Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke

Abstract

The study was approved by the Institutional Review Board, and informed consent of patients was obtained. A total of 145 intracranial Background and Purpose-Ischemic stroke of undetermined cause is a major health issue because of its high frequency and clinical relevance. Histopathologic analysis of human thrombi, retrieved from stroke patients with large-vessel occlusion during mechanical thrombectomy, may provide information about underlying pathologies. This study examines the relationship between stroke causes and histological clot composition to identify specific patterns that might help to distinguish causes of cryptogenic stroke. Methods-Thrombi of 145 consecutive stroke patients with large-vessel occlusion were collected during intracranial mechanical recanalization. The hematoxylin and eosin-stained specimens were quantitatively analyzed in terms of the relative fractions of the main constituents (red and white blood cells and fibrin/platelets). These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the international Trial of Org 10172 in Acute Stroke Treatment criteria. Results-The composition of thrombi from cardioembolic and noncardioembolic stroke patients differed significantly for all main thrombus components. Cardioembolic thrombi had higher proportions of fibrin/platelets (P=0.009), less erythrocytes (P=0.003), and more leucocytes (P=0.035) than noncardioembolic thrombi. Cryptogenic strokes showed strong overlap with cardioembolic strokes but not with noncardioembolic strokes, in terms of both thrombus histology and interventional and clinical outcome parameters. Conclusions-Quantitative evaluation of thrombus composition may help to distinguish between different stroke causes.Our findings support the notion that the majority of cryptogenic strokes are cardioembolic.

Ischemic Stroke

“…As reported by Boeckh-Behrens et al, 10 we also found a strong association of cryptogenic strokes with cardioembolic strokes compared with noncardioembolic strokes, which further strengthens the theory that strokes where the pathogenesis after complete diagnostic workup is classified as cryptogenic are mostly of cardiac origin.…”

“…This supports recent studies by Boeckh-Behrens et al, 8,10 Niesten et al, 13 and Simons et al, 7 that report about an association of high fibrin and low RBC proportion in cardioembolic thrombi and which are contrary to the concept of red and erythrocyte-rich cardioembolic thrombi (Figure 1). The contradictory findings of Kim et al 14 may be related to differences in methods and study population.…”

“…[3][4][5][6][7][8][9] Moreover, first results about the differentiation of cardioembolic versus noncardioembolic stroke suggest that cryptogenic stroke is mostly of cardiac origin. 8,10 However, evidence is limited, especially for immunohistochemical parameters. 11 Our study, therefore, aimed to evaluate further the theory of histological determination of thrombus origin and additionally included immunohistochemical parameters that may help to specify the thrombus origin.…”

Embolic Stroke of Uncertain Source: An Entity Slowly Coming Into Focus

“…Small foci of myocardial injury that generate cerebral emboli is an intriguing mechanism raised by this work. Consistent with this is the recent finding that emboli extracted from the brains of individuals with ESUS during acute stroke treatment show features consistent with cardiogenic emboli 7. AF is associated with elevated troponin and subclinical AF has been suggested as the cause underlying cryptogenic stroke 8, 9.…”

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

“…Mechanical thrombectomy is notable because it allows for histologic evaluation of clots retrieved from human intracranial arteries, potentially broadening our insight into stroke etiology as well as our understanding of clot appearance on imaging studies. Several recent studies involving the histologic analysis of intracranial clots retrieved by mechanical thrombectomy in acute stroke patients have focused on blood cell composition in clots using either hematoxylin and eosin or immunohistochemical staining 2, 3, 4, 5, 6, 7…”