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Background and Purpose: The susceptibility vessel sign, a hypointense signal on MR T2-weighted gradient-recalled echo images, is associated with erythrocyte-predominant thrombi, which are often present in cardioembolism. In contrast, cancer-associated hypercoagulability (CAH)-related stroke, which is presumably caused by fibrin-predominant thrombi, is associated with the absence of the susceptibility vessel sign. We hypothesized that the prevalence of the susceptibility vessel sign may be helpful in distinguishing CAH-related stroke from cardioembolism. This study attempted to validate this hypothesis and investigated the usefulness of the susceptibility vessel sign in differentiating CAH-related stroke from cardioembolism., Materials and Methods: We retrospectively studied patients with both CAH-related stroke (CAH group) and cardioembolism (cardioembolism group) who had major cerebral artery occlusion on MRA that was performed within 6 hours of stroke onset. All patients visited our department from 2015 to 2021. CAH-related stroke was defined as the following: 1) complication of active cancer, 2) pretreatment D-dimer value of >3 μg/mL, 3) multiple vascular territory infarctions, and 4) lack of any other specifically identified causes of stroke. We compared susceptibility vessel sign positivity rates within each group. Multivariable logistic regression analysis was used to assess the association between the absence of the susceptibility vessel sign and CAH-related stroke., Results: Of 691 patients with CAH-related stroke or cardioembolism, major cerebral artery occlusion was observed in 10 patients in the CAH group and 198 patients in the cardioembolism group. The absence of the susceptibility vessel sign was identified in 55 of 208 patients and was significantly more frequent in the CAH group versus the cardioembolism group (90% versus 24%, P  < .05). For predicting CAH-related stroke, the absence of the susceptibility vessel sign demonstrated a sensitivity of 90% (95% CI, 59%-99%), specificity of 78% (95% CI, 71%-83%), a positive predictive value of 18% (95% CI, 10-31), a negative predictive value of 99% (95% CI, 96%-99%), and a likelihood ratio of 4.06. Multivariable logistic regression analysis revealed that the absence of the susceptibility vessel sign was independently associated with CAH-related stroke (OR, 43; 95% CI, 6.8-863; P  < .01)., Conclusions: The absence of the susceptibility vessel sign was more frequent in CAH-related stroke than in cardioembolism. These findings could potentially be helpful for clinical management and differentiating cardioembolism and CAH-related stroke., (© 2024 by American Journal of Neuroradiology.)

Objective: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden., Methods: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events., Results: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0., Interpretation: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Antiplatelet agents are effective for secondary prevention of ischemic stroke and can reduce the severity of first-ever ischemic stroke. However, it is uncertain if prophylactic antiplatelet therapy reduces the severity of recurrent ischemic stroke. The aim of this study was to determine the effect of preceding antiplatelet treatment on the severity of thrombotic stroke (TS) in patients with a prior history of stroke., Methods: From a prospective hospital registry of 1338 consecutive patients with acute ischemic stroke, we identified patients with a prior history of stroke who were admitted for cardioembolic stroke (CE); TS including large-artery atherosclerosis, small vessel occlusion, and branch atheromatous disease; or other cause or cryptogenic stroke (OCS). Cases in each subtype were categorized based on preceding medication: antiplatelet agents (AP) and none (N). Severity of stroke (National Institutes of Health Stroke Scale: NIHSS) on admission was compared between AP and N cases., Results: The total cohort of 252 patients included 83 with CE, 102 with TS, and 67 with OCS. After excluding those with prior anticoagulants, the median NIHSS on admission was lower in AP cases than in N cases (3 vs. 5, p = 0.002). In multivariate analysis, preceding AP treatment was independently associated with minor stroke (NIHSS ≤4) on admission in CE group (OR 8.48, 95% CI 1.71-62.9, p = 0.008) and TS group (OR 4.24, 95% CI 1.44-13.4, p = 0.009)., Conclusion: Preceding antiplatelet treatment in patients with a prior history of stroke may reduce the severity of subsequent thrombotic and cardiogenic stroke., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice., Methods: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time &gt;4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline., Results: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge., Conclusions: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them., (© 2023 S. Karger AG, Basel.)

Introduction: In patients with cancer-associated hypercoagulability (CAH)-related stroke, D-dimer trends after anticoagulant therapy may offer a biomarker of treatment efficacy. The purpose of this study was to clarify the association between D-dimer trends and recurrent stroke after anticoagulant therapy in patients with CAH-related stroke., Methods: We performed retrospective cohort study of consecutive patients with CAH-related stroke at two stroke centers from 2011 to 2020. The ratio of posttreatment to pretreatment D-dimer levels (post/pre ratio) was used as an indicator of D-dimer trends after anticoagulant therapy. Fine-Gray models were used to evaluate the association between post/pre ratio and recurrent stroke., Results: Among 360 acute ischemic stroke patients with active cancer, 73 patients with CAH-related stroke were included in this study. Recurrent stroke occurred in 13 patients (18%) during a median follow-up time of 28 days (interquartile range, 11-65 days). Multivariate analysis revealed that high post/pre ratio was independently associated with recurrent stroke (per 0.1 increase: hazard ratio 2.20, 95% confidence interval 1.61-3.01, p = 0.012)., Conclusion: D-dimer levels after anticoagulant therapy were associated with recurrent stroke in CAH-related stroke patients. Patients with neutral trends in high D-dimer levels after anticoagulant therapy were at high risk of recurrent stroke., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Long-term anticoagulant therapy in oldest-old persons poses the risk of bleeding complications. The aim of this study was to evaluate the long-term benefits of anticoagulant therapy for oldest-old stroke survivors with AF., Methods: Patients with atrial fibrillation (AF) who were 90 years of age or older and were prescribed an anticoagulant on discharge were identified from a set of data from a prospective follow-up registry of 1,484 consecutive patients admitted for ischemic stroke or transient ischemic attack over a 4-year period beginning in 2014. The outcome measures were stroke and death following discharge., Results: Of the 77 identified patients with AF who were 90 years of age or older, 71 were prescribed an anticoagulant (median age 93 years, 73% women). Thirty-nine patients were given a direct oral anticoagulant (DOAC) (median age 92 years, 69% women), and 32 were given warfarin (median age 93 years, 78% women). During the follow-up period (median 466 days), 9 patients (13%) had stroke recurrence (recurrence rate: 14%/year), and 25 patients (35%) died (mortality rate: 33%/year). The type of all recurrent strokes was ischemic, and no fatal bleeding occurred. There was no difference in the incidence of recurrent strokes according to anticoagulant type (DOAC 15%/year, warfarin 13%/year, P = 0.743), but a higher proportion of patients on warfarin died (21% vs. 47%, P = 0.002)., Conclusions: Given that a higher proportion of oldest-old stroke survivors with AF on anticoagulant therapy have recurrent ischemic stroke rather than hemorrhagic stroke, long-term anticoagulant therapy may be justified for secondary stroke prevention., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: There are limited data on the clinical course of patients with non-cardioembolic, mostly atherosclerotic, internal carotid artery occlusion (ICAO). The purpose of this study was to elucidate the frequency and underlying pathogenesis of early recurrent ischemic stroke in symptomatic non-cardioembolic ICAO., Materials and Methods: Consecutive patients with symptomatic non-cardioembolic ICAO were retrospectively reviewed. Those who had a tandem occlusion of the proximal middle cerebral artery (MCA) or underwent endovascular thrombectomy were excluded. Early recurrent stroke was defined as deterioration of the NIHSS score by ≥1 point with new lesions on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the ipsilateral territory of the ICAO within 30 days of the index stroke onset. Patients were classified into two groups on carotid ultrasonography: cervical occlusion and intracranial occlusion. The presumed pathogenesis of recurrent stroke was categorized as embolic or hemodynamic according to the topographical features of subsequent lesions on DWI., Results: Of 36 consecutive medically treated patients with symptomatic non-cardioembolic ICAO without tandem MCA occlusion, 23 patients had cervical occlusion, and 13 had intracranial occlusion. Early recurrent stroke occurred in 16 patients (44.4%), which happened much more with intracranial occlusion than with cervical occlusion (69.2% vs 30.4%, p<0.02). Focusing on the presumed pathogenesis, hemodynamic was more common than embolic (68.8% vs 31.2%), especially with intracranial occlusion (77.8%)., Conclusions: Early recurrent stroke occurs at a high frequency in symptomatic non-cardioembolic ICAO, and intracranial occlusion may be a risk factor for early recurrent stroke. The pathogenesis of recurrence is more often hemodynamic than embolic., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke., Methods: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days., Results: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score ( p  = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group ( p interaction = 0.042)., Conclusion: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.

A 65-year-old woman with a six-year history of paroxysmal nocturnal hemoglobinuria (PNH) was admitted due to weakness in the right leg following a seven-day history of fever and upper respiratory infection. MRI revealed several high-intensity areas in bilateral frontal lobe cortices and the left cerebellum on diffusion-weighted imaging, and signal hypointensity along the course of the cortical vein in the left frontal lobe on T 2 *-weighted imaging. We diagnosed cerebral venous thrombosis and brain infarction, and commenced heparin infusion. She developed right-sided dens hemiparesis on hospital day 6, when brain CT showed subcortical hemorrhage in the left frontal lobe. Despite eculizumab administration and decompressive craniectomy for hematoma, she died on hospital day 26. Thrombosis in PNH has been recognized as a life-threating complication, and intensive treatment including emergent administration of eculizumab is warranted if this situation arises.

Background: There is currently no validated risk prediction model for recurrent events among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Considering that the application of conventional risk scores has contextual limitations, new strategies are needed to develop such a model. Here, we set out to develop and validate a comprehensive risk prediction model for stroke recurrence in AIS patients with AF., Methods: AIS patients with AF were collected from multicenter registries in South Korea and Japan. A developmental dataset was constructed with 5648 registered cases from both countries for the period 2011‒2014. An external validation dataset was also created, consisting of Korean AIS subjects with AF registered between 2015 and 2018. Event outcomes were collected during 1 year after the index stroke. A multivariable prediction model was developed using the Fine-Gray subdistribution hazard model with non-stroke mortality as a competing risk. The model incorporated 21 clinical variables and was further validated, calibrated, and revised using the external validation dataset., Results: The developmental dataset consisted of 4483 Korean and 1165 Japanese patients (mean age, 74.3 ± 10.2 years; male 53%); 338 patients (6%) had recurrent stroke and 903 (16%) died. The clinical profiles of the external validation set (n = 3668) were comparable to those of the developmental dataset. The c-statistics of the final model was 0.68 (95% confidence interval, 0.66 ‒0.71). The developed prediction model did not show better discriminative ability for predicting stroke recurrence than the conventional risk prediction tools (CHADS2, CHA2DS2-VASc, and ATRIA)., Conclusions: Neither conventional risk stratification tools nor our newly developed comprehensive prediction model using available clinical factors seemed to be suitable for identifying patients at high risk of recurrent ischemic stroke among AIS patients with AF in this modern direct oral anticoagulant era. Detailed individual information, including imaging, may be warranted to build a more robust and precise risk prediction model for stroke survivors with AF., Competing Interests: This study was supported by Bristol‒Myers Squibb Korea and the Korea Centers for Disease Control and Prevention (no. 2020ER620200#) and a Grant-in-Aid (H23-Junkanki-Ippan-010) from the Ministry of Health, Labour and Welfare, Japan. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funding sources did not participate in any part of the study, from conception to article preparation.

Purpose: Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) extent or FVH-DWI mismatch as a primary influencing factor of clinical outcome in acute ischemic stroke is controversial. This study elucidated the regional pathophysiology and tissue fate in four types of cortical territories classified by the initial FVH and DWI findings in patients with acute proximal middle cerebral artery (M1) occlusion successfully recanalized using mechanical thrombectomy., Methods: We retrospectively evaluated 35 patients successfully recanalized within 24 h of acute M1 occlusion onset between 2016 and 2019. Each Alberta stroke program early CT score area of M1-M6 were categorized as group A (DWI-, FVH-), B (DWI-, FVH+), C (DWI+, FVH+), or D (DWI+, FVH-). Territorial collateral status was graded on a 4-point scale by initial angiogram. Follow-up head computed tomography (CT) findings on days 2-9 were assessed for the territorial outcome., Results: Overall, 210 cortical territories were identified; of these, 88 (41.9 %) were categorized into group A; 72 (34.3 %), group B; 37 (17.6 %), group C; and 13 (6.2 %), group D. The rate of territories with good collaterals (grade 2 or 3) significantly decreased in the order of groups as 78.3 %, 62.7 %, 27.6 %, and 0%, respectively (P trend <.001). Conversely, the rate of territories with any hypo- or hyper-density on follow-up CT significantly increased in the order of groups as 13.4 %, 23.1 %, 88.5 %, and 85.7 %, respectively (P trend <.001)., Conclusion: Categorization of cortical areas based on the FVH and DWI findings can stratify territorial collateral status and tissue fate., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The aim of this study was to test the hypothesis that the attack interval of multiple transient ischemic attacks (TIAs) is correlated with the underlying pathogenesis of ischemia., Methods: Patients with multiple TIAs, defined as 2 or more motor deficits within 7 days, were studied. The attack interval between the last 2 episodes was classified into 3 groups: 2 episodes within an hour (Hour group), over hours within a day (Day group), and over days within a week (Week group). Patients with a lacunar syndrome, no cortical lesions, and no embolic sources were recognized as having a small vessel disease (SVD) etiology for their multiple events., Results: Of 312 TIA patients admitted over a 9-year period, 50 (37 males, 13 females, mean 67.6 years) had multiple TIAs. Twelve patients were classified as being within the Hour group, 23 within the Day group, and 15 within the Week group. Lacunar syndromes were observed in 30 (75%, 35%, and 67%), embolic sources were detected in 28 (25%, 65%, and 67%), and a high signal lesion on diffusion-weighted imaging was depicted in 30 (75%, 48%, and 67%) patients (18 cortical, 11 subcortical, and one cerebellar). Patients in the Hour group had a significantly higher prevalence of SVD etiology (75%) than those in the Day and Week groups (30%, p = 0.0165; 27%, p = 0.0213, respectively). Four patients had a subsequent stroke within 7 days., Conclusion: Attack intervals of multiple TIAs may be correlated with the underlying pathogenesis of ischemia. Two motor deficits within an hour are more likely to suggest a SVD etiology., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Aims: The bleeding risk of current antithrombotic strategies in clinical settings, including recently developed agents, needs to be clarified., Methods and Design: In an investigator-initiated, prospective, multicentre, observational study, patients with cerebrovascular or cardiovascular diseases who were taking oral antiplatelet or anticoagulant agents were enrolled. Compulsory multimodal magnetic resonance images were acquired at baseline to assess cerebral small vessel disease. Six-month follow-up will be performed for two years. The primary outcome is major bleeding as defined by the International Society on Thrombosis and Hemostasis., Results: Between October 2016 and March 2019, 5306 patients (71.7 ± 11.2 years old, 1762 women) were enrolled. Previous intracranial haemorrhage was documented in 181 patients (3.4%), cerebrovascular disease (including asymptomatic) requiring antithrombotic therapy in 5006 patients (94.3%), and atrial fibrillation in 1061 patients (20.0%). At entry, 3726 patients (70.2%) were taking antiplatelet agents alone, including 551 (10.4%) using dual antiplatelet agents, 1317 (24.8%) taking anticoagulants alone, and the remaining 263 (5.0%) taking both. The leading antiplatelet agent was clopidogrel (2014 patients), and the leading combination of dual antiplatelet medication was clopidogrel plus aspirin (362). Use of direct oral anticoagulants (1029 patients, 19.4%) exceeded warfarin use (554, 10.4%). The number of pivotal bleeding events exceeded 200 in April 2020., Conclusions: This study is expected to provide the incidence of bleeding complications of recent oral antithrombotics in clinical practice and identify their associations with underlying small vessel disease and other biomarkers. Novel risk stratification models for bleeding risk will be able to be created based on the study results., Competing Interests: Declaration of conflicting interests: All of the following conflicts are outside the submitted work. Toyoda received lecture honoraria from Daiichi-Sankyo, Bayer Yakuhin, Nippon Boehringer Ingelheim, and Bristol-Myers Squibb. Hirano received lecture honoraria from Daiichi-Sankyo, Bayer Yakuhin, Nippon Boehringer Ingelheim, Pfizer, and Bristol-Myers Squibb. Hoshino received lecture honoraria from Daiichi-Sankyo and Pfizer. Koga received lecture honoraria from Bayer Yakuhin. Ihara received lecture honoraria from Daiichi-Sankyo, Eisai, and Bayer Yakuhin and research grant from Bristol-Myers Squibb and Panasonic. The other authors had no conflicts of interest., (© European Stroke Organisation 2020.)

The lenticulostriate arteries (LSA) supply the lateral half of the head of the caudate nucleus, entire putamen, anterior limb, genu and the superior part of the internal capsule (IC) and a part of the corona radiata. The LSA consists with medial, intermediate and lateral branches. The medial branches perfuse the lateral segment of the globus pallidus, the head of the caudate nucleus and the anterior limb of the IC. The intermediate branches supply the anterior half of the LSA territory, while the lateral branches supply the posterior half. The anterior cerebral artery (ACA) perforators, predominantly Heubner's artery, perfuse the inferomedial part of the caudate head, the anteromedial part of putamen, the anterior part of the lateral segment of the globus pallidus and anterior limb of the internal capsule. Such territories can be represented by the anterior and ventral basal ganglions. The anterior choroidal artery (AChA) gives off three main groups of branches including the lateral branches that supply the medial temporal lobe, the medial branches that supply the cerebral peduncle and the superior branches that supply the internal capsule and the basal ganglia. The superior branches are further discriminated into proximal branches that supply the anterior one third of the posterior limb of internal capsule (PLIC) and the medial segment of the globus pallidus and distal branches that supply the posterior two-third of PLIC, retro-lenticular part of the internal capsule and the lateral thalamic nuclei. The superficial penetrating arteries, i.e. medullary arteries, arise from the cortical branches of the middle cerebral artery (MCA) and supply the deep white matter. Infarcts caused by the medullary artery occlusion are located in the centrum-semiovale and half of them were caused by embolic mechanism. The centrum-semiovale corresponds to cortical border-zone (BZ) while the corona radiate corresponds to internal BZ.

A small centrum ovale infarct in the territory of the white matter medullary artery can be caused not only by embolism but also small-vessel disease. In our study, thorough screening for emboligenic diseases was performed, including the modality of transesophageal echocardiography (TEE), in patients with an acute, isolated, small (less than 1.5 cm) infarct in the centrum ovale. Of 79 patients enrolled in this study, 45 had emboligenic diseases, in whom a patent foramen ovale was detected in 29 patients, complicated aortic arch lesion in 15, atrial fibrillation in 6, occlusive carotid disease in 2, and others in 2. The majority (80%) of the emboligenic diseases were diagnosed by TEE. Therefore, TEE may be mandatory for the etiologic diagnosis of centrum ovale infarcts.

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P >0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

A 67-year-old woman who had undergone laparoscopic proximal gastrectomy for early gastric cancer 10 months previously was admitted to our hospital due to dysarthria. Brain MRI demonstrated acute multiple small infarcts in the right middle cerebral artery (MCA) and the right posterior inferior cerebellar artery (PICA) territory, and she was diagnosed as embolic stroke. Anticoagulant therapy did not prevent further ischemic stroke. No embolic sources were detected by MR angiography, carotid duplex sonography, transthoracic and transesophageal echocardiography, and Holter electrocardiography. We also performed upper gastrointestinal endoscopy and contrast-enhanced CT of the thoracoabdominal area, but there was no evidence of local recurrence or lymph node metastases of gastric cancer. As the ALP and D-dimer levels were gradually increasing, we performed PET/CT, which revealed fluorodeoxyglucose (FDG) uptake in the vertebra bone, and disseminated carcinomatosis of bone marrow with early gastric cancer was diagnosed after bone marrow biopsy on Day 41. After undergoing chemotherapy, she had no further stroke and died on Day 207.

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF)., Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism., Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00)., Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF., (© 2020 S. Karger AG, Basel.)

Purpose: It is universally recognized that the anterior choroidal artery (AChA) supplies the posterior two-third of the posterior limb of internal capsule (PLIC). On the other hand, the blood supply to the anterior one third of the PLIC has remained undetermined. We posit the anterior one third of the PLIC is also supplied by the AChA referring the previous microsurgical descriptions., Methods: Ninety consecutive patients with isolated acute infarction in the PLIC were studied. We classified patients into 4 groups. 1. The anterior type that involved the anterior one-third part of the PLIC. 2. The posterior type that involved the caudal two-third part of the PLIC, 3. The combined type that located in the full length of the PLIC, 4. The dot type that restricted within PLIC up to10mm in diameter., Results: Patient numbers in groups 1 through 4 were 7 (7.7%), 46 (51.1%), 9 (10.6%) and 28 (31.1%). The anterior type involved the medial part of pallidum (MPP) in 5 patients (71.4%) and none in the lateral thalamus (LT), while the posterior type involved MPP only in 6 patients (13.0%) and LT in 33 patients (71.7%)., Conclusion: Corresponding to previous microsurgical descriptions, an occlusion of the proximal branches may cause anterior type infarct and that of the distal branches may cause posterior type infarcts. The anterior one third of the PLIC is also supplied by the branches of the AChA, albeit the low prevalence., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To study the stroke mechanism of medullary infarction (MI) and their correlation with prognosis., Methods: We collected 81 consecutive patients with acute isolated MI including 50 patients with lateral MI (LMI), 30 with medial MI (MMI) and one with combined MI. The stroke mechanisms were defined as follows: 1. Large artery atherosclerotic occlusive disease (LAOD): with severe stenosis (>50%) or occlusion on the relevant arteries. 2. Penetrating artery disease (PAD): occlusion of penetrating arteries that arise from vertebral artery or basilar artery with no significant stenosis of the vertebro-basilar artery. 3. Dissection: angiographic findings met the criteria. 4. Cardiogenic embolism: abrupt onset with atrial fibrillation. The poor outcome was defined as a condition that includes the mRS ≥2 and/or dysphagia at one year after onset., Results: There were 20 patients with PAD (40%), 18 with dissection (36.0%) and 11 with LAOD (22.0%) in LMI and 17 with PAD (56.6%), 10 with LAOD (33.3%) in MMI. LAOD and dissection compared with PAD were independently correlated with poor outcome in LMI (OR: 12.8, p = 0.029 and OR: 14.9, p = 0.035). LAOD was significantly correlated with poor outcome in MMI (OR: 13.4, p = 0.014)., Conclusions: PAD was the most predominant stroke mechanism in MI and generally showed favorable outcome. Patients with LAOD and dissection showed worse outcome than those with PAD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background We aimed to clarify associations between prior anticoagulation and short- or long-term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42-0.81; P=0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16-0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20-6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

A 61-year-old man, with a history of right clavicular fracture 35 years prior, visited our hospital due to the sudden onset of vertigo and tinnitus following weakness and numbness in his left arm and leg. He also had a 6-month history of right arm pain with overuse. Brain MRI showed acute brain infarcts in the right posterior cerebral artery territory. Intravenous alteplase was administered 188 minutes after onset. Although heparin infusion was commenced on day 2, he had vertigo again on day 9, and MRI showed a recurrent brain infarct in the right posterior inferior cerebellar artery territory. Ultrasound examination revealed occlusion of his right subclavian artery beneath the old right clavicular fracture as well as mobile thrombus in the proximal portion of the right subclavian artery. We speculated that a pseudarthrosis at the site of the old right clavicular fracture had repetitively pressed the right subclavian artery. Subsequently, we considered thrombi, which had developed in the proximal portion of the right subclavian artery, migrated into the right vertebral artery, causing recurrent emboli in the vertebrobasilar artery territory.

Background: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS 2 and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users., Conclusions: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

To prevent early neurological worsening or recurrence in stroke patients with intracranial arterial stenosis or branch atheromatous disease, aggressive antithrombotic therapy, such as dual antiplatelet therapy (DAPT) with or without anticoagulant therapy, is warranted. Such an aggressive antithrombotic therapy, however, may increase the bleeding risk. We studied the risks of DAPT with the anticoagulant argatroban in patients with acute ischemic stroke or transient ischemic attack (TIA). Between October 2011 and September 2015, 341 patients with stroke or TIA, who received DAPT with argatroban within 48 hours after onset, were retrospectively studied. The endpoint was any bleeding event during hospitalization or 30 days after admission. Median duration of DAPT was 12 days, and 66% of the patients received intravenous heparin (median duration, 5 days) following argatroban. No symptomatic intracerebral hemorrhages were observed, while severe, moderate, and mild extracranial hemorrhages occured in one (0.3%), three (0.9%), and four (1.2%) patients, respectively. In conclusion, DAPT with argatroban can be safely administered to patients with acute ischemic stroke or TIA. (Received July 24, 2017; Accepted January 15, 2018; Published May 1, 2018).

Background and purpose Neurological deterioration in acute penetrating artery territory infarction is unpredictable and associated with unfavorable clinical outcomes. The aim of this prospective study was to clarify the cause of neurological worsening and predict clinical outcomes using blood biomarkers. Methods Eight Japanese stroke centers participated. Blood samples were obtained within 24 h (the first sampling) and on day 7 in hospital (the second sampling) in patients with penetrating artery territory infarction, arriving within two days of stroke onset. Symptomatic worsening was defined as a minimum increase of one point on the National Institutes of Health Stroke Scale. Poor outcome was defined as a modified Rankin Scale score of ≥3 at 90 days after ictus. Results Of the 89 patients, 25 (28%) had symptomatic worsening, and 25 (28%) had a poor outcome. Although tumor necrosis factor-alpha, high-sensitivity C-reactive protein levels were significantly increased in both groups at the second sampling, soluble lectin-like oxidized low-density lipoprotein receptor-1, CD40 ligand, and pro-adrenomedullin levels were significantly increased and ADAMTS13 activity was decreased in symptomatic worsening patients ( p < 0.05 for all). After multivariate adjustment, a low number of CD34+ cells at the first sampling was an independent predictor of poor outcome (odds ratio, 0.20; 95% confidence interval, 0.04-0.74, p = 0.011, per 1 cell/µl increase). Conclusions Blood biomarkers associated with atherosclerotic processes seem to be an indication for symptomatic worsening, and the number of CD34+ cells may help to predict three-month functional outcome in patients with penetrating artery territory infarction.

Background: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry., Methods: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years., Results: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001; 1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p = 0.008; respectively) scores were independently associated with all outcome measures., Conclusions: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years., (© 2018 S. Karger AG, Basel.)

Background: This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke., Methods: We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days., Results: One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher -D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42-30.7, p = 0.015)., Conclusions: Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk., (© 2018 S. Karger AG, Basel.)