Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke

Abstract

Objective: To determine whether large (≥3 mm thick) but nonstenotic (<50%) carotid artery atherosclerotic plaque predominantly occurs ipsilateral rather than contralateral to cryptogenic stroke.

Methods: This was a cross-sectional observational study. Using a stroke registry, we identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS). Using CT angiography, we measured carotid plaque size (thickness, mm) and carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial method) for each patient. We dichotomized plaque size at several predefined thresholds and calculated the frequency of plaque size above each threshold ipsilateral vs contralateral to stroke.

Results: We included 85 patients with ESUS. Plaque with thickness ≥5 mm was present ipsilateral to stroke in 11% of patients, and contralateral in 1% (9/85 vs 1/85; p = 0.008). Plaque with thickness ≥4 mm was present ipsilateral to stroke in 19% of patients, and contralateral in 5% (16/85 vs 4/85; p = 0.002). Plaque with thickness ≥3 mm was present ipsilateral to stroke in 35% of patients, and contralateral in 15% (30/85 vs 13/85; p = 0.001). There was no difference in percentage stenosis ipsilateral vs contralateral to stroke (p = 0.98), and weak correlation between plaque size and stenosis (R(2) = 0.26, p < 0.001).

Conclusions: Large but nonstenotic carotid artery plaque is considerably more common ipsilateral than contralateral to cryptogenic stroke, suggesting that nonstenotic plaque is an underrecognized cause of stroke. We measured plaque size using CT angiography, a method that could be easily implemented in clinical practice.

Figure 1. Imaging and histopathologic correlation for a representative patient

Sagittal-oblique reformat (A.a, A.b) of CT angiogram source images demonstrates mild narrowing of the proximal left internal carotid artery (40% according to North American Symptomatic Carotid Endarterectomy Trial). The upper image (A.a) was used to measure the arterial diameter distal to the stenosis and the lower image (A.b) was used to measure the arterial diameter at the stenosis. Axial CT angiogram source image (B) demonstrates a large atherosclerotic plaque (long arrows) adjacent to the carotid artery lumen (short arrow). Axial T1-weighted double inversion recovery black-blood MRI (C) shows a corresponding hyperintense plaque (long arrows) and the carotid lumen (short arrow). Carotid endarterectomy specimen (D, E) demonstrates an approximately 5-mm-thick atherosclerotic plaque (D), and histopathologic section (E) through the plaque with a Movat pentachrome stain at 10× magnification demonstrates features of American Heart Association type VI plaque including disruption (d) of the fibrous cap (fc), presence of erythrocytes indicating acute hemorrhage (arrows), and acute intramural thrombus (t).

Figure 2. Scatterplots of carotid atherosclerotic plaque thickness ipsilateral vs contralateral to cryptogenic stroke for 85 patients

Each of the 4 scatterplots dichotomizes plaque thickness at a different threshold: 2 mm (A), 3 mm (B), 4 mm (C), or 5 mm (D). Each dot represents a patient. The top left quadrant of each scatterplot shows patients with plaque thickness above the threshold only in the carotid artery ipsilateral to ischemic stroke. The bottom right quadrant of each scatterplot shows patients with plaque thickness above the threshold only in the carotid artery contralateral to ischemic stroke. The other 2 quadrants (which have red dots rather than black dots) show patients with bilaterally concordant plaque thickness, either below (bottom left) or above (top right) the threshold. The scatterplots illustrate that in patients with plaque thickness above a threshold of 3 mm on 1 side, the ischemic stroke is more commonly on that same side (21 vs 4, p = 0.0009). The scatterplots illustrate similar results for a 4-mm threshold (13 vs 1, p = 0.0018) and 5-mm threshold (8 vs 0, p = 0.0078).