Presentation of Case

A 49-year-old East Asian man presented to the hospital with a 13-hour history of slurred speech, dizziness, decreased responsiveness, and gait instability.

Brain magnetic resonance imaging demonstrated an acute infarction involving the left frontotemporal region. He was treated with aspirin, clopidogrel, Ginkgo biloba extract, and dl-3-n-butylphthalide, with stabilization of symptoms. Approximately six weeks later, however, he experienced recurrent slurred speech and was readmitted.

Repeat MRI revealed a new acute infarction involving the left frontal lobe within the same vascular territory. Arterial spin-labeling perfusion imaging demonstrated reduced cerebral blood flow throughout the left frontotemporal region. Carotid ultrasonography identified a hyperechoic abnormality at the origin of the left internal carotid artery, interpreted as intima-media thickening. Computed tomography angiography demonstrated localized stenosis of the proximal left internal carotid artery.

Routine laboratory studies, including blood counts, metabolic testing, coagulation studies, cardiac biomarkers, renal function, and hepatic function, were unremarkable.

The patient had no history of hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, smoking, or prior cerebrovascular disease.

What is the differential diagnosis?

Initial Differential Diagnosis

At first glance, this appears to be a relatively straightforward case of recurrent ischemic stroke. However, recurrent stroke occurring over a six-week interval despite dual antiplatelet therapy immediately suggests that an important component of the mechanism has not yet been identified.

The central question is not whether the patient has experienced ischemic strokes. The imaging establishes that diagnosis.

The critical question is:

Why is a 49-year-old man without major vascular risk factors continuing to suffer recurrent infarction despite contemporary secondary stroke prevention?

The differential diagnosis can be organized into five major categories:

1. Cardioembolism
2. Large artery atherosclerotic disease
3. Small vessel disease
4. Hypercoagulable disorders
5. Unusual vascular disorders

Is This Cardioembolism?

Cardioembolism is among the most common causes of recurrent ischemic stroke.

Potential mechanisms include:

• Atrial fibrillation
• Left ventricular thrombus
• Patent foramen ovale
• Valvular disease
• Infective endocarditis
• Atrial cardiopathy

However, several aspects of the case argue against a cardioembolic source.

The recurrent infarctions occurred in the same vascular territory. Cardioembolic strokes often involve different arterial distributions over time because emboli may travel to any intracranial circulation.

Furthermore, no cardiac abnormalities were identified during the diagnostic evaluation.

Although cardioembolism cannot initially be excluded, the pattern increasingly suggests a local arterial source.

Is This Large-Artery Atherosclerosis?

The CTA demonstrated stenosis involving the proximal internal carotid artery.

At first glance, this appears to provide a straightforward explanation.

Yet several inconsistencies emerge.

The patient lacks conventional risk factors. More importantly, the degree of stenosis appears insufficient to explain recurrent embolic events despite aggressive medical therapy.

This discrepancy should immediately prompt caution.

One of the most common cognitive errors in vascular neurology is assuming that every carotid abnormality is atherosclerotic.

The clinician must ask:

Does the imaging abnormality adequately explain the clinical severity?

In this case, the answer appears to be no.

Neuroanatomic Localization

Both infarctions involved the left frontotemporal circulation.

This localization immediately implicates:

• Left internal carotid artery
• Left middle cerebral artery
• Less likely, the proximal anterior cerebral circulation

The recurrent involvement of the same vascular territory strongly suggests a persistent ipsilateral embolic source.

Small vessel disease becomes highly unlikely because lacunar infarctions generally occur within deep perforator territories and rarely recur repeatedly within the same cortical distribution.

The localization therefore points toward a lesion within the extracranial or proximal intracranial arterial circulation.

The Diagnostic Pivot

The most important clue in this case is not the stenosis.

It is the recurrence.

Atherosclerotic lesions primarily threaten patients through progressive narrowing or plaque rupture.

This lesion behaved differently.

Despite medical therapy, embolization continued.

Such behavior suggests a lesion whose primary danger is thrombogenesis rather than stenosis.

Digital subtraction angiography ultimately demonstrated approximately 80% stenosis at the origin of the left internal carotid artery. More importantly, contrast stagnation persisted into the venous phase.

This finding fundamentally alters the differential diagnosis.

Persistent contrast retention implies abnormal local flow dynamics.

Blood enters the region but does not exit efficiently.

Flow stagnation is one of the major prerequisites for thrombosis.

At this point, a carotid web becomes the leading diagnostic consideration.

What Is a Carotid Web?

Carotid web is an intimal variant of fibromuscular dysplasia characterized by a thin shelf-like intraluminal projection extending from the posterior wall of the carotid bulb.

Histologically, carotid webs demonstrate:

• Intimal hyperplasia
• Smooth muscle proliferation
• Fibrosis
• Myxoid degeneration

Unlike atherosclerotic plaque, the primary danger is not progressive stenosis.

The danger lies in abnormal hemodynamics.

The web creates a low-flow recirculation zone distal to the lesion.

Blood stagnates.

Thrombus forms.

Fragments embolize distally into the middle cerebral artery circulation.

This mechanism elegantly explains:

• Recurrent ipsilateral infarction
• Failure of antiplatelet therapy
• Contrast stagnation on angiography
• Lack of conventional vascular risk factors

Why Was the Diagnosis Initially Missed?

This case illustrates several important cognitive biases.

Anchoring Bias

The carotid ultrasound abnormality was initially interpreted as intima-media thickening.

Once this interpretation was accepted, alternative explanations became less likely to be considered.

Availability Bias

Most neurologists encounter atherosclerotic carotid disease daily.

Most encounter carotid web rarely.

Common diagnoses naturally come to mind before uncommon ones.

Premature Closure

After CTA identified carotid stenosis, the diagnostic process could easily have stopped.

Yet the recurrence of stroke despite treatment should have triggered reconsideration.

Hemodynamic Evidence

One of the most fascinating aspects of this report is the computational fluid dynamics analysis.

The simulations demonstrated:

• Reduced flow velocity distal to the web
• Flow recirculation zones
• Vortex formation
• Markedly reduced wall shear stress

These findings provide direct physiologic evidence that the lesion is thrombogenic.

The carotid web was not simply an anatomic curiosity.

It was an active generator of embolic risk.

Final Clinical Diagnosis

Recurrent embolic ischemic stroke caused by a symptomatic carotid web of the left internal carotid artery with superimposed thrombus formation.

Clinical Pearls

• Carotid web is an important cause of cryptogenic stroke in younger adults.
• Recurrent ipsilateral stroke despite antiplatelet therapy should raise suspicion for carotid web.
• Degree of stenosis alone does not determine embolic risk.
• DSA remains the diagnostic gold standard.
• Flow dynamics may be more important than luminal narrowing.
• Carotid endarterectomy provides definitive treatment by removing both the web and associated thrombus.
• Careful review of CTA sagittal reconstructions may reveal subtle shelf-like lesions overlooked on routine imaging.

Key findings in the article supporting this reasoning include recurrent ipsilateral infarction despite antiplatelet therapy, DSA demonstration of severe stenosis with persistent contrast stagnation, intraoperative identification of a valve-like carotid web with adherent thrombus, CFD evidence of flow stagnation and low wall shear stress, and complete freedom from recurrent stroke after carotid endarterectomy.