Should we administer thrombolysis to patients with a National Institutes of Health Stroke Scale (NIHSS) score of less than 4?

Thrombolysis for Acute Ischemic Stroke with NIHSS <4

For patients with NIHSS <4, thrombolysis should generally NOT be administered, with the critical exception being those with NIHSS 3-4 who have clearly disabling deficits (such as isolated aphasia, hand weakness affecting dominant hand function, or gait impairment preventing ambulation)—these patients may benefit from treatment. 1, 2

Evidence-Based Approach by NIHSS Score

NIHSS 0-2: Do Not Thrombolyse

• Patients with NIHSS 0-2 who receive thrombolysis have worse outcomes compared to those who do not receive it 3, 1
• Thrombolysis in this group is associated with:
  • Increased symptomatic intracranial hemorrhage (sICH) risk (adjusted OR 9.32) 3
  • Increased early neurological deterioration (adjusted OR 8.84) 3
  • Lower rates of excellent functional outcome (mRS 0-1) at 3 months (adjusted OR 0.67) 3
  • No improvement in 90-day functional outcomes (adjusted OR 1.046) but marked increase in sICH risk 1

NIHSS 3-5: Selective Thrombolysis Based on Disability

• Patients with NIHSS 3-5 demonstrate significant benefit from thrombolysis with improved 90-day functional outcomes (adjusted OR 3.284) without significant increase in sICH 1
• The benefit is most pronounced when deficits are considered disabling, regardless of the numerical NIHSS score 2
• Common disabling deficits that warrant treatment despite low NIHSS include:
  • Language impairment/aphasia (present in two-thirds of treated patients with NIHSS ≤4) 2
  • Distal hand paresis affecting dominant hand function (present in one-third) 2
  • Gait disorder preventing independent ambulation 2

Critical Clinical Decision Points

The NIHSS Score Limitation

• The NIHSS does not capture all functionally disabling deficits—judgment should be based on individual neurologic deficits and their impact on functional impairment, not solely on the numerical score 2
• In one registry, 16% of all thrombolysis patients had NIHSS ≤4, and ALL were considered functionally impaired (mRS ≥2) 2
• Despite treatment, 26% had unfavorable outcomes and 52% had persisting symptoms at 3 months in the NIHSS ≤4 group 2

Safety Profile Comparison

• NIHSS 0-2: sICH rate significantly elevated with thrombolysis 3, 1
• NIHSS 3-5: No significant increase in sICH (adjusted OR 2.770, p=0.360), END, or stroke recurrence 1
• Historical NINDS data showed only 3% bleeding risk in patients with NIHSS <10 4

Practical Algorithm

Step 1: Determine NIHSS Score

• If NIHSS 0-2 → Do not thrombolyse (harm exceeds benefit) 3, 1

Step 2: For NIHSS 3-4, Assess Functional Disability

• Ask: "Does this deficit prevent the patient from performing essential daily activities?"
• Specific disabling deficits:
  • Aphasia preventing communication 2
  • Hand weakness in dominant hand preventing writing, eating, or self-care 2
  • Gait impairment preventing safe ambulation 2
  • Isolated hemianopia affecting driving/independence

Step 3: If Disabling Deficit Present with NIHSS 3-4

• Proceed with thrombolysis if within time window and no contraindications 1, 2
• Expected benefit: 3-fold increased odds of excellent outcome 1

Step 4: If Non-Disabling Deficit with NIHSS 3-4

• Consider dual antiplatelet therapy (aspirin + clopidogrel for 21 days) instead 4
• This applies to high-risk TIA (ABCD2 ≥4) or minor stroke (NIHSS ≤3) 4

Common Pitfalls to Avoid

• Do not use NIHSS score alone as the sole criterion—a patient with isolated aphasia may score only 3 points but be severely disabled 2
• Do not assume all "mild" strokes are non-disabling—up to 30% of patients with initially mild deficits experience poor functional outcomes 3
• Do not delay decision-making for MRI selection in the NIHSS 0-2 group, as even MRI-selected patients showed no benefit and potential harm 5
• Avoid thrombolysis in rapidly improving symptoms unless the patient still has disabling deficits at the time of treatment decision 4

Special Considerations

MRI-Based Selection

• Even with MRI screening, patients with NIHSS ≤5 showed only 74% favorable outcomes, and the benefit was not clearly superior to clinical selection alone 5
• MRI should not delay treatment decisions in the appropriate NIHSS 3-5 range with disabling deficits 4

Prior Statin Therapy

• Patients on prior statin therapy have better outcomes (adjusted OR 3.46) and may be more likely to benefit from thrombolysis 6