What is the approach to thrombolysis using alteplase (tissue plasminogen activator, tPA) in a patient with a mild ischemic stroke, as indicated by a low National Institutes of Health Stroke Scale (NIHSS) score?

Thrombolysis in Mild Stroke (Low NIHSS)

For patients with mild stroke (NIHSS <5) presenting within 3-4.5 hours, administer IV alteplase if symptoms are potentially disabling, even with low NIHSS scores, as approximately one-third of untreated mild stroke patients develop poor functional outcomes. 1, 2, 3

Key Decision Framework

Define "Potentially Disabling" Symptoms

The critical distinction is not the NIHSS number itself, but whether symptoms are disabling:

• Potentially disabling symptoms include isolated aphasia, isolated hemianopia, gait disturbance, or motor impairment—even if NIHSS is only 2-3 1, 3
• Motor impairment (particularly right motor arm) is a major predictor of poor outcome and should prompt treatment 4
• Approximately 31-40% of untreated mild stroke patients (NIHSS ≤5-6) end up with poor functional outcomes (mRS ≥2) at 3 months 1, 4, 5

Treatment Recommendations by Time Window

Within 3 hours:

• Treat with alteplase for any measurable, potentially disabling deficit regardless of NIHSS score 2, 3
• No lower NIHSS limit exists for treatment within this window 5

3-4.5 hour window:

• Consider alteplase for mild but potentially disabling symptoms (Class IIb recommendation) 3
• The evidence is less robust than the 0-3 hour window, but treatment may be reasonable 3
• Alternative: Dual antiplatelet therapy (aspirin + clopidogrel for 21 days) is a reasonable alternative if thrombolysis is not pursued (Class IIa) 3

Safety Profile in Mild Stroke

The bleeding risk is substantially lower in mild stroke patients:

• Symptomatic intracranial hemorrhage (sICH) rate: <1% to <5% in mild stroke cohorts 6, 5, 7
• One series showed 94% favorable outcomes (mRS 0-1) at 3 months with only one asymptomatic hemorrhage 5
• MRI-screened patients with NIHSS ≤5 had sICH rate <1% 6

Critical Imaging Consideration

Presence of large vessel occlusion changes the equation dramatically:

• Patients with persistent large-artery occlusion on imaging despite mild symptoms are at increased risk of subsequent deterioration 1
• In patients with ICA or MCA main stem occlusion and NIHSS ≤5, 41.4% of non-thrombolysed patients deteriorated within 3 months versus only 15% of thrombolysed patients 7
• Thrombolysis achieved 78.9% recanalization versus 10.5% spontaneous recanalization in this population 7
• Strongly consider thrombolysis if vascular imaging shows large vessel occlusion, even with mild symptoms 7

Predictors of Poor Outcome to Guide Treatment

Factors that predict poor outcome in mild stroke (favoring treatment):

• Age (older patients fare worse) 4
• Cardioembolic etiology (OR 3.29 for poor outcome) 4
• Motor impairment on any NIHSS motor item 4
• Hyperglycemia >11.1 mmol/L (substantially increases sICH risk to 36%) 3

Factors predicting better outcomes:

• Prior statin therapy (aOR 3.46 for excellent outcome) 3, 8
• Non-disabling stroke classification 8
• NIHSS 0-2 versus 3-5 (81.3% vs 48.7% excellent outcomes) 8

Common Pitfalls to Avoid

1. Don't assume "mild" means "benign": The natural history shows one-third have poor outcomes 1, 4

2. Don't rely solely on NIHSS number: A patient with isolated aphasia may have NIHSS of 2-3 but be severely disabled 1

3. Don't miss large vessel occlusion: Obtain vascular imaging when feasible—these patients benefit most from treatment 1, 7

4. Don't withhold treatment for "rapidly improving" symptoms: These patients also have substantial rates of poor outcomes if untreated 1

Standard Dosing

• 0.9 mg/kg (maximum 90 mg total): 10% IV bolus over 1 minute, remaining 90% infused over 60 minutes 2, 9
• Same dosing regardless of stroke severity or NIHSS score 9

Strength of Evidence Caveat

The PRISMS trial (randomizing mild stroke patients to alteplase vs aspirin) did not show benefit 6, creating ongoing equipoise. However, this trial did not use MRI selection, and observational data consistently shows benefit, particularly with large vessel occlusion 6, 7. The 2013 AHA/ASA guidelines acknowledge this uncertainty with a Class IIb recommendation, meaning treatment "may be considered" but risks must be weighed against benefits 1, 3.