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This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke.This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication.Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication.Alteplase appears more beneficial in patients with prior antithrombotic medication.

Background: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. Methods: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of 2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. Results: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect ( P interaction =0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55–2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls ( P =0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls ( P =0.539). Conclusions: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

This study aimed to investigate the association of mild hypertensive retinopathy with cardiovascular disease (CVD) risk.A total of 7,027 residents aged 30-79 years without a history of CVD participated in the annual health checkups and retinal photography assessments. Retinal microvascular abnormalities were graded using the standard protocols and classified according to the Keith-Wagener-Barker classification. Mild hypertensive retinopathy was defined as grades 1 and 2. Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for total CVD and its subtypes according to the presence and absence of mild hypertensive retinopathy.During a median follow-up of 17 years, 351 incident stroke and 247 coronary heart disease (CHD) cases were diagnosed. After adjustment for traditional cardiovascular risk factors, mild hypertensive retinopathy was positively associated with risk of CVD (multivariable HR=1.24; 95% CI, 1.04-1.49) and stroke (1.28; 1.01-1.62) but not with risk of CHD (1.19; 0.89-1.58). Generalized arteriolar narrowing and enhanced arteriolar wall reflex were positively associated with CVD risk, the multivariable HR (95% CI) was 1.24 (1.00-1.54) and 1.33 (1.02-1.74), respectively. Moreover, mild hypertensive retinopathy was positively associated with stroke risk in normotensive participants.Mild hypertensive retinopathy was positively associated with CVD and stroke risk in the urban Japanese population. Especially, generalized arteriolar narrowing and enhanced arteriolar wall reflex were positively associated with CVD risk. These findings suggested that retinal photography could be helpful for cardiovascular risk stratification in the primary cardiovascular prevention.

The single-device simplicity for mechanical thrombectomy (MT) is now challenged by the complementary efficacy of dual-device first-line with a stent retriever and an aspiration catheter.To compare the outcomes after MT initiated with a single device vs dual devices in acute anterior circulation large vessel occlusion.Patients who underwent MT for acute internal carotid artery (ICA) or M1 occlusion between 2015 and 2020 were retrospectively analyzed. We divided patients into 2 groups: single-device first-line, defined as patients who underwent first-device pass with either a stent retriever or aspiration catheter, and dual-device first-line, defined as first-device pass with both devices.One hundred forty-one patients were in the single-device group, and 119 were in the dual-device group. In the dual-device group, coiling or kinking of the extracranial ICA was more frequent ( P = .07) and the guide catheters were less frequently navigated to the ICA ( P.001). 37% of the single-device group was converted to dual-device use. The proportions of mTICI ≥ 2c after the first pass were similar (33% vs 32%. adjusted odds ratio 0.91, 95% CI 0.51-1.62). An mRS score of 0 to 2 at 3 months was achieved similarly (53% vs 48%, P = .46). The total cost for thrombectomy devices was lower in the single-device group ( P.001).The proportions of first-pass mTICI ≥ 2c were not different between the 2 groups with similar functional outcomes, although the dual-device group more likely to have unfavorable vascular conditions.

To assess whether post-stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case-control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE.We performed a post-hoc analysis of the PROgnosis of POST-Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient-echo T2*-weighted images. A logistic regression model with ridge penalties was tuned using 10-fold cross-validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models.The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p 0.0001). Compared with the existing models, the new models with cSS (SeLECT-S and CAVE-S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p = 0.004] for SeLECT-S and 0.88 [p = 0.001] for CAVE-S at the testing data).Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2022.

Background: Although tortuosity of the internal carotid artery (ICA) can pose a significant challenge when performing mechanical thrombectomy, few studies have examined the impact of ICA tortuosity on mechanical thrombectomy outcomes. Methods: In a registry-based hospital cohort, consecutive patients with anterior circulation stroke in whom mechanical thrombectomy was attempted were divided into 2 groups: those with tortuosity in the extracranial or cavernous ICA (tortuous group) and those without (nontortuous group). The extracranial ICA tortuosity was defined as the presence of coiling or kinking. The cavernous ICA tortuosity was defined by the posterior deflection of the posterior genu or the shape resembling Simmons-type catheter. Outcomes included first pass effect (FPE; extended Thrombolysis in Cerebral Infarction score 2c/3 after first pass), favorable outcome (3-month modified Rankin Scale score of 0–2), and intracranial hemorrhage. Results: Of 370 patients, 124 were in the tortuous group (extracranial ICA tortuosity, 35; cavernous ICA tortuosity, 70; tortuosity at both sites, 19). The tortuous group showed a higher proportion of women and atrial fibrillation than the nontortuous group. FPE was less frequently achieved in the tortuous group than the nontortuous group (21% versus 39%; adjusted odds ratio, 0.45 [95% CI, 0.26–0.77]). ICA tortuosity was independently associated with the longer time from puncture to extended Thrombolysis in Cerebral Infarction ≥2b reperfusion (β=23.19 [95% CI, 13.44–32.94]). Favorable outcome was similar between groups (46% versus 48%; P =0.87). Frequencies of any intracranial hemorrhage (54% versus 42%; adjusted odds ratio, 1.61 [95% CI, 1.02–2.53]) and parenchymal hematoma (11% versus 6%; adjusted odds ratio, 2.41 [95% CI, 1.04–5.58]) were higher in the tortuous group. In the tortuous group, the FPE rate was similar in patients who underwent combined stent retriever and contact aspiration thrombectomy and in those who underwent either procedure alone (22% versus 19%; P =0.80). However, in the nontortuous group, the FPE rate was significantly higher in patients who underwent combined stent retriever and contact aspiration (52% versus 35%; P =0.02). Conclusions: ICA tortuosity was independently associated with reduced likelihood of FPE and increased risk of postmechanical thrombectomy intracranial hemorrhage. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02251665.

Aim We evaluated the delay in stroke reperfusion therapy between the pre-coronavirus disease 2019 (COVID-19) period and the with-COVID-19 period, and compared this delay between each phase of the with-COVID-19 period. Methods Patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis and/or mechanical thrombectomy were selected from our single-center prospective registry. The time to perform reperfusion therapy were compared between patients admitted from March 2019 to February 2020 (pre-COVID-19 group) and those from March 2020 to February 2021 (with-COVID-19 group). Patients in the with-COVID-19 group were further divided into three 4-month-long subgroups (first-phase: March to June 2020; second-phase: July to October 2020; third-phase: November 2020 to February 2021), and the time delay of reperfusion therapy were compared between these subgroups. Results Of 1,260 patients with AIS hospitalized in the study period, 265 patients were examined. Compared with the pre-COVID-19 group (133 patients; median age, 79 years), the with-COVID-19 group (132 patients; median age, 79 years) had a longer median door-to-imaging time (25 min vs. 27 min, P=0.04), and a longer door-to-groin puncture time (65 min vs. 72 min, P=0.02). In the three 4-month-long subgroups, the median door-to-needle time (49 min, 43 min, and 38 min, respectively; P=0.04) and door-to-groin puncture time (83 min, 70 min, and 61 min, P＜0.01, respectively) decreased significantly during the with-COVID-19 period. Conclusions The delay in reperfusion therapy increased during the with-COVID-19 period compared with the pre-COVID-19 period. However, the door-to-needle time and door-to-groin puncture time decreased as time elapsed during the with-COVID-19 period.ClinicalTrials.gov Identifier: NCT02251665.

Aims The relationship between left ventricular (LV) function and AF detection in embolic stroke of undetermined source (ESUS) patients with insertable cardiac monitors (ICMs) remains unclear. We investigated the association between LV function and AF detection in patients with ESUS after ICMs implantation. Methods We enrolled patients with ESUS who underwent ICMs implantation from September 2016 to September 2020 using a single-center, prospective registry. LV systolic and diastolic functions were assessed on precordial echocardiography by LV fractional shortening (LVFS) and average E/e', respectively. Associations between characteristics of LV function and detection of AF by ICMs were analyzed. Results Participants comprised 101 patients (median age, 74 years; male, 62%). During a median follow-up period of 442 days (interquartile range (IQR), 202-770 days), AF was detected in 24 patients (24%). Median duration from ICMs implantation to AF detection was 71 days (IQR, 13-150 days). When LVFS and E/e' were dichotomized by cutoff value, each of low LVFS (＜35.5%; adjusted hazard ratio (HR), 4.77; 95% confidence interval (CI), 1.77-12.9) and high E/e' (≥ 8.65; adjusted HR, 4.56; 95%CI, 1.17-17.7) were independently associated with AF detection after adjusting for age and sex. When patients were divided into four groups according to dichotomized LVFS and E/e', the combination of low LVFS and high E/e' was independently associated with AF. Conclusions In patients with ESUS after ICMs implantation, the LV characteristics of low LVFS and high E/e' were associated with AF detection.

The Japanese National Plan for the Promotion of Measures Against Cerebrovascular and Cardiovascular Diseases was formulated on October 27, 2020. One purpose of this plan was to promote research on cerebrovascular and cardiovascular diseases. Therefore, it is necessary to clarify the actual status of stroke treatment in Japan and operate a national stroke database with high public interest completely and accurately. The Japan Stroke Data Bank (JSDB; https://strokedatabank.ncvc.go.jp/en/) was established by the Ministry of Health, Labor and Welfare Scientific Research in Shimane University (Shimane, Japan) in 1999 and was transferred to the National Cerebral and Cardiovascular Center (Osaka, Japan) as a part of the Cardiovascular Disease Registry in 2015. More than 200,000 of stroke cases have been registered using individual forms from more than 100 nationwide stroke centers over ~20 years. Since there are few large-scale stroke registries with nationwide coverage in Asia, including Japan, compared with those in Europe and North America, the role of the JSDB in the plan will be important in the future. To construct a high-quality stroke registry, we aimed to (1) collect detailed data through individual questionnaires for each participating stroke center, (2) link to external databases (e.g., insurance claims and public death registries), (3) improve the quality of treatment at participating hospitals through benchmarking, and (4) obtain stable funding through sustained support from government and academic societies. We also describe the history of the JSDB and changes in the trend of real-world stroke treatment in Japan based on the results of analysis of data in the JSDB.

Introduction We aim to investigate the difference in mechanical thrombectomy (MT) outcome for cancer‐related stroke (CRS) with active and inactive cancer. Methods Of the consecutive acute ischemic stroke (AIS) patients admitted to our institute from 2010 to 2021, patients with cancer who received MT within 24 hours of onset and were enrolled.Outcomes including the favorable outcome (modified Rankin Scale score of 0 to 2) at3 months, 1‐year,and death within 3 months or 1‐yearwere assessed between patients with active and inactive cancer among patients with cancer. The rate offirst pass effect (FPE, extendedThrombolysis in Cerebral Infarction[eTICI] 2c/3 after first pass) and final eTICI 2c/3 achievement were also assessed. Active cancer was defined as a cancer that was diagnosed within 6 months; required chemotherapy or surgical treatment within 6 months; or was recurrent, metastatic, or inoperable. Results Of 59 patients (26 women; median age, 80 years; median NIH Stroke Scale score[NIHSS] 17), 19 (32.2%) patients had an active cancer. Patients with active cancer has less atrial fibrillation (47% vs. 78%,P< 0.01) and higher medianD‐dimer(4.60μg/mLvs. 2.00μg/mL,P< 0.01). There were no significant differences in the favorable outcome at 3 months (26% vs. 45%,P = 0.26) and at 1 year (26% vs. 45%,P = 0.26) between both groups, but death within 3 months (32% vs. 5%,P< 0.01) and within 1 year (42% vs. 8%,P< 0.01) were more frequent in patients with active cancer than those with inactive cancer. Conclusions Long‐term clinical outcomes of patients with active cancer were worse than those with inactive cancer.

Background and ObjectivesThe functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes.MethodsThis is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically.ResultsA total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25–7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27–8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25–2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006).DiscussionOne-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

A 57-year-old man presented with headache, transient right upper extremity weakness and numbness one month after recovery from coronavirus disease 2019 (COVID-19). His medical history included Graves' disease and IgG4-related ophthalmic disease. He had been administered prednisolone. His weakness and numbness were transient and not present on admission. Contrast-enhanced CT and MRI of the head showed thrombi in the superior sagittal sinus, right transverse sinus, sigmoid sinus, and the right internal jugular vein. Digital subtraction angiography showed occlusion at the same sites and mild perfusion delay in the left frontoparietal lobe. We diagnosed the patient with cerebral venous sinus thrombosis and treated him with anticoagulation. The thrombi partially regressed three months later, and perfusion delay became less noticeable. Cerebral venous sinus thrombosis is an important complication of COVID-19. Patients with predisposing factors, including Graves' disease and IgG4-related ophthalmic disease, may be at increased risk of developing cerebral venous sinus thrombosis even after recovery from COVID-19.

Streptococcus mutans, a major cariogenic bacterium, expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, resulting in the impairment of blood brain barrier integrity followed by cerebral bleeding. We here examined the association of Cnm-positive S. mutans with cerebral microbleeds (CMBs) in acute stroke patients selected from a single-center registry database. Of 428 patients who received oral bacterial examinations among 3154 stroke patients, 326 patients who harbored S. mutans were identified. After excluding four patients without imaging data, we compared 72 patients with Cnm-positive S. mutans and 250 with Cnm-negative S. mutans. Deep, lobar and infratentorial CMBs were observed in 46 (63.9%), 36 (50.0%), 25 (34.7%) patients with Cnm-positive S. mutans and 144 (57.6%), 114 (45.6%), 101 (40.4%) with Cnm-negative S. mutans. Possession of Cnm-positive S. mutans was related to higher numbers of both deep and lobar, but not infratentorial, CMBs (risk ratios 1.57 [1.07‒2.30], deep; 5.44 [2.50‒11.85], lobar). Statistical significance persisted after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy (risk ratios 1.61 [1.14‒2.27], deep; 5.14 [2.78‒9.51], lobar). Our study indicated that reduction of Cnm-positive S. mutans may serve as a therapeutic approach for improving the prognosis of stroke patients.

Background: The unknown onset stroke can be categorized into two groups; wake-up stroke (WUS) and non-wake-up unwitnessed stroke with a time of onset unavailable due to aphasia, impaired consciousness, or cognitive impairment (non-wake-up unknown onset stroke, non-WUS). We aimed to assess the differences in efficacy and safety of intravenous thrombolysis (IVT) for these subgroups. Methods: Patients with an unknown onset stroke from the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing IVT with placebo/standard treatment. A favorable outcome was defined as a modified Rankin Scale score 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22-36 hours and 90-day mortality. The effect of IVT was compared between the treatment groups in the WUS and non-WUS with mixed-effect logistic-regression analysis. Results: A total of 634 patients (233 women [36.8%], median age 70 years [IQR 61-76]) were analyzed. In patients with non-WUS (n=92 [14%]), advanced age, atrial fibrillation, vessel occlusion on MRA and high NIHSS score were more prevalent (P Conclusions: The benefit of IVT was significant in patients with WUS. Excellent outcome was also numerically more prevalent in non-WUS but this did not reach significance, probably due to the lack of statistical power.

Purpose: We aim to clarify the association between history of cancer with clinical outcomes after ischemic stroke (IS) or hemorrhagic stroke (HS). Methods: Study participants were adult patients within seven days after onset of IS or HS from the register of the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between 2000 and 2021, whose modified Rankin Scale score at discharge was available. Participants were divided into three groups [active cancer (AC) group, inactive cancer (iAC) group, and without cancer group]. Outcomes including good functional outcome, representing modified Rankin Scale score 0-2 at discharge, and in-hospital death was compared between the groups using multivariate analysis by forward-backward stepwise selection method for stroke subtype. AC was defined as cancer diagnosed within six months, requiring chemotherapy or surgical treatment, metastatic, or inoperable. Results: Of 171292 stroke patients, including 128145 with IS and 43147 with HS, 1074 patients had AC (women 42.5%; median age, 77 years; median (interquartile range) baseline National Institutes of Health Stroke Scale 5 [2–15]; IS 84.3%), 6337 patients had iAC (37.9%; 73 years; 4 [2–13]; 79.5%), and 163881 patients did not have cancer (42.4%; 73years; 4 [2–12]; 74.6%). Good functional outcome after IS was less common in cancer patients [AC; 39.4%, adjusted odds ratio (OR) 0.78, 95% confidence interval (CI) 0.71-0.86: iAC; 49.1%, adjusted OR 0.92, 95% CI 0.85-0.99] than those without cancer (56.3%), and mortality in cancer patients was higher (AC; 10.6%, adjusted OR 1.77, 95% CI 1.56-2.01: iAC; 5.6%, adjusted OR 1.26, 95% CI 1.09-1.47) than those without cancer (4.4%). Good functional outcome after HS was less common in cancer patients [AC; 22.0%, adjusted OR 0.81, 95% CI 0.61-1.07: iAC; 24.6%, adjusted OR 0.78, 95% CI 0.64-0.94] than those without cancer (35.3%), and mortality after HS was higher in AC patients (29.8%) than those without cancer (15.9%, adjusted OR 1.61, 95% CI 1.26-2.07) Conclusions: IS patients with AC and those with iAC significantly had less achievement of good functional outcomes and more in-hospital death, and HS patients with AC led to more in-hospital death than patients without cancer.

Purpose: We aimed to clarify the association between optimal mismatch ratio and favorable outcome of acute ischemic stroke-large vessel occlusion (AIS-LVO) patients who underwent endovascular therapy (EVT) by Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) and ischemic core volume (ICV). Methods: We enrolled consecutive patients from 2017 to 2021 with prestroke modified Rankin scale (mRS) scores of 0 to 2 who were available for computed tomography perfusion or perfusion-weighted imaging before treatment and underwent EVT for anterior AIS-LVO within 24 hours from onset. Patients with ICV less than 10 mL or those who did not achieve successful recanalization with extended Thrombolysis In Cerebral Infarction scale score ≥2b were excluded. We dichotomized patients by ASPECTS (≥6 and 70 mL). Sensitivity and specificity were calculated from receiver operating characteristic (ROC) curve and to identify the optimal mismatch ratio for achieving favorable outcome, defined as mRS score 0 to 2 at 3 months. Results: Eighty patients (women, 31; median age, 75 [interquartile range (IQR), 69-83] years; median NIHSS score, 19 [14-24]; median ASPECTS, 7 (IQR, 6-9); median ICV, 32 (IQR, 16-64) mL] were enrolled. Of these, 45 (56%) patients had favorable outcomes. The threshold of optimal mismatch ratio for favorable outcomes were 11.2 in patients with ASPECTS ≥6 [area under curve (AUC) 0.55, P=0.47; sensitivity 0.25, specificity 0.92], 3.1 in those with ASPECTS Conclusions: The cut-off values of optimal mismatch ratio for favorable outcomes were 11 in patients with ASPECTS ≥6 or ICV

Introduction: Side-to-side relative reduction in end-diastolic velocity (EDV) of the common carotid artery (CCA) may discriminate ipsilateral anterior circulation large vessel occlusion (LVO), which will contribute faster patient triage for reperfusion therapy. We evaluated the discriminative accuracy of this simple sonographic index for anterior circulation LVO in acute stroke population, including intracerebral hemorrhage (ICH). Methods: Among patients with acute stroke admitted to our institute between 2016-2018, those who underwent both carotid ultrasonography and head MRA or CTA within 24 hours after last known normal time were reviewed. Relative EDV reduction was calculated as a ratio by dividing the CCA EDV lower side by the EDV higher side. Anterior circulation LVO was defined as occlusion of the internal carotid artery (ICA) or M1 segment of the middle cerebral artery on the lower EDV side. Discriminative performance of relative EDV reduction for anterior circulation LVO was assessed by receiver operating characteristics analysis. Results: A total of 688 patients (411 males; median age 77 years; 87 with anterior circulation LVO) were analyzed. When compared to no occlusion, value of relative EDV reduction was remarkably lower in ICA occlusion, followed by that in M1 occlusion (Figure). Area under the curve (AUC) of relative EDV reduction for ICA occlusion was 0.96 (95% confidence interval [CI] 0.94-0.99) with an appropriate cut-off value of 0.50 (sensitivity 94%, specificity 94%). When the discrimination target was set to anterior circulation LVO, the AUC was 0.78 (95% CI 0.72-0.85) with an appropriate cut-off value of 0.67 (sensitivity 69%, specificity 83%). At this cut-point, 51% of patients with M1 occlusion was classified as false negative. Conclusions: The discriminative performance of the relative CCA EDV reduction in acute stroke population was excellent for ICA occlusion and acceptable for anterior circulation LVO.

Background and Purpose: Whether specific patient groups have benefited from advances of treatment technologies including acute reperfusion therapy is uncertain. We aimed to investigate long-term trends of acute reperfusion therapy and functional outcomes according to the stroke severity using a large clinical registry. Methods: In the nationwide, hospital-based, multicenter, prospective registry cohort from the Japan Stroke Data Bank between January 2000 and December 2020, patients with ischemic stroke were studied. The baseline National Institutes of Health Stroke Scale (NIHSS) score of 10 or more was considered as possible large vessel occlusions (LVOs). Secular changes were assessed per 5-year categories (2000-2005, 2006-2010, 2011-2015, 2016-2020). Outcomes included favorable outcome (mRS score was 0 to 2 at discharge), and in-hospital mortality. Results: Of 235,695 patients, 127,741 ischemic stroke patients (76,850 men [60.2 %]; median age 75, [interquartile range, 66-82] years) with available data on NIHSS score were analyzed. NIHSS score was ≥10 in 31,747 patients (24.9%). In both patients with NIHSS ≥10 and those with NIHSS Conclusions: Over the 20-year period, acute reperfusion therapy has increasingly been provided to patients with NIHSS ≥10. Favorable outcomes significantly increased in patients with NIHSS ≥10 but decreased in those with NIHSS

Background: Cerebral small vessel disease (SVD) has received attention as a risk stratification tool for antithrombotic-related intracranial hemorrhage but may also be a predictor for bleeding in other organs. Purpose: To determine the excess risk of antithrombotic-related bleeding due to cerebral SVD burden. Methods: Patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were prospectively enrolled from 52 hospitals across Japan between 2016 and 2019. Multimodal brain MRI was acquired at baseline for all patients under prespecified conditions. All MRI examinations were interpreted by a central diagnostic radiology committee for cerebral microbleeds, lacunes, white matter hyperintensities, and enlarged basal ganglia perivascular spaces, for calculation of a total SVD score (range 0-4). The primary outcome was major bleeding during 2-year follow-up. Secondary outcomes included bleeding in each site and ischemic events. Event risks according to SVD score were estimated with multivariable Cox proportional hazards models. Results: Of the analyzed 5250 patients (1736 women; median age, 73 years; 9933 patient-years follow-up), antiplatelets and anticoagulants were administered at baseline in 3948 and 1565, respectively. Median of the total SVD score was 2 (IQR 1-3). As SVD score increased, advanced age, hypertension, anemia, and chronic kidney disease were more prevalent (P Conclusions: The total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting a broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy.

Purpose: This study aimed to explore the association between carotid intima-media thickness (IMT) and the Suita Risk Score for cardiovascular events and all-cause and cause-specific death. Methods: We studied 4,870 Japanese individuals (mean age 55.0±12.2 years, without CVD at the baseline; women 53.9%) who completed a baseline survey and carotid atherosclerosis in the Suita and were then followed for 14.8 years of the median. Carotid IMT was evaluated by high-resolution ultrasonography with atherosclerotic indexes of IMT in the common carotid artery (CCA) and carotid artery bulb (Bulb). We defined Mean CIMT as the mean of the IMT of the proximal and distal walls for both sides of the CCA on a longitudinal scan at a point 10 mm proximal from the beginning of the dilation of each carotid artery bifurcation. The maximum IMT in the CCA (max-CIMT) and the entire area (max-IMT) were defined as the maximum measurable IMT in the scanned CCA and the entire scanned carotid artery areas for both sides. The risks of all-cause mortality across carotid IMT were compared using Cox proportional-hazards models adjusting for the Suita risk score. The 95% CIs of the C-statistic was estimated using 200 bootstrap samples. Similarly, the standard error for the difference in C-statistic between each model was estimated from the bootstrap samples and used to calculate a P value for the difference. Results: We observed 923 deaths during 14.8 years as a median. The fourth quartiles of mean CIMT observed increased risks of all causes of mortalities and CVD mortality (hazard ratio (HR)=2.65, 95%CIs,1.93-3.63; HR=4.89, 95%CIs,1.88-12.72), max-CIMT (HR=1.99, 95%CIs,1.47-2.70; HR=2.92, 95%CIs, 1.21-7.06), and max-IMT (HR=2.13, 95%CIs,1.63-2.78; HR=2.69, 95%CIs, 1.30-5.58), respectively, compared to the first quartiles of then. C-statistic significantly improved by adding the fourth quartiles of mean CIMT and max-IMT to the Suita risk score for all-cause death (+0.003, 95%CIs, 0.0002-0.005, P=0.03 and +0.006, 95%CIs, 0.002-0.010, P Conclusion: Additional assessment of carotid IMT to the Suita risk score may be helpful to improve the predictive ability for all causes of mortalities, not for CVD mortalities.

Background Acute myocardial infarction (AMI) infrequently occurs after acute stroke. The Heart‐brain team approach has a potential to appropriately manage this poststroke cardiovascular complication. However, clinical outcomes of AMI complicating acute stroke (AMI‐CAS) with the heart‐brain team approach have not been characterized. The current study investigated cardiovascular outcomes in patients with AMI‐CAS managed by a heart‐brain team. Methods and Results We retrospectively analyzed 2390 patients with AMI at our institute (January 1, 2007–September 30, 2020). AMI‐CAS was defined as the occurrence of AMI within 14 days after acute stroke. Major adverse cerebral/cardiovascular events (cardiac‐cause death, nonfatal myocardial infarction, and nonfatal stroke) and major bleeding events were compared in subjects with AMI‐CAS and those without acute stroke. AMI‐CAS was identified in 1.6% of the subjects. Most AMI‐CASs (37/39=94.9%) presented ischemic stroke. Median duration of AMI from the onset of acute stroke was 2 days. Patients with AMI‐CAS less frequently received primary percutaneous coronary intervention (43.6% versus 84.7%; P P P P P =0.009). These relationships still existed even after adjusting for clinical characteristics and medication use (major adverse cerebral/cardiovascular event: HR, 1.87 [95% CI, 1.02–3.42]; P =0.04; major bleeding: HR, 2.67 [95% CI, 1.03–6.93]; P =0.04). Conclusions Under the heart‐brain team approach, AMI‐CAS was still a challenging disease, reflected by less adoption of primary percutaneous coronary intervention and antithrombotic therapies, with substantially elevated cardiovascular and major bleeding risks. Our findings underscore the need for a further refined approach to mitigate their ischemic/bleeding risks.

Introduction: Stroke remains a major cause of death and disability in Japan and worldwide. Detecting individuals at high risk for stroke to apply preventive approaches is recommended. This study aimed to develop a stroke risk prediction model among urban Japanese using cardiovascular risk factors. Methods: We followed 6,641 participants aged 30–79 years with neither a history of stroke nor coronary heart disease. The Cox proportional hazard model estimated the risk of stroke incidence adjusted for potential confounders at the baseline survey. The model’s performance was assessed using the receiver operating characteristic curve and the Hosmer-Lemeshow statistics. The internal validity of the risk model was tested using derivation and validation samples. Regression coefficients were used for score calculation. Results: During a median follow-up duration of 17.1 years, 372 participants developed stroke. A risk model including older age, current smoking, increased blood pressure, impaired fasting blood glucose and diabetes, chronic kidney disease, and atrial fibrillation predicted stroke incidence with an area under the curve = 0.76 and p value of the goodness of fit = 0.21. This risk model was shown to be internally valid (p value of the goodness of fit in the validation sample = 0.64). On a risk score from 0 to 26, the incidence of stroke for the categories 0–5, 6–7, 8–9, 10–11, 12–13, 14–15, and 16–26 was 1.1%, 2.1%, 5.4%, 8.2%, 9.0%, 13.5%, and 18.6%, respectively. Conclusion: We developed a new stroke risk model for the urban general population in Japan. Further research to determine the clinical practicality of this model is required.

Background and aims Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined. Methods A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography. Summary of review Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00–1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02–1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00–1.05 per hour). Conclusions Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.

Objectives: Acute ischemic stroke (AIS) is a significant and devastating complication in patients with end-stage renal disease on hemodialysis (ESRD/HD). Since one-third of AIS in ESRD/HD patients occurs during or soon after dialysis, patients are more likely to present within the time window when intravenous thrombolysis (IVT) can be performed. IVT may improve prognosis in ESRD/HD patients with AIS. However, ESRD/HD patients have been excluded from large trials and may have been withheld from IVT due to concerns about bleeding complications. To date, there is no clear evidence and firm guidance on the safety and efficacy of IVT in ESRD/HD patients with AIS. This narrative review aimed to evaluate critical scientific data on the benefits and risks of IVT use in patients with ESRD/HD and AIS. Materials and Methods: We searched the electronic database of PubMed for studies evaluating the relationship between AIS, ESRD/HD, and IVT. Reference sections and additional publications were also searched manually. Studies on AIS in patients with ESRD/HD requiring maintenance dialysis that referred to IVT were included. Results: In total, 560 studies were found in the PubMed electronic database during the period covered, of which 10 met the selection criteria. IVT for AIS in ESRD/HD patients could improve neurological outcomes and be safely performed even with the possibility of hemorrhagic complications associated with hypertension. Despite the high complication and mortality rates in ESRD/HD patients with AIS after IVT, the association with IVT was unclear. Conclusions: IVT for AIS in ESRD/HD patients may improve outcomes and should not be withheld based solely on ESRD/HD status.

Background We investigated the impact of the ring finger protein 213 p.R4810K variant, a founder variant for moyamoya disease in East Asians, on endovascular therapy outcomes in patients with acute anterior‐circulation large‐vessel occlusion stroke in comparison with noncarriers. Methods Of the consecutive patients with ischemic stroke admitted to our institute from 2011 to 2021, patients who underwent endovascular therapy for acute occlusion of the intracranial internal carotid artery or M1 segment of the middle cerebral artery were included. Outcomes were instant reocclusion, final modified Thrombolysis in Cerebral Infarction reperfusion ≥2b, and early reocclusion. Instant reocclusion was defined as the occurrence of reocclusion during the procedure, and early reocclusion was defined as reocclusion detected on magnetic resonance angiography within 2 weeks after the confirmation of successful reperfusion. Results Of the 277 patients analyzed (128 women; median age, 76 years), 10 patients (3.6%) carried the ring finger protein 213 p.R4810K variant. Variant carriers were younger ( P =0.01) and more frequently had intracranial atherosclerotic disease‐related large‐vessel occlusion as a cause of acute large‐vessel occlusion ( P P P =0.22). Early reocclusion was more frequent in variant carriers compared with noncarriers (60.0% versus 0.4%; P Conclusions Instant and early reocclusions were more frequent in variant carriers who underwent endovascular therapy for acute anterior‐circulation large‐vessel occlusion compared with noncarriers.

Background We investigated the impact of the p.R4810K variant of RNF213 (ring finger protein 213) gene, a susceptibility gene of moyamoya disease in East Asia, on the outer diameter of cervical parts of carotid and vertebral arteries (VAs). Methods We examined consecutive Japanese patients with ischemic stroke who underwent carotid ultrasonography between 2015 and 2019. Patient background and the carotid ultrasonography‐measured outer diameter of extracranial cervical arteries, including the common carotid artery, internal carotid artery, external carotid artery, and cervical VA, were compared between variant carriers and noncarriers. Outer diameters of each artery were defined as the mean distance from far to near wall adventitia of right and left target arteries using carotid ultrasonography. The average diameter of both cervical portions of common carotid arteries, internal carotid arteries, external carotid arteries, and the dominant side diameter of both cervical VAs were used. Results Of the 617 adult patients (204 women; median age, 74 years) analyzed, 26 (4.2%) carried the RNF213 p.R4810K variant. Variant carriers were significantly younger ( P P Conclusion RNF213 p.R4810K variant carriers have smaller cervical arterial outer diameters in both anterior and posterior circulations than noncarriers with ischemic stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02251665.

Background We elucidated the safety of treatment with alteplase at 0.6 mg/kg within 24 hours for patients on direct oral anticoagulants (DOACs) before ischemic stroke onset. Methods and Results Consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis using alteplase at 0.6 mg/kg from 2011 to 2021 were enrolled from our single‐center prospective stroke registry. We compared outcomes between patients taking DOACs and those not taking oral anticoagulants within 48 hours of stroke onset. The primary safety outcome was the rate of symptomatic intracranial hemorrhage with a ≥4‐point increase on the National Institutes of Health Stroke Scale score from baseline. The efficacy outcome was defined as 3‐month modified Rankin Scale score of 0 to 2 after stroke onset. Of 915 patients with acute ischemic stroke who received intravenous thrombolysis (358 women; median age, 76 years; median National Institutes of Health Stroke Scale score, 10), 40 patients took DOACs (6 took dabigatran, 8 took rivaroxaban, 16 took apixaban, and 10 took edoxaban) within 24 hours of onset and 753 patients did not take any oral anticoagulants. The rate of symptomatic intracranial hemorrhage was comparable between patients on DOACs and those not on oral anticoagulants (2.5% versus 2.4%, P =0.95). The rate of favorable outcomes was comparable between the 2 groups (59.4% versus 58.2%, P =0.46), although the admission National Institutes of Health Stroke Scale score was higher in patients on DOACs. No significant differences showed in any intracranial hemorrhage within 36 hours or mortality at 3 months. Conclusions Intravenous thrombolysis would be safely performed for patients on DOACs following the recommendations of the Japanese guidelines. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02251665.

Although catheter ablation (CA) has become a standard therapeutic approach to atrial fibrillation (AF), it imposes a low but relevant risk of thromboembolic complications of around 0.5%-1%, including ischemic strokes, and has an additional risk of clinically silent cerebral embolisms (SCEs) of 10%-40%. Both cryoballoon (CB) and radiofrequency (RF) ablation are routinely used clinically worldwide, yet there are few prospective data comparing the incidence of cerebral embolism after CA of AF between CB and RF ablation.The aim of the Embo-Abl study will be to compare the incidence of cerebral embolisms on 3 T diffusion-weighted image magnetic resonance imaging (MRI) after CA of AF between CB and RF ablation in patients with AF in a prospective, multicenter, open-label, controlled, randomized fashion. The primary endpoint of the Embo-Abl study will be the occurrence of MRI-detected SCE 1-3 days after CA. The patients will be registered and randomly assigned to either the CB or RF ablation group in a 1:1 ratio. The study cohort will include 230 patients with AF from a multicenter in Japan.The results of this study are currently under investigation.The Embo-Abl study will be the first to compare the incidence of periprocedural cerebral embolisms caused by CA of AF between CB and RF ablation in a prospective, multicenter, randomized, controlled fashion.

A 54-year-old man suddenly developed impaired consciousness and left hemiplegia due to a right thalamic hematoma. Emergent ventricular drainage for acute hydrocephalus improved the level of consciousness, but macrosquare-wave jerks (MSWJ) consisting of a right-ward intrusive saccade and corrective saccade appeared. The MSWJ disappeared on day 2 when follow-up CT revealed improvement of hydrocephalus. However, on day 36, after ventricular drainage was clamped, the MSWJ reappeared. After ventriculoperitoneal shunt, MSWJ again subsided. In this patient, hydrocephalus may have stretched the superior colliculus, thereby decreasing activity of the fixation neurons and then omnipause neurons, and eventually resulting in the reversible MSWJ.

Background and ObjectiveThe clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110–139 mm Hg) against the standard (target, 140–179 mm Hg) among patients with ICH.MethodsWe conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis.ResultsAmong the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m2; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60–89, and 2, respectively. Compared with normal eGFR (≥90 mL/min/1.73 m2), higher odds of death or disability were noted among those with eGFR values of 2(adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25–3.26) but not among those with eGFR values of 60–89 mL/min/1.73 m2(OR, 1.01; 95% CI, 0.70–1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55–1.44), 1.13 (0.68–1.89), and 3.60 (1.47–8.80) in patients with eGFR values of ≥90, 60–89, and 2, respectively (pfor interaction = 0.02).DiscussionDecreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment.Trial Registration InformationClinicaltrials.gov identifier:NCT01176565.Classification of EvidenceThis study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control.

Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n = 119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5 h of onset. MR-proADM levels in HAIS were compared to healthy controls (n = 1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case-control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17-15.02], p 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (r

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337–450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09–6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93–3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.

Various embolic sources and pathogenetic mechanisms underlie cryptogenic stroke (CS). We investigated the association of etiological diversity with short-term outcomes in patients with CS using a modified atherosclerosis (A), small-vessel disease (S), cardiac pathology (C), other causes (O), and dissection (D) (ASCOD) system.Patients with CS who underwent transesophageal echocardiography were registered in this multicenter, observational study. In the modified classification system, O and D were inapplicable and thus excluded. Instead, atherosclerosis, small-vessel disease, cardiac pathology-CS classification was specifically constructed for the etiological diagnosis of CS. We utilized this system to explore the mechanism of CS by grading each pathology and evaluated its association with poorer modified Rankin Scale scores of 3-6 at hospital discharge.A total of 672 patients (68.7±12.8 years, 220 females) were analyzed. In the multiple logistic regression model, female sex (odds ratio [OR], 1.87 [1.15-3.04]; P=0.012), body mass index (OR, 0.93 [0.88-0.99]; P=0.025), National Institute of Health Stroke Scale score (OR, 1.16 [1.12-1.21]; P＜0.001), CHADS2 score (OR, 1.56 [1.30-1.86]; P＜0.001), D-dimer (OR, 1.04 [1.01-1.08]; P=0.015), diffusion-weighted image (DWI) lesion size (OR, 1.44 [1.10-1.89]; P=0.009), and S＋C score (OR, 1.26 [1.03-1.56]; P=0.029) were associated with poor functional outcome at discharge whereas the S＋C score was marginally associated with poor functional outcome after excluding 137 patients with a premorbid modified Rankin Scale score of ≥ 3.The coexistence of small-vessel disease and cardiac pathology might be associated with poor in-hospital functional outcome in CS.

BackgroundThe procoagulant state in cancer increases the thrombotic risk, and underlying cancer could affect treatment strategies and outcomes in patients with ischemic stroke. However, the histopathological characteristics of retrieved thrombi in patients with cancer have not been well studied. This study aimed to assess the histopathological difference between thrombi in patients with and without cancer.MethodsWe studied consecutive patients with acute major cerebral artery occlusion who were treated with endovascular therapy between October 2010 and December 2016 in our single-center registry. The retrieved thrombi were histopathologically investigated with hematoxylin and eosin and Masson’s trichrome staining. The organization and proportions of erythrocyte and fibrin/platelet components were studied using a lattice composed of 10×10 squares.ResultsOf the 180 patients studied, 17 (8 women, age 76.5±11.5 years) had cancer and 163 (69 women, age 74.1±11.2 years) did not. Those with cancer had a higher proportion of fibrin/platelets (56.6±27.4% vs 40.1±23.9%, p=0.008), a smaller proportion of erythrocytes (42.1±28.3% vs 57.5±25.1%, p=0.019), and higher serum D-dimer levels (5.9±8.2 vs 2.4±4.3 mg/dL, p=0.005) compared with the non-cancer cases. Receiver operating characteristic curve analysis showed the cut-off ratio of fibrin/platelet components related to cancer was 55.7% with a sensitivity of 74.8%, specificity 58.8% and area under the curve (AUC) value of 0.67 (95% CI 0.53 to 0.81), and the cut-off ratio of erythrocyte components was 44.7% with a sensitivity of 71.2%, specificity 58.9% and AUC value of 0.66 (95% CI 0.51 to 0.80).ConclusionsThromboemboli of major cerebral arteries in patients with cancer were mainly composed of fibrin/platelet-rich components.

Background and ObjectivesGynecologic diseases such as uterine fibroids, endometriosis, and adenomyosis are common in women of reproductive age. Case reports and small case series have reported ischemic stroke in women with such common noncancerous gynecologic diseases, and their cause of stroke is frequently attributed to cryptogenic stroke or unconventional mechanisms related to hypercoagulability. However, stroke etiology and prognosis are not well known. We assessed the prevalence of and stroke mechanisms related to common noncancerous gynecologic diseases using hospital-based clinical data.MethodsWe retrospectively identified consecutive female patients with common noncancerous gynecologic diseases (uterine fibroids, endometriosis, and adenomyosis) diagnosed with ischemic stroke/transient ischemic attack (TIA) between the ages of 20 and 59 years admitted to 10 stroke centers in Japan by reviewing prospectively collected data between 2017 and 2019. The clinical, laboratory, and neuroimaging features were evaluated and compared between patients with conventional stroke mechanisms (CSMs) (large artery atherosclerosis, small vessel occlusion, cardioembolism, and other determined etiology) and non-CSMs (cryptogenic stroke and causes related to hypercoagulability such as nonbacterial thrombotic endocarditis and paradoxical embolism) according to the Trial of Org 10172 in Acute Stroke Treatment criteria.ResultsOf the 470 female patients with ischemic stroke/TIA, 39 (8%) (37 ischemic stroke and 2 TIA) had common noncancerous gynecologic diseases. The most common gynecologic diseases were uterine fibroids in 24 (62%) patients, followed by endometriosis in 9 (23%) and adenomyosis in 6 (15%). Twenty patients (51%) were assigned to the non-CSMs group, and 19 patients (49%) were assigned to the CSMs group. Adenomyosis and endometriosis were more frequent in the non-CSMs group than in the CSMs group. CA125 and D-dimer levels were higher in the non-CSMs group than in the CSMs group. Multiple vascular territory infarcts were frequent in patients with adenomyosis (60%) and endometriosis (43%) in the non-CSMs group. No stroke recurrence or death was observed within 3 months after discharge in both the CSMs and non-CSMs groups. Outcomes at 3 months after discharge were similar in both groups.DiscussionIn patients with common noncancerous gynecologic diseases, hypercoagulopathy may play a role in the pathogenesis of ischemic stroke/TIA without CSMs.