When do we administer thrombolytics, such as alteplase (tissue plasminogen activator), for acute ischemic stroke, and does the National Institutes of Health Stroke Scale (NIHSS) score or other scores matter?

Thrombolytic Therapy for Acute Ischemic Stroke

Thrombolytics should be administered to eligible patients with acute ischemic stroke within 4.5 hours of symptom onset, with the greatest benefit seen when given as early as possible, and patient selection should be based on established inclusion/exclusion criteria rather than specific NIHSS or VAN score cutoffs. 1

Time Windows for Thrombolytic Administration

Standard Time Window (0-3 hours)

• IV alteplase (0.9 mg/kg, maximum 90 mg; 10% as bolus, remainder over 60 minutes) is strongly recommended for eligible patients within 3 hours of symptom onset 1
• This time window has the strongest evidence (Class I, Level A recommendation) and greatest benefit-to-risk ratio 1

Extended Time Window (3-4.5 hours)

• IV alteplase is recommended for eligible patients between 3-4.5 hours of symptom onset, though with additional exclusion criteria 1, 2
• Additional exclusion criteria for the 3-4.5 hour window include:
  • Age >80 years
  • History of both diabetes and prior stroke
  • NIHSS score >25
  • Use of oral anticoagulants
  • Imaging evidence of ischemic injury involving more than one-third of MCA territory 1

Role of Stroke Severity Scores

NIHSS Score Considerations

• NIHSS score is not used as an absolute inclusion/exclusion criterion for thrombolysis within the 0-3 hour window 1, 3
• For patients with severe stroke (NIHSS >25) in the 3-4.5 hour window, benefit is uncertain (Class IIb, Level C-LD) 1
• For mild strokes (low NIHSS) within 3 hours, treatment may be considered as these patients can still benefit (Class IIb, Level C-LD) 1
• NIHSS should be used for assessment and documentation but not as the sole determinant for treatment eligibility 3

VAN Score

• The VAN (Vision, Aphasia, Neglect) score is not specifically mentioned in major guidelines as a criterion for thrombolytic eligibility 1
• VAN score is more commonly used to identify large vessel occlusions for potential mechanical thrombectomy rather than for IV thrombolysis decisions 3

Patient Selection Algorithm

1. Confirm acute ischemic stroke diagnosis:

   • Clinical assessment showing focal neurological deficits
   • Neuroimaging (CT/MRI) excluding hemorrhage

2. Determine time of symptom onset:

   • Known time of symptom onset or last known well
   • For wake-up strokes, use last known well time

3. Assess eligibility based on time window:

   • 0-3 hours: Standard inclusion/exclusion criteria
   • 3-4.5 hours: Additional exclusion criteria apply

4. Check for absolute contraindications:

   • Intracranial hemorrhage on imaging
   • Severe head trauma or stroke in past 3 months
   • Major surgery within 14 days
   • Gastrointestinal/urinary bleeding within 21 days
   • Platelet count <100,000/mm³
   • INR >1.7 if on oral anticoagulants
   • Blood pressure >185/110 mmHg despite treatment 1, 3

5. Evaluate stroke severity:

   • Document NIHSS score for baseline assessment
   • For severe strokes (NIHSS >25) in 3-4.5 hour window, consider risk/benefit carefully
   • For mild strokes, treatment is still recommended if disabling symptoms are present 1

Special Considerations

• Blood pressure management: Maintain BP <185/110 mmHg before thrombolysis and <180/105 mmHg after treatment 1, 3
• Blood glucose: Check immediately; treat hypoglycemia (<60 mg/dL) before thrombolysis 1
• Rapid treatment: Once the decision to administer thrombolysis is made, treatment should be initiated as quickly as possible ("time is brain") 1
• Post-thrombolysis monitoring: Close neurological monitoring every 15 minutes for the first 2 hours to detect potential hemorrhagic complications 3

Common Pitfalls to Avoid

1. Delaying treatment while waiting for additional tests beyond necessary neuroimaging 1, 3
2. Withholding treatment for mild strokes that may still be disabling 1
3. Overreliance on specific scores rather than overall clinical picture and established inclusion/exclusion criteria 1, 3
4. Excluding patients with early improvement who still have disabling deficits 1
5. Rigid application of time windows without considering individual benefit-risk profiles 1

The evidence consistently shows that earlier treatment leads to better outcomes, with a clear time-dependent effect on efficacy 1, 2. While stroke severity scores like NIHSS provide valuable information, they should not be the sole determinant of treatment eligibility, especially within the 0-3 hour window where benefit has been demonstrated across severity ranges 1.