What are the benefits and considerations of using thrombolysis with tissue plasminogen activator (tPA) in patients with brainstem infarcts?

Benefits of Thrombolysis in Brainstem Infarcts

Primary Recommendation

Brainstem infarcts should be treated with IV tPA using the same eligibility criteria and protocols as other ischemic strokes, as the location in the brainstem does not constitute a contraindication and patients derive similar benefits in functional outcomes. 1, 2

Evidence-Based Benefits

The benefits of thrombolysis in brainstem infarcts mirror those demonstrated in general acute ischemic stroke populations:

Functional Outcome Improvements

• Within 3 hours of symptom onset, IV tPA (0.9 mg/kg, maximum 90 mg) produces 154 additional patients with good functional outcome (mRS 0-1) per 1,000 treated, representing a substantial improvement in disability-free survival. 1

• Between 3-4.5 hours, thrombolysis still provides benefit with 69 additional excellent outcomes (mRS 0-1) per 1,000 patients treated (OR 1.34,95% CI 1.06-1.68). 1

• The recanalization rate with IV tPA reaches approximately 75% in appropriately selected patients, compared to only 12.5% with anticoagulation alone. 3

Time-Dependent Treatment Algorithm

For patients presenting within 3 hours:

• Administer IV tPA 0.9 mg/kg (maximum 90 mg) with 10% as bolus over 1 minute, followed by 90% infused over 60 minutes (Grade 1A recommendation). 2
• This represents the strongest evidence window with the most favorable benefit-to-risk ratio. 1

For patients presenting between 3-4.5 hours:

• Use the same IV tPA dosing protocol if standard eligibility criteria are met (Grade 2C recommendation). 4, 2
• Additional exclusion criteria apply: age >80 years, oral anticoagulant use regardless of INR, NIHSS >25, or history of both stroke and diabetes. 2

Beyond 4.5 hours:

• IV tPA is not recommended (Grade 1B recommendation against use). 4

Critical Imaging Considerations for Brainstem Strokes

• Obtain CT or MRI prior to thrombolysis to exclude hemorrhage, but do not delay treatment for advanced imaging if non-contrast CT is negative for hemorrhage. 1, 2

• Early ischemic changes on baseline CT are not a contraindication to tPA therapy—31% of patients in the NINDS trial had early ischemic changes with no difference in benefit-risk profile. 1

• Blood pressure must be lowered below 185/110 mmHg before initiating IV thrombolysis. 2

• Only blood glucose assessment must precede IV tPA administration—hyperglycemia >11.1 mmol/L increases symptomatic ICH risk to 36%. 2

Safety Profile in Brainstem Infarcts

The hemorrhagic risk with brainstem thrombolysis follows the same pattern as other stroke locations:

• Symptomatic ICH occurs in 4-6% of appropriately selected and dosed patients. 2
• Fatal ICH risk increases with tPA (OR 3.70,95% CI 2.36-5.79), with absolute risks of 3.5% with tPA versus 0.8% with placebo. 1
• The mortality increase is balanced favorably by functional outcome improvements—23 additional deaths per 1,000 are offset by 154 additional good outcomes per 1,000 in the 0-3 hour window. 1

Special Considerations for Basilar Artery Occlusion

For brainstem infarcts due to basilar artery occlusion with large clot burden:

• Administer IV tPA first without delay, even if mechanical thrombectomy is being considered. 2
• Do NOT wait to evaluate response to IV thrombolysis before proceeding with catheter angiography for mechanical thrombectomy. 2
• Intraarterial thrombolysis may be considered as rescue therapy when early recanalization with IV thrombolysis is not achieved, particularly for basilar artery occlusions. 2, 3
• Combined IV and intraarterial approaches provide recanalization rates of 72-88% with modern stent retrievers for large vessel occlusions. 2

Common Pitfalls to Avoid

• Do not withhold tPA based solely on brainstem location—the anatomic location does not change eligibility criteria. 1
• Do not delay IV tPA to obtain MRI or advanced imaging if non-contrast CT excludes hemorrhage and meets time window. 2
• Do not delay IV thrombolysis to assess for mechanical thrombectomy eligibility in patients with suspected basilar occlusion. 2
• Do not administer tPA if blood pressure cannot be controlled below 185/110 mmHg prior to treatment. 2
• Delay antiplatelet therapy for 24 hours after tPA administration to minimize hemorrhagic risk. 4

Post-Thrombolysis Management

• Monitor closely for symptomatic ICH in the first 24-48 hours after treatment. 4, 5
• Obtain follow-up imaging if neurological deterioration occurs to assess for hemorrhagic transformation. 5
• For patients with hemorrhagic transformation HI1 (small petechiae), antiplatelet therapy may be initiated within 24-48 hours; for HI2, PH1, or PH2, delay antiplatelets for 7-10 days. 5