What are the next steps for a patient with suspected ischemic stroke after a CT (Computed Tomography) scan with imaging did not show any evidence of stroke?

Next Steps After Negative CT in Suspected Ischemic Stroke

If the initial CT scan does not show evidence of stroke in a patient with suspected ischemic stroke, obtain follow-up MRI of the brain to confirm or exclude the diagnosis, as MRI with diffusion-weighted imaging is significantly more sensitive for detecting acute ischemic changes than CT. 1

Immediate Follow-Up Imaging

• Follow-up CT or MRI is reasonable to confirm the diagnosis when initial imaging does not demonstrate a symptomatic cerebral infarct in patients with suspected ischemic stroke 1
• MRI with diffusion-weighted imaging (DWI) is highly sensitive for detecting acute ischemic changes that may not be visible on initial CT, particularly for small cortical infarcts, subcortical lesions, and posterior fossa strokes 1
• For suspected TIA specifically, follow-up MRI is reasonable to predict risk of early stroke and support the diagnosis when initial head imaging does not show infarction 1

Timing Considerations

• Complete the diagnostic evaluation within 48 hours of symptom onset, as recommended for patients with ischemic stroke or TIA 1
• A repeat brain scan at 24 hours after the initial event helps confirm diagnosis and is required before starting anticoagulants or antiplatelet agents 2
• The 24-hour follow-up imaging is particularly important as it may reveal evolving infarction not visible on the initial scan 2

Additional Vascular Imaging

Proceed with comprehensive vascular imaging regardless of initial CT findings, as identifying the underlying vascular pathology is critical for secondary prevention:

• Noninvasive cervical carotid imaging (carotid ultrasound, CTA, or MRA) is recommended to screen for stenosis in patients who are candidates for revascularization 1
• CTA from aortic arch to vertex is ideal for assessing both extracranial and intracranial circulation and can identify large vessel occlusions, dissections, or significant stenosis 1
• Vascular imaging should be completed within 24 hours of hospitalization or 48 hours of symptom onset due to high early risk of recurrent stroke in patients with symptomatic carotid stenosis 1

Essential Diagnostic Workup

Complete the following investigations even with negative initial CT 1:

• 12-lead ECG to screen for atrial fibrillation and atrial flutter 1
• Laboratory tests: complete blood count, coagulation studies (PT/PTT), glucose, HbA1c, creatinine, and lipid profile 1
• Echocardiography (with or without contrast) is reasonable in cryptogenic stroke to evaluate for cardiac sources of embolism 1
• Long-term cardiac rhythm monitoring is reasonable in cryptogenic stroke patients to detect intermittent atrial fibrillation 1

Important Clinical Caveats

• CT is relatively insensitive for detecting acute ischemic stroke, especially within the first 6 hours, and particularly for small cortical infarcts, subcortical lesions, and posterior circulation strokes 1, 3
• Early infarct signs on CT (hyperdense artery sign, loss of gray-white differentiation, sulcal effacement) may be present in up to 82% of patients with middle cerebral artery territory ischemia within 6 hours 1
• Posterior circulation strokes may require follow-up MRI even when initial MRI is negative, as these are notoriously difficult to detect on initial imaging 2
• Do not assume stroke mimics without completing the full diagnostic evaluation—conditions like brain tumors can occasionally mimic stroke, and MRI with contrast may be helpful in the secondary workup 1

Treatment Implications

• Do not delay appropriate acute stroke treatment while waiting for additional imaging if clinical suspicion remains high and the patient is within treatment windows 1
• The absence of visible infarction on initial CT does not preclude thrombolytic therapy within 3 hours if clinical presentation is consistent with acute ischemic stroke and hemorrhage has been excluded 1