Management of anticoagulation in patients with infective endocarditis.

Infective endocarditis (IE) carries a high risk of vascular complications (e.g., cerebral embolism, intracerebral hemorrhage, and renal infarction), which are correlated with increased early and late mortality. Although anticoagulation is the cornerstone for management of thromboembolic complications, it remains controversial and challenging in patients with IE. An appropriate anticoagulation strategy is crucial to improving outcomes and requires a good understanding of the indication, timing, and regimen of anticoagulation in the setting of IE. Observational studies have shown that anticoagulant treatment failed to reduce the risk of ischemic stroke in patents with IE, supporting that IE alone is not an indication for anticoagulation. In the absence of randomized controlled trials and high-quality meta-analyses, however, current guidelines on IE were based largely on observational data and expert opinion, providing few specific recommendations on anticoagulation. A multidisciplinary approach and patient engagement are required to determine the timing and regimen of anticoagulation in patients with IE, especially in specific situations (e.g., receiving warfarin anticoagulation at the time of IE diagnosis, cerebral embolism or ischemic stroke, intracerebral hemorrhage, or urgent surgery). Collectively, individualized strategies on anticoagulation management of IE should be based on clinical evaluation, available evidence, and patient engagement, and ultimately be developed by the multidisciplinary team.

Microembolic signals and antiplatelet therapy in Moyamoya angiopathy.

BACKGROUND: Embolism as a cause of stroke is widely neglected in Moyamoya angiopathy (MMA), and recommendations for use of antiplatelet therapy (APT) vary. We examined the presence of microembolic signals (MES) during transcranial Doppler (TCD) monitoring and assessed the effects of APT on the occurrence of MES in MMA. PATIENTS AND METHODS: We retrospectively analysed patients with MMA treated at our centre between 2011 and 2021. TCD was performed at first presentation and at most visits, while number of visits varied between individual patients. TCD was performed for 30 min bilaterally. Patient demographics, vascular risk factors, and antiplatelet treatment were collected from each clinic visit and ischemic and haemorrhagic episodes were captured as recorded during follow-up visits. RESULTS: 209 patients were included in the analysis (mean age 38.7 ± 15.3, 28% male). 21 patients with 27 MES-positive TCD examinations were identified (10%). Patient characteristics were similar in MES-positive and MES-negative groups. However, recent ischemic events were detected at a significantly higher rate in MES-positive patients (42.9% vs 4.8%, p < 0.001). After MES detection, change of antiplatelet drug regime was performed, leading to loss of MES in all cases. Dual APT was preferably used in the MES-positive group (p < 0.001) but no significant difference of haemorrhage during follow-up-visits was observed. Reduction of APT before bypass-surgery triggered MES in four patients. CONCLUSION: APT is required in patients with MMA. MES monitoring may help to identify risk patients in need of intensified APT.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial.

Background and Purpose- Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods- We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results- In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0-3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions- A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

An Embolic Stroke in a Patient With PROC p.Lys193del.

We report a 58-year-old woman who suddenly developed brain infarction with weakness of the left lower extremity and left perioral dysesthesia during postoperative tamoxifen therapy for breast cancer and prednisolone therapy for rheumatoid arthritis. Diffusion-weighted images detected multiple areas of hyperintensity in the posterior circulation system of the brain. Despite extensive examinations, we could not identify any embolic sources except hypoplasia of the right vertebral artery. We found decreased activity of protein C against its antigen level (activity: 59% versus antigen: 122%) with enhanced activity of coagulation factor VIII (178%) and von Willebrand factor (285%). DNA sequencing identified trinucleotide deletion of the PROC gene leading to 1 amino acid deletion at Lys-193 (p.Lys193del). We speculate that the PROC gene polymorphism may have participated in tamoxifen- and prednisolone- associated hypercoagulable state, leading to development of an embolic stroke in this patient.

Atrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.

Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status: The NAVIGATE ESUS Trial.

BACKGROUND: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.

Tailoring the Approach to Embolic Stroke of Undetermined Source: A Review.

Importance: One-third of ischemic strokes have no identifiable cause after standard evaluation. In 2014, researchers termed these embolic strokes of undetermined source (ESUS) and argued that this entity would respond to anticoagulation. Two recent randomized clinical trials have not upheld this hypothesis, leading to questions about the ESUS concept. Observations: This article proposes that ESUS remains a useful concept, the clinical effect of which can be enhanced by considering 2 subsets defined by their likelihood of responding to anticoagulation. Recent studies indicate that some ESUS cases result from subclinical atrial fibrillation, atrial cardiopathy, unrecognized myocardial infarction, patent foramen ovale, or cancer, while other cases result from nonstenosing large-artery atherosclerosis, aortic atherosclerosis, or nonatherosclerotic vasculopathies. Evidence suggests that anticoagulation will prove superior to antiplatelet therapy for cases in the first group of causative mechanisms but not those in the second group, suggesting the need for personalized therapy. Conclusions and Relevance: Although the ESUS concept as currently constructed cannot guide treatment, efforts to better understand ESUS and develop therapies tailored to specific mechanisms are likely to help reduce the burden of stroke.

Cerebral embolism during edoxaban administration for venous thromboembolism in a patient with lung adenocarcinoma: A case report.

RATIONALE: The efficacy of direct oral anticoagulants (DOACs) in the treatment and prophylaxis of cancer-related venous thromboembolism (VTE) is reportedly similar to that of heparin. However, the effect of DOACs on the prophylaxis of cancer-related arterial thromboembolism (ATE) remains unclear. To our knowledge, we present the 1st case where cerebral ATE was encountered during edoxaban administration for VTE in a patient with lung adenocarcinoma. PATIENT CONCERNS: In March 2017, a 63-year-old female was diagnosed with lung adenocarcinoma (cT2aN3M1b stage IVa) along with having asymptomatic VTE; thus, 60 mg/day edoxaban administration was initiated. In addition, 1st-line chemotherapy generated a partial antitumoral response. However, owing to lung cancer progression, a secondary treatment with pembrolizumab administration was initiated. The patient suddenly experienced aphasia 11 days after pembrolizumab administration. DIAGNOSIS: The patient was diagnosed as multiple cerebral ATE using brain magnetic resonance imaging. However, VTE recurrence was not observed. Based on the findings of lung cancer progression and increased coagulation, cerebral ATE was diagnosed as Trousseau syndrome. INTERVENTIONS: DOAC administration was switched to heparin administration. OUTCOMES: Coagulation profile normalized and aphasia improved without any further disease symptoms. LESSONS: We considered that DOACs are effective for the treatment and prophylaxis of VTE but may be insufficient for ATE prevention. Therefore, DOACs should be replaced with heparin to prevent ATE when cancer and coagulation become uncontrollable with DOAC.

Thrombus Reformation in the Pulmonary Vein Stump Confirmed 16 Months After Cerebral Embolism on the Day After Left Upper Lobectomy for Lung Cancer.

Cerebral embolism is a very serious complication after lung cancer surgery. In such cases, cerebral embolism is caused by a thrombus formed in the pulmonary vein stump. Most such cases have been reported to occur within 10 days after left upper lobectomy. The patients were treated with anticoagulation therapy to prevent the recurrence of cerebral embolism, and recurrence or thrombus reformation has not been reported to the best of our knowledge. We present a 68-year-old man with a cerebral embolism detected on the day after left upper pulmonary lobectomy for lung cancer. The patient was treated with unfractionated heparin and his neurological symptoms improved. Heparin treatment was subsequently changed to aspirin for the prevention of recurrence; however, thrombus formation in the vein stump was asymptomatically confirmed 16 months after the surgery by contrast-enhanced computed tomography. This is the first case to our knowledge of thrombus reformation in the pulmonary vein stump after a cerebral embolism associated with lung cancer surgery. In our case, anticoagulation therapy was not continued to prevent recurrence, and antiplatelet therapy was performed instead, which might be associated with the thrombus reformation.

Implications of Janus Kinase 2 Mutation in Embolic Stroke of Unknown Source.

The role of genetic mutations in cerebral ischemia is not completely understood. Among these genetic variations, Philadelphia-negative gain-of-function mutation in the janus kinase 2 (JAK2) protein leads to overexpression of the genes involved in cell growth and proliferation, and has been linked to development of hematological malignancies, specifically, myeloproliferative neoplasms (MPNs; essential thrombocythemia [ET], polycythemia vera [PV], and primary myelofibrosis). Overt ET and PV are known to induce a prothrombotic state that leads to development of vascular complications, including cerebral arterial or venous thrombosis. Thromboembolism can precede overt presentation of an MPN by 2-3 years. As such, for the selected cases of embolic stroke or cerebrovascular sinus thrombosis with otherwise undetermined source and persistent thrombocytosis or polycythemia, in the absence of a confirmed MPN diagnosis, screening for JAK2 mutation may be reasonable, as early diagnosis and appropriate treatment can influence outcome by preventing recurrent thrombotic events. In this article, we review the literature on the genetics, pathogenesis, clinical manifestations, and treatment of JAK2-associated thrombosis, and present 2 cases of JAK2-associated cerebral arterial infarction and cerebral and systemic venous thromboembolism with otherwise negative etiology workup for stroke.

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. RESULTS: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. CONCLUSIONS: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.

Paradoxical Cerebral Embolism after Gastrointestinal Endoscopy in a Patient with Crohn's Disease.

Development of paradoxical cerebral embolism requires both unstable venous thrombosis and right-to-left shunt (RLS). Gastrointestinal endoscopy (GE) has the potential to affect intrathoracic and abdominal venous thrombi and to enhance RLS because the procedure alters intrathoracic and abdominal pressure. We describe a patient with Crohn's disease who developed paradoxical cerebral embolism after GE. Both an unstable venous thrombus in the superior vena cava and RLS through patent foramen ovale were thought to be responsible for the stroke. Considering that patients with digestive system diseases undergo GE as a routine examination or therapy, screenings for hypercoagulable state and intrathoracic and abdominal thrombi are important to prevent thromboembolism related to GE.

Calcified Cerebral Embolism Due to a Calcified Amorphous Tumor.

A 59-year-old man developed brain embolism in the frontal and parietal cortex. Brain CT showed a high-density spot in the upper branch of the left middle cerebral artery, indicating calcified cerebral embolism. Calcified amorphous tumor attached to the mitral valve was identified as the cause of embolism. After surgical resection, anticoagulation was started and recurrent stroke did not occur.

[Platelet inhibition in patients with coronary, cerebral and peripheral macroangiopathy : What, when and how long?] / Thrombozytenaggregationshemmer bei koronarer, zerebraler und peripherer Makroangiopathie : Was, wann, wie lange?

BACKGROUND: Inhibition of platelet aggregation can reduce the rate of vascular events in patients with coronary artery disease, carotid artery stenosis and symptomatic peripheral arterial disease. The choice of platelet inhibitors in monotherapy and combination therapy as well as the duration of dual platelet inhibition depend on the clinical situation and individual patient characteristics. GOAL: The present review summarizes the latest data from clinical trials and recommendations regarding platelet inhibition in coronary, cerebral and peripheral arterial disease. DATA: A large number of randomized trials on platelet inhibition in different clinical situations have been performed, allowing evidence-based recommendations on the choice of drugs and duration of treatment. Moreover, new guidelines of European professional societies on platelet inhibition in patients with coronary, cerebral and peripheral arterial disease have been recently published. CONCLUSION: Based on latest randomized trials and major society guidelines, a number of recommendations on platelet inhibition in stable coronary artery disease, after stent implantation, after acute coronary syndromes and in cerebral and peripheral arterial disease can be made.

Biomarkers of cerebral microembolic signals.

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+CD25high 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.

Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis. METHODS: We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. RESULTS: ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction (P=0.83). Hazard ratio in ESUS patients was 0.87 (95% confidence interval, 0.68-1.10; P=0.24). However, hazard ratio was 0.51 (95% confidence interval, 0.29-0.90; P=0.02) in ESUS patients with ipsilateral stenosis <50% or aortic arch atherosclerosis (n=961) and 0.98 (95% confidence interval, 0.76-1.27; P=0.89) in the remaining ESUS patients (n=3368; P for heterogeneity =0.04). CONCLUSIONS: In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca). CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Recurrent Stroke Due to Metastatic Pulmonary Tumor Emboli as an Important Clinical Entity.

We present an autopsy case of repetitive stroke due to tumor emboli, indistinguishable from thromboembolism with a hypercoagulable state in its clinical course. A 72-year-old man diagnosed with stage IVA oropharyngeal squamous cell carcinoma received chemoradiotherapy. Follow-up imaging revealed mediastinal lymph nodes and pulmonary metastasis. One year later, the patient experienced right arm weakness, and brain magnetic resonance imaging showed acute ischemic lesions in multiple vascular territories. He was diagnosed with paradoxical cerebral embolism due to cancer-associated venous thrombosis and treated with rivaroxaban. However, newly developed cerebral infarcts were confirmed 1 month later. Then, rivaroxaban treatment was switched to subcutaneous unfractionated heparin injection. He was admitted again for stroke recurrence and died of respiratory failure 8 days after admission. Autopsy demonstrated pulmonary metastasis invading the veins and tumor emboli in the culprit cerebral arteries. D-dimer was kept constant at a slightly higher level, ranging from 1 to 3 µg/mL during the course of recurrence. We should consider tumor embolism in the differential diagnosis of recurrent stroke along with pulmonary tumor and resistance to heparin preparations with unchanged D-dimer levels.

Spontaneous dissecting aneurysm of the left atrium complicated by cerebral embolism: A report of two cases with review of literature.

Left atrial dissection is a very uncommon complication of cardiac surgery and usually causes significant hemodynamic compromise. Little is known about spontaneous dissection of the left atrium. Two patients, one middle-aged man and another elderly woman were evaluated following stroke. Routine trans-thoracic echocardiogram showed vertical division of the left atrium with both chambers communicating with each other through an orifice. Detailed trans-oesophageal echocardiographic study revealed dissection of the left atrium producing an additional false chamber (pseudo-aneurysm) placed posterior to the left atrial appendage and above the postero-lateral aspect of mitral annulus. Spontaneous dissection of the left atrium is extremely rare, and there is no report of cerebral embolism associated with it. Review of literature reveals interesting facets of this rare entity.

A novel mouse model of thromboembolic stroke.

BACKGROUND: We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolving the clot blocking blood flow through a cerebral artery. To mimic the clinical situation, we developed a new mouse model of thromboembolic stroke, and tested the efficacy of tPA in WT and DR2-Tg mice. New Method Autologous blood is withdrawn into a PE-8 catheter filled with 2 IU α-thrombin. After exposing the catheter briefly to air, the catheter is reintroduced into the external (ECA) and advanced into the internal carotid artery (ICA) to allow for intravascular injection of thrombin at the MCA bifurcation. To validate the model, we tested the effect of tPA on laser-Doppler perfusion (LDP) over the MCA territory and infarct size in WT and DR2-Tg mice. RESULTS: The procedure results in a consistent drop in LDP, and leads to a highly reproducible ischemic lesion. When administered at 15min after thrombosis, tPA restored LDP and resulted in a significant reduction in infarct size at 24h after thrombosis in both WT and DR2-Tg. COMPARISON WITH EXISTING METHODS: Our model significantly reduces surgery time, requires a single anesthesia exposure, and produces a consistent and predictable infarction, with low variability and mortality. CONCLUSION: We validated the efficacy of tPA in restoring blood flow and reducing infarct in a new model of endovascular thromboembolic stroke in the mouse.