Cancer-Associated Stroke: Thrombosis Mechanism, Diagnosis, Outcome, and Therapeutic Strategies.

Cancer can induce hypercoagulability, which may lead to stroke. This occurs when tumor cells activate platelets as part of their growth and metastasis. Tumor cells activate platelets by generating thrombin and expressing tissue factor, resulting in tumor cell-induced platelet aggregation. Histopathological studies of thrombi obtained during endovascular thrombectomy in patients with acute stroke and active cancer have shown a high proportion of platelets and thrombin. This underscores the crucial roles of platelets and thrombin in cancer-associated thrombosis. Cancer-associated stroke typically occurs in patients with active cancer and is characterized by distinctive features. These features include multiple infarctions across multiple vascular territories, markedly elevated blood D-dimer levels, and metastasis. The presence of cardiac vegetations on echocardiography is a robust indicator of cancer-associated stroke. Suspicion of cancer-associated stroke during endovascular thrombectomy arises when white thrombi are detected, particularly in patients with active cancer. Cancer-associated stroke is almost certain when histopathological examination of thrombi shows a very high platelet and a very low erythrocyte composition. Patients with cancer-associated stroke have high risks of mortality and recurrent stroke. However, limited data are available on the optimal treatment regimen for stroke prevention in these patients. Thrombosis mechanism in cancer is well understood, and distinct therapeutic targets involving thrombin and platelets have been identified. Therefore, direct thrombin inhibitors and/or antiplatelet agents may effectively prevent stroke recurrence. Additionally, this strategy has potential benefits in cancer treatment as accumulating evidence suggests that aspirin use reduces cancer progression, metastasis, and cancer-related mortality. However, clinical trials are necessary to assess the efficacy of this strategy involving the use of direct thrombin inhibitors and/or antiplatelet therapies.

Effectiveness of endovascular treatment for in-hospital stroke vs. community-onset stroke: a propensity score-matched analysis.

BACKGROUND: The effectiveness of endovascular treatment for in-hospital stroke remains debatable. We aimed to compare the outcomes between patients with in-hospital stroke and community-onset stroke who received endovascular treatment. METHODS: This prospective registry-based cohort study included consecutive patients who underwent endovascular treatment from January 2013 to December 2022 and were registered in the Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy study and Yonsei Stroke Cohort. Functional outcomes at day 90, radiological outcomes, and safety outcomes were compared between the in-hospital and community-onset groups using logistic regression and propensity score-matched analysis. RESULTS: Of 1,219 patients who underwent endovascular treatment, 117 (9.6%) had in-hospital stroke. Patients with in-hospital onset were more likely to have a pre-stroke disability and active cancer than those with community-onset. The interval from the last known well to puncture was shorter in the in-hospital group than in the community-onset group (155 vs. 355 min, p<0.001). No significant differences in successful recanalization or safety outcomes were observed between the groups; however, the in-hospital group exhibited worse functional outcomes and higher mortality at day 90 than the community-onset group (all p<0.05). After propensity score matching including baseline characteristics, functional outcomes after endovascular treatment did not differ between the groups (OR: 1.19, 95% CI 0.78-1.83, p=0.4). Safety outcomes did not significantly differ between the groups. CONCLUSION: Endovascular treatment is a safe and effective treatment for eligible patients with in-hospital stroke. Our results will help physicians in making decisions when planning treatment and counseling caregivers or patients.

Coagulation Factor Expression and Composition of Arterial Thrombi in Cancer-Associated Stroke.

BACKGROUND: Cancer is associated with an increased risk of stroke. Tumor cells activate platelets, induce a coagulation cascade, and generate thrombin. The composition of thrombi may reflect the mechanism of thrombosis, aiding the determination of the treatment strategy. Here, we investigated the composition and expression of coagulation factors in the thrombi of patients with cancer-associated stroke. METHODS: Patients with stroke who underwent endovascular thrombectomy between September 2014 and June 2020 and whose cerebral thrombi were obtained were divided into those with cancer-associated stroke (cancer group) and propensity score-matched patients without cancer (control group), using 1:1 matching based on age and sex. Immunohistochemistry was performed of the thrombi, and the composition and expression of coagulation factors were compared between groups. RESULTS: Among the 320 patients who underwent endovascular thrombectomy and who had thrombi obtained, this study included 23 patients with cancer and 23 matched controls. In both groups, the median age was 65 years, and 12 patients (52.2%) were men. Platelet composition was significantly higher in the cancer group than in the control group (median [interquartile range], 51.3% [28.0%-61.4%] versus 9.5% [4.8%-14.0%]; P<0.001). Among coagulation factors, thrombin (26.2% [16.2%-52.7%] versus 4.5% [1.3%-7.2%]; P<0.001) and tissue factors (0.60% [0.34%-2.06%] versus 0.37% [0.22%-0.60%]; P=0.024) were higher and factor X was lower (1.25% [0.39%-3.60%] versus 2.33% [1.67%-4.48%]; P=0.034) in the cancer group. There was a positive correlation between thrombin and platelets in the cancer group (r=0.666; P=0.001) but not in the control group (r=-0.167; P=0.627). CONCLUSIONS: Cerebral thrombi in patients with cancer-associated stroke showed higher proportions of platelets, thrombin, and tissue factors, suggesting their key roles in arterial thrombosis in cancer and providing a therapeutic perspective for preventing stroke in patients with cancer-associated stroke.

Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Preprocedural determination of an occlusion pathomechanism in endovascular treatment of acute stroke: a machine learning-based decision.

OBJECTIVE: To evaluate whether an occlusion pathomechanism can be accurately determined by common preprocedural findings through a machine learning-based prediction model (ML-PM). METHODS: A total of 476 patients with acute stroke who underwent endovascular treatment were retrospectively included to derive an ML-PM. For external validation, 152 patients from another tertiary stroke center were additionally included. An ML algorithm was trained to classify an occlusion pathomechanism into embolic or intracranial atherosclerosis. Various common preprocedural findings were entered into the model. Model performance was evaluated based on accuracy and area under the receiver operating characteristic curve (AUC). For practical utility, a decision flowchart was devised from an ML-PM with a few key preprocedural findings. Accuracy of the decision flowchart was validated internally and externally. RESULTS: An ML-PM could determine an occlusion pathomechanism with an accuracy of 96.9% (AUC=0.95). In the model, CT angiography-determined occlusion type, atrial fibrillation, hyperdense artery sign, and occlusion location were top-ranked contributors. With these four findings only, an ML-PM had an accuracy of 93.8% (AUC=0.92). With a decision flowchart, an occlusion pathomechanism could be determined with an accuracy of 91.2% for the study cohort and 94.7% for the external validation cohort. The decision flowchart was more accurate than single preprocedural findings for determining an occlusion pathomechanism. CONCLUSIONS: An ML-PM could accurately determine an occlusion pathomechanism with common preprocedural findings. A decision flowchart consisting of the four most influential findings was clinically applicable and superior to single common preprocedural findings for determining an occlusion pathomechanism.

Neutrophil Recruitment in Arterial Thrombus and Characteristics of Stroke Patients with Neutrophil-Rich Thrombus.

PURPOSE: Neutrophils contribute to thrombosis. However, there is limited information on the temporal course of neutrophil recruitment in thrombosis, the contribution of neutrophils to thrombus growth, and the characteristics of stroke patients with neutrophil-rich thrombi. MATERIALS AND METHODS: After inducing carotid artery thrombosis in Institute of Cancer Research mice using ferric chloride, aged thrombi were produced by ligating the distal portion of the carotid artery in mice for 0.5, 1, 2, 3, 6, or 24 h. For thrombus analysis in stroke patients, we used registry data and thrombi that were obtained during intra-arterial thrombectomy. Immunohistochemistry was performed to determine thrombus composition. RESULTS: In the thrombi of 70 mice, Ly6G positive cell counts (neutrophils) and histone H3-positive cell counts increased in a time-dependent manner (both p<0.001). Ly6G-positive cell count was strongly correlated with histone H3-positive cell counts (r=0.910, p<0.001), but not with thrombus size (p=0.320). In 75 stroke patients, atrial fibrillation and cardioembolism were more frequent in the higher neutrophil group (32/37, 86.5%) than in the lower neutrophil group (19/38, 50%) (p=0.002). The median erythrocyte fraction was higher [52.0 (interquartile range 39.9-57.8)] in the higher neutrophil group than in the lower neutrophil group [40.3 (interquartile range 23.5-53.2)]. The fraction of neutrophils was positively correlated with that of erythrocytes (R=0.35, p=0.002). CONCLUSION: Neutrophils were recruited and increased in arterial thrombosis in a time-dependent manner; however, they were not associated with the growth of formed thrombi. Neutrophil fractions in the thrombi of stroke patients appeared to be associated with atrial fibrillation and erythrocyte fraction.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Early depression screening and short-term functional outcome in hospitalized patients for acute ischemic stroke.

Background: Patients with ischemic stroke are at high risk for post-stroke depression (PSD). There are limited data regarding the clinical impact of early PSD, assessed in hospitalized patients with acute ischemic stroke. Methods: This hospital-based observational cohort study included consecutive patients with acute ischemic stroke or transient ischemic attack between July 2019 and June 2021. In the study hospital, all admitted patients were systematically screened for depression. The depression was screened using the Patient Health Questionnaire-9 (PHQ-9), and PHQ-9 positivity indicated early PSD, which was defined as a score of >4. Logistic regression analyses were used to compare the rates of poor functional outcomes at 3 months in patients with and without PHQ-9 positivity. Results: Among 1339 patients admitted during the study period, 775 were included, with a median age of 68.0 years, and 316 (40.8%) were women. A total of 111 (14.3%) patients were PHQ-9 positive. History of cancer and early neurological deterioration were independently associated with PHQ-9 positivity. Poor functional outcomes at 3 months were observed in 147 patients (18.8%). PHQ-9 positivity independently showed a 2.2-fold increased risk of poor functional outcome at 3 months (Odds ratio 2.23; 95% confidence interval 1.05-4.73, P = 0.037). Conclusions: Patients with history of cancer and early neurological deterioration were at risk for early PSD. Early PSD was independently associated with poor functional outcomes at 3 months. The identification of early depression could offer opportunities for further questioning and exploration of symptoms, as well as interventions.

Clinical outcomes of rescue stenting for failed endovascular thrombectomy: a multicenter prospective registry.

BACKGROUND: Mechanical thrombectomy (MT) is a primary endovascular modality for acute intracranial large vessel occlusion. However, further treatment, such as rescue stenting, is occasionally necessary for refractory cases. We aimed to investigate the efficacy and safety of rescue stenting in first-line MT failure and to identify the clinical factors affecting its clinical outcome. METHODS: A multicenter prospective registry was designed for this study. We enrolled consecutive patients who underwent rescue stenting for first-line MT failure. Endovascular details and outcomes, follow-up patency of the stented artery, and clinical outcomes were summarized and compared between the favorable and unfavorable outcome groups. RESULTS: A total of 78 patients were included. Intracranial atherosclerotic stenosis was the most common etiology for rescue stenting (97.4%). Seventy-seven patients (98.7%) were successfully recanalized by rescue stenting. A favorable outcome was observed in 66.7% of patients. Symptomatic intracranial hemorrhage and mortality were observed in 5.1% and 4.0% of patients, respectively. The stented artery was patent in 82.1% of patients on follow-up angiography. In a multivariable analysis, a patent stent on follow-up angiography was an independent factor for a favorable outcome (OR 87.6; 95% CI 4.77 to 1608.9; p=0.003). Postprocedural intravenous maintenance of glycoprotein IIb/IIIa inhibitor was significantly associated with the follow-up patency of the stented artery (OR 5.72; 95% CI 1.45 to 22.6; p=0.013). CONCLUSIONS: In this multicenter prospective registry, rescue stenting for first-line MT failure was effective and safe. For a favorable outcome, follow-up patency of the stented artery was important, which was significantly associated with postprocedural maintenance of glycoprotein IIb/IIIa inhibitors.

Characterization of Ferric Chloride-Induced Arterial Thrombosis Model of Mice and the Role of Red Blood Cells in Thrombosis Acceleration.

PURPOSE: The ferric chloride (FeCl3)-induced thrombosis model is widely used for thrombosis research. However, it lacks standardization with uncertainty in the exact mechanism of thrombosis. This study aimed to characterize thrombus formation in a mouse model. MATERIALS AND METHODS: We investigated thrombus formation and stability using various FeCl3 concentrations (10%, 20%, 30%, 40%, and 50%, w/v) in carotid arteries of the Institute of Cancer Research (ICR) and C57BL/6N mice using the FeCl3-induced thrombosis model. We also investigated thrombus histopathology using immunohistochemistry and electron microscopy. RESULTS: Higher FeCl3 concentrations induced dose-dependent, faster, larger, and more stable thrombus formation in both strains of mice. However, the ICR mice showed better dose-responses in thrombus formation and stability compared to the C57BL/6N mice. Thrombi were fibrin- and platelet-rich without significant changes across FeCl3 concentrations. However, the content of red blood cells (RBCs) increased with increasing FeCl3 concentrations (p for trend <0.001) and inversely correlated with time to occlusion (r=-0.65, p<0.001). While platelets and fibrin were evenly distributed over the thrombus, RBCs were predominantly located near the FeCl3 treatment area. Transmission electron microscopy showed that RBCs attached to and were surrounded by aggregates of degranulated platelets, suggesting their potential role in platelet activation. CONCLUSION: Faster and larger thrombus formation is induced in a dose-dependent manner by a wide range of FeCl3 concentrations, but the stable thrombus formation requires higher FeCl3 concentrations. Mouse strain affects thrombus formation and stability. RBCs and their interaction with platelets play a key role in the acceleration of FeCl3-induced thrombosis.

Effect of leukopenia induced by cyclophosphamide on the initial stage of arterial thrombosis in mice.

INTRODUCTION: Leukocytes are found in organizing thrombi and are associated with thrombus growth. However, their role in the initial stage of thrombus formation is not well known. We investigated the role of leukocytes in the early stage of arterial thrombosis by inducing leukopenia. METHODS: In this double-blind, randomized, placebo-controlled study, 72 Institute of Cancer Research mice were randomly treated with intraperitoneal 100 mg/kg cyclophosphamide or normal saline. The primary outcome was time to occlusion after FeCl3 treatment. We also compared thrombus size, histological composition, and association with peripheral blood cell counts between cyclophosphamide and control groups. RESULTS: Cyclophosphamide treatment significantly decreased leukocyte counts by 82.8% compared to placebo (P < 0.001). The time to occlusion was significantly longer in the cyclophosphamide group (3.31 ± 1.59 min) than in the control group (2.30 ± 1.14 min; P = 0.003). The immunoreactivity for Ly6G-positive cells, intracellular histone H3, and released histone H3 in thrombi was significantly reduced in the cyclophosphamide group by 92.8%, 50.2%, and 34.3%, respectively. Time to occlusion had a moderate negative correlation with leukocyte count in peripheral blood (r = -0.326, P = 0.022) in the entire group. CONCLUSIONS: Cyclophosphamide-induced leukopenia attenuated thrombus formation during the early stage of arterial thrombosis. Our findings suggest the potential role of leukocytes in the initial stage of arterial thrombosis.

The role of cardiac CT throughout the full cardiac cycle in diagnosing patent foramen ovale in patients with acute stroke.

OBJECTIVES: We explored the hypothesis that the diagnostic performance of cardiac computed tomography (CT) throughout the full cardiac cycle would be superior to single-phase CT and comparable to transesophageal echocardiography (TEE) in diagnosing patent foramen ovale (PFO). METHODS AND RESULTS: From May 2011 to April 2015, 978 patients with stroke were diagnosed with PFO by TEE. In patients with stroke, cardiac CT was performed if the patients had more than two cardiovascular risk factors. We prospectively enrolled 70 patients with an indication for cardiac CT. Cardiac CT images were reconstructed at 10% increments of the R-R interval. The sensitivity of cardiac CT throughout the full cardiac cycle in diagnosing PFO was compared to that for TEE and single-phase cardiac CT. To evaluate the specificity of cardiac CT, we analyzed patients without PFO confirmed by TEE who underwent cardiac CT within 1 month of pre-cardiac surgery. Sixty-six patients with cardiac CT and TEE were included in the final analysis. Throughout the full cardiac cycle, cardiac CT had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing PFO, compared to TEE as a reference. PFO was primarily detected in the 60% and 70% intervals in 10-phase reconstructed images. The sensitivity of PFO diagnosis with cardiac CT was 81.8% when analyzing both the 60% and 70% intervals instead of the full cardiac cycle. CONCLUSION: Cardiac CT throughout the full cardiac cycle outperforms single-phase cardiac CT in detecting PFO. Cardiac CT can be used as an alternative method to TEE for detecting PFO in stroke patients. KEY POINTS: • Throughout the full cardiac cycle, cardiac computed tomography (CT) had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing patent foramen ovale (PFO), compared to transesophageal echocardiography. • The sensitivity of diagnosing patent foramen ovale with cardiac CT was 81.8% when analyzing 60% and 70% R-R intervals instead of the full cardiac cycle. • Cardiac CT with retrospective electrocardiographic gating throughout the full cardiac cycle can increase the detectability of PFO, compared to single-phase cardiac CT.

Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Clinical impact of estradiol/testosterone ratio in patients with acute ischemic stroke.

BACKGROUND: Sex hormones may be associated with a higher incidence of ischemic stroke or stroke-related events. In observational studies, lower testosterone concentrations are associated with infirmity, vascular disease, and adverse cardiovascular risk factors. Currently, female sexual hormones are considered neuroprotective agents. The purpose of this study was to assess the role of sex hormones and the ratio of estradiol/testosterone (E/T) in patients with acute ischemic stroke (AIS). METHODS: Between January 2011 and December 2016, 146 male patients with AIS and 152 age- and sex-matched control subjects were included in this study. Sex hormones, including estradiol, progesterone, and testosterone, were evaluated in the AIS patient and control groups. We analyzed the clinical and physiological levels of sex hormones and hormone ratios in these patients. RESULTS: The E/T ratio was significantly elevated among patients in the stroke group compared to those in the control group (P = 0.001). Categorization of data into tertiles revealed that patients with the highest E/T ratio were more likely to have AIS [odds ratio (OR) 3.084; 95% Confidence interval (CI): 1.616-5.886; P < 0.001) compared with those in the first tertile. The E/T ratio was also an independent unfavorable outcome predictor with an adjusted OR of 1.167 (95% CI: 1.053-1.294; P = 0.003). CONCLUSIONS: These findings support the hypothesis that increased estradiol and reduced testosterone levels are associated with AIS in men.

Association between flat-panel computed tomography hyperattenuation and clinical outcome after successful recanalization by endovascular treatment.

OBJECTIVE: Hyperattenuation on CT scanning performed immediately after endovascular treatment (EVT) is known to be associated with the final infarct. As flat-panel CT (FPCT) scanning is readily accessible within their angiography suite, the authors evaluated the ability of the extent of hyperattenuation on FPCT to predict clinical outcomes after EVT. METHODS: Patients with successful recanalization (modified Thrombolysis in Cerebral Infarction grade 2b or 3) were reviewed retrospectively. The extent of hyperattenuation was assessed by the Alberta Stroke Program Early CT Score on FPCT (FPCT-ASPECTS). FPCT-ASPECTS findings were compared according to functional outcome and malignant infarction. The predictive power of the FPCT-ASPECTS with initial CT images before EVT (CT-ASPECTS) and follow-up diffusion-weighted images (MR-ASPECTS) was also compared. RESULTS: A total of 235 patients were included. All patients were treated with mechanical thrombectomy, and 45.5% of the patients received intravenous tissue plasminogen activator. The mean (± SD) time from stroke onset to recanalization was 383 ± 290 minutes. The FPCT-ASPECTS was significantly different between patients with a favorable outcome and those without (mean 9.3 ± 0.9 vs 6.7 ± 2.6) and between patients with malignant infarction and those without (3.4 ± 2.9 vs 8.8 ± 1.4). The FPCT-ASPECTS was an independent factor for a favorable outcome (adjusted OR 3.28, 95% CI 2.12-5.01) and malignant infarction (adjusted OR 0.42, 95% CI 0.31-0.57). The area under the curve (AUC) of the FPCT-ASPECTS for a favorable outcome (0.862, cutoff ≥ 8) was significantly greater than that of the CT-ASPECTS (0.637) (p < 0.001) and comparable to that of the MR-ASPECTS (0.853) (p = 0.983). For malignant infarction, the FPCT-ASPECTS was also more predictive than the CT-ASPECTS (AUC 0.906 vs 0.552; p = 0.001) with a cutoff of ≤ 5. CONCLUSIONS: The FPCT-ASPECTS was highly predictive of clinical outcomes in patients with successful recanalization. FPCT could be a practical method to immediately predict clinical outcomes and thereby aid in acute management after EVT.

Outcome of Stroke Patients with Cancer and Nonbacterial Thrombotic Endocarditis.

BACKGROUND AND PURPOSE: Nonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known. METHODS: We included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up. RESULTS: Among the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P<0.001). In a multivariate Cox proportional hazard analysis, the presence of NBTE was independently associated with composite outcomes of mortality and stroke events (hazard ratio, 1.941; 95% confidence interval, 1.052 to 3.690). CONCLUSIONS: NBTE should be suspected as a potential cause of stroke in patients with metastatic cancer. Patients with NBTE have a high risk of recurrent stroke and mortality. Future studies are necessary to determine strategies to reduce stroke recurrence in patients with NBTE.

Collateral augmentation treatment with a combination of acetazolamide and head-down tilt in a rat ischemic stroke model.

Cerebral collaterals is crucially important in the pathophysiology of acute ischemic stroke and associated with outcome after reperfusion therapy. We explored the effectiveness of collateral augmentation treatment with a combination of acetazolamide (ACZ) and head-down tilt (HDT) in the transient middle cerebral artery occlusion (MCAO) rat model. Transient MCAO was induced in all animals for 1.5 h, followed by reperfusion for 22.5 h. Seventy-two male Wistar rats were divided into four treatment groups: control, ACZ, HDT, and combination. Twenty sham rats, which underwent surgery, were randomly allocated to these groups. Twenty-four hours after MCAO or sham surgery, we measured the infarction volume, brain edema (aquaporin-4 [AQP4], and brain water content), and neurological deficits (Garcia and Longa tests). Collateral augmentation treatments were associated with reduced infarction volume, less brain edema, and better neurological outcomes compared with untreated animals. More specifically, ACZ and HDT treatments resulted in small infarction volumes, and HDT was associated with a low AQP4 expression and improved neurological score, while the combination of ACZ and HDT improved neurological scores and reduced brain water content. This study shows that collateral augmentation treatments are associated with a better stroke prognosis compared with untreated animals after transient MCAO. The combination of ACZ and HDT seems to have some synergistic effect, but was not proven to be superior to HDT treatment alone.

Effects of first pass recanalization on outcomes of contact aspiration thrombectomy.

BACKGROUND: First pass recanalization (FPR, defined as achieving a modified Thrombolysis in Cerebral Ischemia (mTICI) grade 2c/3 with a single pass of a thrombectomy device) effect has not yet been evaluated in contact aspiration thrombectomy (CAT). We evaluated FPR effect on clinical outcomes and FPR predictors in CAT. METHODS: All consecutive patients who underwent frontline CAT for anterior circulation large vessel occlusion with recanalization (mTICI 2b-3) were identified from registries at six stroke centers. The patients were dichotomized into FPR and non-FPR groups. Clinical features and outcomes were compared between the groups. Multivariate analyses were performed to determine whether FPR was independently associated with clinical outcomes and to identify predictors of FPR. RESULTS: Of the 429 patients who underwent frontline CAT, recanalization was successful in 344 patients (80.2%; mean age 68.7±11.0 years; M:F ratio 179:165). The FPR group had a higher rate of good outcome (modified Rankin Scale score 0-2) than the non-FPR group. Furthermore, the good outcome rate was higher in the FPR group than in patients who achieved mTICI 2c/3 with multiple passes or rescue treatment. FPR (OR 2.587; 95% CI 1.237 to 5.413) remained independently associated with good outcomes, in addition to age, baseline National Institute Health Stroke Scale, and coronary artery disease. The use of a balloon guide catheter (OR 3.071; 95% CI 1.699 to 5.550) was the only predictor of FPR. CONCLUSIONS: Patients in the FPR group had better clinical outcomes than the non-FPR group in CAT. FPR was independently associated with a good outcome. The use of a balloon guide catheter was the only predictor of FPR.

Body mass index and clinical outcomes in patients after ischaemic stroke in South Korea: a retrospective cohort study.

OBJECTIVES: Although obesity is a risk factor for stroke, its impact on mortality in patients with stroke remains unclear. In this study, we aimed to evaluate the relationship between body mass index (BMI) and mortality due to ischaemic stroke among adults aged 20 years and above in Korea. DESIGN: Retrospective cohort study. SETTING: A tertiary-hospital-based stroke registry linked to the death records. PARTICIPANTS: 3599 patients admitted for ischaemic stroke from January 2007 to June 2013. OUTCOME MEASURES: The HRs for all-cause and stroke-related mortality were calculated using Cox proportional hazards models. Progression from stroke-related mortality was assessed using the Fine-Grey competing risk model, treating other-cause mortality as a competing risk. Adjustments were made for age, gender, smoking status, Charlson comorbidity index, cardiovascular or non-cardiovascular comorbidities, stroke severity, severity related to other medical conditions, complications and enrolment year. We repeated the analysis with stratification based on age groups (less than 65 vs 65 years and above). RESULTS: For stroke-related mortality, there was no significant difference among the four BMI groups. The risk of all-cause mortality was 36% higher in the underweight group than in the normal weight group (long-term HR=1.36, 95% CI: 1.04 to 1.79), whereas the mortality risk of the obese group was significantly lower (HR=0.66, 95% CI: 0.54 to 0.81). Although this relationship was not estimated in the younger group, it was found that obesity had a protective effect on the all-cause mortality in the elderly (long-term HR=0.66, 95% CI: 0.52 to 0.83). CONCLUSIONS: Obesity is more likely to reduce mortality risk than normal weight, especially in elderly patients.