Abstract
Introduction: Around 25-40% of ischemic strokes are cryptogenic or strokes of undetermined etiology. Determination of stroke etiology can be challenging, requiring extensive diagnostic testing including long term monitoring for occult atrial fibrillation. Recent studies suggest that inflammation (monocytes/ macrophages driven) and fibrosis in the atrial substrate leads to atrial fibrillation/ cardioembolic strokes. Therefore, we hypothesized that clots collected from patients with cardioembolic stroke during thrombectomy will have increased myeloid derived inflammatory cells as compared to other stroke etiologies. Methods: 54 thrombi were obtained during mechanical thrombectomy in patients with ischemic strokes after consent. They were formalin fixed, embedded, sliced and stained with CD11b, a marker for myeloid derived cells and some lymphoid cells. Mean of five 20x images from two slices per patient was quantified by image J and used for analysis. The relationship between stroke etiology (TOAST) and number of CD11b positive cells was assessed using Mann-Whitney U test and multilinear regression models. Results: Mean patient age was 64.2±12.5 years, 33.3% were women, 81.5% had hypertension, 22.2% had diabetes mellitus, and 37% had hyperlipidemia. Thrombi with cardioembolic etiology had significantly higher number of CD11b positive cells (248.2±137.4, n=27) as compared to strokes from large artery atherosclerosis (133.3±95.7, n=11), p=0.02. Cryptogenic strokes also had significantly higher number of CD11b positive cells, (212.1± 104.8, n=13) when compared to strokes from large artery atherosclerosis, p=0.04, n=11, even after controlling for hypertension, hyperlipidemia, heart disease, diabetes mellitus and age. No difference was seen in CD11b positive cell numbers between cardioembolic and cryptogenic strokes, p=0.4. Conclusion: Cardioembolic and cryptogenic stroke thrombi have increased CD11b positive cells as compared to strokes from large artery atherosclerosis. The shared histology of cardioembolic and cryptogenic strokes suggests that many of the cryptogenic strokes may be due to undiagnosed cardioembolism. Future studies using flow cytometry on thrombi can be a novel area of research for stroke etiology.
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