What are the potential causes and next steps for a female patient with hypertension, previous vestibulopathy, and right-sided retinal detachment, who presents with recurrent bifrontal and temporal headaches, vertiginous dizziness, and nausea, and has multiple punctuate acute infarcts of the left occipital and temporal region with segmental stenosis of the M2 of the left Middle Cerebral Artery (MCA), despite initial treatment with intravenous (IV) Paracetamol, IV Dramamine, and Clopidogrel (CoPlavix)?

Potential Causes and Next Steps for Recurrent Symptoms

This patient most likely has an arterial dissection, vasculitis, or cardioembolic source causing recurrent emboli, and requires immediate vascular imaging (MRA/CTA from aortic arch to vertex), echocardiography with bubble study, hypercoagulability workup, and vasculitis screening—with consideration for ICU admission given the pattern of recurrent infarcts despite antiplatelet therapy. 1, 2

Critical Assessment of Current Situation

The recurrence of symptoms three days after initiation of antiplatelet therapy with multiple acute infarcts and segmental M2 stenosis indicates an ongoing embolic or inflammatory process that is not adequately controlled. 1, 2 The CRP being "only [LAB_VALUE]" does not exclude vasculitis, as some forms present with normal inflammatory markers. 1

Key red flags in this presentation:

• Multiple punctate infarcts in different vascular territories suggest embolic rather than large vessel atherosclerotic disease 1, 2
• Segmental M2 stenosis in a patient without traditional atherosclerotic risk factors (beyond hypertension) raises concern for arterial dissection or vasculitis 1, 3
• Recurrent symptoms despite antiplatelet therapy indicates treatment failure or wrong diagnosis 1, 4
• History of retinal detachment may suggest underlying vasculopathy or connective tissue disorder 1

Most Likely Differential Diagnoses

1. Arterial Dissection (Highest Priority)

Cervical artery dissection accounts for approximately 2% of all ischemic strokes and up to 15% of ischemic strokes among younger patients. 1 The segmental M2 stenosis pattern is highly suspicious for dissection. 1

• Dissection can present with headache, neck pain, and Horner syndrome before cerebral ischemia develops in 50-95% of cases 1
• The bifrontal and temporal headache pattern fits with carotid dissection 1
• Associated vestibulopathy could represent vertebral artery dissection 1, 5
• Risk factors include connective tissue disorders (suggested by retinal detachment history), FMD (15% association with dissection), and hypertension 1

2. Vasculitis (Primary CNS or Systemic)

The segmental stenosis pattern and multiple punctate infarcts are classic for cerebral vasculitis. 1 Normal or mildly elevated CRP does not exclude vasculitis, particularly primary CNS vasculitis which often has normal inflammatory markers. 1

3. Cardioembolic Source

Multiple punctate infarcts in different territories strongly suggest cardioembolism. 1, 3 Paroxysmal atrial fibrillation can present with recurrent emboli despite antiplatelet therapy. 3

4. Fibromuscular Dysplasia (FMD)

FMD is most commonly encountered in middle-aged women and can manifest with stroke, TIA, carotid dissection, or spontaneous dissection. 1 The association with retinal detachment and hypertension raises this possibility. 1

5. Hypercoagulable State

Recurrent infarcts despite antiplatelet therapy may indicate a prothrombotic condition requiring anticoagulation rather than antiplatelet therapy. 1, 2

Immediate Diagnostic Workup Required

Vascular Imaging (STAT Priority)

• MRA or CTA from aortic arch to vertex to evaluate for dissection, vasculitis, or FMD 1, 2
• Look specifically for: vessel wall irregularity, "string of beads" appearance (FMD), intimal flap (dissection), or segmental narrowing (vasculitis) 1
• CTA may be superior to MRA for detecting subtle dissection 1

Cardiac Evaluation

• Transthoracic echocardiogram with bubble study to evaluate for patent foramen ovale, atrial septal defect, or cardiac thrombus 1, 2, 3
• 24-hour Holter monitoring to detect paroxysmal atrial fibrillation 3
• ECG to assess for atrial fibrillation or other arrhythmias 1, 2

Laboratory Workup

• Complete blood count with platelets to assess for thrombocytopenia or polycythemia 1, 2
• Comprehensive metabolic panel including creatinine and electrolytes 1, 2
• Erythrocyte sedimentation rate (ESR) and CRP (repeat if not already done) 1
• Hypercoagulability panel: antiphospholipid antibodies (anticardiolipin, anti-β2 glycoprotein I, lupus anticoagulant), protein C, protein S, antithrombin III, factor V Leiden, prothrombin gene mutation 1, 2
• Vasculitis workup: ANA, ANCA, complement levels (C3, C4), rheumatoid factor 1
• Lipid panel and hemoglobin A1c to assess atherosclerotic risk factors 1, 2
• Lactate dehydrogenase (LDH) and haptoglobin to evaluate for thrombotic microangiopathy 1, 2

Additional Imaging

• Repeat MRI brain with DWI/FLAIR to assess for new infarcts or progression 1, 6
• Vessel wall MRI if available, to distinguish between dissection, vasculitis, and atherosclerosis 1

Management Modifications

Antiplatelet Therapy Reassessment

The current regimen of clopidogrel (CoPlavix) alone may be inadequate. 4

• Consider dual antiplatelet therapy (aspirin 81-325 mg plus clopidogrel 75 mg daily) for symptomatic moderate-severe carotid stenosis, though evidence is limited for routine use 4
• If dissection is confirmed, anticoagulation with heparin followed by warfarin or DOAC is typically recommended over antiplatelet therapy, though no randomized trials exist comparing the two 1
• If cardioembolic source is identified, switch to anticoagulation (warfarin or DOAC depending on the source) 1, 3

Blood Pressure Management

The patient's blood pressure control is critical but must be carefully managed to avoid hypoperfusion in the setting of cerebral ischemia. 1

• For acute ischemic stroke, avoid blood pressure reduction within the first 5-7 days unless BP exceeds 220/120 mmHg 1, 2
• Target BP <140/90 mmHg after stabilization (≥3 days post-stroke) 1
• If dissection is confirmed, maintain BP <140/90 mmHg to prevent extension 1

Symptomatic Management

• Continue IV antiemetics (Dramamine/dimenhydrinate) for nausea and vertigo as needed 7
• Avoid excessive use of vestibular suppressants as they may delay central compensation 5, 7
• Consider vestibular physical therapy once acute phase resolves 5, 7

Admission and Monitoring Requirements

This patient requires ICU or stroke unit admission for continuous monitoring given recurrent symptoms despite treatment. 1, 2

• Continuous cardiac telemetry to detect arrhythmias 1, 2
• Frequent neurological assessments (every 2-4 hours) to detect progression 1, 2
• Blood pressure monitoring with avoidance of excessive drops that could worsen cerebral perfusion 1, 2

Critical Pitfalls to Avoid

• Do not assume this is simple atherosclerotic disease given the patient's age, sex, and pattern of infarcts 1, 3
• Do not continue antiplatelet monotherapy if dissection or cardioembolic source is identified—these require anticoagulation 1, 3
• Do not aggressively lower blood pressure in acute stroke unless >220/120 mmHg, as this can worsen cerebral perfusion 1, 2
• Do not dismiss normal CRP as excluding vasculitis—primary CNS vasculitis often has normal inflammatory markers 1
• Do not delay vascular imaging—dissection can progress and requires urgent diagnosis 1

Specific Next Steps Algorithm

Within 24 hours:

1. Obtain MRA or CTA from arch to vertex 1, 2
2. Perform echocardiogram with bubble study 1, 2, 3
3. Send hypercoagulability and vasculitis labs 1, 2
4. Start 24-hour Holter monitoring 3

If dissection confirmed:

• Initiate anticoagulation with heparin 1
• Neurosurgery consultation for potential endovascular intervention if symptoms progress 1

If vasculitis suspected:

• Neurology consultation for consideration of cerebral angiography and possible brain/meningeal biopsy 1
• Consider empiric corticosteroids if high suspicion 1

If cardioembolic source identified:

• Switch to anticoagulation (warfarin or DOAC) 1, 3
• Cardiology consultation for source management 1, 3

If all workup negative:

• Consider vessel wall MRI or conventional angiography 1
• Escalate to dual antiplatelet therapy (aspirin plus clopidogrel) 4
• Consider hematology consultation for occult hypercoagulable state 1, 2