Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI

Kim, S.K.; Yoon, Woong; Kim, T.S.; Kim, H.S.; Heo, Tag; Park, M.S.

doi:10.3174/ajnr.a4402

Cited by 188 publications

(201 citation statements)

References 20 publications

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“…The contradictory findings of Kim et al 14 may be related to differences in methods and study population. The patient collective of Kim et al, on the one hand, was too small to draw a strong conclusion because especially the number of patients with atherosclerosis of large arteries was small (8 patients) compared with the group of patients with cardioembolism.…”

Section: Discussioncontrasting

confidence: 42%

Ischemic Stroke

Sporns

Hanning

Schwindt

et al. 2017

Stroke

179

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We prospectively included a cohort of 198 consecutive ischemic stroke patients with occlusion of the carotid-T or middle cerebral Background and Purpose-The introduction of stent retrievers allows for a complete extraction and histological analysis of human thrombi. Ischemic stroke is a major health issue, and differentiation of underlying causes is highly relevant to prevent recurrent stroke. Therefore, histopathologic analysis of the embolic clots after removal may provide valuable information about underlying pathologies. This study analyzes histological clot composition and aims to identify specific patterns that might help to distinguish causes of ischemic stroke. Methods-Patients with occlusion of the carotid-T or middle cerebral artery who underwent thrombectomy at our university medical center between December 2013 and February 2016 were included. Samples were histologically analyzed (hematoxylin and eosin, Elastica van Gieson, and Prussian blue), additionally immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. These data, along with additional clinical and interventional parameters, were compared for different stroke subtypes, as defined by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Results-One hundred eighty-seven patients were included, of these, in 77 patients, cardioembolic; in 46 patients, noncardioembolic; and in 64 patients, cryptogenic pathogenesis was determined. Cardioembolic thrombi had higher proportions of fibrin/platelets (P=0.027), less erythrocytes (P=0.005), and more leucocytes (P=0.026) than noncardioembolic thrombi. We observed a strong overlap of cryptogenic strokes and cardioembolic strokes concerning thrombus histology. The immunohistochemical parameters CD3, CD20, and CD68/KiM1P showed no statistically noticeable differences between stroke subtypes. Conclusions-Histological thrombus features vary significantly according to the underlying cause and may help to differentiate between cardioembolic and noncardioembolic stroke. In addition, our study supports the hypothesis that most cryptogenic strokes have a cardioembolic cause.

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Section: Discussioncontrasting

confidence: 42%

Ischemic Stroke

Sporns

Hanning

Schwindt

et al. 2017

Stroke

179

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“…Paramagnetic intracellular deoxyhemoglobin leads to a nonuniform magnetic field causing marked signal loss on the GRE sequence because of spin dephasing. It was previously established that the presence of an SVS on GRE imaging was markedly associated with a higher red blood cell count in the clot, whereas fibrin‐dominant clots were associated with the absence of an SVS 3, 12. Fibrin‐dominant clots are typically formed because of endothelium injury overlies the complicated plaque in the setting of advanced atherosclerosis 13.…”

Section: Discussionmentioning

confidence: 99%

“…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…”

Section: Introductionmentioning

confidence: 99%

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

Baek

Kim

Yoon

et al. 2018

Ann Clin Transl Neurol

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ObjectiveIn this study we investigate the association between the expression of inflammatory mediators measured in clots retrieved by mechanical thrombectomy, stroke etiology, and the susceptibility vessel sign (SVS) on gradient‐echo (GRE) MR imaging in acute ischemic stroke patients.MethodsWe performed molecular analysis of intracranial clots retrieved by mechanical thrombectomy from 82 patients with acute stroke. Seventy‐two of these patients underwent GRE imaging before endovascular therapy. We measured the relative expression of inflammatory mediators by performing the quantitative real‐time polymerase chain reaction on the retrieved clots and assessed associations between the expression of inflammatory mediators and stroke subtypes as well as with GRE SVS.ResultsClassifications of stroke etiology for the cohort were as follows: cardioembolism (51, 62.2%), large artery atherosclerosis (9, 11%), and undetermined etiology (22, 26.8%). Clots associated with large artery atherosclerosis showed significantly higher interleukin (IL)‐1β expression than clots from both cardioembolism and undetermined etiology (P = 0.008). A positive SVS was identified in 48 of 72 patients (66.7%) who had GRE imaging. IL‐1β, tumor necrosis factor‐α, and matrix metalloproteinase‐9 expressions were significantly higher in clots with a negative SVS than in those with a positive SVS (P = 0.010, 0.049, and 0.004, respectively).InterpretationExpression of inflammatory mediators in intracranial clots differs significantly based on stroke etiology or presence or the absence of SVS on GRE imaging. This study suggests that molecular analysis of inflammatory mediators in retrieved clots is a promising tool for determining stroke mechanism in acute ischemic stroke patients.

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“…Factors for the absence of FR include stent maldeployment at a segment distal to the thrombus, atherothrombotic occlusion, thrombus properties, [8][9][10] and insufficient stent deployment. Furthermore, additional distal thrombus or vascular collapse due to disturbance of microcirculation may result in the absence of FR.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Flow Restoration/Re-occlusion and Recanalization during Deployment of Stent Retriever

Kokuzawa

Yamada

Kanou

et al. 2018

JNET

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Objective: There has been no detailed study reporting the relationship between flow restoration (FR)/re-occlusion status and recanalization results during the acute thrombectomy using stent retrievers. In this study, we examined the influence of FR/re-occlusion during stent deployment on recanalization in our experiences. Subjects and Methods:In all, 24 patients with cardiogenic cerebral embolism underwent thrombectomy with a TREVO stent retriever (10 males, 14 females, mean age: 77.2 years). Intravenous tissue plasminogen activator (tPA) infusion was preceded in 17 of 24 patients, occlusion sites were as follows: internal carotid artery, 9 patients; M1 of middle cerebral artery, 13 patients; and basilar artery, 2 patients. We investigated the relationship between the presence or absence of FR/re-occlusion and grade of recanalization thrombolysis in cerebral infarction (TICI). We also examined the interval from FR until re-occlusion and frequency of stent deployment. Results:In the first session of stent deployment, FR and subsequent re-occlusion were observed in 11 patients (11/24, 46%). Of these, TICI 2b or higher grade recanalization was achieved in nine patients (9/11, 81%). Of 10 patients who had FR but no re-occlusion in the first session of stent deployment (10/24, 42%), TICI 2b or higher scale recanalization was achieved in 4 (4/10, 40%). In three patients without FR (3/24, 13%), TICI 2b or higher scale recanalization was not achieved. Of the above 11 patients who showed FR and subsequent re-occlusion in the first session of stent deployment, the waiting time until re-occlusion was 5 minutes in seven patients and 10 minutes in four patients.Of the 10 patients who had FR but no re-occlusion, the waiting time was 5 minutes in four patients, 10 minutes in four patients, and 20 minutes in two patients. In 9 of the 24 patients, several sessions of stent deployment were required, and the total frequency of stent deployment was 37 times. In 37 sessions of stent deployment showed the achievement of FR and re-occlusion in 17 sessions (17/37, 46%). Of these, TICI 2b or higher scale recanalization was achieved in 14 (14/17, 82%). Of 12 sessions with FR but no re-occlusion (12/37, 32%), TICI 2b or higher scale recanalization was achieved in 5 (5/12, 41%). TICI 2b or higher scale recanalization was not achieved in eight sessions without FR (8/37, 22%). Conclusion:Flow restoration immediately after stent deployment was a necessary condition for recanalization. If re-occlusion is confirmed after FR, satisfactory recanalization may be achieved at a high percentage. The results demonstrated that satisfactory recanalization was not achieved without FR, and less likely without re-occlusion following FR.

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Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI

Cited by 188 publications

References 20 publications

Ischemic Stroke

Ischemic Stroke

Inflammatory mediator expression within retrieved clots in acute ischemic stroke

Relationship between Flow Restoration/Re-occlusion and Recanalization during Deployment of Stent Retriever

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