What are the next steps for a patient with a normal MRI (Magnetic Resonance Imaging) but high clinical suspicion of stroke?

Normal MRI in Suspected Stroke: Diagnostic Approach

If the initial MRI is normal but clinical suspicion for stroke remains high, repeat MRI within 1-2 days is reasonable to confirm the diagnosis, particularly for posterior circulation strokes where initial imaging may be falsely negative. 1, 2

Key Diagnostic Considerations

Understanding MRI Limitations in Acute Stroke

• Approximately 25% of acute stroke cases with initially negative CT will show evidence of acute/subacute infarction on follow-up MRI within 1-2 days 1
• Even MRI with diffusion-weighted imaging (DWI) can have false negatives, particularly for small posterior fossa strokes (approximately 50% missed within the first 48 hours) 3
• About one-third of patients with stroke symptoms lasting <24 hours have a DWI-positive lesion, meaning two-thirds may initially appear normal 1, 2

When to Repeat Imaging

For posterior circulation strokes specifically, follow-up MRI may be appropriate to confirm diagnosis even when the initial MRI is negative 1. This is critical because:

• Posterior fossa infarcts are particularly difficult to visualize on initial imaging 3
• The size of the stroke affects detectability on DWI, with smaller strokes being more difficult to visualize 3
• Clinical suspicion should drive the decision to repeat imaging 2

Timing of Repeat MRI

• Perform follow-up MRI within 1-2 days if initial imaging is negative but clinical suspicion remains high 2
• Some experts recommend delayed MRI at 3-7 days if initial imaging was negative but clinical suspicion persists 3
• MRI sensitivity is highest in the acute phase and declines over time, so earlier repeat imaging is preferable 2

Alternative Diagnostic Workup

Vascular Imaging Considerations

If not already performed, consider:

• MR angiography (MRA) or CT angiography (CTA) of head and neck to evaluate for large vessel occlusion or significant stenosis 1, 3
• Both MRA and CTA reliably exclude high-grade intracranial atherosclerotic stenosis 1
• Early identification of symptomatic vertebrobasilar stenosis identifies patients at high risk of recurrent stroke 1

Cardiac and Systemic Evaluation

Even with negative imaging, if clinical diagnosis suggests TIA/stroke:

• Initiate appropriate secondary prevention strategies as recommended by AHA/ASA guidelines 2
• Perform cardiac rhythm monitoring as longer monitoring increases AF detection rates (16.1% with 30-day event recorder vs 3.2% with standard monitoring) 1
• Consider echocardiography (transthoracic or transesophageal) to evaluate for cardioembolic sources 1
• Obtain toxicology screening in appropriate populations (cocaine increases stroke risk >6-fold in young adults) 1

Laboratory Evaluation for Stroke Mimics

Consider testing for systemic conditions that may mimic stroke:

• Hypercoagulable workup in patients <50 years of age 1
• C-reactive protein if infectious endocarditis suspected (CRP ≥10 mg/L increases likelihood with OR 22) 1
• Monogenic causes may be detected in 7% using diagnostic algorithms 1

Clinical Decision Algorithm

1. If initial MRI negative but high clinical suspicion persists:

   • Repeat MRI with DWI, FLAIR, and gradient-echo sequences within 1-2 days 2
   • Consider earlier repeat if posterior circulation stroke suspected 1

2. If repeat MRI remains negative:

   • Consider delayed MRI at 3-7 days with blood-sensitive sequences 3
   • Evaluate for stroke mimics (migraine aura, seizure, functional symptoms) 4
   • Continue secondary prevention if clinical diagnosis remains likely 2

3. Regardless of imaging results:

   • Initiate appropriate antiplatelet therapy if clinical diagnosis supports TIA/stroke 2
   • Pursue cardiac monitoring and vascular imaging as indicated 1

Critical Pitfalls to Avoid

• Do not assume a negative initial MRI definitively rules out stroke, especially for small posterior fossa infarcts that may be missed in the first 24-48 hours 3, 2
• Do not delay secondary prevention measures while awaiting confirmatory imaging if clinical diagnosis is likely 2
• Do not use contrast-enhanced MRI for primary stroke diagnosis as it adds no diagnostic value and may delay treatment 3
• Do not rely solely on imaging when clinical presentation strongly suggests stroke—MRI evidence of acute ischemia was found in 42% of patients meeting National Institute of Neurological Disorders and Stroke criteria for TIA/stroke 4

Prognostic Implications

• Patients with MRI evidence of acute ischemia have significantly higher stroke risk (18% by 18 months) compared to those without (1%), with age-adjusted hazard ratio of 13 4
• Confirming stroke diagnosis with imaging helps with patient education and may promote adherence to prevention regimens 1