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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.)

Competing Interests: Disclosures None.

An 88-year-old woman with atrial fibrillation was admitted to our hospital due to the right hemiplegia and aphasia. MRA shows the left middle cerebral artery M2 occlusion. After intravenous rt-PA, her symptoms improved. She was diagnosed with cardioembolic stroke, and was treated with direct oral anticoagulation therapy. However, she had repeated stereotypical transient right hemiparesis a week after index stroke. Her symptoms were considered capsular warning syndrome (CWS). After cilostazol was administered, no further transient neurological deteriorations occurred. CWS can coexist with acute cardioembolic stroke, and cilostazol was effective.

Introduction: We investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan., Methods: This prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately., Results: The mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5-6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01-1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51-111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18-51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03-1.17), LVO (aOR: 14.88, 95%CI: 2.33-94.97), and log 10 D-dimer (aOR: 3.38, 95%CI: 1.01-11.26)., Conclusion: Upon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log 10 D-dimer., Registration: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226., (Copyright © 2023. Published by Elsevier B.V.)

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke., Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset., Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022., Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset., Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test., Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups., Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study., Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

Introduction: Soluble C-type lectin-like receptor 2 (sCLEC-2) is a new biomarker for platelet activation, which can be easily measured by usual blood collection. We conducted the CLECSTRO, a prospective, observational cohort study, to evaluate the clinical implications of sCLEC-2 in patients with acute ischaemic stroke (AIS) and transient ischaemic attack (TIA)., Methods and Analysis: The participants are patients with AIS/TIA and control patients required for differentiation from AIS/TIA. The target population is 600, including the patients and controls, who would be recruited from eight stroke centres across Japan. The inclusion criteria are AIS within 24 hours of onset and a modified Rankin Scale (mRS) score of 0-2, TIA within 7 days of onset, and contemporary patients required for differentiation from AIS/TIA. Plasma sCLEC-2 will be measured by high-sensitive chemiluminescent enzyme immunoassay using residual blood samples from routine laboratory examinations at the first visit in all patients and 7 days later or at discharge in patients with AIS/TIA. The outcomes include plasma levels of sCLEC-2 in patients with AIS/TIA and controls, sCLEC-2/D-dimer ratio in non-cardioembolic and cardioembolic AIS/TIA, correlation of sCLEC-2 with recurrence or worsening of stroke, severity of stroke, infarct size, ABCD 2 score in TIA and outcome (mRS) at 7 days and 3 months., Ethics and Dissemination: This study was approved by the Ethical Committee of the University of Yamanashi as the central ethical committee in agreement with the ethical committees of all collaborative stroke centres. Informed consent will be obtained by an opt-out form from the patients at each stroke centre according to the Ethical Guidelines for Medical and Biological Research Involving Human Subjects by the Japanese Ministry of Health, Labour and Welfare., Trial Registration Numbers: NCT05579405, UMIN000048954., Competing Interests: Competing interests: SU reports consultant fees from LSI Medience Corporation. KS-I has a patent related to the sCLEC-2 assay (JP-6078845). MK is an advisor of LSI Medience Corporation. HW and MK are inventors of a patent application related to sCLEC-2 measurement in AIS and TIA (JP application 2021-091606)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Pretreatment ischemic core volume is conceptually equal to follow-up infarct volume (FIV) in patients with successful recanalization. However, there is sometimes an absolute volume difference (AD) between pretreatment core volume and FIV. The aim was to compare the AD values between the Bayesian and the singular value decomposition (SVD) methods with time from onset-to-imaging in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy., Methods: Consecutive AIS patients were included if they had the following: (1) anterior large vessel occlusion (internal carotid or middle cerebral artery); (2) within 24 h of onset; (3) pretreatment CT perfusion (CTP); (4) successful recanalization (mTICI ≥ 2b); and (5) 24-h diffusion-weighted imaging (DWI). FIV was measured on 24-h DWI. The AD value between FIV and the pretreatment core volume was calculated for Bayesian and SVD methods. Spearman's rank correlation coefficient (rho) was calculated as appropriate., Results: In the 47 patients enrolled (25 men; median age 78 years; median baseline National Institutes of Health Stroke Scale, 22), the median time from onset-to-imaging and onset-to-recanalization was 136 and 220 min, respectively. Shorter onset-to-imaging time was correlated with a larger AD value, and more trend was seen in the SVD method (rho =  - 0.28, p = 0.05) compared with the Bayesian method (rho =  - 0.08). A larger pretreatment core volume was correlated with a larger AD value, and this tendency was slightly stronger for the SVD (rho = 0.63, p < 0.01) than for the Bayesian (rho = 0.32, p = 0.03) method., Conclusions: The Bayesian method might be more correlated with FIV than the SVD method in patients with a large ischemic lesion immediately after stroke onset, but not perfect., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown., Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26-52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose-response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete., Findings: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0-4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79-1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93-1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85-1·32]; t statistic -0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91-2·71])., Interpretation: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke., Funding: Bayer AG., Competing Interests: Declaration of interests All coauthors or their institutions received financial support from Bayer for participation in the PACIFIC-Stroke trial except HM, PC, BK, and CN who are employees of Bayer. HM, PC, BK, and CN do not hold any stock or stock options with Bayer., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Mechanical thrombectomy (MT) is effective in acute ischemic stroke patients ≥80 years old with large vessel occlusion (LVO). However, data for patients ≥90 years old remain very limited, and factors influencing functional outcomes are unclear. This study aimed to investigate factors influencing functional outcomes in patients ≥90 years old treated with MT for acute LVO., Methods: This retrospective observational study used prospectively collected data from the Tokyo/tama-REgistry of Acute endovascular Thrombectomy (TREAT) study. Inclusion criteria were as follows: 1) patients ≥90 years old treated with MT for LVO and 2) prestroke modified Rankin Scale (mRS) score, 0-3. The functional outcome was defined based on the mRS score at 90 days after the procedure: good functional outcome, mRS score 0-3 and poor functional outcome, mRS score 4-6., Results: Data were analyzed for 104 patients ≥90 years old. The good functional outcome was observed in 25 patients (24.0%), and the poor functional outcome was observed in the remaining 79 patients. Significant differences were identified in initial National Institutes of Health Stroke Scale (NIHSS) score, modified Thrombolysis in Cerebral Infarction grade 2b-3, modified Thrombolysis in Cerebral Infarction grade 3, and any intracranial hemorrhage and hemorrhagic infarction in univariate analyses. Multivariable analysis confirmed the initial NIHSS score (odds ratio, 1.08; 95% confidence interval, 1.01-1.17; P = 0.045) and any intracranial hemorrhage (odds ratio, 11.6; 95% confidence interval, 1.43-95.0; P = 0.022) as independent factors for the functional outcome., Conclusions: An initial high NIHSS score and any intracranial hemorrhage are independent factors for the poor functional outcome in acute ischemic stroke patients ≥90 years old treated with MT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to measure the impact of the COVID-19 pandemic on the volumes of annual stroke admissions compared with those before the pandemic in Japan. We conducted an observational, retrospective nationwide survey across 542 primary stroke centers in Japan. The annual admission volumes for acute stroke within 7 days from onset between 2019 as the pre-pandemic period and 2020 as the pandemic period were compared as a whole and separately by months during which the epidemic was serious and prefectures of high numbers of infected persons. The number of stroke patients declined from 182,660 in 2019 to 178,083 in 2020, with a reduction rate of 2.51% (95% confidence interval [CI], 2.58%-2.44%). The reduction rates were 1.92% (95% CI, 1.85%-2.00%; 127,979-125,522) for ischemic stroke, 3.88% (95% CI, 3.70%-4.07%, 41,906-40,278) for intracerebral hemorrhage, and 4.58% (95% CI, 4.23%-4.95%; 13,020-12,424) for subarachnoid hemorrhage. The admission volume declined by 5.60% (95% CI, 5.46%-5.74%) during the 7 months of 2020 when the epidemic was serious, whereas it increased in the remaining 5 months (2.01%; 95% CI, 1.91%-2.11%). The annual decline in the admission volume was predominant in the five prefectures with the largest numbers of infected people per million population (4.72%; 95% CI, 4.53%-4.92%). In conclusion, the acute stroke admission volume declined by 2.51% in 2020 relative to 2019 in Japan, especially during the months of high infection, and in highly infected prefectures. Overwhelmed healthcare systems and infection control practices may have been associated with the decline in the stroke admission volume during the COVID-19 pandemic.

Background: The present observational study aimed to clarify the association between bridging therapy with heparin before starting rivaroxaban and clinical outcomes after ischemic stroke or transient ischemic attack (TIA) in patients with non-valvular atrial fibrillation (NVAF)., Methods and results: Patients with NVAF who experienced acute ischemic stroke or TIA of the middle cerebral artery territory and started rivaroxaban within 30 days after onset were enrolled and were followed up for 90 days. Outcome measures were ischemic events, major bleeding, their composite, and death or disability 90 days after onset. Ischemic events were defined as ischemic stroke, TIA, and systemic embolism. Of 1,308 analyzed patients, 638 received bridging therapy with unfractionated or low-molecular-weight heparin with a median of 10,000 IU/day. Associations between bridging therapy and ischemic events or major bleeding were not statistically significant individually, but the association between bridging therapy and their composite was statistically significant (multivariable-adjusted hazard ratio, 1.80; 95% confidence interval, 1.01-3.29). The association between bridging therapy and death or disability 90 days after onset was not statistically significant., Conclusions: The composite of ischemic events and major bleeding was more frequent in patients with NVAF who received bridging therapy with low-dose heparin than in those who started treatment directly with rivaroxaban after ischemic stroke or TIA.

Background: The optimal timing of initiating oral anticoagulants after reperfusion therapy for ischemic stroke is unknown. Factors related to early initiation of rivaroxaban and differences in clinical outcomes of stroke patients with nonvalvular atrial fibrillation (NVAF) who underwent reperfusion therapy was investigated., Methods: From data of 1,333 NVAF patients with ischemic stroke or transient ischemic attack (TIA) in a prospective multicenter study, patients who started rivaroxaban after intravenous thrombolysis and/or mechanical thrombectomy were included. The clinical outcomes included the composite of ischemic events (recurrent ischemic stroke, TIA, or systemic embolism) and major bleeding at 3 months., Results: Among the 424 patients, the median time from index stroke to starting rivaroxaban was 3.2 days. On multivariable logistic regression analysis, infarct size (odds ratio [OR], 0.99; 95%CI, 0.99-1.00) was inversely and successful reperfusion (OR, 2.13; 95%CI, 1.24-3.72) was positively associated with initiation of rivaroxaban within 72 hours. 205 patients were assigned to the early group (< 72 hours) and 219 patients (≥ 72 hours) to the late group. Multivariable Cox regression models showed comparable hazard ratios between the two groups at 3 months for ischemic events (hazard ratio [HR], 0.18; 95%CI, 0.03-1.32) and major bleeding (HR, 1.80; 95%CI, 0.24-13.54)., Conclusions: Infarct size and results of reperfusion therapy were associated with the timing of starting rivaroxaban. There were no significant differences in the rates of ischemic events and major bleeding between patients after reperfusion therapy who started rivaroxaban < 72 hours and ≥ 72 hours after the index stroke., Clinical Trial Registration: Unique identifier: NCT02129920; URL: https://www.clinicaltrials.gov., Competing Interests: I have read the journal’s policy and have the following conflicts. Dr. Koge reports no disclosures. Dr. Yamagami reports research grants from Bristol-Myers Squibb, Terumo, JIMRO, and Striker; lecturer’s fees from Stryker, Terumo, Medtronic, Medico’s Hirata, Johnson and Johnson, Bayer, Daiichi-Sankyo, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, and Otsuka Pharmaceutical; and membership of the advisory boards for Daiichi-Sankyo and Biomedical Solutions. Dr. Toyoda reports lecturer’s fees from Daiichi Sankyo, Boehringer Ingelheim, Bayer, and Bristol-Myers Squibb. Dr. Yasaka reports lecturer’s fees from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb and CSL Behring. Dr. Hirano reports lecturer’s fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, and Medtronic. Dr. Hamasaki reports no disclosures. Dr. Nagao reports lecturer’s fee from Bayer Yakuhin. Dr. Yoshimura reports lecture fees from Boehringer, Ingelheim, Bayer, Daiichi-Sankyo, Phizer, BMS, Takeda, Sanofi, Otsuka, Tanabe-Mitsubishi, Medtronic, Stryker, and Medico’s Hirata and research support from BMS and Takeda. Dr. Fujishige reports no disclosures. Dr. Tempaku reports no disclosures. Dr. Uchiyama reports honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, AstraZeneka, and Takeda. Dr. Mori reports lecture fees from Johnson & Johnson, Otsuka, Novartis, Daiichi-Sankyo, Sumitomo Dainippon Pharma, Sosei, Kyowahakko-Kirin, Toshiba, Medtronic, and Nihon Medi-Physics and research support from Eisai, Daiichi-Sankyo, Novartis, Fuji Film RI, General Electric, MHWL, MEXT, and JSPS. Dr. Koga reports honoraria from Bayer Yakuhin, Bristol-Myers-Squibb, Otsuka, Daiichi-Sankyo, Nippon Boehringer Ingelheim and Takeda, scientific advisory board from Ono, and research supports from Takeda, Daiichi-Sankyo, Nippon Boehringer Ingelheim, Astellas, Pfizer and Shionogi, outside the submitted work. Dr. Minematsu reports honoraria from Bayer Yakuhin, Otsuka Pharmaceutical, Behringer Ingelheim, AstraZeneca, Pfizer, Mitsubishi Tanabe Pharma Corporation, Japan Stryker, Dai-ichi Sankyo, Astellas Pharma, Nippon Chemiphar, Fuji Film RI Pharma, MSD, Kyowa Hakko Kirin, Sanofi, advisory board from CSL Behring, Bayer Yakuhin, EPS, Corporation, HEALIOS K.K., T-PEC Corporation and BMS. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background The aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents. Methods and Results Patients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0-4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m 2 ), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11-2.39) at category G4 (eGFR 15-<30 mL/min per 1.73 m 2 ) and 2.05 (95% CI, 1.33-3.16) at G5 (eGFR <15 mL/min per 1.73 m 2 ). Corresponding odds ratios relative to urinary albumin-to-creatinine ratio (ACR) category A1 (ACR <30 mg/g) were 1.29 (95% CI, 1.12-1.49) for category A2 (ACR 30-<300 mg/g) and 1.37 (95% CI, 1.05-1.77) for A3 (ACR ≥300 mg/g). When combined eGFR and ACR categories were assessed, risks for SVD score increment generally increased as eGFR decreased and ACR increased. Conclusions Both reduced eGFR and albuminuria were independently associated with increased cerebral SVD burden in patients requiring oral antithrombotic medication mainly for secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502; URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023669.

Purpose: To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke., Methods: This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months., Results: A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5-8.48) and in the ADAPT group it was 1.35 (0.37-4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37-0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups., Conclusion: In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: An association has been reported between delays in the onset-to-door (O2D) time for mechanical thrombectomy (MT) and outbreaks of coronavirus disease 2019 (COVID-19). However, the association between other MT time courses or functional outcomes and COVID-19 outbreaks remains unclear. We compared the time courses of stroke pathways or functional outcomes in 2020 (the COVID-19 era) with those in 2019 (the pre-COVID-19 era) in Tokyo, Japan., Materials and Methods: This retrospective observational study used data from the Tokyo-tama-REgistry of Acute endovascular Thrombectomy (TREAT), a multicenter registry of MT for acute large vessel occlusion in the Tokyo Metropolitan Area. Patients who had undergone acute MT from January 2019 to December 2020 were included. Patients were classified by the year they had undergone MT (2019 or 2020)., Results: In total, 477 patients were analyzed. O2D time was significantly longer in 2020 (146.0 min) than in 2019 (105.0 min; p = 0.034). No significant difference in door-to-puncture time (D2P) time or modified Rankin Scale (mRS) score 0-2 at 90 days was seen between 2019 and 2020. In the subgroup analysis, O2D time was significantly longer in the first half of 2020 compared with 2019. Multivariable logistic regression analysis revealed that the year 2020 was a independent predictor of longer O2D time, but not for mRS score 0-2 at 90 days., Conclusions: Although O2D time was significantly longer in the COVID-19 compared with the pre-COVID-19 era, D2P may not be significantly delayed and functional outcomes may not be different, despite the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest Yoshiaki Shiokawa has received research grants from AbbVie GK and ONO Pharmaceitocal CO., LTD. Teruyuki Hirano has received honoraria from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Otsuka Pharma, Pfizer, and Sanofi. All the other authors have nothing to disclosure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A 51-year-old man with a history of renal cell carcinoma presented with sudden aphasia, right hemiparesis, and dysesthesia. MRA showed left middle cerebral artery occlusion, and he was diagnosed with acute ischemic stroke and treated with intravenous recombinant tissue plasminogen activator and endovascular thrombectomy. The pathological diagnosis of the retrieved thrombus was consistent with the already-known pathological findings of the primary renal cell carcinoma. Therefore, a diagnosis of cerebral embolism caused by tumor cells was made. The pathological findings of the retrieved thrombi were important in determining the cause of ischemic stroke.

Decreased cell-mediated immunity can reactivate Varicella zoster virus (VZV), which can lead to various neurological complications, including vasculopathy. We herein report the case of a patient with acute stroke with progressive internal carotid artery stenosis due to VZV vasculopathy after chemotherapy for malignant lymphoma. Treatment for VZV vasculopathy improved the stenosis and prevented recurrent stroke. VZV vasculopathy is an important treatable cause of stroke in immunosuppressed patients.

Background and Purpose: Delays in recognition and assessment of in-hospital strokes (IHS) can lead to poor outcomes. The aim was to examine whether reorganized IHS code protocol can reduce treatment time., Methods: IHS code protocol was developed, educational workshops were held for medical personnel. In the protocol, any medical personnel should directly consult a stroke neurologist before any diagnostic studies. Time intervals were compared between the pre- and post-implementation periods and between direct consultation with a stroke neurologist (DC group) and non-DC group in the post-implementation period., Results: A total of 145 patients were included (pre, 42; post, 103). Time from recognition to stroke neurologist assessment (91 vs. 35 min, p = 0.002) and time from recognition to neuroimaging (123 vs. 74, p = 0.013) were significantly lower in the post-implementation period. Time from stroke neurologist assessment to groin puncture was significantly lower (135 vs. 81, p = 0.037). In the post-implementation period, DC group showed significant time savings from last known well (LKW) to recognition (93 vs. 260, p = 0.001), LKW to stroke neurologist assessment (145 vs. 378, p = 0.001), and recognition to stroke neurologist assessment (16 vs. 76, p < 0.001) compared with non-DC group., Conclusions: Reorganization of IHS code protocol reduced time from stroke recognition to assessment and treatment time. Reorganized IHS code and direct consultation with a stroke neurologist improved the initial response time., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The perfect defense from SARS-CoV-2 infection prioritizes triaging acute stroke patients during the COVID-19 pandemic. In April 2020, the Japan Stroke Society (JSS) urgently announced a protected code stroke (PCS), JSS-PCS, informing all medical staff of the essential requirements. Patients under investigation should be accepted under PCS. The points of the proposed PCS are (1) wearing reliable PPE, (2) putting of surgical mask on the patient, and (3) response with the minimum required number of personnel. It is strongly recommended to prepare individualized protocols for PCS in each stroke center.

Background and Purpose: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic., Methods: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center., Conclusion: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We herein reported a patient with acute ischemic stroke in the bilateral medial medullary and the left tegmentum of the pons who presented with various neurological symptoms. Fusing digital subtraction angiography (DSA) and MRI (DSA-MR fusion imaging) could reveal the infarct-relevant arteries. A 41-year-old male presented with headache, bilateral arm's dysesthesia, quadriplegia, left Horner's syndrome, upbeat nystagmus, internuclear ophthalmoplegia and left peripheral facial paralysis. Diffusion weighted MRI (DWI) revealed the high intensity lesion in the bilateral medial medullary and the left tegmentum of the pons. MRA showed right vertebral artery (VA) occlusion. A high intensity on T 1 weighted imaging was shown on the right VA vessel wall. DSA-MR fusion imaging revealed the anterior spinal artery (ASA) occlusion proximal to the infarction. The stenosis was located at the origin of the right VA perforating branch distributing into the infarct lesion. The steno-occlusive lesion of ASA and VA perforating branch due to VA dissection resulted in infarction in the pontomedullary junction and caused various neurological symptoms. DSA-MR fusion imaging would prove the radiological anatomy of infarct-relevant arteries and clarify the etiology of ischemic stroke.

Objective: It is not clear how patients with large vessel occlusion (LVO) who have undergone mechanical thrombectomy (MT) were transported to hospitals by emergency medical services. Here, we describe the current status of the stroke delivery system in a large city., Methods: We investigated data from 328 patients (male, n = 199; average age, 74.8 ± 12.9 years) who underwent MT at 12 facilities in the Tama area of Tokyo, between January 2015 and December 2017. The patients were classified according to the destination institution as Stroke A eligible (group A, n = 266 [8.2%]), Tertiary critical care center (group T; n = 35 [10.7%]), and other destinations such as emergency rooms (group O; n = 27 [8.2%]), and then reasons for using Emergency Medical Service (EMS) services and outcomes were compared among the groups., Results: Rates of milder stroke, and middle cerebral artery occlusion were significantly higher in group A than T, whereas that of vertebral-basilar artery occlusion was significantly lower in group A than in groups T and O. The amount of elapsed time from door to picture (DTP) was significantly lower in group A. The time from onset to recanalization, as well as rates of successful recanalization and favorable outcomes (90-day modified Rankin scale 0-2) did not significantly differ regardless of destination., Conclusions: Most patients with LVO in the Tama area were categorized into group A. DTP was significantly lower in group A., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics., Conclusions: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Rationale: Bridging therapy with endovascular therapy (EVT) and intravenous thrombolysis (IVT) has been reported to improve outcomes for acute stroke patients with large-vessel occlusion in the anterior circulation. While the IVT may increase the reperfusion rate, the risk of hemorrhagic complications increases. Whether EVT without IVT (direct EVT) is equally effective as bridging therapy in acute stroke remains unclear., Aim: This randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator for acute stroke with ICA and M1 occlusion aims to clarify the efficacy and safety of direct EVT compared with bridging therapy., Methods and Design: This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-endpoint clinical trial. The target patient number is 200, comprising 100 patients receiving direct EVT and 100 receiving bridging therapy., Study Outcome: The primary efficacy endpoint is a modified Rankin Scale score of 0-2 at 90 days. Safety outcome measures are any intracranial hemorrhage at 24 h., Discussion: This trial may help determine whether direct EVT should be recommended as a routine clinical strategy for ischemic stroke patients within 4.5 h from onset. Direct EVT would then become the choice of therapy in stroke centers with endovascular facilities., Trial Registration: UMIN000021488.

Thrombectomy has demonstrated clinical efficacy against acute ischemic stroke caused by intracranial occlusion of the internal carotid artery (ICA), even if performed 6-24 h after onset. This study investigated the outcomes of thrombectomy performed 6-24 h after stroke onset caused by extracranial ICA occlusion. Of 586 stroke patients receiving thrombectomy during the past 3 years and registered in the Tama Registry of Acute Endovascular Thrombectomy database, 24 were identified with ICA occlusion (14 extracranial and 10 intracranial), known to be well 6-24 h before presentation, and with pre-stroke modified Rankin Scale (mRS) score of 0 or 1. Clinical outcomes measured were the rate of functional independence at 90 days according to mRS score of 0-2 and 90 day mortality rate. Of patients with extracranial ICA occlusion, two received additional carotid stenting with thrombectomy. The median interval between the last time the patient was known to be well and hospital arrival was 601 (interquartile range, 476-729 min). Both the rate of functional independence at 90 days and 90 day mortality were comparable between patients with extracranial or intracranial ICA occlusion (36% vs. 40% and 7% vs. 10%, respectively). No symptomatic intracranial hemorrhages occurred within 24 h following treatment of extracranial ICA occlusion. Thrombectomy performed 6-24 h after extracranial ICA results in acceptable functional outcome. Further clinical study is warranted to better define the temporal window of thrombectomy for acceptable functional outcome in patients with extracranial ICA occlusion.

Background: The Tama-REgistry of Acute endovascular Thrombectomy (TREAT) is a multicenter registry of endovascular thrombectomy in the Tama area of Tokyo. The objective of this study was to confirm the real-world status of 2 paradigms of transportation., Methods: This was a retrospective analysis of data from TREAT. Patients were divided into 2 groups and 2 periods: directly admitted to an endovascular thrombectomy-capable center (ECC; group D)/secondary transfer from a non-ECC (group S), and the first period/the second period. Transfer distance, workflow metrics, and clinical outcomes were analyzed., Results: A total of 326 patients, including 264 in group D and 62 in group S, were analyzed. The median distance from the onset-to-ECC was 3.62km for group D and 7.87km for group S (P < .001). The median onset-to-needle (OTN) time was longer for group S (168 minutes) than group D (138 minutes; P = .006). The median onset-to-reperfusion (OTR) time was significantly shorter for group D (247 minutes) than for group S (304 minutes; P = .029). With respect to the 2 periods, there was no significant difference in onset-to-puncture time between the 2 groups in the first period (207 minutes versus 243.5 minutes, respectively, P = .50), while there was one in the second period (164 minutes versus 246.5 minutes, respectively, P = .02)., Conclusions: This region-wide registry study showed longer OTN and OTR times, with no improvement of the time course over time in patients transported via non-ECCs. These results should be used to create a regional medical policy for the management of acute ischemic stroke., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The efficacy of early anticoagulation in acute stroke with nonvalvular atrial fibrillation (NVAF) remains unclear. We performed a study to evaluate the risk of recurrent ischemic stroke (IS) and major bleeding in acute IS patients with NVAF who started rivaroxaban. This observational study evaluated patients with NVAF and acute IS/transient ischemic attack (TIA) in the middle cerebral arterial territory who started rivaroxaban within 30 days after the index IS/TIA. The primary endpoints were recurrent IS and major bleeding within 90 days after the index IS/TIA. The relationship between the endpoints and the time to start rivaroxaban was evaluated by correlation analysis using cerebral infarct volume, determined by diffusion-weighted magnetic resonance images within 48 hours of onset of the index IS/TIA. Of 1309 patients analyzed, recurrent IS occurred in 30 (2.3%) and major bleeding in 11 (0.8%) patients. Among patients with known infarct size (N = 1207), those with small (<4.0 cm3), medium (≥4.0 and <22.5 cm3), and large (≥22.5 cm3) infarcts started rivaroxaban a median of 2.9, 2.9, and 5.8 days, respectively, after the index IS/TIA. Recurrent IS was significantly less frequent when starting rivaroxaban ≤14 days versus ≥15 days after IS (2.0% versus 6.8%, P = 0.0034). Incidences of recurrent IS and major bleeding in whom rivaroxaban was started <3 days (N = 584) after IS were also low: 1.5% and 0.7%, respectively. Initiation of rivaroxaban administration in acute IS or TIA was associated with a low recurrence of IS (2.3%), and a low incidence of major bleeding events (0.8%) for 90 days after the index stroke. For the prevention of recurrent attacks in acute IS patients with NVAF, it is feasible to start the administration of rivaroxaban within 14 days of onset. Rivaroxaban started within 3 days of onset may be a feasible treatment option for patients with a small or medium-sized infarction., Competing Interests: I have read the journal's policy and have the following conflicts. Yasaka M received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sumitomo-Dainippon, Sanofi, Otsuka, CSL Behring, Ezai, Tanabe-Mitsubishi, Medtronic, Boston Scientific, and Sekisui Medical and research support from Sanofi, Boehringer Ingelheim, and Daiichi-Sankyo. Minematsu K received lecture fees from Bayer Healthcare, Otsuka Pharmaceutical, Boehringer-Ingelheim, AstraZeneca, Pfizer, Mitsubishi Tanabe Pharma Cooperation, Japan Stryker, Kowa, Nihon Medi-Physics Co, BMS, Sawai Pharmaceutical Co., Sumitomo Dainippon Pharma Co Ltd, Medico’s Hirata, Daiichi Sankyo, Astellas Pharma, Kyowa Hakko Kirin Pharma, Inc, Sanofi, MSD, Eisai Co., Nippon Chemiphar, and Towa Pharmaceutical Co. Toyoda K received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sumitomo-Dainippon, Sanofi, Otsuka, CSL Behring, Tanabe-Mitsubishi, and Kyowa-Kirin and research support from Bayer, Daiichi-Sankyo, Pfizer, Takeda, and Japan Agency for Medical Research and Development (AMED: 17ek0210091h0001, 15ek0210055h0001). Mori E received lecture fees from Johnson & Johnson, Otsuka, Novartis, Daiichi-Sankyo, Sumitomo Dainippon Pharma, Sosei, Kyowahakko-Kirin, Toshiba, Medtronic, and Nihon Medi-Physics and research support from Eisai, Daiichi-Sankyo, Novartis, Fuji Film RI, General Electric, MHWL, MEXT, and JSPS. Hirano T received lecture fees from Astellas, Bayer, Boehringer Ingelheim, BMS, CSL Behring, Daiichi-Sankyo, Eisai, Medtronic, Otsuka, Pfizer, Sumitomo-Dainippon, Sanofi, Takeda, and Tanabe-Mitsubishi and research support from Astellas, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eisai, MSD, Otsuka, Tanabe-Mitsubishi, and JSPS KAKENHI (Grant Number 25461320, PI, 2014-2016; Grant Number 16K09731, PI, 2016-2017). Hamasaki T received lecture fees from Johnson & Johnson and research support from Teikoku Pharmaceuticals. Yamagami H received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sanofi, Otsuka, Tanabe-Mitsubishi, Medtronic, Striker, and Medico’s Hirata and research support from Boehringer Ingelheim and BMS. Nagao T received lecture fees from Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi, Sankyo, Sumitomo Dainippon, Eisai, FP, Kyowa Hakko Kirin, Medtronic, Mochida, Nippon Boehringer Ingelheim, Novartis, Otsuka, Pfizer, Sanofi, Takeda, and Mitsubishi Tanabe. Yoshimura S received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Pfizer, BMS, Takeda, Sanofi, Otsuka, Tanabe-Mitsubishi, Medtronic, Stryker, and Medico’s Hirata and research support from BMS and Takeda. Uchiyama S received lecture fees from Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Takeda, Sumitomo Dainippon, Sanofi, Otsuka, Mitsubishi Tanabe, AstraZeneca, Shionogi, and Astellas Amgen and research support from the Japan Cardiovascular Research Foundation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Anticoagulation therapy, particularly subcutaneous heparin therapy, is recommended for cancer-associated thrombosis. However, not starting or discontinuing anticoagulation was not rare. The aim of the present study was to examine the practical issues related to anticoagulation therapy and effects of subcutaneous heparin therapy for cancer-associated stroke., Methods: Patients with cancer-associated stroke in our stroke center between October 2014 and August 2017 who were diagnosed as having acute ischemic stroke based on diffusion-weighted imaging were retrospectively enrolled. Baseline clinical characteristics, heparin injection, reasons for no subcutaneous heparin therapy, and clinical outcomes were collected., Results: A total of 59 patients with cancer-associated stroke (75 ± 10 years old, male 42%) were enrolled. Lung cancer was the most frequently observed cancer (n = 17, 29%), followed by gastric cancer (n = 8, 14%) and pancreatic cancer (n = 8, 14%). Of the 19 patients (32%) who underwent subcutaneous heparin therapy, it was discontinued in 9 (47%), mainly because of patients' medical conditions (deterioration of cancer or hemorrhagic complication). Ten patients with long-term subcutaneous heparin therapy did not have stroke recurrence. In contrast, among nine patients who discontinued subcutaneous heparin therapy, three (33%) had recurrence of ischemic stroke. Of the 40 patients without subcutaneous heparin therapy, the main reasons for no subcutaneous heparin therapy were the patients' medical conditions (n = 22, 55%)., Conclusions: Although subcutaneous heparin therapy was given to only one third of cancer-associated stroke patients, long-term subcutaneous heparin therapy might prevent recurrence of cancer-associated stroke., (Copyright © 2018. Published by Elsevier Inc.)

Background and Purpose: To improve results of acute thrombectomy, the time from stroke onset to efficient recanalization must be minimized. Studies have confirmed the importance of rapid treatment, workflow, and efficient team-based care for acute thrombectomy in large vessel occlusion. This study examined the challenges facing mechanical thrombectomy in the Tama area (population, 4.3 million), a densely populated urban area of Tokyo, Japan, and analyzed retrospective data from the Tama-REgistry of Acute endovascular Thrombectomy., Methods: This study was a retrospective observational study using data from Tama-REgistry of Acute endovascular Thrombectomy, a multicenter registry of mechanical thrombectomy for acute ischemic stroke in the Tama area of Tokyo. The survey covered 396 patients with large vessel occlusion who underwent acute thrombectomy between January 2015 and March 2017. Participating facilities are 12 of the 13 recanalization therapy-capable stroke centers., Results: We analyzed 326 cases for which modified Rankin Scale score at 90days was available, of which 264 cases were directly admitted, and 62 cases were transferred from other stroke centers. Median time from stroke onset to hospital arrival was 111 minutes, and from arrival to efficient recanalization was 135 minutes. Efficient recanalization was achieved in 257 cases (78.8%), symptomatic hemorrhage developed in 19 cases (5.8%), and modified Rankin Scale 0-2 at 90days was seen in 129 cases (39.6%). The vast majority of patients (n = 299, 94.3%) were transferred within 10km to the enrolling hospital., Conclusions: These results provide useful information about the emergent transfer system for patients with large vessel occlusion in a densely populated urban area., (Copyright © 2018. Published by Elsevier Inc.)

A 80-years-old woman suddenly presented with aphasia, right hemiparesis, and dysesthesia. MRA showed the left middle cerebral artery occlusion. She was diagnosed as hyperacute ischemic stroke. She was treated with intravenous recombinant tissue plasminogen activator and underwent endovascular thrombectomy. On admission, she had a fever and high C reactive protein, and was treated with antibiotic therapy. The pathological diagnosis of the retrieved thrombus revealed the cluster of the gram positive cocci. The blood culture was negative and thransthoracic echocardiogram did not detect the vegetation. She was finally diagnosed as cardioembolic stroke due to infective endocarditis based on the pathological diagnosis of the retrieved thrombus. The pathological diagnosis of the retrieved thrombus was quite important to clarify the cause of ischemic stroke.

Background: Mechanical thrombectomy (MT) has become the standard of care for acute ischemic stroke with large vessel occlusion; however, evidence remains insufficient for MT for elderly patients, especially with respect to factors affecting their outcomes., Methods: This study was a retrospective analysis of a multicenter registry of MT, called Tama Registry of Acute Endovascular Thrombectomy. Patients were divided by their age into 2 groups: Nonelderly (NE; < 80) and elderly (E; ≥80). Factors related to a good outcome (modified Rankin scale score ≤2) were examined in each group. Onset to reperfusion time (OTR) was stratified into 4 categories: category 1, 0 - ≤180 min; category 2, > 180 - ≤360 min; category 3, > 360 min or onset time not identified; and category 4, effective recanalization not achievable., Results: 143 NE patients and 78 E patients were included in this study. The E group had less chance of achieving a good outcome (NE group 51%, E group 35%; p = 0.024). In the NE group, lower OTR category was an independent prognostic factor for good outcome (p = 0.037, OR = 1.09). However, in the E group, OTR category was not a significant predictor on multivariate analysis. Instead, effective recanalization (p = 0.0081, OR 1.40) and lower National Institute of Health Stroke Scale score at presentation (p = 0.0032, OR 1.02) were the independent predictors., Conclusions: In MT for elderly patients, effective recanalization improved the patients' outcome but OTR affected less. Further studies are warranted to establish the appropriate patient selection and treatment strategies., (© 2018 S. Karger AG, Basel.)

Background: The functional independence measure (FIM) is a standard tool to provide a detailed evaluation of ADL of patients with disabilities. This study aimed to show the differences in FIM scores as an outcome predictor between patients with anterior circulation (AC) and posterior circulation (PC) strokes., Methods: Consecutive patients with acute ischemic stroke hospitalized within 7 days after onset were investigated. Baseline NIHSS scores, 1st-FIM (< 72 h after -admission to stroke unit), 2nd-FIM (< 72 h before discharge), and modified Rankin Scale (mRS) scores were collected. Logistic regression analyses were used to identify predictors of a favorable outcome (mRS 0-2) at 3-month after stroke., Results: Three hundred eighty-five patients (median age, 78 years; male, 59%; median length of stroke unit stay, 20 days) were included. The median baseline NIHSS, 1st- and 2nd-FIM scores were 4 (interquartile range 2-9), 65 (33-91), and 98 (54-122) respectively. Baseline NIHSS (3 vs. 4, p = 0.01) and mRS score at 3-month (1 vs. 2, p = 0.01) were lower, and 1st-FIM (75 vs. 64, p < 0.01) and 2nd-FIM (113 vs. 95, p = 0.01) were higher in 82 patients with PC than 303 patients with AC strokes. On multivariate logistic regression analysis, 2nd-FIM score was an independent predictor of favorable outcomes in both PC (OR 1.18, 95% CI 1.04-1.48, p < 0.01) and AC (OR 1.12, 95% CI 1.06-1.20, p < 0.01) strokes. The optimal cutoff scores of 2nd-FIM for predicting favorable outcome were 104 for PC (sensitivity 0.82, specificity 0.88) and 93 for AC (0.88-0.90) strokes., Conclusions: The differences in outcome predictability by FIM score between AC and PC strokes should be considered, although FIM scores at discharge from stroke unit were useful to predict a favorable outcome., (© 2019 S. Karger AG, Basel.)

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with increasing prevalence in Japan. Although prothrombin time-international normalized ratio (PT-INR) targets for monitoring warfarin therapy in patients with nonvalvular AF (NVAF) are well defined, real-world patient characteristics and PT-INR levels remain unknown among Japanese patients with NVAF who initiate and continue warfarin (warfarin maintainers) versus those who switch from warfarin to direct oral anticoagulants (DOACs; warfarin switchers)., Methods: Patients with NVAF receiving oral anticoagulants between February 2013 and June 2015 were identified using a nationwide electronic medical record (EMR) database from 69 hospitals in Japan. Demographics and characteristics of patients, PT-INR, time in therapeutic range (TTR), and frequency in range (FIR) of PT-INR between warfarin maintainers and warfarin switchers were assessed., Results: A total of 1705 patients met inclusion criteria and were examined (1501 warfarin maintainers versus 204 warfarin switchers). CHADS 2 , CHA 2 DS 2 -VASc, and HAS-BLED scores were comparable between groups. However, these scores were significantly higher among warfarin switchers at the time of switching than at the time of warfarin initiation. Furthermore, TTR and FIR of PT-INR were lower in warfarin switchers than in maintainers. Nevertheless, TTR and FIR were below 50% (PT-INR, 1.6-2.6) in both patient groups., Conclusions: In this EMR-based clinical study, patients who switched to DOACs had both poor or inadequate PT-INR control and higher risk factors of stroke. Many patients receiving warfarin did not achieve sufficient PT-INR therapeutic range. DOACs could be recommended in Japanese patients with NVAF with inadequate PT-INR control and increased risk of stroke., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Outcome of acute stroke patients with embolic large vessel occlusion can be improved dramatically, if the effective and rapid reperfusion of the occluded vessel achieved. Since 2015, when the evidence of acute endovascular therapy established its efficacy, such scenario became no longer uncommon. Along with introduction of direct oral anticoagulant (DOAC), many options of antithrombotic therapy for acute ischemic stroke also became available. This review summarize the recent advances on acute ischemic stroke therapy.

Endovascular recanalization for acute major cerebral artery occlusion is effective within a short time after symptom onset. However, its efficacy in the elderly remains unknown. We assessed the efficacy of our comprehensive stroke center's reduction of this time in 28 consecutive patients for elderly patients (defined as patients aged ≥75 years) with acute major cerebral artery occlusion treated with intravenous injection of tissue plasminogen activator, followed by thrombus retrieval by endovascular therapy. The patients were divided into groups according to whether they were treated before implementation of the time reduction measure (from January 2012 to May 2014) or after (from June 2014 to May 2015). The onset-to-door, onset-to-needle, onset-to-recanalization (O2R), door-to-image (D2I), door-to-needle (D2N), door-to-puncture (D2P), door-to-recanalization (D2R), and puncture-to-recanalization time intervals were compared between the two groups. There were 14 patients (including 8 elderly patients ≥80 years) before and 14 patients (including 10 elderly patients ≥80 years) after the time reduction measure. The mean duration of each of the following time intervals was significantly reduced after the time reduction measure (P < 0.05). To reduce the O2R time, the D2P time is the first time interval that can be reduced. At our center, conferences were regularly held to raise awareness among staff and make specific changes in the workflow, and overall time reduction was achieved. Similar results were obtained in elderly patients.

Background and Aim: A new insertable cardiac monitor, Reveal LINQ (Medtronic, Dublin, Ireland), was approved for clinical use in Japan in March 2016 for detecting atrial fibrillation in patients who develop ischemic stroke with no clearly definable etiology even after extensive workup, so-called cryptogenic ischemic stroke. Cooperation between a specialist of the Japan Stroke Society and a trained cardiologist or cardiac surgeon is needed both for appropriate patient selection and appropriate management of the device. In this paper, the clinical significance of and diagnostic methods for cryptogenic stroke and covert atrial fibrillation are explained, along with our proposal for the clinical indications for this new device., Methods, Results, and Conclusion: The majority of cryptogenic ischemic strokes are considered to be embolic. In particular, covert atrial fibrillation is drawing attention as the causal emboligenic disease, and it was identified in 30% of patients with long-term observation using an insertable cardiac monitor. Should atrial fibrillation be present, there is a high risk of recurrent stroke, and the cardioembolic stroke that appears is generally severe. The ability to identify atrial fibrillation would be beneficial for preventing stroke recurrence, as anticoagulants can then be used as an established method of secondary prevention. Because the use of insertable cardiac monitors is somewhat invasive, and long-term care systems are also needed, patients suitable for examination using the new device would need to be identified on the basis of detailed diagnostics in accordance withcurrent medical practice in Japan., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: In the acute phase of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF), the recurrence rate is high. Nonvitamin K antagonist oral anticoagulants may be appropriate for prevention of early recurrence because they have a much lower risk of hemorrhagic stroke than warfarin., Methods: RELAXED (Recurrent Embolism Lessened by rivaroxaban, an Anti-Xa agent, of Early Dosing for acute ischemic stroke and transient ischemic attack with atrial fibrillation) study is an observational study designed to investigate the optimal timing to start administration of rivaroxaban for prevention of recurrence in NVAF patients in the acute phase of cardioembolic stroke (ClinicalTrials.gov: NCT02129920 and UMIN-clinical trials registry: UMIN000013932). It will evaluate the efficacy and safety of rivaroxaban with regard to infarct size, timing of initiation of rivaroxaban medication, and other patient characteristics. A total of 2000 consecutive patients with acute ischemic stroke in the territory of the middle cerebral artery and NVAF will be enrolled in 100 institutes throughout Japan, and they will receive rivaroxaban within 30 days of the index stroke for secondary prevention of stroke. The infarct size within 48 hours after stroke onset will be measured by diffusion-weighted magnetic resonance imaging. The primary efficacy endpoint is recurrent ischemic stroke, and the primary safety endpoint is major bleeding during the observational period of 3 months after stroke onset. The optimal timing to start treatment with rivaroxaban during the acute stage of ischemic stroke will be determined by analysis of the correlation between primary endpoints and the size of cerebral infarct., Conclusions: The RELAXED observational registry study will elucidate the optimal timing of the initiation of rivaroxaban in acute cardioembolic stroke associated with NVAF., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

"Dystypia", characterized by an impairment of typing on a keyboard, is a unique neurobehavioral syndrome. A 77-year-old right-handed woman developed a relatively selective impairment of typing after ischemic stroke. The MRI documented new scattered ischemic lesions in the middle cerebral artery territory of the left hemisphere and an old infarct lesion in the frontal area of the right hemisphere. The standard neuropsychological tests showed no aphasia, normal praxis, intact visuospatial ability, and a mild visual memory disturbance. The detailed analysis documented severe impairment of writing and reading abilities for Romaji (Romanized Japanese), spelled by alphabet letters and the most common way to input Japanese into computers. The writing and reading abilities for other Japanese linguistic modalities such as kanji (morphogram: Chinese character), kana (syllabogram: Japanese proper character), and alphabet letters, were not or minimally impaired. A disturbance of linguistic processing for Romaji may be the main underlying neural mechanism for dystypia in this patient.

Background: Nontraumatic convexal subarachnoid hemorrhage (cSAH) rarely occurs subsequent to acute ischemic stroke. The incidence, clinical background characteristics, and outcomes in acute ischemic stroke patients with cSAH were investigated., Methods: Our stroke center database was reviewed to identify patients with acute ischemic stroke/transient ischemic attack (TIA) who demonstrated acute cSAH within 14 days of admission between 2005 and 2011. Background characteristics, clinical course, and outcomes at discharge and 3 months after onset were investigated in these patients., Results: Of 4953 acute stroke/TIA patients, cSAH was observed in 8 (.14%) patients (7 men, mean age 71 years): 7 were detected incidentally, and the other was found immediately after a convulsion. Two patients died during their hospital stay, 1 died after discharge, and 3 were dependent at 3 months. Major artery occlusion or severe stenosis was observed in 5 patients. Two patients subsequently developed subcortical hemorrhage. On gradient echo imaging, lobar cerebral microbleeds were observed in 2 patients, and chronic superficial siderosis was observed in 2 patients., Conclusions: In this retrospective review of cases with ischemic stroke and cSAH, over half of patients had occlusion of major arteries. Cerebral amyloid angiopathy was suggested by magnetic resonance imaging findings and subsequent events in 3 patients. The overall outcome was unfavorable although the causal relationship with cSAH was unclear., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Some patients who present with an acute feeling of imbalance are experiencing an ischemic stroke that is not evident on computed tomography (CT) scans. The aim of this study was to compare ischemic stroke and nonischemic vertigo patient groups and to investigate independent factors associated with ischemic stroke. We examined 332 consecutive patients with an acute feeling of imbalance who showed no neurologic findings or responsible lesions on CT scan at the hyperacute phase. We examined their clinical backgrounds, physical findings, and laboratory examinations, with ischemic stroke diagnosed by later CT and/or magnetic resonance imaging (MRI). We identified 41 (12.3%) ischemic stroke patients. Atrial fibrillation (odds ratio 4.1; 95% confidence interval 1.4-11.5), white blood cell count (10(3)/μL, 1.4; 1.2-1.6), head and/or neck pain (4.6; 2.1-10.3), first attack of imbalance feeling (3.3; 1.1-12.2), and dizziness (3.7; 1.7-8.3) were significant and independent factors associated with ischemic stroke among patients with an acute feeling of imbalance. We used these factors to calculate an "imbalance score"; 1 point was given for the presence of each factor and a score of 3-5 points was independently associated with ischemic stroke. An awareness of these factors may indicate that further examinations including MRI are necessary to rule out ischemic stroke., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: To analyse the 9-year trend in oral intake ability 3 months after onset in acute stroke patients, with a view to indirect clarification of advances in acute stroke treatment and swallowing rehabilitation., Methods: A database of patients admitted to our hospital (Saiseikai Kumamoto Hospital, Kumamoto) with acute ischaemic stroke between 2003 and 2011 was analysed. Exclusion criteria were: patients with premorbid modified Rankin Scale score ≥ 1; those who died during hospital stay; and those whose outcomes after 3 months were not recorded. Mode of nutritional intake was investigated with a questionnaire posted to the patient 3 months after stroke onset. Patients were divided into 2 groups according to mode of nutritional intake: an oral intake group and a non-oral intake group. Whether the date or year of admission were related to the proportion of patients with oral intake, independent of other factors, was investigated using a logistic regression model., Results: Of a total of 2,913 patients, 2,677 (91.9%) were included in the oral intake group. The proportion of patients with oral intake 3 months after stroke increased significantly over the period of analysis (p = 0.034 by Cochran-Armitage test). On logistic regression analysis, the trend was significant after adjustment for age, sex, vascular risk factors, stroke subtype, and stroke severity on admission (odds ratio 1.098, 95% confidence interval 1.029-1.173; per 1 year)., Conclusion: The proportion of ischaemic stroke patients in the institution studied who were capable of oral intake at 3 months post-stroke increased significantly over the past decade, independent of other patient characteristics.

A 69-year-old man who had essential thrombocythemia, for which he was taking no medications, suddenly developed aphasia and right hemiplegia and was admitted to the hospital. He was thought to have had an embolic stroke and was initially treated with warfarin. Although the international normalized ratio was in the therapeutic range, he had 3 additional ischemic stroke episodes with the same symptoms after the index stroke. Magnetic resonance angiographic examinations revealed serial changes in middle cerebral artery stenosis. After administration of an antiplatelet agent and hydroxyurea, he had no additional strokes., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

In Japan, intravenous alteplase, a recombinant tissue-type plasminogen activator (rt-PA), was approved for an indication of ischemic stroke in 2005 on the basis of the results of a clinical trial with a unique dose of the drug (0.6 mg/kg). The Japan Stroke Society published the guidelines for intravenous application of rt-PA and organized training sessions for proper use all over Japan in an effort to promote the safe, widespread use of intravenous alteplase. Seven years following its approval, clinical experience with intravenous alteplase has accumulated, additional evidence of intravenous alteplase has been found in Japan and overseas, and the medical environment has substantially changed, including approvals for new drugs and medical devices. Notably, the use of alteplase in the extended therapeutic time window (within 4.5 hours of symptom onset) became covered by insurance in Japan in August 2012. To address these changing situations, we have decided to prepare the revised guidelines. In preparing the second edition, we took care to make its contents more practical by emphasizing information needed in clinical practice. While the first edition was developed with emphasis on safety in light of limited clinical experience with intravenous alteplase in Japan in 2005, this second edition is a substantial revision of the first edition mainly in terms of eligibility criteria, on the basis of accumulated evidence and the clinical experience., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

This study investigated the incidence and clinical features of reversed discrepancy (RD) in patients with hyperacute ischemic stroke. Sixty-two patients with anterior circulation ischemic stroke were enrolled. All patients underwent computed tomography (CT) and magnetic resonance imaging within 3 hours and received therapy with intravenous tissue plasminogen activator. The relationships between the Alberta Stroke Programme Early CT Score on CT and diffusion-weighted imaging (DWI); deep white matter lesion on DWI (DWI-W), CT, or magnetic resonance imaging after 24 hours; dramatic improvement (defined as a change in National Institutes of Health Stroke Scale score of ≥ 10 points or a total National Institutes of Health Stroke Scale score of 0 or 1 after 24 hours); and thrombolysis-related hemorrhage were assessed. Two investigators identified RD when the early ischemic change was detected on CT but no obvious hyperintensity was noted on DWI. RD was found in 10 patients (16.1%), located in the basal ganglia in 5 patients (50%), in the basal ganglia plus the cortical area in 3 patients (30%), and in the cortical area in 2 patients (20%). Four of these 10 patients had an infarction of the basal ganglia and a DWI-W lesion. All 4 patients with both RD in the basal ganglia (bRD) and DWI-W (the bRD+W+ group) had an infarction of the basal ganglia within 24 hours. In contrast, all 4 patients with bRD but without DWI-W (the bRD+W- group) had no basal ganglia infarction. Dramatic improvement after intravenous tissue plasminogen activator therapy was significantly less common in the bRD+W+ group (0 of 4 patients) than in the bRD+W- group (3 of 4 patients; P = .0285). Our findings suggest that the presence of both bRD and a DWI-W lesion can be used to predict whether dramatic improvement will occur and whether the basal ganglia will progress to infarction., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Although the carotid artery stump as an embolic source for ischemic stroke has been well described, there have been few systematic reports of a similar syndrome in the posterior circulation (PC) after vertebral artery (VA) origin occlusion. The aim of this study was to identify the incidence and characteristics of acute ischemic stroke with VA stump syndrome. Of 3463 consecutive patients who were admitted within 7 days after onset, 865 patients with acute ischemic stroke in the PC were enrolled. The diagnostic criteria of VA stump syndrome included: (1) acute ischemic stroke in the posterior circulation; (2) the VA origin occlusion identified on MRA, duplex ultrasound, CT angiography, and/or conventional angiography; (3) presence of distal antegrade flow in the ipsilateral VA; and (4) absence of other causes of ischemic stroke. Of the 865 patients with PC stroke, 12 (1.4%) were diagnosed as having VA stump syndrome. The ischemic lesions included the cerebellum in all patients. Nine patients had multiple ischemic lesions in the brain stem, thalamus, or posterior lobe other than cerebellum. On duplex ultrasound, a to-and-fro flow pattern was observed in the culprit VA in 10 patients. Three patients had recurrences of ischemic stroke in the PC during the acute phase. VA stump syndrome was not a rare mechanism of PC stroke, and there was a high rate of stroke recurrence during the acute phase. Vascular assessment by a multimodality approach can be used to promptly detect VA stump syndrome., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) is established as an effective treatment for patients with acute ischemic stroke. No distinction to the presence of chronic kidney disease (CKD) was made in previous clinical trials. In this chapter, three clinical studies that investigated renal dysfunction on the effect of rt-PA were reviewed and a meta-analysis was performed. In total, 344 patients with CKD and 504 patients without were treated within 3 h of symptom onset. Patients with CKD showed decreased odds of being alive and independent compared to patients with normal renal function (OR 0.60, 95% CI 0.45-0.81). Symptomatic intracranial hemorrhage occurred more in patients with CKD than without (OR 3.38, 95% CI 1.60-7.15). Risk of fatal outcome was also significantly higher in patients with CKD (OR 3.15, 95% CI 1.82-5.45)., (Copyright © 2013 S. Karger AG, Basel.)

When cerebral infarction develops during pregnancy, treatment without adverse effects must be considered not only for the mother but also for the fetus. Because pregnant women were excluded from many clinical trials, clear treatment guidance for them is not shown in the package inserts or guidelines of many drugs. We report the case of a 35-year-old woman (gravida 3, para 2) who developed sudden onset of left visual field defect, left hemiparesis, and dysesthesia over the left forearm during her fourth month of pregnancy. Brain diffusion-weighted MRI showed high intensity areas in the right occipital lobe, and magnetic resonance angiography revealed an occlusion of the right posterior cerebral artery. She was treated with an intravenous injection of recombinant tissue plasminogen activator 2 h 55 min after symptom onset, and the visual field and sensorimotor deficits improved. MRA obtained 3 days after the onset showed recanalization of the right posterior cerebral artery. We also conducted electrocardiography, neck vascular ultrasound, cardiovascular ultrasound, transcranial Doppler recordings from the temple area, and laboratory examinations for complete blood count, biochemistry, coagulation factors, endocrine secretion, and autoantibodies. Reduced protein S activity (35%) along with high intensity transient signals on transcranial Doppler indicated microemboli to be the embolic source. All other tests were negative. Anticoagulation therapy was initiated to prevent recurrence. She was initially given intravenous heparin, and then switched to warfarin therapy at 15 weeks of gestation. The patient delivered a healthy infant via caesarean section. Although reports and experiences of thrombolytic therapy with injection of recombinant tissue plasminogen activator during pregnancy remain scant, this therapy might be carefully used, especially after due consideration and understanding of the risks and benefits for both mother and fetus.

Background: The significance of early ischemic changes (EICs) on computed tomography (CT) in selecting candidates for thrombolysis remains controversial. The Alberta Stroke Program Early CT Score (ASPECTS) provides a semiquantitative scale that scores EICs within the middle cerebral artery territory using a 10-point grading system. We examined whether ASPECTS can predict the response to intravenous thrombolysis within 3 hours of stroke onset and incidence of secondary hemorrhage., Methods: Data from the Japan Alteplase Clinical Trial (J-ACT), in which 103 patients were included, were evaluated to assess the efficacy and safety of 0.6 mg/kg alteplase within 3 hours. All CT hardcopies were reevaluated retrospectively using the ASPECTS system. Multivariate logistic regression analysis was undertaken to determine whether an effect of ASPECTS existed on a defined favorable outcome as 0 or 1 on the modified Rankin Scale at 3 months, and symptomatic intracranial hemorrhage (sICH) within 36 hours., Results: The median ASPECTS value was 10 (range 3 to 10), and 56.3% revealed no evidence of EICs. ASPECTS had no effect on the patients' outcome, although a higher age and National Institutes of Health Stroke Scale score were negatively associated with a favorable outcome. On the other hand, lower ASPECTS was significantly associated with sICH (odds ratio [OR] 2.224; 95% confidence interval [CI] 1.227-4.032; P = .0084) and systolic blood pressure (OR 1.090; 95% CI 1.007-1.180; P = .0323) and the pre-ictal use of antiplatelet medications (OR 15.551; 95% CI 1.144-211.374; P = .0393)., Conclusions: In J-ACT, patients with low ASPECTS values have an increased risk of thrombolysis-related sICH., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

We hypothesized that extensive early ischemic changes increase subsequent intracranial hemorrhage (ICH) in patients within 3 h of onset regardless of intravenous tPA (IV-tPA). We have established a modified scoring method, ASPECTS+W, including deep white matter lesions on DWI (DWI-W) in addition to the original ASPECTS regions. We aimed to elucidate whether CT-ASPECTS, DWI-ASPECTS, and ASPECTS+W could be useful tools in helping to predict subsequent ICH in acute ischemic stroke. One-hundred sixty-four consecutive patients with anterior circulation ischemic stroke were enrolled. All patients underwent both MRI and CT within 3 h of onset. ASPECTS+W was defined as an 11-point method combining the ten ASPECTS regions and DWI-W. The relationships of CT-ASPECTS, DWI-ASPECTS, and ASPECTS+W with ICH within the initial 36 h were assessed. Thirty-six patients (22%) were treated with IV-tPA. Follow-up CT was obtained in 159 patients, and 19 (12%) developed ICH. Patients with ICH had higher baseline NIHSS scores (median, 25 vs. 13, p = 0.010), a higher rate of IV-tPA (42 vs. 20%, p = 0.041), lower CT-ASPECTS (median, 7 vs. 10, p = 0.008), lower DWI-ASPECTS (6 vs. 9, p = 0.001), lower ASPECTS+W (6 vs. 9, p = 0.001), and higher DWI-W lesions (74 vs. 47%, p = 0.048) than those without ICH. ICA or M1 proximal occlusion was more frequently seen in patients with ICH (68 vs. 32%, p = 0.004) than in those without ICH. On multivariate regression analysis, lower ASPECTS+W (OR 0.75, 95% CI 0.58-0.96, p = 0.027) and administration of IV-tPA (OR 9.13, 95% CI 2.15-46.21, p = 0.004) independently predicted ICH development. In conclusion, ASPECTS+W is a useful tool for predicting ICH development independent of IV-tPA.