Thrombolysis for NIHSS <6: Clinical Decision Framework
Yes, thrombolysis can be administered to patients with NIHSS <6, but the decision must be based on whether symptoms are potentially disabling rather than the numeric score alone. The critical distinction is between "minor but disabling" versus "minor and non-disabling" symptoms, as approximately one-third of untreated mild stroke patients develop poor functional outcomes 1.
Key Decision Algorithm
Step 1: Assess if Symptoms Are Potentially Disabling
Potentially disabling symptoms that warrant thrombolysis (even with NIHSS <6):
- Isolated aphasia (may score only 2-3 on NIHSS but severely disabling) 1
- Isolated hemianopia 1
- Gait disturbance 1
- Motor impairment affecting dominant hand 1
- Any deficit the patient considers functionally limiting 2
Non-disabling symptoms where thrombolysis benefit is uncertain:
- Isolated sensory symptoms 3
- Minimal weakness not affecting function 3
- Symptoms patient does not consider limiting 3
Step 2: Apply Time-Based Recommendations
Within 0-3 hours:
- Administer alteplase for potentially disabling symptoms (Class IIb recommendation) 1, 4
- Benefits likely outweigh risks even for mild strokes 2
- Standard dose: 0.9 mg/kg (max 90 mg), 10% bolus over 1 minute, 90% infusion over 60 minutes 2, 4, 5
Within 3-4.5 hours:
- Consider alteplase for potentially disabling symptoms, though evidence is less certain 1, 4
- May be reasonable option with similar effectiveness to 0-3 hour window 1
Step 3: Screen for Large Vessel Occlusion (LVO)
Critical consideration: Patients with LVO have dramatically different prognosis and benefit most from treatment 1. Obtain CTA to identify proximal occlusions (ICA, M1, M2) 2. The presence of LVO changes mild stroke from potentially benign to high-risk for deterioration 1.
Evidence-Based Stratification by NIHSS Score
NIHSS 0-2: Exercise Caution
- Real-world data shows potential harm signals in this group 6
- Associated with increased early neurological deterioration (aOR 8.84) and sICH (aOR 9.32) 6
- Lower rate of excellent outcome (mRS 0-1) with thrombolysis (aOR 0.67) 6
- Recommendation: Generally avoid thrombolysis unless symptoms are clearly disabling and patient has LVO 6, 7
NIHSS 3-5: Consider Treatment
- Better functional outcomes with thrombolysis compared to NIHSS 0-2 group 7
- Increased rate of excellent outcome (mRS 0-1) with treatment (aOR 1.21) 6
- Recommendation: Treat if symptoms are potentially disabling 1, 7
- Prior statin therapy predicts better outcomes (aOR 3.46) 7
NIHSS 5-14 (Moderate Stroke): Strong Consideration
- Lower dose alteplase (0.6 mg/kg) shows significant sICH reduction (OR 0.13) with comparable efficacy 8
- This is the subgroup where treatment benefit is most clear 8
Safety Considerations and Contraindications
Absolute contraindications remain standard regardless of NIHSS score 2, 4, 5:
- Evidence of ICH on CT
- BP >185/110 mmHg (must lower before treatment)
- Platelets <100,000/mm³
- INR >1.7
- Active bleeding
- Recent major surgery/trauma
Special risk factors in mild stroke:
- Hyperglycemia >11.1 mmol/L substantially increases sICH risk (36% in one series) 7
- Patients on dual antiplatelet therapy have increased bleeding risk but benefits may still outweigh risks 4
Alternative to Thrombolysis
Dual antiplatelet therapy (aspirin + clopidogrel for 21 days) is a reasonable alternative for patients with minor, non-disabling stroke (Class IIa) 1. This avoids hemorrhagic risk while providing effective secondary prevention.
Common Pitfalls to Avoid
- Don't assume "mild" means "benign": 31-40% of untreated mild stroke patients have poor outcomes at 3 months 1
- Don't rely solely on NIHSS number: A patient with isolated aphasia may have NIHSS 2-3 but be severely disabled 1
- Don't miss large vessel occlusion: These patients benefit most from treatment regardless of initial NIHSS 1
- Don't withhold treatment for "rapidly improving" symptoms: These patients also have substantial rates of poor outcomes if untreated 1
- Don't treat NIHSS 0-2 routinely: This subgroup shows potential harm signals in registry data 6
Practical Implementation
The 2023 World Stroke Organization guidelines do not specify an NIHSS cutoff for thrombolysis eligibility 2. The focus should be on functional disability rather than numeric thresholds. However, mechanical thrombectomy criteria do specify NIHSS ≥6 for LVO patients 2, highlighting that lower scores may not warrant invasive intervention unless symptoms are clearly disabling.