How can carotid artery stenosis lead to ipsilateral stroke?

Mechanisms of Ipsilateral Stroke from Carotid Artery Stenosis

Carotid artery stenosis causes ipsilateral stroke primarily through two mechanisms: artery-to-artery thromboembolism from unstable atherosclerotic plaque (the dominant mechanism), and less commonly through hemodynamic compromise in cases of severe stenosis with exhausted cerebrovascular reserve.

Primary Mechanism: Thromboembolism

The predominant pathway by which carotid stenosis leads to ipsilateral stroke is through plaque surface thrombus formation and distal embolization to the ipsilateral cerebral hemisphere 1. This occurs when:

• Atherosclerotic plaques in the carotid artery develop surface irregularities, ulceration, or intraplaque hemorrhage that promote local thrombus formation 1
• These thrombi fragment and embolize distally through the internal carotid artery into the ipsilateral middle cerebral artery territory 2, 3
• Plaque characteristics associated with higher embolic risk include ulceration, echolucency, intraplaque hemorrhage, and high lipid content 1

Asymptomatic embolization detected by transcranial Doppler predicts future stroke risk, with an adjusted odds ratio of 8.10 for ischemic events in patients with detectable embolic signals compared to those without 2. The presence of embolic signals correlates with plaque ulceration (relative risk 4.94) and is an independent predictor of stroke in both symptomatic and asymptomatic carotid stenosis 2.

Secondary Mechanism: Hemodynamic Compromise

Hemodynamic insufficiency plays a less common but clinically important role in stroke pathogenesis, particularly in specific high-risk scenarios 1:

• Severe stenosis (>90%) can reduce cerebral perfusion pressure distal to the stenosis 4
• Exhausted cerebrovascular reactivity (impaired CO2 vasodilatory response) identifies patients at highest risk for disabling stroke, with a 27% per month stroke rate versus 5.2% in those with preserved reactivity 4
• Patients with exhausted cerebrovascular reserve have an odds ratio of 9.7 for disabling stroke before endarterectomy 4

Important Caveat: Low Flow May Be Protective

Paradoxically, poststenotic narrowing of the internal carotid artery (ICA/CCA ratio <0.42) is associated with lower stroke risk (8% versus 25% at 5 years), suggesting that severely reduced flow may be insufficient to carry emboli to the brain 5. This indicates that low flow alone is not usually sufficient to cause ischemic stroke distal to symptomatic carotid stenosis 5.

Anatomical Basis for Ipsilateral Distribution

Strokes from carotid stenosis are typically ipsilateral because:

• The internal carotid artery supplies the ipsilateral anterior circulation, including the middle cerebral artery territory 6, 7
• Neural pathways decussate (cross) in the medulla, so right carotid territory strokes cause left-sided weakness and vice versa 6
• Right internal carotid artery strokes manifest as left-sided weakness, left-sided sensory loss, and other left-sided deficits 6, 7

Exception: Contralateral Embolization

Importantly, contralateral stroke can occur through the Circle of Willis, particularly when bilateral stenosis is present 8. Recent computational modeling demonstrates that thromboemboli from left or right carotid sources show non-zero contralateral transport across the Circle of Willis, which can create diagnostic ambiguity regarding which carotid is truly symptomatic 8.

Risk Stratification by Stenosis Severity

The relationship between stenosis severity and stroke risk is complex 1:

• 60-74% stenosis: 3.0% annual ipsilateral stroke risk 1
• 75-94% stenosis: 3.7% annual ipsilateral stroke risk 1
• 95-99% stenosis: 2.9% annual ipsilateral stroke risk (paradoxically lower) 1
• Complete occlusion: 1.9% annual stroke risk 1

The decreased risk with near-occlusion and complete occlusion supports the protective effect of severely reduced flow 1, 5.

Critical Clinical Pitfall

Approximately 45% of ipsilateral strokes in patients with asymptomatic carotid stenosis are attributable to lacunes or cardioembolic sources rather than the carotid stenosis itself 1. This underscores the necessity to fully evaluate patients with carotid stenosis for other treatable causes of stroke, including atrial fibrillation, small vessel disease, and other cardiac sources 1.

Timing of Highest Risk

The risk of ipsilateral stroke is highest in the first few weeks following a symptomatic event 3, 4. In symptomatic patients, there is a significant inverse relationship between the number of embolic signals detected and time elapsed since last symptoms 2. This temporal pattern emphasizes the importance of urgent evaluation and treatment when indicated 3.