Can we thrombolyse (administer thrombolytic therapy, such as alteplase (tissue plasminogen activator, tPA)) a patient with a clinically suspected acute ischemic stroke but with a negative Magnetic Resonance Imaging (MRI) result?

MRI-Negative Stroke and Thrombolysis

Yes, you can and should administer thrombolysis to a patient with clinically suspected acute ischemic stroke even if the MRI is negative, provided the patient meets standard eligibility criteria and hemorrhage has been excluded. The decision to thrombolyse is based on clinical presentation and time from symptom onset, not on the presence of visible ischemia on imaging.

Primary Decision Framework

The fundamental principle is that imaging is performed to exclude hemorrhage, not to confirm ischemia before administering thrombolysis 1. The primary goals of imaging in the 0-4.5 hour window are to exclude intracranial hemorrhage and assess for large hypodensity, not to definitively visualize acute ischemia 1.

Key Evidence Supporting Treatment

• Standard CT imaging has limited sensitivity for hyperacute ischemia: Non-contrast CT is the standard imaging modality for thrombolysis eligibility, and it frequently shows no acute changes in the first hours after stroke onset 1.

• MRI DWI can be falsely negative: Even diffusion-weighted imaging, which is more sensitive than CT, can be negative in the hyperacute phase, particularly with small infarcts, posterior circulation strokes, or very early presentation 2.

• Clinical diagnosis drives treatment: The landmark NINDS trial that established tPA efficacy used only non-contrast CT to exclude hemorrhage, not to confirm ischemia 3. Patients were treated based on clinical stroke syndrome within 3 hours, and this remains the standard 4, 5.

Algorithmic Approach to the MRI-Negative Stroke Patient

Step 1: Confirm Clinical Stroke Syndrome

• Verify acute focal neurological deficit consistent with vascular territory 4, 5
• Exclude stroke mimics (seizure, hypoglycemia, migraine, conversion disorder) through clinical assessment and glucose measurement 5
• Document NIHSS score to quantify deficit severity 4, 5

Step 2: Verify Imaging Excludes Hemorrhage

• Confirm MRI sequences included GRE/SWI to exclude hemorrhage with high sensitivity 1
• Verify no intracranial hemorrhage (excluding microbleeds, which are not contraindications) 1, 4
• Check for large established infarct (though absence of DWI signal does not exclude acute stroke) 2

Step 3: Apply Standard Thrombolysis Eligibility Criteria

• Within 3 hours: Treat all eligible patients regardless of imaging findings beyond hemorrhage exclusion 4, 5, 3
• Within 3-4.5 hours: Apply standard inclusion/exclusion criteria; negative MRI does not preclude treatment 4, 5, 6
• Blood pressure <185/110 mmHg before initiating treatment 4, 5
• No absolute contraindications (prior ICH, active bleeding, recent surgery) 4, 5

Step 4: Administer Thrombolysis Without Delay

• Give alteplase 0.9 mg/kg (maximum 90 mg) with 10% bolus over 1 minute, remainder over 60 minutes 4, 5
• Target door-to-needle time <60 minutes, ideally <30 minutes 4, 5
• Do not delay for additional imaging to "prove" ischemia is present 1

Critical Pitfalls to Avoid

Do Not Wait for Positive Imaging

The absence of visible ischemia on MRI is not a contraindication to thrombolysis 1. Requiring positive DWI findings would inappropriately exclude many patients who would benefit, particularly those presenting very early or with small vessel occlusions 2.

Do Not Obtain MRI If It Delays Treatment

Additional MRI imaging must not delay thrombolysis decision-making 1. If MRI was obtained and is negative, proceed with treatment based on clinical grounds rather than obtaining repeat imaging 1.

Recognize MRI Limitations in Hyperacute Stroke

• DWI sensitivity is not 100% in the first hours after symptom onset 2
• Small lacunar infarcts may not be visible even on DWI 2
• Posterior circulation strokes are more likely to be MRI-negative initially 2

Special Consideration: Wake-Up Stroke Exception

The one scenario where positive MRI findings are required is for wake-up strokes or unclear onset >4.5 hours from last known well, where DWI-FLAIR mismatch is used to identify patients who may benefit from thrombolysis 1, 4, 5, 6. However, this is an expansion of eligibility beyond standard criteria, not a restriction of standard treatment 5, 6.

Integration with Mechanical Thrombectomy

• Obtain vascular imaging (CTA or MRA) to identify large vessel occlusion if endovascular therapy is available 1, 7, 4, 5
• Administer alteplase immediately even if mechanical thrombectomy is planned; do not wait to assess response 7, 4, 5
• Negative MRI does not exclude large vessel occlusion; vascular imaging is essential 1, 7

Bottom Line

Treat the patient, not the scan. A negative MRI in a patient with acute stroke symptoms within the treatment window and no contraindications should prompt immediate thrombolysis, not diagnostic uncertainty 1, 4, 5. The imaging has served its purpose by excluding hemorrhage; the clinical syndrome and time window determine treatment eligibility 3, 6.