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Background: Cerebral edema, a significant complication arising from acute ischemic stroke (IS), has a critical influence on morbidity and mortality. p38MAPK has been shown to promote neuronal apoptosis and brain damage. However, the role of the p38MAPK inhibitor SKF-86002 in protecting against ischemic injury and cerebral edema remains unclear., Methods: Infarct area was examined by TTC staining in middle cerebral artery occlusion (MCAO) mice. Neurological score and brain water content were evaluated. TUNEL and NeuN staining were used to assess neuronal apoptosis and the survival of neurons. Blood-brain barrier (BBB) permeability was determined by Evans blue. Double immunofluorescence staining detected the colocalization of AQP4 and CX43 in astrocytes. IHC staining revealed CX43 and AQP4 expression. EDU staining detected the proliferation of Oxygen and glucose deprivation/reoxygenation (OGD/R)-treated astrocytes. Levels of oxidative stress markers were determined using commercial kits. ELISA was used to assess the secretion of pro-inflammatory factors. RT-qPCR measured the expression of CX43, AQP4 and pro-inflammatory factors. Western blot analyzed the levels of p-p38/p38, AQP4 and CX43. Co-immunoprecipitation (Co-IP) determined the interaction between CX43 and AQP4., Results: SKF-86002 attenuated brain damage, edema, and neuronal apoptosis in MCAO mice. Astrocyte proliferation was suppressed, and oxidative stress and inflammation were alleviated by SKF-86002 treatment. SKF-86002 negatively regulated p38 signaling and the expression of AQP4 and CX43. Additionally, the expression of CX43/AQP4 within astrocytes was modulated by SKF-86002., Conclusion: In summary, SKF-86002 alleviated IS injury and cerebral edema by inhibiting astrocyte proliferation, oxidative stress and inflammation. This effect was associated with the suppression of CX43/AQP4, suggesting that SKF-86002 shows promise as a novel therapeutic approach for preventing IS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

We described a rare case of acute ischemic stroke due to calcified cerebral emboli from calcified carotid plaque (CCP). Radiological examinations revealed that the CCP had an irregular configuration containing a calcified nodule and scattered spotty calcifications, and a large calcified plate. The patient underwent carotid endarterectomy to prevent embolic recurrence. Histopathological examination confirmed the presence of an erupted plaque with a disrupted fibrous cap. Calcified nodular protrusion and spotty calcifications in CCP are predictive of a high risk of embolic stroke with plaque rupture. Thus, careful treatment strategies are crucial to prevent the CCP-related embolic recurrence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

This is a case of a patient who underwent an esophageal dilatation for benign esophageal strictures. As a consequence of the procedure, she developed an esophageal rupture and multiple cerebral and cerebellar air emboli resulting in infarction. The patient died after being placed on comfort care measures. The postmortem examination revealed focal breach of the esophageal mucosa but no sites of cardiac or vascular shunting that could account for the transit of air from the esophagus to the central nervous system. The phenomenon of vascular air entry as a consequence of upper gastrointestinal endoscopic intervention is an uncommon but very serious complication of balloon dilatation therapy. Instances of progression to intracranial arterial gas embolism are even less common, but are well described in a small number of case reports. We present a fatal case of central nervous system air embolism post-balloon dilatation therapy with associated antemortem imaging, autopsy, and microscopic images followed by a discussion of potential mechanisms of entry of air into the brain., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: Cerebral emboli are generated by every step of standard carotid angioplasty and stenting. Primary carotid stenting (PCS) is a technique in which the use of balloon angioplasty (BA) is minimized to decrease the embolic load. The primary aim of this study is to establish the number of emboli generated by each step of primary stenting and determine the relationship to new diffusion (DWI) lesions on subsequent magnetic resonance imaging (MRI)., Methods: Eighty-five patients with severe, symptomatic carotid stenosis were prospectively recruited and underwent carotid stenting. Intraoperative transcranial Doppler was performed in 77 patients. The number and size of microemboli for each of seven procedural steps were recorded. Correlation was made with the number and location of new DWI lesions., Results: PCS was performed in 73 patients. BA was required in 12 patients. The mean number of microemboli was 114, and most microemboli were generated by stent deployment, followed by BA. Balloon techniques generated significantly more emboli than primary stenting ( p = 0.017). There was a significant relationship between total microemboli and new DWI lesions ( p = 0.009), and between new DWI lesions in multiple territories and the severity of pretreatment stenosis ( p = 0.002)., Conclusions: During PCS, more emboli are generated by stent deployment than during any other stage of the procedure. When BA is necessary, more malignant emboli are generated but total emboli are unchanged and there is no difference in new diffusion lesions on MRI. PCS is safe and is not inferior to historical controls for the generation of new DWI lesions.

Objective: Basilar artery occlusion (BAO) is a severe condition with high mortality. However, surgical procedures and outcomes of BAO with different pathologic subtypes have not been fully clarified. This study compared the surgical procedures and clinical outcomes of mechanical thrombectomy in different subtypes of BAO., Methods: Eighty-six patients with acute BAO receiving endovascular treatment between October 2015 and July 2019 were retrospectively analyzed and placed in 3 groups: pure embolism (group 1), arterial-arterial embolism from steno-occlusion of the tandem vertebral artery (group 2), and in situ atherosclerotic thrombosis (group 3). Recanalization rates, procedure times, surgical characteristics, and clinical outcomes were analyzed., Results: Groups 1, 2, and 3 included 33 (38.4%), 17 (19.8%), and 36 (41.9%) patients, respectively. The overall successful recanalization rate was 95.3%, and the good outcome rate was 61.6%. The procedure time in group 1 was shorter than the time in groups 2 and 3 (P < 0.001). The clinical good outcome rate was higher in group 2 than in group 1 (88.2% vs. 54.5%; P = 0.017). Groups 1 and 3 had similar good outcome rates (54.5% vs. 55.6%; P = 0.933). Twenty-seven patients received stent angioplasty: 10 of 17 in group 2 (58.8%) and 17 of 36 in group 3 (47.2%)., Conclusions: The outcome of endovascular treatment for BAO varies among patients with different pathologic mechanisms. Patients with embolism from tandem vertebral artery steno-occlusion achieved the best outcomes. Rescue treatment was more common in patients with embolic BAO with tandem vertebral artery steno-occlusion and BAO with in situ atherosclerotic thrombosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Resorbable topical hemostatic agents are widely used in surgical procedures to control intraoperative bleeding. There have been multiple reports of complications from use of these agents, including pulmonary vasculature thromboembolism, cerebral venous sinus occlusion, and postoperative inflammatory mass lesions each containing the hemostatic agent. We report 2 cases of inadvertent intra-arterial embolization of hemostatic agent. Both cases followed elective surgical cervical spinal procedures, during which gelatin-based local hemostatic agents were used to control unanticipated bleeding. Postoperatively, both patients exhibited neurologic defects and were found to have infarcts of the brain. At autopsy, vertebrobasilar thromboemboli containing foreign material grossly and microscopically consistent with hemostatic matrix material were found in both cases. These are the first reports of hemostatic agent embolization resulting in cerebral infarcts and leading to death., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke. Despite successful recanalization, a limited subset of patients benefits from the new treatment. Human MRI studies have shown that during removal of the thrombus, a shower of microclots is released from the initial thrombus, possibly causing new ischemic lesions. The aim of the current study is to quantify tissue damage following microembolism., Materials and Methods: In a rat model, microembolism was generated by injection of a mixture of polystyrene fluorescent microspheres (15, 25 and 50 µm in diameter). The animals were killed at three time-points: day 1, 3 or 7. AMIRA and IMARIS software was used for 3D reconstruction of brain structure and damage, respectively., Conclusions: Microembolism induces ischemia, hypoxia and infarction. Infarcted areas persist, but hypoxic regions recover over time suggesting that repair processes in the brain rescue the regions at risk., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Fat embolism syndrome (FES) is a change in physiology resulting from mechanical causes, trauma, or sepsis. Neurological manifestations of FES can vary from mild cognitive changes to coma and even cerebral oedema and brain death. Here, we present an unusual case of cerebral fat emboli that occurred in the absence of acute chest syndrome or right-to-left shunt., Case Presentation: A previously healthy 57-year-old right-handed male was admitted to our department because of unconsciousness after a car accident for 3 days. He suffered from multiple fractures of the bilateral lower extremities and pelvis. This patient had severe anaemia and thrombocytopenia. Head MRI showed multiple small lesions in the whole brain consistent with a "star field" pattern, including high signals on T2-weighted (T2w) and fluid-attenuated inversion recovery (FLAIR) images in the bilateral centrum semiovale; both frontal, parietal and occipital lobes; and brainstem, cerebellar hemisphere, and deep and subcortical white matter. Intravenous methylprednisolone, heparin, mannitol, antibiotics and nutritional support were used. Although this patient had severe symptoms at first, the outcome was favourable., Conclusions: When patients have long bone and pelvic fractures, multiple bone fractures and deteriorated neurological status, cerebral fat embolism (CFE) should be considered. Additionally, CFE may occur without an intracardiac shunt. The early diagnosis and appropriate management of FES are important, and prior to and following surgery, patients should be monitored comprehensively in the intensive care unit. With appropriate treatment, CFE patients may achieve good results.

Considering its intolerance to ischemia, it is of critical importance for the brain to efficiently process microvascular occlusions and maintain tissue perfusion. In addition to collateral microvascular flow and enzymatic degradation of emboli, the endothelium has the potential to engulf microparticles and thereby recanalize the vessel, through a process called angiophagy. Here, we set out to study the dynamics of angiophagy in relation to cytoskeletal remodeling in vitro and reperfusion in vivo. We show that polystyrene microspheres and fibrin clots are actively taken up by (brain) endothelial cells in vitro, and chart the dynamics of the actin cytoskeleton during this process using live cell imaging. Whereas microspheres were taken up through the formation of a cup structure by the apical endothelial membrane, fibrin clots were completely engulfed by the cells, marked by dense F-actin accumulation surrounding the clot. Both microspheres and fibrin clots were retained in the endothelial cells. Notably, fibrin clots were not degraded intracellularly. Using an in vivo microembolization rat model, in which microparticles are injected into the common carotid artery, we found that microspheres are transported by the endothelium from the microvasculature into the brain parenchyma. Microembolization with microspheres caused temporal opening of the blood-brain barrier and vascular nonperfusion, followed by microsphere extravasation and restoration of vessel perfusion over time. Taken together, angiophagy is accompanied by active cytoskeletal remodeling of the endothelium, and is an effective mechanism to restore perfusion of the occluded microvasculature in vivo.

Background: As access to patient emboli is limited, embolus analogs (EAs) have become critical to the research of large vessel occlusion (LVO) stroke and the development of thrombectomy technology. To date, techniques for fabricating standardized human blood-derived EAs are limited in the variety of compositions, and the mechanical properties relevant to thrombectomy are not quantified., Methods: EAs were made by mixing human banked red blood cells (RBCs), plasma, and platelet concentrate in 10 different volumetric percentage combinations to mimic the broad range of patient emboli causing LVO strokes. The samples underwent histologic analysis and tensile testing to mimic the pulling action of thrombectomy devices, and were compared to patient emboli., Results: EAs had histologic compositions of 0-96% RBCs, 0.78%-92% fibrin, and 2.1%-22% platelets, which can be correlated with the ingredients using a regression model. At fracture, EAs elongated from 81% to 136%, and the ultimate tensile stress ranged from 16 to 949 kPa. These EAs' histologic compositions and tensile properties showed great similarity to those of emboli retrieved from LVO stroke patients, indicating the validity of such EA fabrication methods. EAs with lower RBC and higher fibrin contents are more extensible and can withstand higher tensile stress., Conclusions: EAs fabricated and tested using the proposed new methods provide a platform for stroke research and pre-clinical development of thrombectomy devices., Competing Interests: Declarations of Competing Interest LES is a founder of Endovascular Engineering Inc., Ann Arbor, Michigan. YL serves on the Scientific Advisory Board of this company. This company is indirectly related to this manuscript as it's developing medical devices for thrombectomy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: One-fifth of ischemic strokes are embolic strokes of undetermined source (ESUS). Their theoretical causes can be classified as cardioembolic versus noncardioembolic. This distinction has important implications, but the categories' proportions are unknown., Methods: Using data from the Cornell Acute Stroke Academic Registry, we trained a machine-learning algorithm to distinguish cardioembolic versus non-cardioembolic strokes, then applied the algorithm to ESUS cases to determine the predicted proportion with an occult cardioembolic source. A panel of neurologists adjudicated stroke etiologies using standard criteria. We trained a machine learning classifier using data on demographics, comorbidities, vitals, laboratory results, and echocardiograms. An ensemble predictive method including L1 regularization, gradient-boosted decision tree ensemble (XGBoost), random forests, and multivariate adaptive splines was used. Random search and cross-validation were used to tune hyperparameters. Model performance was assessed using cross-validation among cases of known etiology. We applied the final algorithm to an independent set of ESUS cases to determine the predicted mechanism (cardioembolic or not). To assess our classifier's validity, we correlated the predicted probability of a cardioembolic source with the eventual post-ESUS diagnosis of atrial fibrillation., Results: Among 1083 strokes with known etiologies, our classifier distinguished cardioembolic versus noncardioembolic cases with excellent accuracy (area under the curve, 0.85). Applied to 580 ESUS cases, the classifier predicted that 44% (95% credibility interval, 39%-49%) resulted from cardiac embolism. Individual ESUS patients' predicted likelihood of cardiac embolism was associated with eventual atrial fibrillation detection (OR per 10% increase, 1.27 [95% CI, 1.03-1.57]; c-statistic, 0.68 [95% CI, 0.58-0.78]). ESUS patients with high predicted probability of cardiac embolism were older and had more coronary and peripheral vascular disease, lower ejection fractions, larger left atria, lower blood pressures, and higher creatinine levels., Conclusions: A machine learning estimator that distinguished known cardioembolic versus noncardioembolic strokes indirectly estimated that 44% of ESUS cases were cardioembolic.

Background: Arterial thoracic outlet syndrome is a rare condition characterized by a subclavian artery pathology associated with a bone abnormality. It is rarely associated with thromboembolic stroke. The mechanism of cerebral embolism associated with thoracic outlet syndrome have rarely been demonstrated. We present here a fully studied case with a high probability of reverse flow embolism., Case Presentation: A 24-year-old man with a known arterial thoracic outlet syndrome presented with a right cerebral posterior artery brain infarction. An ultrasound examination depicted the compression of the right subclavian artery in the scalene defile with a post stenotic aneurysm and the presence of a floating thrombus in this aneurysm. There was a reverse flow during diastole in this aneurysm. Anticoagulation was carried out with the disappearance of the floating thrombus with no new clinical or brain MRI event. Corrective surgery of this thoracic outlet syndrome was performed one month after stroke., Conclusion: Very few cases of stroke in arterial thoracic outlet syndrome have been described with thorough dynamic vascular imaging. To our knowledge, this is the fourth reported case that advocates for a reverse flow embolism mechanism in stroke associated with thoracic outlet syndrome, and the first to realize an extensive ultrasound and doppler workup.

Background and Purpose: Detailed insight into the composition of thrombi retrieved from patients with ischemic stroke by mechanical thrombectomy might improve pathophysiologic understanding and therapy. Thus, this study searched for links between histologic thrombus composition and stroke subtypes and mechanical thrombectomy results., Materials and Methods: Thrombi from 85 patients who had undergone mechanical thrombectomy for acute ischemic stroke between December 2016 and March 2018 were studied retrospectively. Thrombi were examined histologically. Preinterventional imaging features, stroke subtypes, and interventional parameters were re-analyzed. Statistical analysis was performed with the Kruskal-Wallis test, Mann-Whitney U test, or Spearman correlation as appropriate., Results: Cardioembolic thrombi had a higher percentage of macrophages and a tendency toward more platelets than thrombi of large-artery atherosclerotic stenosis ( P = .021 and .003) or the embolic stroke of undetermined source ( P = .037 and .099) subtype. Thrombi prone to fragmentation required the combined use of contact aspiration and stent retrieval ( P = .021) and were associated with an increased number of retrieving maneuvers ( P = .001), longer procedural times ( P = .001), and a higher lymphocyte content ( P = .035)., Conclusions: We interpreted the higher macrophage and platelet content in cardioembolic thrombi compared with large-artery atherosclerotic stenosis or embolic stroke of undetermined source thrombi as an indication that the latter type might be derived from an atherosclerotic plaque rather than from an undetermined cardiac source. The extent of thrombus fragmentation was associated with a more challenging mechanical thrombectomy and a higher lymphocyte content of the thrombi. Thus, thrombus fragmentation not only might be caused by the recanalization procedure but also might be a feature of a lymphocyte-rich, difficult-to-retrieve subgroup of thrombi., (© 2020 by American Journal of Neuroradiology.)

Rationale: Fat embolism syndrome (FES) is characterized by the classical triad of cerebral, respiratory, and cutaneous manifestations. In contrast, cerebral fat embolism (CFE), corresponding to incomplete pure type FES, is much rarer and usually follows trauma. CFE typically shows a "starfield" pattern on diffusion-weighted magnetic resonance imaging due to the involvement of multiple small arteries. We report 2 unusual cases of CFE that showed a nontraumatic etiology and the involvement of a single dominant cerebral artery., Patient Concerns: Case 1 was a 33-year-old woman without a history of trauma who visited the emergency room due to hemiparesis and hemisensory deficits. She was a heavy smoker and had used oral contraceptives for several years. Most importantly, she had 2 experiences of autologous fat grafting 2 months previously. Magnetic resonance angiography (MRA) revealed acute occlusion of the right middle cerebral artery. Case 2 was an 80-year-old man suddenly presented with dizziness, ataxia, and left-sided sensorimotor dysfunction. He had a history of hypertension, untreated atrial fibrillation, and chronic alcoholism. MRA demonstrated the occlusion of the distal basilar artery., Diagnosis: Case 1: Microscopic findings demonstrated variable sized fat vacuoles intermixed with moderate amounts of thrombi. Case 2: Histologically, mature adipocytes were intermingled with fibrin, blood cells, and a fragment of entrapped soft tissue resembling the vessel wall., Intervention: Case 1 and 2 underwent aspirational thrombectomy guided by transfemoral cerebral angiography., Outcome: Case 1 recovered well but Case 2 still suffers from gait ataxia., Lessons: CFE can rarely occur in various nontraumatic conditions, with or without evident etiology. Furthermore, it may not show characteristic clinicopathological manifestations. Therefore, careful follow up of those who have undergone procedures that are likely to trigger FES or who have hemodynamic or hypercoagulable risk factors is needed.

Septic cerebral emboli can be a challenging diagnosis to give, especially if atypical bacterial infections are the cause of it. Correct diagnosis of this condition can change the management route of the patient and result in a nonsurgical treatment. To our best knowledge, this is the first case of septic cerebral embolus caused by Corynebacterium mucifaciens reported. In this study, a 65-year-old diabetic patient who have developed ketoacidosis and went into coma was investigated for a case of septic cerebral embolization. The patient developed a sudden right-sided hemiparesis, and the radiological findings showed a tumor-like lesion on the left hemisphere at the level of the internal capsule. At first glance, presence of a metastatic tumor could not be excluded; therefore, further laboratory tests and examinations were done to rule out metastatic lesions. The blood culture of the patient revealed a case of bacteremia caused by Corynebacterium mucifaciens and then a septic cerebral embolus was suspected, but due to the rarity of this pathogen causing such complications as well as the similarity of the lesion to a metastatic brain tumor, a biopsy was performed and the histopathological findings confirmed the diagnosis of a septic cerebral embolus. Corynebacterium mucifaciens should be considered a human pathogen in immunocompromised patients and it can cause cerebral septic embolization. Metastatic brain tumors and tuberculomas should be excluded; if the uncertainty of a metastatic tumor remains, biopsy can be performed and histological findings can amplify the diagnosis of septic cerebral embolus.

Background and Purpose:  Cardioembolism is a postulated mechanism of embolic stroke of undetermined source (ESUS). We investigated endothelial glycocalyx, aortic elastic properties, oxidative stress, and their association with left atrial (LA) function in ESUS and healthy individuals., Methods:  In 90 ESUS patients (age 50.4 ± 13.2) and 90 controls with similar risk factors, we measured: (1) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5-25 µm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity (PWV), central systolic blood pressure (cSBP), and augmentation index (AIx), (3) LA volume and strain using speckle-tracking imaging, and (4) malondialdehyde (MDA) and protein carbonyls (PCs), as oxidative stress markers., Results:  Compared with controls, ESUS had higher PWV, PBR, MDA, and PC levels as well as higher LA volume and reduced reservoir LA strain ( p  < 0.05). PBR > 1.2 μm of microvessel ranging from 5 to 9 μm and PWV > 10.2 m/s were associated with ESUS on multivariable analysis (odds ratio: 2.374 and 5.429, p  < 0.05, respectively) and increased the c-statistic of the initial model from 0.54 to 0.71. In ESUS, glycocalyx damage (increased PBR) was related with increased PWV ( p  < 0.01) which was linked with LA reservoir strain after controlling for age, sex, and risk factors ( p  = 0.03). Increased MDA and PC were related with glycocalyx damage, increased PWV ( r  = 0.67 and r  = 0.52), AIx, cSBP, and aortic atheroma ( p  < 0.01)., Conclusion:  Arterial function and endothelial glycocalyx are severely impaired in ESUS and are linked to LA dysfunction suggesting their contribution to ESUS pathogenesis., Clinical Trial Registration:  URL-http://www.clinicaltrials.gov. Unique identifier: NCT03609437., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Oesophago-pericardial fistula following any electrophysiological procedure is a rare, and potentially, life-threatening condition. Initial presentation can easily be misdiagnosed, as symptoms vary and are not specific. Echocardiography is an invaluable tool to diagnose and rule out complications. We present the case of a 68-year-old patient who developed an oesophago-pericardial fistula complicated with purulent pericarditis, sepsis and cerebral air embolism. In conclusion, this case report encourages physicians to use strategies that may help with early diagnosis and lead to potential lifesaving interventions., (© Royal College of Physicians 2019. All rights reserved.)

Background: A revised classification of cerebellar infarctions (CI) may uncover unrecognized associations with etiologic stroke subtypes. We hypothesized that obliquely oriented small cortical cerebellar infarction (SCCI) representing end zone infarctions on MRI would be associated with cardiac embolism., Methods: We retrospectively analyzed consecutive stroke patients recruited between January-December 2016 in our center. Analyzed baseline characteristics: sex, age, cardiovascular risk factors, history of stroke or atrial fibrillation (AF). TOAST classification was used for determining stroke subtype. Acute infarction location (anterior/posterior/mixed anterior-posterior circulation), acute uni- or multiterritorial infarction, and acute or chronic CI/SCCI/non-SCCI were assessed by MRI, and vertebrobasilar stenosis/occlusion by vessel imaging. Pre-specified analysis was also performed in patients without known high cardioembolic risk (known AF history or acute multiterritorial infarction)., Results: We included 452 patients (CI in 154, isolated SCCI in 55, isolated non-SCCI in 50, and mixed SCCI/non-SCCI in 49). Both SCCI and non-SCCI were associated with AF history (SCCI, p = 0.021; non-SCCI, p = 0.004), additional acute posterior circulation infarction (p < 0.001 both CI-subtypes), multiterritorial infarctions (SCCI, p = 0.003; non-SCCI, p < 0.001) and cardioembolic more frequent than large-artery atherosclerosis origin (p < 0.001 for both CI-subtypes). SCCI was associated with older age (p < 0.001), whereas non-SCCI was associated with stroke history (p = 0.036) and vertebrobasilar stenosis/occlusion (p = 0.002). SCCI were older (p = 0.046) than non-SCCI patients, had less frequently prior stroke (p < 0.001), and more frequent cardioembolic infarction (p = 0.025). In patients without known high cardioembolic risk (n = 348), SCCI was strongly associated with subsequent cardioembolism diagnosis (OR 3.00 [CI 1.58-5.73, p < 0.001]). No such association was present in non-SCCI., Conclusions: Acute or chronic SCCI are strongly associated with a cardioembolic origin.

Background: Instability of atherosclerotic plaques is associated with the occurrence of stroke. Microembolic signals (MESs) are an indicator of unstable plaque. A relationship between plasma osteoprotegerin (OPG) and ischemic stroke has already been identified. The aim of this study was to investigate whether plasma OPG levels have a relationship with MESs and to evaluate the feasibility of OPG as a biomarker of stroke severity and occurrence of MESs., Methods: Our study consisted of 127 patients with large artery atherosclerosis stroke and 56 controls. Patients were classified into subgroups based on stroke severity and the occurrence of MESs. MES-monitoring was performed for 60 min using transcranial Doppler within 72 h of stroke onset. Stroke severity at admission was assessed by the National Institutes of Health Stroke Scale., Results: Plasma OPG levels were significantly associated with stroke, MESs, and stroke severity at admission (adjusted OR [95% CI]: 1.002 [1.001-1.003] p < 0.001; 1.002 [1.001-1.003] p = 0.001; 1.001 [1.000-1.002] p = 0.028). When plasma OPG levels were used to determine the stroke severity, the area under the receiver-operating characteristic curve (AUC) was 0.734 (95% CI: 0.625-0.843) based on a cutoff value of 1998.44 pg/ml; the sensitivity and specificity of this test were 80.6% and 65.6%, respectively. Furthermore, when the levels of OPG were used to distinguish the presence of MESs, the AUC was 0.766 (95% CI: 0.672-0.860); the cutoff value was 2107.91 pg/ml. The sensitivity of this cutoff value was 68.8% and the specificity was 73.7%., Conclusions: Plasma OPG levels correlate with stroke severity and the occurrence of MESs.

Background: Endovascular thrombectomy (EVT) has shown efficacy in acute ischemic stroke (AIS) patients with infective endocarditis (IE). The possibility to undertake advanced histopathological clot analysis following EVT offers a new avenue to establish the etiological basis of the stroke - which is often labelled "cryptogenic." In this paper, we present our findings from four consecutive patients with IE who underwent EVT following an AIS at our tertiary referral comprehensive stroke centre., Methods: Comprehensive histopathological analysis of clot retrieved after EVT, including morphology, was undertaken., Results: The consistent observation was the presence of dense paucicellular fibrinoid material mixed/interspersed with clusters of bacterial cocci. This clot morphology may be specific to septic embolus due to IE unlike incidental bacteraemia and could possibly explain the refractoriness of such clots to systemic thrombolysis., Conclusion: Detailed morphological and histopathological analysis of EVT-retrieved clots including Gram staining can assist in etiological classification of the clot. Understanding the composition of the clot may be of clinical value in early diagnostics and mapping treatment planning in IE.

Objective: Ischaemic brain lesions and brain abscesses are frequent in both human and animal cases of septic embolic stroke. However, existing models of brain infection do not reflect central aspects of septic embolic stroke. Our aim was to compare septic and non-septic embolic stroke in order to identify gene expressions, inflammatory mediators and brain damage in a rat model., Methods: We created precisely located focal brain infarcts in a rat model of Staphylococcus aureus infected embolic stroke. To cause septic embolic stroke we used a fibrin-rich embolus with bacteria, while every rat in the control group received a non-infected embolus. 64 rats were randomized to receive sham-surgery, sterile embolic stroke or septic embolic stroke. All groups were compared for brain pathology, mortality, gene expressions and inflammatory mediators using histology and reverse transcription quantitative real-time PCR., Results: Although infarct volumes did not differ, septic embolic stroke caused higher mortality than sterile embolic stroke (p=  0.002). Brain abscesses were observed only in the septic group. Approximately 400-500 fold increases were observed for Orm1 and Cxcl2 respectively (1.00E-08 < p < 1.92E-07) in the septic group compared to the sterile group, and these were the most dramatically regulated genes in septic embolic stroke compared to sterile embolic stroke., Conclusions: Septic embolic stroke caused brain abscesses, increased mortality and upregulated Orm1 and Cxcl2 gene expressions compared to non-infected embolic stroke. The dramatic Orm1 increase observed in the septic group is unprecedented and suggests a significant biological role of Orm1 during septic neuroinflammation.

Background and Purpose: In order to assess the association of microparticles derived from activated platelets (PMP) or endothelial cells (EMP) with risk markers for recurrent embolic events in patients with symptomatic carotid artery disease, we studied the associations between PMP/EMP and three risk markers: plaque haemorrhage (PH), micro-embolic signals and cerebral diffusion abnormalities., Methods: Patients with recently symptomatic high-grade carotid artery stenosis (60-99%, 42 patients, 31 men; mean age 75 ± 8 years) and 30 healthy volunteers (HV, 11 men; mean age 56 ± 12 years) were prospectively recruited. Patients were characterised by carotid magnetic resonance imaging (presence of PH [MRI PH]), brain diffusion MRI (cerebral ischaemia [DWI+]) and transcranial Doppler ultrasound (micro-embolic signals [MES+]). PMP and EMP were classified by flow cytometry and expressed as log-transformed counts per microlitre., Results: MES+ patients (n = 18) had elevated PMP (MES+ 9.61 ± 0.57) compared to HV (8.80 ± 0.73; p < 0.0001) and to MES- patients (8.55 ± 0.85; p < 0.0001). Stroke patients had elevated PMP (9.49 ± 0.64) and EMP (6.13 ± 1.0) compared to non-stroke patients (PMP 8.81 ± 0.73, p = 0.026, EMP 5.52 ± 0.65, p = 0.011) and HV (PMP 8.80 ± 0.73, p = 0.007, and EMP 5.44 ± 0.47, p = 0.006). DWI+ patients (n = 16) showed elevated PMP (DWI+ 9.53 ± 0.64; vs. HV, p = 0.002) and EMP (DWI+ 5.91 ± 0.99 vs. HV 5.44 ± 0.47; p = 0.037). Only PMP but not EMP were higher in DWI+ versus DWI- patients (8.67 ± 0.90; p = 0.002). No association was found between PMP and EMP with MRI PH., Conclusions: PMP and EMP were associated with stroke and recent cerebrovascular events (DWI+) but only PMP were also associated with ongoing (MES+) thrombo-embolic activity suggesting a differential biomarker potential for EMP to index cerebral ischaemia while PMP may predict on-going thrombo-embolic activity., (The Author(s). Published by S. Karger AG, Basel.)

Objectives: The aim of this study was to evaluate the debris captured by the Claret Sentinel cerebral embolic dual-filter protection device during transfemoral transcatheter aortic valve replacement (TAVR) with different valve types., Background: Risk for embolization of debris during TAVR may vary by TAVR device., Methods: The filters of 100 consecutive patients were collected and captured debris was analyzed by histopathology and histomorphometry. Three valve types were implanted: the balloon-expandable Edwards SAPIEN 3 (n = 42), the self-expandable Medtronic Evolut R (n = 35), and the mechanically implantable Boston Scientific Lotus (n = 23)., Results: Among the 3 groups there was no difference in baseline data, including Society of Thoracic Surgeons score for mortality, calcification, or pre-dilation. The type of captured debris did not differ among the 3 valve types in the proximal or distal filter. With the balloon-expandable valve, there were significantly more patients with large debris measuring ≥1,000 μm. The number of particles in the proximal filter was significantly lower with the Lotus (89.8 ± 106.3) compared with the Evolut R (187.3 ± 176.9) and Edwards SAPIEN 3 (172.3 ± 133.5) valves (p = 0.035). Total tissue area in the proximal filter was significantly smaller for the Lotus compared with the other 2 valve types (7.1 ± 6.3, 20.1 ± 19.0, and 21.3 ± 15.1 mm 2 ; p = 0.0014). In contrast, for the distal filter, there were no differences with respect to valve type for total tissue area, particle size, and number of particles., Conclusions: A significant difference was observed in the size and number of captured tissue particles with the double-filter embolic protection device among different valve types in patients undergoing TAVR. The largest particles were observed in patients treated with a balloon-expandable valve., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We describe a patient-specific simulation based investigation on the role of Circle of Willis anatomy in cardioembolic stroke. Our simulation framework consists of medical image-driven modeling of patient anatomy including the Circle, 3D blood flow simulation through patient vasculature, embolus transport modeling using a discrete particle dynamics technique, and a sampling based approach to incorporate parametric variations. A total of 24 (four patients and six Circle anatomies including the complete Circle) models were considered, with cardiogenic emboli of varying sizes and compositions released virtually and tracked to compute distribution to the brain. The results establish that Circle anatomical variations significantly influence embolus distribution to the six major cerebral arteries. Embolus distribution to MCA territory is found to be least sensitive to the influence of anatomical variations. For varying Circle topologies, differences in flow through cervical vasculature are observed. This incoming flow is recruited differently across the communicating arteries of the Circle for varying anastomoses. Emboli interact with the routed flow, and can undergo significant traversal across the Circle arterial segments, depending upon their inertia and density ratio with respect to blood. This interaction drives the underlying biomechanics of embolus transport across the Circle, explaining how Circle anatomy influences embolism risk.

Central nervous system (CNS) hematologic malignancies, whether primary or secondary, are uncommon and their clinical presentations vary. Intravascular lymphoma (IVL) is a very rare, aggressive systemic malignancy that is often difficult to diagnose and susceptible to early CNS involvement. Blast crisis in myeloid leukemias can cause widespread neoplastic emboli. Here, we report two adult patients (72 years and 22 years of age) who presented with altered mental status followed by rapid decline in their conditions leading to death. No prior significant medical history was present for either patient, while acute myeloid leukemia was diagnosed in the younger patient immediately before death. During autopsy, we performed imprint and squash preparations, and frozen sections of representative cerebral cortex, cerebellum, leptomeninges, and the pituitary gland. In the older patient, presence of IVL was readily detected on cytologic preparations. Diffuse involvement of brain vasculature and perivascular parenchyma with acute myeloid leukemia was identified in the other patient. Although examination of the fresh brain is not routinely performed during autopsy, these cases are presented to illustrate that imprint and squash preparations can provide a rapid and reliable provisional autopsy diagnosis in select patients., (© 2018 Wiley Periodicals, Inc.)

Objectives: This study investigated differences between transcatheter heart valve (THV) types and regarding debris captured by a cerebral embolic protection system (Claret Medical Sentinel, Santa Rosa, California)., Background: Differences of THV types and cerebral injury after transcatheter aortic valve replacement (TAVR) are not well understood., Methods: A total of 246 patients pooled from 2 prospective studies (SENTINEL [Cerebral Protection in Transcatheter Aortic Valve Replacement] trial, N = 100; SENTINEL-H [Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement] trial, N = 146) were included in the analysis. Histopathologic assessment and histomorphometric analyses of debris were compared with THV types. Analyses were differentiated by particle size (≥150, ≥500, and ≥1,000 μm), particle count, total particle area, and maximum of largest dimension. Only commercially available THVs were included: 16% Evolut R (EvR), 15% Lotus, 59% SAPIEN 3 (S3), and 10% SAPIEN XT (XT)., Results: Particles were captured in 99% of patients. There was a significantly higher amount of debris related to the vascular bed (valve tissue, arterial wall, calcification) in EvR patients compared with S3 patients; 53% of all patients irrespective of valve type had at least 1 particle ≥1 mm. Larger particles (≥500 and ≥1,000 μm) were significantly more frequent in EvR than XT and S3 patients. Lotus patients with particles ≥1,000 μm were significantly more frequent than in S3 patients. Particle count, total particle area, and maximum of largest dimension were significantly higher in both Lotus and EvR patients compared with S3 and XT., Conclusions: Debris was captured in 99% of patients, of whom 53% had at least 1 particle of debris >1 mm. The number and size of particles captured during a procedure in which EvR or Lotus THV was used were higher and larger than with a Sapien THV. Regardless, embolic debris, including large particles, is universal across valve types and provides mechanistic support for the potential benefit of using cerebral embolic protection in all TAVR procedures., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A 25-year-old woman presented with acute onset of right hemiplegia and global aphasia with National Institutes of Health Stroke Scale score of 19. Computed tomography angiography demonstrated occlusion of the left proximal middle cerebral artery. She was thrombolysed with intravenous recombinant tissue plasminogen activator (0.6 mg/kg) within 3 hours of onset of symptoms and was taken up for mechanical thrombectomy. The retrieved specimen appeared pale white and soft; histopathologic examination revealed a papillary neoplasm composed of papillae with hyalinized cores lined by endothelium, consistent with papillary fibroelastoma of cardiac origin. Transesophageal echocardiography showed no abnormalities, which can be explained by complete embolization of the mass into the cerebral circulation. On follow-up after 5 months, the patient recovered with only minimal aphasia and no cardiac symptoms. Our experience with this case highlights the importance of histopathologic examination of the mechanical thrombectomy specimen, as it provided the only clue to the etiology of stroke., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the value of left vertebral artery filter protection in addition to the current filter-based embolic protection technology to achieve complete cerebral protection during TAVR., Background: The occurrence of cerebrovascular events after transcatheter aortic valve replacement (TAVR) has fueled concern for its potential application in younger patients with longer life expectancy. Transcatheter cerebral embolic protection (TCEP) devices may limit periprocedural cerebrovascular events by preventing macro and micro-embolization to the brain. Conventional filter-based TCEP devices cover three extracranial contributories to the brain, yet leave the left vertebral artery unprotected., Methods: Patients underwent TAVR with complete TCEP. A dual-filter system was deployed in the brachiocephalic trunk and left common carotid artery with an additional single filter in the left vertebral artery. After TAVR all filters were retrieved and sent for histopathological evaluation by an experienced pathologist., Results: Eleven patients received a dual-filter system and nine of them received an additional left vertebral filter. In the remaining two patients, the left vertebral filter could not be deployed. No periprocedural strokes occurred. We found debris in all filters, consisting of thrombus, tissue derived debris, and foreign body material. The left vertebral filter contained debris in an equal amount of patients as the Sentinel filters. The size of the captured particles was similar between all filters., Conclusions: The left vertebral artery is an important entry route for embolic material to the brain during TAVR. Selective filter protection of the left vertebral artery revealed embolic debris in all patients. The clinical value of complete filter-based TCEP during TAVR warrants further research., (© 2017 Wiley Periodicals, Inc.)

Cerebral air embolism is caused by gas bubbles in the vascular system. These bubbles can cause cerebral ischemia by obstructing encephalic blood vessels. It is frequently associated with blunt and penetrating chest trauma as well as iatrogenic interventions. Lung trauma involving laceration of the respiratory tract, lung parenchyma, and blood vessels may result in direct communication of these structures, driving air or gas into the pulmonary venous system. We report a case of a blunt chest trauma that led to massive arterial air embolism that was possible to recognize with the help of postmortem computed tomographic scan examination.

The optimal timing of cardiac surgery remains unclear for patients with neurological complications of infective endocarditis (IE). However, neuroimaging findings may allow more refined clinical decision-making. We analyzed clinical and advanced neuroimaging data for 135 patients with IE who had preoperatively diagnosed ischemic cerebral complications (86 patients) or hemorrhagic complications (49 patients), between January 1997 and May 2013. The effect of early surgery (within 3 and 7 days of ischemic and hemorrhagic complications respectively) on in-hospital mortality and 1-year adverse outcomes (mortality, relapse, or new embolic events) was estimated. Small cerebral emboli (≤2 cm) led to early surgery (cases with ischemic complications: 57% vs 26%, p = 0.04; cases with hemorrhagic complications: 56% vs 13%, p = 0.02). Early surgery was not significantly associated with increased rates of in-hospital mortality and 1-year adverse outcomes among patients with ischemic complications (14% vs 9%, odds ratio [OR] 1.67, 95% confidence interval [CI] 0.44-6.38, p = 0.52; 17% vs 14%, OR 1.27, 95% CI 0.39-4.14, p = 0.7 respectively). Only 1 patient (4%) with hemorrhagic complications experienced in-hospital mortality in the early surgery group, and early surgery was not significantly associated with 1-year adverse outcomes (21% vs 12%, OR 1.93, 95% CI 0.41-9.16, p = 0.46). The risks of in-hospital mortality and 1-year adverse outcome were not increased, even if cardiac surgery had been carried out earlier than previously described. Our findings suggest that early surgery, when indicated, may be performed for patients with IE and neurological complications, especially if the cerebral embolus has a diameter of ≤2 cm.

Increasing epidemiological evidence suggests an association between migraine with aura (MA) and cardiovascular events. There is experimental as well as clinical evidence implying cerebral microembolism as a potential trigger for MA attacks. Microembolism may also account for some of the ischemic MRI lesions more commonly observed in MA than in general population. Limited size of clinically-silent MRI lesions suggests isolated occlusion of a small vessel. However, it is not known whether selective thrombosis of a small arteriole (e.g. single mouse penetrating arteriole - PA), can induce cortical spreading depression (CSD), the putative cause of migraine aura and, hence, trigger an MA attack. For this, we mimiced thrombosis of a small vessel caused by microembolism by selectively occluding a PA just before diving into the cortex (radius; 10-25 µm) in the mouse. Clotting was induced with FeCl 3 applied focally over the PA by a glass micropipette for 3 min. DC potential changes were recorded and the alterations in cortical blood flow were monitored by laser speckle contrast imaging. Mice were kept alive for 1-4 weeks and brain sections were stained with H&E or luxol-fast blue to evaluate changes induced by PA occlusion. We found that single PA occlusion consistently triggered a CSD originating from the tissue around the PA soon after occlusion and induced delayed, small ischemic lesions within territory of the affected vessel a few weeks later. These findings suggest that cerebral microembolism can lead to MA attacks and may account for some of the silent brain lesions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Object: We investigated possible associations among the presence of cholesterol crystals in embolic debris, the proportions of debris components, and postoperative cerebral embolism in patients undergoing carotid artery stenting (CAS)., Methods: Sixty-seven consecutive procedures were performed for internal carotid artery stenosis with CAS at our hospital between November 2015 and February 2018. Procedures for emergency CAS for stroke in evolution or crescendo transient ischemic attack were excluded (n = 12). The embolic debris from remaining procedures (n = 55) was stained with hematoxylin-eosin and the red blood cells, white blood cells, and fibrin were quantified by color-based segmentation. Cholesterol crystals and calcification were examined histopathologically. Diffusion-weighted imaging (DWI) was performed 1-3 days after CAS, and the images were used to classify procedures according to the presence of new lesions., Results: Of the 55 CAS procedures, new DWI lesions were identified after 32. One patient had symptomatic cerebral embolism. Higher proportions of patients with cholesterol crystals in embolic debris (17 vs. 78%, p < 0.001) and higher proportion of white blood cells (mean 2.3 [0-9.9] vs. 4.2% [0-29.9%], p < 0.01) were observed in the embolic debris of procedures with and without new DWI lesions., Conclusions: Cholesterol crystals were common in the embolic debris from patients with postoperative ischemic lesions after CAS. These results suggest that inflammatory destabilization of the intraplaque lipid component is related to postprocedural DWI lesions., (© 2019 S. Karger AG, Basel.)

Objectives: This study sought to assess long-term left atrial appendage (LAA) closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach with computed tomographic angiography., Background: LAA closure is associated with a low risk for atrial fibrillation-related embolic stroke. The Atriclip exclusion device allows epicardial LAA closure, avoiding the need for post-operative oral anticoagulation. Previous data with Atriclip during open chest procedures show a high efficacy rate of closure >95%., Methods: Three-dimensional volumetric 2-phase computed tomographic angiography ≥90 days post-implantation was independently assessed by chest radiology for complete LAA closure on all consented subjects identified retrospectively as having had a TT-placed Atriclip at Vanderbilt University Medical Center from June 13, 2011, to October 6, 2015., Results: Complete LAA closure (defined by complete exclusion of the LAA with no exposed trabeculations, and clip within 1 cm from the left circumflex artery) was found in 61 of 65 subjects (93.9%). Four cases had incomplete closure (6.2%). Two clips were placed too distally, leaving a large stump with exposed trabeculae. Two clips failed to address a secondary LAA lobe. No major complications were associated with TT placement of the Atriclip. Follow-up over 183 patient-years revealed 1 stroke in a patient with complete LAA closure and no thrombus (hypertensive cerebrovascular accident)., Conclusions: Angiographic LAA closure efficacy with a TT-placed Atriclip is high (93.9%). The clinical significance of a remnant stump is unknown. Confirmation of complete LAA occlusion should be made before cessation of systemic anticoagulation., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Stroke is a major cause of mortality and morbidity around the world. Microembolic signals (MES), as the markers of unstable atherosclerotic plaque, can predict the occurrence and prognosis of ischemic stroke (IS). MES can also assess the efficacy of antithrombotic agents and predict the recurrence probability of IS. Unstable plaques are the main source of MES; thus, numerous biomarkers of atherosclerotic plaque instability are highly likely to predict the presence of MES. This study aims to review recent biomarker candidates for MES or microembolism. Current research indicates that the following are independent markers for positive MES: high level of serum soluble P-selectin, chemokine (C-X-C motif) ligand 16 (CXCL16) and fibrinogen, high neutrophil count, reduced ratio of CD4+CD25 high regulatory T cells (Tregs) and the C allele of tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) rs3102735. However, a more integrated profile of biomarkers for MES is needed to improve the stratification of patients with carotid stenosis and enhance the effectiveness of therapeutic interventions and prevention for IS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

It has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether shortIt has been reported that restriction of reperfusion after thrombolytic therapy in ischemic stroke may reduce tissue plasminogen activator (tPA) adverse effects and extend its time window. We examined whether short-term and mild local brain cooling can prevent hyperemia and/or adverse effects of delayed tPA in rat embolic stroke model. Male animals were subjected to embolic stroke and then randomly classified into control (saline), tPA (1mg/kg; i.v.), local hypothermia (LH), and tPA+LH. The drug was injected at 6 h after ischemia. LH was conducted by direct ipsilateral (injured) hemisphere cooling at 6.5h after stroke and maintained for approximately 30min. Cerebral blood flow was monitored in duration of 60 minute after tPA administration and hyperemic response was measured. Infarct volume, blood-brain barrier (BBB) disruption, edema formation, neurological deficits, and matrix metalloproteinase-9 (MMP-9) level were measured 48 h later. A combination of tPA+LH significantly diminished infarct volume in comparison with the tPA (P< 0.001) and control (P<0.05) groups. Combination therapy also decreased BBB leakage (P<0.001), MMP-9 level or edema (P<0.05) and improved neurological functions at 24 and 48h after stroke. LH caused a gradual decrease in hyperemic response after thrombolysis compared to the control (P<0.05) or tPA (P<0.001) groups. LH alone also reduced infarct volume, BBB leakage or edema (P<0.05). The short-term local brain hypothermia may mitigate reperfusion injury following delayed tPA therapy and extend its time window up to 6h., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Trousseau syndrome is defined as a variant of intravascular thromboembolism that is induced by cancer. It may manifest itself as cerebral embolisms in some cases; however, when the cancer is not diagnosed, this identification may be difficult. Therefore, cerebral embolisms are often treated without identifying the cancer, which can worsen a patient's condition. The purpose of this study was to determine the differences in clinical features between cerebral embolisms induced by cancer (Trousseau syndrome) and those that are due to other causes, such as cardiogenic embolisms and artery-to-artery stroke. A total of 83 patients, admitted to our hospital between April 2005 and March 2013 with cerebral embolisms, were included in this study. Of these, 9 (10.8%) were diagnosed with Trousseau syndrome, 63 (75.9%) had cardiogenic embolisms and 11 (13.2%) had artery-to-artery embolisms. Patients with embolic stroke of undetermined source (ESUS) were excluded from the study. We retrospectively investigated the localization of the infarctions, cancer type, and pathology, and the levels of primary fibrin/fibrinogen degradation products (FDP). From the nine patients with Trousseau syndrome, eight had adenocarcinomas and all had elevated initial FDP. Bilateral cerebral embolisms were significantly more common in Trousseau syndrome patients than cardiogenic embolisms (P=0.00026) and artery-to-artery embolisms (P=0.0016). All of them contained microembolisms as observed by magnetic resonance imaging (MRI). This study suggests that bilateral infarctions presenting microembolisms are important features of cerebral embolism attributed to Trousseau syndrome., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

An 89-year-old woman with chronic atrial fibrillation, hypertension, chronic heart failure, and dementia was admitted to our hospital due to multiple small cerebral and cerebellar infarctions. Transthoracic echocardiogram revealed a floating calcified mass lesion arising from the endocardium of the posterior portion of the mitral annulus with mitral annular calcification. Furthermore, the mass had a heterogeneity of the echogenicity. The mass was diagnosed as a calcified amorphous tumor based on specific echocardiographic features. Serial echocardiograms showed shrinkage and disappearance of the mass, and magnetic resonance image revealed new infarction in the left occipital lobe. Embolization of the mass appeared to cause systemic embolism., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

We design and synthesize EpCAM antibodies with Fc-domain site-specific linkers that allow preferential alignment when coated on microfluidic devices for capturing circulating tumor cells (CTCs) from colorectal cancer patients. The aligned coating is shown to increase the capture efficiency of CTCs and microemboli by 1.6 and 3.0-fold, respectively (both P < 0.05).

Cerebral air embolism is a recognized life-threatening complication, sometimes iatrogenic. Its timely diagnosis is essential because it can result in neurologic deficits or death. We report a case of a 58-year-old man who died from cerebral air embolism diagnosed by nonenhanced computed tomography scan of the head after a cardiac bypass surgery with Biventricular Assist Device and multiple vascular line placements. Autopsy revealed extensive subcutaneous emphysema, intravascular and perivascular air bubbles in the central nervous system and associated cerebral and cerebellar hemorrhagic infarction. The autopsy was helpful in documenting the extent of the air embolism and its appearance in soft tissue and central nervous system.

The mechanism of thrombus formation in Trousseau syndrome remains unclear. The purpose of this study was to investigate specific pathological findings of the thrombi in Trousseau syndrome. The authors report on 2 cases of thrombi in Trousseau syndrome from large cerebral vessels removed by endovascular therapy and compared with thrombi in atherosclerosis or cardiac embolism. The first patient, a 67-year-old man, was transferred to our hospital for sudden onset consciousness disturbance and tetraparesis. He had been diagnosed with stage IV lung cancer. The magnetic resonance (MR) angiography demonstrated basilar artery occlusion. An endovascular thrombectomy was performed. The second patient, an 84-year-old woman, was transferred to our hospital for sudden onset motor aphasia and right-sided motor weakness. She has a history of stage IV pancreatic body cancer. The MR angiography demonstrated left middle cerebral artery occlusion. An endovascular thrombectomy was performed for the floating thrombus. Macroscopic findings of retrieved thrombi were observed immediately after thrombectomy. The thrombi in Trousseau syndrome were white in color and solid against manual compression, whereas thrombi from other causes were red and fragile. In terms of microscopic findings, the thrombi in Trousseau syndrome mainly contained fibrin. On the other hand, thrombi associated with atherosclerosis or cardiac embolism had smaller area of fibrin with a considerable amount of red and white blood cells. The thrombi in Trousseau syndrome, which caused occlusion of large cerebral vessel, almost exclusively consisted of fibrin., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Embolus-related cerebral injury is still a serious adverse event after cardiopulmonary bypass (CPB). But there is no stable animal model for basic and clinical research purposes. We chose miniature pig to establish a stable animal model of embolus-related cerebral injury after CPB and verified the validity of results by correlating the histopathological findings with those of diffusion-weighted magnetic resonance imaging (DW-MRI). Based on different treatment regimens, 24 male miniature pigs were randomly assigned into four groups: Control, CPB, embolus, and CPB-embolus groups. DW-MRI was performed before and after surgery to diagnose and locate the brain lesions. Histopathological changes in brain tissues were examined using H&E and Nissl staining. All surgical procedures were uneventful with 100% postoperative survival of pigs. Two animals in the Embolus group and six animals in the CPB-embolus group showed signs of ischemic penumbra on DW-MRI performed 6 h after surgery. Consistent with the results of DW-MRI, histopathological examination showed necrosis and ischemic lesions. In this paper, we demonstrate the feasibility and validity of a pig model of embolus-related cerebral injury associated with CPB. This model may be used in the future for basic and translational research., (© 2016 by the Society for Experimental Biology and Medicine.)

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., (© 2016 American Heart Association, Inc.)