effect 9
- Prior statin therapy predicts better outcomes (aOR 3.46), while hyperglycemia >11.1 mmol/L substantially increases symptomatic ICH risk to 36% 3, 9
Common Pitfalls to Avoid
- Don't automatically exclude patients based solely on NIHSS >25 within 3 hours—current guidelines support treatment despite older contraindication lists 6, 1
- Don't withhold treatment for "minor" symptoms without assessing disability—aphasia, visual field cuts, or dominant hand weakness may have low NIHSS scores but be clearly disabling 3
- Don't apply the 0-3 hour NIHSS flexibility to the 3-4.5 hour window—the NIHSS ≤25 cutoff is specifically for extended window patients 1
- Don't use NIHSS as the primary selection criterion beyond 4.5 hours—imaging trumps clinical scores in delayed presentations 1
Dosing Consistency Across NIHSS Scores
- The standard dose remains 0.9 mg/kg (maximum 90 mg) regardless of NIHSS score: 10% bolus over 1 minute, then 90% infusion over 60 minutes 2
- No dose adjustment is needed based on stroke severity, though some have explored lower doses (0.6 mg/kg) for moderate strokes (NIHSS 5-14) when concerned about bleeding risk—this is not standard practice 3