In a 42‑year‑old man with an initial hyperacute right parietal infarct and severe M1 (middle cerebral artery) stenosis who received intravenous thrombolysis, why did his infarct enlarge on repeat MRI/MRA despite apparent improvement of the M1 stenosis, and what should be done next?

Neurological Deterioration Despite Vessel Recanalization After Thrombolysis

Direct Answer

The most likely cause of this patient's worsening infarct despite improved M1 stenosis is hemorrhagic transformation with mass effect, reperfusion injury to already-infarcted tissue, or cerebral edema from the initial large infarct—not inadequate recanalization. 1

Why Infarcts Worsen Despite Vessel Improvement

Hemorrhagic Transformation

• Hemorrhagic transformation is a common complication of severe stroke that results from blood-brain barrier disruption, loss of microvascular integrity, and reperfusion of already-necrotic tissue. 1
• This complication may be associated with worsening of existing deficits or sudden rapid decline due to new mass effect, even when the vessel has recanalized. 1
• The pathophysiology involves matrix metalloproteinases (MMP-9), inflammatory mediators, and reactive oxygen species triggered by thrombolytic agents. 1
• Reperfusion and blood-brain barrier disruption synergistically increase hemorrhagic transformation risk. 1

Cerebral Edema and Mass Effect

• Peak swelling from large hemispheric infarcts occurs several days after ischemia onset, which matches this patient's timeline of next-day deterioration. 1
• The most reliable clinical symptom of tissue swelling is decreased level of consciousness. 1
• Early nausea, vomiting, female sex, congestive heart failure, and leukocytosis are associated with edema after large stroke. 1

Inadequate Collateral Flow Despite Recanalization

• Recanalization does not guarantee clinical improvement—outcome depends critically on collateral circulation, baseline stroke severity, lesion location, lesion volume, and time from onset. 1
• Early recanalization of MCA occlusion has favorable effects on infarct size and clinical outcome only in conjunction with good transcortical collateral blood flow. 1
• The relation between recanalization and clinical outcome is dependent on the precise site of arterial occlusion and collateral arterial supply—improved outcome is associated with more distal occlusions and better collateral flow. 1

Reperfusion Injury

• Recanalization itself can lead to upregulation of MMP-3 or MMP-9, causing further tissue damage. 1
• Large infarcts that undergo thrombolysis may be more susceptible to reperfusion injury mechanisms. 1

Immediate Next Steps

1. Urgent Repeat Imaging to Identify the Cause

• Obtain immediate non-contrast CT or MRI to differentiate hemorrhagic transformation from pure edema. 1, 2
• Look specifically for:
  • Hemorrhagic transformation (petechial hemorrhage or frank hematoma) 1, 2
  • Midline shift indicating mass effect 1
  • Extent of hypodensity on CT or restricted diffusion on DWI 1

2. If Hemorrhagic Transformation is Present

• Immediately stop any antithrombotic agents including aspirin. 2
• Administer cryoprecipitate (10 units initial dose) as first-line therapy to reverse the fibrinolytic state, targeting fibrinogen ≥150 mg/dL. 2
• Infuse platelets (6-8 units) to rapidly correct the systemic fibrinolytic state created by tPA. 2
• The 30-day mortality rate for post-thrombolysis intracranial hemorrhage exceeds 60%, requiring aggressive reversal. 2
• Maintain systolic blood pressure 130-150 mmHg to prevent hematoma expansion while avoiding hypotension that worsens penumbra. 3, 2

3. If Pure Edema Without Hemorrhage

• Monitor closely for signs of malignant cerebral edema requiring decompressive hemicraniectomy. 1
• Maintain blood pressure control (systolic 130-150 mmHg) to balance perfusion needs against hemorrhagic transformation risk. 3
• Elevate head of bed 30 degrees and maintain normothermia. 1
• Consider osmotic therapy if signs of herniation develop. 1

4. Consider Mechanical Thrombectomy (If Not Already Done)

• If only IV thrombolysis was given and the patient is still within 6 hours of onset, urgent mechanical thrombectomy should be considered despite the worsening, as the improved M1 stenosis may not represent complete recanalization. 3
• The American Heart Association/American Stroke Association recommends mechanical thrombectomy using stent retrievers within 6 hours for M1 occlusions with NIHSS ≥6 and ASPECTS ≥6. 3
• IV tPA is relatively ineffective for M1 occlusions, with recanalization rates of only 30% compared to 70% for intra-arterial approaches. 1
• The technical goal should be TICI 2b/3 reperfusion. 3

5. Perfusion Imaging to Assess Salvageable Tissue

• Obtain CT or MR perfusion imaging to determine if there is remaining penumbra that could benefit from further intervention. 1
• Assess collateral flow patterns—the combination of increased time to enhancement and increased regional cerebral blood volume indicates good collateral flow. 4
• If significant perfusion-diffusion mismatch exists, this supports consideration of additional revascularization attempts. 1

Critical Pitfalls to Avoid

Do Not Assume Recanalization Equals Success

• Improved stenosis on MRA does not guarantee adequate tissue perfusion—collateral circulation is the critical determinant of outcome. 1, 4
• Proximal M1 stenosis has worse outcomes than distal occlusions even with similar recanalization rates. 5, 6, 7

Do Not Delay Recognition of Hemorrhagic Transformation

• Any change in level of consciousness, blood pressure elevation, deterioration in motor examination, new headache, or nausea/vomiting should trigger immediate imaging for hemorrhagic transformation. 2
• Neurological assessments should occur every 15 minutes during the first 2 hours post-thrombolysis, then every 30 minutes for 6 hours. 2

Do Not Restart Antithrombotics Prematurely

• Avoid all antithrombotic drugs including aspirin until after 24-hour post-thrombolysis imaging excludes intracranial hemorrhage. 2

Do Not Miss the Window for Decompressive Surgery

• For large MCA infarcts with malignant edema, early decompressive hemicraniectomy (within 48 hours) improves survival, but surgical evacuation of hemorrhage should only occur after sufficient reversal of coagulopathy. 1, 2

Prognosis Considerations

• The baseline NIHSS and extent of initial infarct are stronger predictors of outcome than recanalization status alone. 1
• Proximal M1 occlusions have significantly worse outcomes than distal occlusions, with lower recanalization rates and higher mortality. 1, 7
• This patient's young age (42 years) is favorable, but the severe neurological worsening (grade 1-2 motor power) indicates a large infarct with poor prognosis. 3, 7