What is the best initial treatment for a patient presenting with right-sided weakness due to a proximal anterior circulation occlusion with a moderate-sized infarct core?

Treatment Recommendation for Proximal Anterior Circulation Occlusion with Moderate Infarct Core

For a patient with right-sided weakness from proximal anterior circulation occlusion and moderate-sized infarct core, the optimal treatment is combined tPA and mechanical thrombectomy (Option D), provided the patient presents within the appropriate time windows and meets eligibility criteria. 1, 2

Time-Dependent Treatment Algorithm

If Presenting Within 4.5 Hours of Symptom Onset

• Administer IV tPA immediately while simultaneously mobilizing the interventional team for mechanical thrombectomy—do not wait to assess clinical response to tPA before proceeding to the angiography suite 3, 1
• The American Heart Association explicitly recommends against delaying endovascular therapy while observing tPA response, as landmark trials (MR CLEAN, ESCAPE) that established thrombectomy efficacy included 83.7-91.5% of patients receiving IV thrombolytics alongside mechanical intervention 3, 1
• IV tPA should be given at 0.9 mg/kg (maximum 90 mg) with 10% as bolus and 90% as infusion over 60 minutes, per standard protocols 3

If Presenting Between 4.5-6 Hours of Symptom Onset

• Proceed directly to mechanical thrombectomy without tPA, as the patient is beyond the 4.5-hour window for thrombolytic eligibility but still within the 6-hour window for thrombectomy in proximal anterior circulation occlusions 3, 1
• Patients with proximal vessel occlusions (ICA or M1) should have ASPECTS ≥6, NIHSS ≥6, and pre-stroke mRS 0-1 for optimal benefit 3, 1

If Presenting Between 6-12 Hours of Symptom Onset

• Advanced perfusion imaging is mandatory to confirm salvageable tissue before proceeding with mechanical thrombectomy 2
• Patient must meet either DAWN criteria (clinical-imaging mismatch with age <80 years, NIHSS ≥10, and core <31 mL) or DEFUSE-3 criteria (ischemic core <70 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL) 2
• If salvageable tissue is confirmed, proceed with mechanical thrombectomy alone (tPA is contraindicated beyond 4.5 hours) 3

Why Combined Therapy Outperforms Monotherapy

Evidence Supporting Combined Approach

• The ESCAPE trial demonstrated adjusted odds ratio of 2.6 (95% CI 1.7-3.8) for improved functional outcomes with combined therapy versus standard care alone, with functional independence rates of 53.0% versus 29.3% 4
• The MR CLEAN trial showed adjusted OR of 1.67 (95% CI 1.21-2.30) favoring combined intervention, with absolute difference of 13.5% in functional independence (32.6% versus 19.1%) 3, 1
• Mortality was significantly reduced with combined therapy (10.4% versus 19.0% in control group, P=0.04) 4

Why Thrombectomy Alone is Insufficient

• IV tPA achieves recanalization in less than 50% of large vessel occlusions, with particularly poor results in proximal occlusions like M1 1
• Among patients with proximal vessel occlusion in the anterior circulation, 60-80% die within 90 days or fail to regain functional independence despite alteplase treatment alone 4

Why tPA Alone is Inadequate

• Mechanical thrombectomy achieves TICI 2b/3 recanalization in 59-87.8% of cases with stent retrievers, far exceeding tPA monotherapy 1, 3
• The adjusted odds ratio for improved functional outcomes with combined therapy versus medical management alone is 1.67, indicating significant benefit of adding mechanical intervention 1

Technical Implementation Details

Workflow Optimization

• Target door-to-groin puncture time under 110 minutes from hospital arrival to maximize functional outcomes 1, 2
• Every 30-minute delay reduces probability of favorable outcome by approximately 10.6% 1
• Median time from CT to first reperfusion should be approximately 84 minutes 4

Thrombectomy Technique

• Stent retrievers are the preferred first-line device, achieving superior recanalization rates compared to other modalities 1, 3
• The procedural goal is TICI 2b/3 reperfusion (successful recanalization of ≥50% of affected territory) 1, 2
• Direct aspiration (ADAPT technique) may be used as first-line with stent retriever as rescue if needed 3

Post-Procedure Management

• Maintain blood pressure ≤180/105 mmHg for 24 hours after thrombectomy to optimize outcomes and reduce hemorrhagic complications 5, 2
• Delay aspirin administration until 24 hours post-thrombolysis if IV tPA was given 5
• Monitor closely for hemorrhagic transformation and neurological deterioration 5

Critical Pitfalls to Avoid

Timing Errors

• Never delay mechanical thrombectomy to observe tPA response—this is the most common and consequential error, as both treatments should proceed in parallel 3, 1
• Do not proceed with thrombectomy if imaging shows ASPECTS of 0, no perfusion mismatch, or large established infarct core (>70 mL by DEFUSE-3 criteria) in the extended time window 2

Patient Selection Errors

• Observation alone (Option C) is never appropriate for proximal anterior circulation occlusion with moderate infarct core, as this represents a highly treatable emergency with proven mortality benefit from intervention 4, 3
• Do not exclude patients based solely on time if they present 6-12 hours from onset—advanced imaging may identify salvageable tissue 2

Contraindications to Consider

• IV tPA is contraindicated beyond 4.5 hours from symptom onset 3
• Mechanical thrombectomy should not be performed if baseline imaging demonstrates large established infarct without salvageable penumbra in the extended window 2

Expected Outcomes with Combined Therapy

• Functional independence (mRS 0-2) at 90 days: 53.0% with combined therapy versus 29.3% with standard care alone 4
• Mortality reduction: 10.4% with combined therapy versus 19.0% with standard care 4
• Successful recanalization (TICI 2b/3): 59-87.8% with modern stent retriever devices 1, 3
• Symptomatic intracerebral hemorrhage occurs in approximately 3.6% of patients receiving combined therapy 4

Special Consideration: Moderate Infarct Core

• The term "moderate-sized infarct core" typically corresponds to ASPECTS 3-5, which now has evidence supporting endovascular treatment with numbers needed to treat of 4.7 for better functional outcomes 1
• Patients with ASPECTS 3-5 should still receive combined therapy if within appropriate time windows, as recent evidence extends treatment eligibility to larger core volumes than previously recommended 1