Stroke Management Guidelines

Jul 1, 2025

Overview

This lecture reviewed updated guidelines for the management of acute ischemic stroke, focusing on pre-hospital care, thrombolytic and antiplatelet therapy, and indications for mechanical thrombectomy.

Guideline Classification and Evidence

  • Recommendations use "Class" (strength) and "Level" (quality) of evidence.
  • Class 1: Strong, must do; Class 2a: Moderate; Class 2b: Weak; Class 3: Do not do.
  • Level A: Highest evidence (multiple RCTs); Level B: Single RCT; Level C: Consensus/expert opinion.

Pre-Hospital Stroke Care

  • EMS should use stroke severity scales, but current tools are only moderately accurate for large vessel occlusion (LVO).
  • Bypassing the nearest hospital for a thrombectomy-capable center is reasonable if it does not significantly delay alteplase (tPA) administration and comprehensive care is <30 min away.
  • Patients ineligible for alteplase should be taken directly to a thrombectomy-capable center if possible.

Thrombolytic Therapy Updates

  • Alteplase may be used beyond 4.5 hours from last known well if advanced imaging (MRI or CT perfusion) demonstrates salvageable brain tissue.
  • Alteplase is not recommended for mild, non-disabling strokes (NIHSS 0–5).
  • Tenecteplase is a reasonable alternative for patients eligible for thrombectomy, offering simpler dosing.

Antiplatelet Therapy

  • Mild stroke or TIA patients not receiving alteplase should receive dual antiplatelet therapy (aspirin + clopidogrel) within 24 hours for 21 days, then aspirin alone.
  • This reduces recurrent stroke risk without increasing major bleeding rates.

Mechanical Thrombectomy

  • Mechanical thrombectomy is recommended up to 16 hours after last known well for eligible LVO patients (Class 1, Level A).
  • It is reasonable to consider up to 24 hours if imaging shows a mismatch between clinical deficit and core infarct (Class 2a, Level B).
  • Key trials: DAWN (6–24 h) and DEFUSE 3 (6–16 h), using advanced imaging to select patients.

Special Protocols and Clinical Scenarios

  • Wake-up strokes with resolved symptoms should be managed like other TIAs—dual antiplatelet therapy for 21 days.
  • Relative alteplase contraindications (recent surgery, aneurysm) require clinical judgment and documentation.
  • For patients with >4.5 hr onset at non-thrombectomy centers, prioritizing transfer for thrombectomy is preferred; advanced imaging may guide alteplase use when thrombectomy is not possible.

Key Terms & Definitions

  • Alteplase (tPA) — A thrombolytic agent used for acute ischemic stroke.
  • Tenecteplase — An alternative thrombolytic, easier to administer with a single bolus.
  • Mechanical Thrombectomy — Procedure to remove clots from large cerebral arteries.
  • Large Vessel Occlusion (LVO) — Blockage in major brain arteries, often requiring thrombectomy.
  • Modified Rankin Scale (mRS) — Disability scale used in stroke outcome assessment.
  • NIH Stroke Scale (NIHSS) — Tool for quantifying stroke severity.

Action Items / Next Steps

  • Review advanced imaging protocols for stroke (CTP, MRI).
  • Update pre-hospital and ED protocols based on latest guidelines.
  • Ensure documentation of rationale when deviating from guideline recommendations.
  • Assign readings on DAWN and DEFUSE 3 trials for deeper understanding.

Certainly! Here is a comprehensive, in-depth summary and review of the lecture on acute ischemic stroke guidelines presented by Dr. Robert L. Allende:

Comprehensive Summary and Review: Acute Ischemic Stroke Guidelines

Speaker and Context

  • Dr. Robert L. Allende, Professor of Neurosurgery and Emergency Medicine, Medical Director of Neuro ICU at University of New Mexico.
  • Focus: Updated 2019 American Heart Association/American Stroke Association (AHA/ASA) guidelines on acute ischemic stroke.
  • Emphasis on evidence-based recommendations, controversies, and practical clinical applications.

1. Guideline Framework: Strength and Quality of Recommendations

  • Class of Recommendation (Strength):

    • Class I: Strong recommendation; must do. Failure to comply may risk malpractice.
    • Class IIa: Moderate recommendation; reasonable to do.
    • Class IIb: Weak recommendation; may consider doing.
    • Class III: Not recommended; no benefit or potential harm.

  • Level of Evidence (Quality):

    • Level A: High-quality evidence from multiple randomized controlled trials (RCTs) or meta-analyses.
    • Level B: Moderate evidence from a single RCT or non-randomized studies.
    • Level C: Expert opinion or consensus without strong trial data.

2. Pre-Hospital Stroke Care and EMS Protocols

  • Stroke Severity Scales:

    • EMS uses stroke severity scales to identify suspected strokes and potential large vessel occlusions (LVO).
    • Current scales have moderate accuracy (AUC 0.7–0.85), with positive predictive value for LVO around 50–60%.
    • Limitations: Risk of over-triage or missed LVOs; better tools needed.

  • Pre-Hospital Bypass Decisions:

    • If eligible for alteplase (tPA), bypassing the nearest alteplase-capable hospital to go directly to a thrombectomy-capable center is a Class IIb, Level B recommendation.
    • Must balance potential delay in alteplase administration against faster access to thrombectomy.
    • If bypass delays alteplase beyond eligibility, patient should receive alteplase at the nearest hospital first, then transfer.
    • If patient is ineligible for alteplase (e.g., outside time window, anticoagulated), direct transport to thrombectomy-capable center is recommended (Class IIb, Level C).

  • Systems of Care:

    • EMS protocols should be locally tailored, considering geography, transport times, and hospital capabilities.
    • Collaboration between EMS agencies and hospitals is essential for protocol development.

3. Thrombolytic Therapy Updates

  • Alteplase (tPA) Use Beyond 4.5 Hours:

    • Traditionally limited to within 4.5 hours of last known well.
    • New evidence supports use beyond 4.5 hours in select patients with salvageable brain tissue identified by advanced imaging (MRI DWI/FLAIR mismatch or CT perfusion).
    • Wake-Up Stroke Trial (2018): Showed benefit of alteplase in patients with unknown onset time but MRI evidence of recent stroke.
    • EXTEND Trial (2019): Demonstrated benefit of alteplase up to 9 hours post-onset in patients with perfusion mismatch on CT or MRI.
    • Recommendation: Class IIa, Level B for alteplase beyond 4.5 hours guided by imaging.

  • Alteplase Not Recommended for Mild, Non-Disabling Strokes:

    • NIH Stroke Scale (NIHSS) 0–5 with non-disabling symptoms.
    • Based on PRISMS trial showing no benefit and possible harm.
    • Recommendation: Avoid alteplase in this group (Class III, No Benefit).

  • Tenecteplase (TNK) as an Alternative:

    • Single bolus administration simplifies dosing and transport logistics.
    • EXTEND-IA TNK trial showed TNK is at least as effective as alteplase in patients eligible for thrombectomy.
    • Recommendation: Reasonable alternative in thrombectomy candidates (Class IIb).

4. Antiplatelet Therapy in Minor Stroke and TIA

  • Dual Antiplatelet Therapy (DAPT):

    • For patients with minor ischemic stroke or TIA not receiving thrombolysis.
    • Initiate aspirin plus clopidogrel within 24 hours, continue for 21 days, then aspirin alone.
    • Supported by CHANCE (China) and POINT (North America/Europe) trials.
    • Benefits: Significant reduction in recurrent stroke risk without significant increase in major bleeding.
    • Recommendation: Class I, Level A (strong recommendation).

  • Rationale for Success:

    • Early initiation in high-risk period post-stroke.
    • Short duration (21 days) limits bleeding risk.
    • Exclusion of patients at high bleeding risk.

5. Mechanical Thrombectomy

  • Time Windows:

    • Established: Within 6 hours of last known well for LVO.
    • New evidence extends window to 16 hours (Class I, Level A) and up to 24 hours in select patients (Class IIa, Level B).

  • Key Trials:

    • DAWN Trial: 6–24 hours, selected patients with mismatch between clinical deficit and infarct size on imaging.
    • DEFUSE 3 Trial: 6–16 hours, selected patients with small core infarct and large penumbra on perfusion imaging.

  • Patient Selection:

    • Pre-stroke modified Rankin Scale (mRS) ≤2 (independent).
    • Large vessel occlusion in anterior circulation (ICA, M1 MCA).
    • Small infarct core volume (varies by age and NIHSS).
    • Favorable mismatch ratio between ischemic penumbra and core infarct.

  • Outcomes:

    • Significant improvement in functional independence at 90 days.
    • Reduced disability and mortality.

6. Special Clinical Scenarios and Protocols

  • Wake-Up Strokes and TIAs:

    • Patients waking with symptoms that resolve (TIA) should be treated with dual antiplatelet therapy.
    • Not candidates for thrombolysis or thrombectomy once symptoms resolve.

  • Relative Contraindications to Alteplase:

    • Recent major surgery, intracranial aneurysm, etc.
    • Clinical judgment required; documentation of rationale is essential.
    • Example: Post-op patient given alteplase after surgeon confirmed manageable bleeding risk.

  • Patients Presenting >4.5 Hours at Non-Thrombectomy Centers:

    • Priority is transfer to thrombectomy-capable center.
    • Advanced imaging (MRI or CT perfusion) can guide alteplase use if thrombectomy is not feasible.
    • No direct head-to-head trials comparing alteplase vs thrombectomy in this window; transfer preferred.

7. Imaging Modalities in Stroke

  • MRI:

    • Diffusion-weighted imaging (DWI) detects early ischemic changes.
    • FLAIR sequence helps estimate stroke age (DWI positive, FLAIR negative suggests recent stroke).
    • Used in wake-up stroke protocols.

  • CT Perfusion (CTP):

    • Measures cerebral blood flow (CBF), cerebral blood volume (CBV), and Tmax (time to maximum contrast).
    • Identifies infarct core (irreversibly damaged tissue) and penumbra (salvageable tissue).
    • Used in EXTEND and DEFUSE 3 trials for patient selection.

8. Summary of Key Recommendations

| Topic | Recommendation Class | Level of Evidence | Key Points | |-------------------------------|----------------------|-------------------|---------------------------------------------------------------------------------------------| | Pre-hospital stroke severity scales | I | B | Use scales, but recognize limitations in LVO detection. | | Pre-hospital bypass to thrombectomy center | IIb | B | Reasonable if alteplase not delayed and center <30 min away. | | Alteplase beyond 4.5 hours (imaging-guided) | IIa | B | Use MRI or CT perfusion to select patients. | | Alteplase in mild, non-disabling stroke | III (No benefit) | B | Avoid use. | | Tenecteplase for thrombectomy candidates | IIb | B | Reasonable alternative to alteplase. | | Dual antiplatelet therapy in minor stroke/TIA | I | A | Start within 24 hours, continue 21 days, then aspirin alone. | | Mechanical thrombectomy 6–16 hours | I | A | Strongly recommended for eligible LVO patients. | | Mechanical thrombectomy 16–24 hours | IIa | B | Reasonable in select patients with favorable imaging. |

9. Practical Clinical Pearls

  • Always document rationale when deviating from guidelines.
  • Early collaboration between EMS, ED, neurology, and radiology optimizes stroke care.
  • Advanced imaging is critical for patient selection beyond traditional time windows.
  • Dual antiplatelet therapy is a major change in secondary stroke prevention for minor strokes.
  • Tenecteplase may simplify logistics in thrombectomy candidates.
  • Mechanical thrombectomy has revolutionized outcomes for LVO strokes, extending treatment windows.

10. Future Directions and Controversies

  • Need for improved pre-hospital LVO detection tools.
  • Ongoing trials may refine alteplase use in mild strokes.
  • Further research on tenecteplase vs alteplase in broader populations.
  • Optimization of transfer protocols and telemedicine for rural stroke care.

Conclusion

This lecture provided a thorough update on acute ischemic stroke management, emphasizing evidence-based guidelines, recent trial data, and practical considerations. The integration of advanced imaging, expanded treatment windows, and new pharmacologic options like tenecteplase are reshaping stroke care. Clinicians must balance timely intervention with patient-specific factors, using these guidelines to optimize outcomes.

If you want, I can also help you create a detailed study guide or highlight key points for exam preparation based on this summary!

Full transcript