What is the most appropriate management for a patient with 12 hours of lower limb weakness, normal vitals, normal coagulation profile, and normal platelet count, with imaging showing a small to moderate ischemic core and proximal anterior circulation occlusion?

Management of Acute Ischemic Stroke with Proximal Anterior Circulation Occlusion at 12 Hours

This patient requires combined intravenous tPA and mechanical thrombectomy (Option C), as they present within the extended window with a small to moderate ischemic core and proximal anterior circulation occlusion—criteria that define salvageable tissue warranting aggressive dual intervention. 1

Why Combined Therapy is the Correct Answer

The evidence overwhelmingly supports combining tPA with mechanical thrombectomy rather than either intervention alone:

• The 2015 AHA/ASA guidelines establish that patients beyond 3 hours from onset with proximal vessel occlusion should undergo both vascular imaging and perfusion studies when mechanical thrombectomy is contemplated, and the presence of a small to moderate ischemic core makes this patient an ideal candidate 2

• In the landmark ESCAPE trial, which enrolled patients up to 12 hours from onset, 91.5% of intervention patients received IV alteplase in addition to thrombectomy, demonstrating that combined therapy is the standard approach 2, 3

• The MR CLEAN trial showed that 89% of enrolled patients (445 of 500) received intravenous tPA before randomization to thrombectomy, with the adjusted common odds ratio of 1.67 favoring the combined intervention approach 2, 4

• A 2017 meta-analysis of 1,845 patients confirmed that mechanical thrombectomy plus thrombolysis significantly reduces disability compared to medical treatment alone (OR: 2.087; 95% CI: 1.718-2.535), with 16 additional patients per 100 achieving good outcomes 5

Critical Imaging Criteria Met

This patient's imaging findings place them squarely within treatment eligibility:

• The small to moderate ischemic core indicates salvageable tissue, which is the key determinant for intervention at 12 hours—not the time window itself 1

• Proximal anterior circulation occlusion is specifically the target lesion for combined therapy, as intravenous thrombolysis alone is less efficacious for proximal thrombus compared to distal occlusions 2

• The ESCAPE trial specifically required a small infarct core by ASPECTS and proximal intracranial arterial occlusion in the anterior circulation, achieving 53.0% functional independence versus 29.3% in controls 3

Why Other Options Are Incorrect

Option A (tPA alone) is inadequate:

• Intravenous thrombolysis appears more efficacious for distal than proximal thrombus, and this patient has a proximal occlusion requiring mechanical intervention 2
• At 12 hours, tPA alone without thrombectomy would miss the opportunity for superior recanalization rates (59% TICI 2b/3 in MR CLEAN with combined therapy) 2

Option B (Manual embolectomy alone) is suboptimal:

• The evidence base for thrombectomy was established in trials where the vast majority received IV tPA first—isolating mechanical intervention contradicts the proven protocol 2, 4
• Stent retrievers were used in 81.5% of MR CLEAN intervention patients, but this was in addition to, not instead of, thrombolysis 4

Option D (Observe) is contraindicated:

• Observation would result in a 19.0% mortality rate versus 10.4% with intervention, and only 19.1% functional independence versus 32.6% with combined therapy 3
• The 2015 AHA/ASA guidelines make clear that proximal large-vessel occlusion may be more effectively treated with combined therapy than usual care alone 2

Practical Implementation Steps

Execute the following algorithm immediately:

1. Confirm eligibility with rapid advanced imaging to verify the small to moderate core and exclude large established infarct (ASPECTS >5, core <70 mL by DEFUSE-3 criteria) 1

2. Initiate IV tPA immediately at standard dosing (0.9 mg/kg, maximum 90 mg) while simultaneously preparing for thrombectomy—do not delay mechanical intervention waiting for tPA response 2, 1

3. Proceed to groin puncture with target door-to-puncture time <90 minutes, using stent retrievers as first-line mechanical device 1, 3

4. Achieve TICI 2b/3 reperfusion as the procedural goal, which was accomplished in 59% of MR CLEAN patients and correlates with improved functional outcomes 2, 4

Critical Pitfalls to Avoid

Do not make these common errors:

• Never delay thrombectomy to complete a full tPA infusion—the ESCAPE trial demonstrated that rapid workflow (median 84 minutes from CT to first reperfusion) is essential for benefit 3

• Do not proceed if imaging shows ASPECTS of 0-5 or core >70 mL—these patients fall outside proven benefit criteria and risk hemorrhagic transformation 1

• Do not use time from onset as the sole exclusion criterion—tissue viability, not time, determines eligibility at 12 hours 1

• Avoid proceeding without confirming normal coagulation—though this patient has normal coagulation profile and platelets, this must be verified before tPA administration 2

Post-Intervention Management

Maintain blood pressure ≤180/105 mmHg for 24 hours after thrombectomy to optimize outcomes and reduce hemorrhagic complications 1

Monitor closely for symptomatic intracerebral hemorrhage, which occurred in 3.6% of intervention patients in ESCAPE (not significantly different from controls at 2.7%) 3