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Abstract Background Guidelines provide various recommendations for the use of proton pump inhibitors (PPI) to prevent upper gastrointestinal (UGI) bleeding in acute myocardial infarction (MI) treatment with dual antiplatelet therapy (DAPT). We evaluated the effects of PPIs in reducing the risk of severe UGI bleeding in patients with MI receiving DAPT. Methods This retrospective cohort study included patients admitted for acute MI between 2014 and 2018, based on a nationwide health claims database in Korea. Primary outcome was admission for severe UGI bleeding requiring transfusion within 1 year of MI diagnosis. A multivariable Cox regression model was used to calculate the association between PPI use and severe UGI bleeding risk. Results Of 100,556 patients with MI on DAPT (mean age, 63.7 years; 75.4% men), 37% were prescribed PPIs. Based on risk assessment for UGI bleeding, among 6,392 (6.4%) high-risk and 94,164 (93.6%) low-risk patients, 50.5% and 35.8% received PPIs, respectively. Overall, 0.5% of the patients experienced severe UGI bleeding within 1 year after MI. The use of PPI was associated with a reduced risk of severe UGI bleeding (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.47–0.70; P

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

Abstract The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes. Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (

Abstract Introduction Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). We investigated the primary preventive effect of statins on CVD according to the level of fatty liver index (FLI), which is a marker of NAFLD. Methods We conducted a nested case–control study on the basis of a nationwide health screening cohort in Korea. The participants were divided into tertiles (T1, T2, and T3) according to their FLI score. Cases were defined as individuals who developed CVD (composite of myocardial infarction and stroke). Three controls were matched to each case and multivariable conditional logistic regression analysis was performed. Results Within a cohort of 206,263 participants without prior CVD, 7044 individuals suffered the primary outcome. For the nested case–control study, we selected these 7044 cases along with their corresponding 20,641 matched controls. Individuals in the T3 tertiles of FLI had a higher risk of CVD than those in the T1 tertile [adjusted odds ratio (OR) 1.30; 95% confidence interval (CI) 1.20–1.40, P

Abstract Background Cardiovascular disease (CVD) is a major complication in type 1 diabetes mellitus (T1D) patients. Previous studies have suggested that statins may be helpful for prevention of CVD in T1D, but there are limited data on the role of statins in T1D. We investigated the relationship between statin treatment and cardiovascular risk in T1D patients using a population-based cohort. Methods We conducted a retrospective cohort study using the Korean nationwide health insurance database from January 2007 to December 2017. This study included 11,009 T1D patients aged ≥ 20 years without a prior history of CVD. The primary outcome was a composite development of stroke or myocardial infarction. Statin use during follow-up was treated as a time-varying variable. We performed a multivariable time-dependent Cox regression analysis adjusting for sex, age, type of insurance, hypertension, renal disease, and use of antiplatelets and renin–angiotensin–aldosterone system inhibitors. Results During the mean follow-up of 9.9 ± 3.7 years of follow-up, 931 T1D patients (8.5%) suffered primary outcome. Statin treatment was associated with a reduced risk of the primary outcome (adjusted hazard ratio, 0.76; 95% confidence interval 0.66–0.88; p

Abstract Introduction Retinal artery occlusion (RAO) is a major cause of acute visual loss and patients with RAO have an increased risk for subsequent cardiovascular events. However, there is little evidence of whether the use of statins is associated with the prevention of cardiovascular events in patients with RAO. We investigated whether statin treatment in patients with RAO is associated with a lower risk of cardiovascular events. Methods This study was a historical cohort study with nested case–control analysis. Using the nationwide health insurance claims database in Korea, we retrospectively established a cohort of newly diagnosed RAO patients without prior cardiovascular events between January 2008 and March 2020. We defined the case group as those who had cardiovascular events (stroke or myocardial infarction) and the control group as RAO patients without primary outcome matched by sex, age, comorbidities, and duration of follow-up (1:2 incidence density sampling). Conditional logistic regression was performed. Results Among 13,843 patients newly diagnosed with RAO, 1030 patients had cardiovascular events (mean follow-up period of 6.4 ± 3.7 years). A total of 957 cases were matched to 1914 controls. Throughout the study period, the proportion of patients taking statin was less than half. Statin treatment after RAO was associated with a low risk of cardiovascular events (adjusted OR, 0.637; 95% CI 0.520–0.780; P

Abstract Introduction Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D. Methods This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014–2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone. Results From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61–0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64–0.78; p

Background Approximately 10% of patients with acute ischemic stroke with large‐vessel occlusion (LVO) have mild neurological deficits. Although leptomeningeal collaterals (LMCs) are the major determinant of clinical outcomes for patients with acute ischemic stroke with LVO, the contribution of baseline LMC status to subsequent infarct progression in patients with mild stroke with LVO is poorly defined. Methods This observational study included patients with acute anterior circulation LVO and mild stroke symptoms (National Institutes of Health Stroke Scale < 6) from a prospectively collected, multicenter, national stroke registry. The Alberta Stroke Program Early Computed Tomography Score was quantified on the initial and follow‐up images. An infarct progression, defined as any Alberta Stroke Program Early Computed Tomography Score decrease between the initial versus follow‐up scans, was categorized as either 0/1/2+. The LMCs on the baseline images were graded as good, fair, or poor. Results Of the 623 included patients (mean age, 67.6±13.4 years; 380 [61.0%] men; 186 [29.9%] with reperfusion treatment), the baseline LMC was graded as good in 331 (53.1%), fair in 219 (35.2%), and poor in 73 (11.7%). The Alberta Stroke Program Early Computed Tomography Score decrement was noted as 0 in 288 (46%) patients, 1 in 154 (24%), and 2+ in 181 (29%). A poor LMC was associated with an infarct progression (adjusted odds ratio, 2.05 [95% CI, 1.22–3.47]). Conclusions Poor collateral blood flow was associated with infarct progression in patients with acute ischemic stroke with LVO and mild symptoms. In this selective population, early assessment of collateral blood flow status can help in early detection of patients susceptible to infarct progression.

Background d‐Dimer level is a marker of hypercoagulability, which is associated with thrombus formation and resolution. We investigated the value of d‐dimer levels in predicting outcomes of acute ischemic stroke in patients who underwent endovascular treatment (EVT). Methods We analyzed data of patients who underwent only EVT from the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) registry. d‐Dimer levels were routinely measured in 10 of 15 participating hospitals. Patients were grouped into tertiles (tertile 1, tertile 2, and tertile 3) according to d‐dimer levels (lowest, moderate, and highest, respectively). We compared serial scores on the National Institutes of Health Stroke Scale at baseline, on day 1 of hospitalization, and at discharge; functional outcome 3 months after EVT; and rate of mortality within 6 months after EVT. Results In the 170 patients, the median d‐dimer level was 477 ng/mL (interquartile range, 249–988 ng/mL). In tertile 3, the National Institutes of Health Stroke Scale score was higher at discharge than on day 1 of hospitalization. Poor outcome 3 months after EVT (modified Rankin Scale score, ≥3) was more common with high d‐dimer levels (26.3% of tertile 1, 57.1% of tertile 2, and 76.4% of tertile 3; P

OBJECTIVES Retinal vein occlusion (RVO) is associated with an increased risk of future cardiovascular events. Statin therapy is a key cornerstone in prevention for patients at high cardiovascular risk. However, little is known about the role of statin therapy for patients with RVO. This study evaluated whether statin treatment in patients with RVO was associated with a lower risk of cardiovascular events. METHODS A population-based, nested case-control study was conducted with a cohort of newly diagnosed RVO patients without prior cardiovascular disease between 2008 and 2020 using a nationwide health claims database in Korea. From this cohort of RVO patients, we identified cases of cardiovascular events (stroke or myocardial infarction) after RVO and matched controls based on sex, age, insurance type, antiplatelet use, and underlying comorbidities using 1:2 incidence density sampling. RESULTS Using a cohort of 142,759 patients with newly diagnosed RVO, we selected 6,810 cases and 13,620 matched controls. A significantly lower risk of cardiovascular events (adjusted odds ratio, 0.604; 95% confidence interval, 0.557 to 0.655) was observed in RVO patients with statin treatment than in those without statin treatment. Statin treatment was associated with a reduced risk for both stroke and myocardial infarction after RVO. Longer statin treatment after RVO was associated with a lower risk for cardiovascular events. CONCLUSIONS Statin treatment was associated with a lower risk for future cardiovascular events in patients with newly diagnosed RVO. Further studies are warranted to clarify the potential cardiovascular preventive role of statins in patients with RVO.

Abstract In ischemic stroke patients undergoing endovascular treatment (EVT), we aimed to test the hypothesis that cerebral microbleeds (CMBs) are associated with clinical outcomes, while estimating the mediating effects of hemorrhagic transformation (HT), small-vessel disease burden (white matter hyperintensities, WMH), and procedural success. From a multicenter EVT registry, patients who underwent pretreatment MR imaging were analyzed. They were trichotomized according to presence of CMBs (none vs. 1–4 vs. ≥ 5). The association between CMB burden and 3-month mRS was evaluated using multivariable ordinal logistic regression, and mediation analyses were conducted to estimate percent mediation. Of 577 patients, CMBs were present in 91 (15.8%); 67 (11.6%) had 1–4 CMBs, and 24 (4.2%) had ≥ 5. Increases in CMBs were associated with hemorrhagic complications (β = 0.27 [0.06–0.047], p = 0.010) in multivariable analysis. The CMB effect on outcome was partially mediated by post-procedural HT degree (percent mediation, 14% [0–42]), WMH (23% [7–57]) and lower rates of successful reperfusion (6% [0–25]). In conclusion, the influence of CMBs on clinical outcomes is mediated by small-vessel disease burden, post-procedural HT, and lower reperfusion rates, listed in order of percent mediation size.

Abstract We performed pupillometer testing on 132 patients with Parkinson’s disease, stratified into two groups according to the disease stage. Neurological examinations and pupillometry were performed in the ON state. Patients in the Hoehn and Yahr stages 1 and 2 comprised the early group, and patients in stages 3–5 formed the late group. We performed age- and sex-matched (2:1) propensity score matching to compensate for the effect of age on pupil light reflex. Eight pupillometer parameters were measured and compared between the two groups. After the propensity score matching, the early group had 64 patients and the late group had 32 patients. The late group had a longer disease duration and took a higher levodopa equivalent dose than the early group. The constriction velocity (P = 0.006) and maximum constriction velocity (P = 0.005) were significantly faster in the early group than in the late group. Pupil size, minimum diameter, and dilation velocity were similar in both groups. The pupillary contraction velocity decreased with the disease progression, suggesting that the progression of Parkinson’s disease could be identified by the pupil constriction velocity.

Background and purposeThere is much uncertainty in endovascular treatment (EVT) decisions in patients with acute large vessel occlusion (LVO) and mild neurological deficits.MethodsFrom a prospective, nationwide stroke registry, all patients with LVO and baseline NIHSS

Background and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. Methods Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. Results Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). Conclusions The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Abstract Background Isolated anterior cerebral artery territory (ACA) infarction is a rare phenomenon, and is known to have distinctive clinical features. Little is known regarding the clinical prognosis of isolated ACA territory infarction with associated factors, and its impact on dwelling and job status. We investigated the short- and long-term outcomes of anterior cerebral artery (ACA) territory infarction, and the associated factors involved in the development of the distinctive symptoms. Methods This retrospective study in a prospective cohort of acute ischaemic stroke patients included consecutively enrolled patients with isolated ACA territory infarction. We investigated the functional status using the modified Rankin scale (mRS) score at discharge, three months’ post-discharge, and one-year post-discharge. We also investigated the occlusion site of the ACA (proximal vs. distal); presence of distinctive symptoms of ACA territory infarction including behaviour changes, indifference, aphasia, and urinary incontinence; and the effect of these symptoms on dwelling and job status one year after discharge. Results Between April 2014 and March 2019, 47 patients with isolated ACA territory infarction were included. Twenty-nine patients (61.7 %) had good outcomes (mRS ≤ 2) at discharge; however, the mRS score increased at three months (40; 85.1 %, p

Abstract The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p

Abstract Background Although stent retriever (SR) is recommended as a frontline device of endovascular treatment (EVT) for embolic large artery occlusion causing acute ischemic stroke, contact aspiration (CA) device showed similar efficacy in the recent trials. However, the efficacy of the both devices as first-line therapy for intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion has not yet been established. Therefore, we compared the immediate effects and final outcomes of SR and CA as first-line devices for treating ICAS-related occlusions. Methods We retrospectively analyzed the data of patients who underwent EVT for acute ischemic stroke from the registry of three Korean hospitals. Patients with ICAS-related occlusion who were treated within 24 h of onset of the symptoms were included. We investigated immediate reperfusion performance, immediate safety outcomes, and 3-month clinical outcomes for the two first-line devices. Results Of the 720 registered patients, 111 were eligible for this study. Forty-nine patients (44.1%) used SR and 62 (55.9%) used CA as the first-line device. Achieving successful reperfusion immediately after first-line thrombectomy was more frequent in the SR group than that in the CA group (77.6% vs. 43.5%, p = 0.001), with fewer additional rescue treatments (12.2% vs. 59.7%, p

Abstract Background Compared with embolic occlusions, intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusions (LVOs) often require rescue treatment following mechanical thrombectomy (MT). Herein, we hypothesized that local tirofiban infusion can be effective and safe for remnant stenosis in LVO during endovascular treatment and can improve clinical outcomes. Methods This observational multicenter registry study (January 2011 to February 2016) included patients with ICAS who underwent endovascular treatment for LVO within 24 h after stroke onset. An underlying fixed focal stenosis at the occlusion site observed on cerebral angiography during and after MT was retrospectively determined as a surrogate marker of ICAS. Procedural and clinical outcomes were compared between the tirofiban and non-tirofiban groups. Results Of 118 patients, 59 received local tirofiban infusion. Compared to the non-tirofiban group, patients were older (non-tirofiban group versus tirofiban group; median, 63 years vs. 71 years, p = 0.015) and the onset-to-puncture time was longer (median, 275 min vs. 395 min, p = 0.036) in the tirofiban group. The median percent of residual stenosis prior to rescue treatment tended to be higher in the tirofiban group (80 [71–86] vs. 83 [79–90], p = 0.056). Final reperfusion success (modified Treatment In Cerebral Ischemic 2b–3) was more frequent (42.4%vs. 86.4%, p = 0.016) and post-procedure parenchymal hematoma type 2 and/or thick subarachnoid hemorrhages were less frequent (15.3%vs. 5.1%, p = 0.068) in the tirofiban group. The frequency of favorable outcomes 3 months after endovascular treatment (modified Rankin Scale 0–2) was significantly higher in the tirofiban group (32.2% vs. 52.5%, p = 0.025), and tirofiban administration was an independent predictor of favorable outcomes (odds ratio, 2.991; 95% confidence interval, 1.011–8.848; p = 0.048). Conclusions Local tirofiban infusion can be a feasible adjuvant treatment option for patients with ICAS-LVO.

Background and Purpose Nonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known. Methods We included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up. Results Among the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P

Purpose Emergent intracranial occlusions causing acute ischemic stroke are often related to extracranial atherosclerotic stenosis. This study aimed to investigate the association between post-procedure intracerebral hemorrhage (ICH) and emergent extracranial artery stenting and assess their effects on clinical outcomes in patients with acute ischemic stroke. Materials and Methods We retrospectively analyzed patients undergoing hyperacute endovascular treatment for cervicocephalic vascular occlusion in three Korean hospitals between January 2011 and February 2016. Patients who had extracranial artery involvement and were treated from 24 hours of symptom onset to puncture were included in this study, and they were divided into the extracranial stenting (ES) and non-ES groups. Any type of petechial hemorrhages and parenchymal hematoma was defined as ICH for the current study. Results In total, 76 patients were included in this study. Among them, 56 patients underwent ES, and 20 patients did not. Baseline characteristics, risk factors, laboratory data, treatment methods, successful reperfusion rates, and baseline stenotic degrees of extracranial internal carotid artery did not differ between these two groups. However, atrial fibrillation was more frequent in patients without than with ES (P=0.002), and post-procedure ICH was more frequent in patients with than without ES (P=0.035). Logistic regression models revealed that ES was independently associated with post-procedure ICH (odds ratio [OR], 7.807; 95% confidence interval [CI], 1.213–50.248; P=0.031), and ICH was independently associated with poor clinical outcomes (OR, 0.202; 95% CI, 0.054–0.759; P=0.018); however, ES itself was not associated with clinical outcomes (OR, 0.530; 95% CI, 0.117–2.395; P=0.409). Notably, ICH and ES had interaction for predicting good outcomes (P=0.041). Conclusion Post-procedure ICH was associated with ES and poor clinical outcomes. Therefore, ES should be cautiously considered in patients with hyperacute stroke.

Introduction: In patients with intracranial large vessel occlusion (LVO) who undergo endovascular treatment (EVT), recanalization failure may be related to intracranial atherosclerotic stenosis (ICAS). We evaluated whether the risk factors of recanalization failure could possibly be a marker of ICAS among various types of LVO.Methods: From a multicenter registry, patients with middle cerebral artery M1 segment occlusions who underwent thrombectomy within 24 h were included. Based on the on-procedure and post-procedure angiographic findings, patients were classified into embolic, ICAS-related, tandem occlusion, and recanalization failure groups. Recanalization failure was defined if the occluded vessel could not be recanalized by stent retrieval, contact aspiration, or local lytics treatment. Risk factors, imaging markers, and EVT methods were compared between groups.Results: Among 326 patients, 214 were classified as embolism, 76 as ICAS, 16 as tandem, and 20 as recanalization failure. The group with recanalization failure showed higher scores on the National Institutes of Health Stroke Scale (NIHSS) (median, 16.0 vs. 14.5 vs. 14.0 vs. 17.0, p = 0.097), frequent atrial fibrillation (59.3 vs. 18.4 vs. 0 vs. 40.0% p < 0.001), and elevation in erythrocyte sedimentation rate (ESR) (14.5 ± 15.7 vs. 15.0 ± 14.1 vs. 21.2 ± 19.5 vs. 36.0 ± 32.9, p < 0.001) among the groups. The rate of computed tomography angiography-based truncal-type occlusion in recanalization failure group was not as high as that in the ICAS group (8.1 vs. 37.5 vs. 0 vs. 16.7%, p < 0.001). Balloon guide catheters (BGC) were less frequently utilized in the recanalization failure group as compared to their use in the other groups (72.0 vs. 72.4 vs. 62.5 vs. 30.0%, p = 0.001). In the multivariable analysis, initial higher NIHSS [odds ratio (OR), 1.11 95% confidence interval (CI), 1.01–1.22 p = 0.027], higher ESR (OR, 1.03 CI, 1.01–1.05 p = 0.006), and non-use of BGCs (OR, 3.41 CI, 1.14–10.17 p = 0.028) were associated with recanalization failure. In M1 occlusions, the predominant mechanism of recanalization failure was presumed to be embolic in 80% and due to ICAS in 20%.Conclusion: The analysis of recanalization failures does not suggest an underlying predominant ICAS mechanism. Sufficient utilization of thrombectomy devices and procedures may improve the rates of recanalization.

Purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). However, it remains unclear which stroke patients should undergo evaluation for asymptomatic CAD, and which screening tools are appropriate. We investigated the role of coronary artery calcium (CAC) score as a screening tool for asymptomatic but severe CAD in acute stroke patients. We determined the selection criteria for CAC screening based on risk factors and cerebral atherosclerosis.Materials and Methods: The present study included consecutive patients with acute stroke who had undergone cerebral angiography and multi-detector computed tomography coronary angiography. Severe CAD was defined as left main artery disease or three-vessel disease. Enrolled patients were randomly assigned to two sets; a set for developing selection criteria and a set for validation. To develop selection criteria, we identified associated factors with severe CAD regarding clinical factors and cerebral atherosclerosis. CAD predictability of selection criteria with the CAC score was calculated.Results: Overall, 2,658 patients were included. Severe CAD was present in 360 patients (13.5%). CAC score was associated with CAD severity (P < 0.001). In the development set (N = 1,860), severe CAD was associated with age >65 years [odds ratio (95% confidence interval), 2.62 (1.93–3.55)], male sex (1.81 [1.33–2.46]), dyslipidemia (1.77 [1.25–2.61]), peripheral artery disease (2.64 [1.37–5.06]) and stenosis in the cervicocephalic branches, including the internal carotid (2.79 [2.06–3.78]) and vertebrobasilar arteries (2.08 [1.57–2.76]). We determined the combination of clinical and arterial factors as the selection criteria for CAC evaluation. The cut-off criterion was two or more elements of the selection criteria. The area under the curve (AUC) of the selection criteria was 0.701. The AUC significantly improved to 0.836 when the CAC score was added (P < 0.001). In the validation set (N = 798), the AUC of the selection criteria only was 0.661, and that of the CAC score was 0.833. The AUC of the selection criteria + CAC score significantly improved to 0.861(P < 0.001).Conclusion: The necessity for CAC evaluation could be determined based on the presence of risk factors and significant stenosis of the cervicocephalic arteries. CAC evaluation may be useful for screening for severe CAD in stroke patients.

Background Retinal artery occlusion can lead to sudden visual loss without pain. The acute management of retinal artery occlusion remains unresolved. Case Report A 65-year-old male was hospitalized to an emergency room for visual loss on the left side within 6 hours of onset. Combined occlusion at retinal artery and ciliary artery was confirmed by an ophthalmologist and we assessed ophthalmic artery occlusion. However, MRA revealed no significant steno-occlusion of internal carotid artery. Transfemoral cerebral angiography was carried out immediately and showed a movable thrombus at the orifice of the ophthalmic artery. We decided on endovascular thrombectomy to prevent permanent visual loss. Finally, his visual acuity was improved after successful thrombectomy. Conclusions Although MRA is intact, small thrombus right at the orifice of the ophthalmic artery can cause a sudden monocular visual loss due to occlusion of the retinal artery. In this setting, urgent endovascular thrombectomy can offer visual improvement.

The stable and seamless connection of the mobile communication system is expected to closely link an unprecedented number of things, including smart cars such as autonomous vehicles, in the near future. These vehicles will operate based on the data transmitted over hundreds of sensors. However, an attacker could remotely control a car by intercepting and tampering with these data, and even threaten the life of the driver. In this paper, we propose a code-based authentication scheme that provides both secure booting and lightweight data integrity checking to prevent unauthorized remote control. First, we split some of the core code involved in booting the car, and divide it into several secret pieces known as a share polynomial. One of these is distributed to the driver and is then used to reconstruct the booting code, allowing only the driver with this share polynomial to recover the code and start the car. The remaining share polynomials are distributed to the vehicle control unit and used to generate a lightweight pairwise key. Since the proposed scheme requires only multiplication to generate the pairwise key, it is computationally efficient compared to conventional schemes that require expensive exponential computation. Additional communication is not required to set up the pairwise key, because it needs nothing but the id value of the partner. Thus, our scheme is highly suitable for low-performance devices inside the car. We used the Robot OS system, a widely used autonomous vehicle platform, to implement the proposed scheme and evaluated its feasibility on various test cases.

Abstract Background Accurate evaluation of diplopia during bedside physical examination is challenging. We developed a new computerized red glass test (CRT) to detect, localize, and quantify diplopia and investigated whether the CRT is useful and feasible. Methods During the CRT, a white dot randomly appears on a monitor. Because a red glass is applied on the right eye, a patient can see one white dot and one red dot when diplopia is present. We defined the degree of diplopia as the direct distance of the two points with the largest deviation and compared the degree with the Hess score and Hess area ratio. Results We prospectively enrolled 14 patients with binocular diplopia. Test–retest reliability of the CRT was excellent (overall intraclass correlation coefficient = 0.948, 95% CI 0.939–0.956). The degree of diplopia in the CRT was well correlated with both the Hess score (r = 0.719, p = 0.005) and the Hess area ratio (r = −0.620, p = 0.018). Conclusions The CRT can easily detect the presence of diplopia and provided the quantitative values of the degree of diplopia. The CRT was useful and feasible for improving routine bedside examination.

The prediction of successful recanalization following thrombolytic or endovascular treatment may be helpful to determine the strategy of recanalization treatment in acute stroke. Thrombus can be detected using noncontrast computed tomography (CT) as a hyperdense artery sign or blooming artifact on a T2*-weighted gradient-recalled image. The detection of thrombus using CT depends on slice thickness. Thrombus burden can be determined in terms of the length, volume, and clot burden score. The thrombus size can be quantitatively measured on thin-section CT or CT angiography/magnetic resonance angiography. The determination of thrombus size may be predictive of successful recanalization/non-recanalization after intravenous thrombolysis and endovascular treatment. However, cut-offs of thrombus size for predicting recanalization/non-recanalization are different among studies, due to different methods of measurements. Thus, a standardized method to measure the thrombus is necessary for thrombus imaging to be useful and reliable in clinical practice. Software-based measurements may provide a reliable and accurate assessment. The measurement should be easy and rapid to be more widely used in practice, which could be achieved by improvement of the user interface. In addition to prediction of recanalization, sequential measurements of thrombus volume before and after the treatment may also be useful to determine the efficacy of new thrombolytic drugs. This manuscript reviews the diagnosis of thrombus, prediction of recanalization using thrombus imaging, and practical considerations for the measurement of thrombus burden and density on CT.

Background: Overweight contributes to type 2 diabetes mellitus (T2DM) development. Although the obesity paradox has been suggested in many vascular diseases, little information is available about stroke patients with T2DM. We investigated whether body mass index (BMI) has a differential impact on the incidence of major adverse cardiovascular events (MACE) in patients with ischemic stroke and T2DM.Methods: This retrospective study used a prospective cohort of patients with acute ischemic stroke and included consecutive patients with T2DM after excluding those with active cancer or who died within 1 month of an index stroke. We investigated the long-term risk of MACE (stroke, myocardial infarction, unstable angina, coronary revascularization procedure, and death) according to BMI.Results: Among the 1,338 patients, MACE occurred in 415 patients (31.1%) during a median follow-up of 3.6 years. Compared to the normal weight group, MACE occurred more frequently in the underweight group [adjusted hazard ratio (HR) 1.55, 95% confidence interval (CI): 1.01–2.38], but less frequently in the overweight group (adjusted HR: 0.87, 95% CI: 0.70–1.08) and obese group (adjusted HR: 0.58, 95% CI: 0.41–0.86) group. In analyses of association between BMI and each component of MACE, stroke and cardiovascular mortality indicated an L- and a U-shaped pattern, respectively. However, fatal or non-fatal stroke showed an inverse pattern, and fatal or non-fatal cardiovascular events showed a reversed J-shaped pattern.Discussions: This study showed the overall presence of the obesity paradox in stroke patients with T2DM. However, obese patients had different risks of cardiovascular events and stroke.

Background: Differentiation of embolic and atherosclerotic occlusions is difficult prior to endovascular treatment (EVT) of acute ischemic stroke due to intracranial large artery occlusions. CTA-determined occlusion type has been reported to be associated with a negative cardiac embolic source and stent retriever failure, a potential of intracranial atherosclerosis (ICAS)-related occlusions. In this study, we evaluated the agreement between preprocedural identification of CTA-determined truncal-type occlusion (TTO) and postprocedural evaluation of underlying fixed focal stenosis (FFS) in the occlusion site.Methods: Patients who underwent intracranial EVT for acute ischemic stroke within 24 h of onset and who had baseline CTA were identified from a multicenter registry collected between January 2011 and May 2016. Preprocedural occlusion type was classified as TTO (target artery bifurcation saved) or branching-site occlusion (bifurcation involved) on CTA. As for postprocedural identification, FFS was evaluated by stepwise analyses of procedural and postprocedural angiographies. The agreement between TTO and FFS was evaluated in respective intracranial vascular beds. Receiver operating characteristics analyses were also performed.Results: A total of 509 patients were included [intracranial internal carotid artery (ICA): 193, middle cerebral artery (MCA) M1: 256, and vertebrobasilar artery (VBA): 60]. In preprocedural identification, 33 (17.1%), 41 (16.0%), and 29 patients (48.3%) had TTOs, respectively. TTOs had good agreement with angiographic FFS in M1 (positive predictive value: 63.4%, negative predictive value: 83.2%, likelihood ratio: 5.42, Pmultivariate < 0.001) and VBA (72.4%, 96.8%, and 4.54, respectively, Pmultivariate = 0.004), but not in intracranial ICA occlusions (Pmultivariate = 0.358). The area under the receiver operating characteristics curve was the largest for VBA (0.872, p < 0.001), followed by MCA M1 (0.671, p < 0.001), and intracranial ICA (0.551, p = 0.465).Conclusions: Agreement between preprocedural TTO and postprocedural FFS, both of which are surrogate markers for ICAS-related occlusions, is highest for VBA, followed by MCA M1 occlusions. There is no significant association in intracranial ICA.

Background: Solitaire, a representative stent retriever, has shown high performance in removing embolic clots. However, its reperfusion potential in intracranial atherosclerotic stenosis (ICAS)-related occlusions has rarely been reported. In this ROSE ASSIST study, we hypothesized that Solitaire device is as effective and safe for removing in situ thrombi in ICAS-related occlusions as it is for removal of embolic occlusions.Methods: Data from ASIAN KR, an observational multicenter registry (n = 720) enrolling patients who have undergone endovascular treatment for acute cervicocephalic artery occlusions, were retrospectively reviewed. Through blinded evaluations, occlusions were classified as ICAS-related (significant fixed focal stenosis observed at the occlusion site during endovascular treatment) or embolic (no or minimal stenosis observed). Among patients treated within 720 min after stroke onset, those who undertook Solitaire thrombectomy and whose underlying etiology was ICAS-related or embolic were included. The primary endpoint was immediate successful reperfusion (modified Treatment In Cerebral Ischemia 2b−3) after Solitaire stent retrieval. The safety endpoint included intracerebral hemorrhagic transformation and subarachnoid hemorrhage. Comparative analyses were performed between embolic and ICAS-related occlusions with 2:1 propensity score matching.Results: In total, 303 patients (embolic, 228; ICAS-related, 75) were included in the analyses. As for the primary endpoint, the immediate successful reperfusion rate following Solitaire thrombectomy did not differ between the two etiologic groups after propensity score matching (73.1% embolic vs. 65.8% ICAS-related, p = 0.261). The final successful reperfusion grade was also similar in the two groups (79.3 vs. 72.0%, p = 0.219). The grades and frequencies of intracerebral hemorrhagic transformation and subarachnoid hemorrhage did not differ between groups (p = 0.134 and p = 0.269, respectively).Conclusions: The immediate reperfusion performance in terms of thrombus removal of Solitaire thrombectomy for ICAS-related occlusions was similar to that for embolic occlusions.

Background and Purpose Cerebral small vessel disease (SVDs) are related with large artery atherosclerosis. However, the association between aortic atheroma (AA) and cerebral small vessel disease has rarely been reported. This study evaluated the relationship between presence and burden of AAs and those of SVDs in patients with acute ischemic stroke. Methods We included 737 consecutive patients who underwent transesophageal echocardiography (TEE) and brain magnetic resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were classified as complex aortic plaque (CAP) and simple aortic plaque (SAP). Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar infarctions (ALIs), and total SVD score, were investigated. Results AA was found by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One or more types of SVDs was found in 269 (36.4%) patients. In multivariable analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13), high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA than those without AA. Each 1-point increase in total SVD score increased the odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP (OR 1.54, 95% CI 1.35-1.75). Conclusions In this study, patients with AA frequently had cerebral SVDs. Larger burden of AA was associated with advanced cerebral SVDs. Our findings give an additional information for positive relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute ischemic stroke patients.

Background and Purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation.

INTRODUCTION:Cardioembolic (CE) risks is usually considered as the main mechanism of ischemic stroke in non-valvular atrial fibrillation (NVAF) patients. However, a substantial number of ischemic strokes in NVAF patients are related to non-CE mechanisms. The aim of this study was to investigate the non-CE risk factors in ischemic stroke patients had NVAF. METHODS:We included 401 patients (65.6% male, 68.6 ± 9.6 years old) who had been hospitalized due to ischemic stroke and had a known or newly diagnosed NVAF. The CE (intracardiac thrombus, dense spontaneous echo contrast, or low left atrial appendage flow velocity) and non-CE (complex aortic plaque, significant carotid stenosis, or intracranial arterial stenosis) risk factors were investigated at the time of the index stroke. RESULTS:The number of CE and non-CE risk factors increased with increasing CHA2DS2-VASc scores (p for trends < 0.001). The presence of CE risk factors was independently associated with persistent atrial fibrillation (p < 0.001), body mass index (p = 0.003), heart failure (p = 0.003), and left atrial volume index (p < 0.001). In contrast, the presence of non-CE risk factors was independently associated with age (p < 0.001), hypertension (p = 0.049), diabetes (p = 0.030), and coronary artery calcium score (CACS; p < 0.001). CACS had the added value in predicting non-CE risk factors of ischemic stroke regardless of the CHA2DS2-VASc risk category (p < 0.001). CONCLUSION:Non-CE risk factors in ischemic stroke patients with NVAF are associated with high CHA2DS2-VASc score and CACS. Atherosclerotic non-CE risk factors should be considered as potential mechanisms of stroke even in patients with AF-associated ischemic stroke.

To our knowledge, little is known regarding whether white matter hyperintensities (WMH) affect the prognosis of cryptogenic stroke (CS) patients. Understanding this association may be helpful with expecting the prognosis of CS patients.This retrospective observational study enrolled consecutive CS patients who underwent brain MRI and comprehensive cardiac evaluation. Severe WMH was defined as Fazekas' score ≥3. We defined poor functional outcome as modified Rankin Scale score ≥3 at 3 months. Long-term mortality and causes of death were identified using national death certificates and assessed by Kaplan-Meier method and regression analysis model.Among 2732 patients with first-ever ischemic stroke, 599 (21.9%) patients were classified as having CS. After exclusions, 235 patients were enrolled and followed up for a median of 7.7 years (IQR, 6.7-9.0). Severe WMH were found in 81 (34.5%) patients. After adjustments, severe WMH were an independent predictor for poor functional outcomes at 3 months (OR 5.25, 95% CI, 2.07-13.31). Subgroup analysis showed that severe WMH were an independent predictor for long-term mortality only in younger patients (age < 65) (HR 3.11, 95% CI, 1.29-7.50), but not in older patients (HR 1.19, 95% CI, 0.63-2.23).Severe WMH were independently associated with short-term functional outcomes in CS patients and independently associated with long-term mortality in younger CS patients. Grading WMH is of value in predicting prognosis of CS patients with young age.

RAO is caused by various etiologies and subsequent vascular events may be associated with underlying etiologies. Our aim is to investigate the etiologies of RAO, the occurrence of subsequent vascular events and their association in patients with RAO.We analyzed data from 151 consecutive patients presenting with acute non-arteritic RAO between 2003 and 2013 in a single tertiary-care hospital. The primary outcome was the occurrence of a vascular event defined as stroke, myocardial infarction, and vascular death within 365 days of the RAO onset. The Kaplan-Meier survival analysis and Cox proportional hazard model were used to estimate the hazard ratio of the vascular events.Large artery atherosclerosis (LAA) was the etiology more frequently associated with of RAO (41.1%, 62/151). During the one year follow-up, ischemic stroke and vascular events occurred in 8.6% and 9.9% of patients, respectively. Ten vascular events occurred in RAO patients attributed to LAA and 4 occurred in undetermined etiology. RAO patients with LAA had a nearly four times higher risk of vascular events compared to those without LAA (hazard ratio 3.94, 95% confidence interval 1.21-12.81). More than a half of all events occurred within one month and over three fourths of ischemic strokes occurred ipsilateral to the RAO.After occurrence of RAO, there is a high risk of a subsequent vascular event, particularly ipsilateral stroke, within one month. LAA is an independent factor for the occurrence of a subsequent vascular event. Management for the prevention of secondary vascular events is necessary in patients with RAO especially with LAA. Large clinical trials are needed to confirm these findings.

The presence of white matter hyperintensity (WMH) is related to poor long-term outcomes in stroke patients. However, the long-term outcome is unknown in patients with both large artery atherosclerosis (LAA) and WMH.We investigated the impact of WMH on long-term outcome in patients with LAA. Consecutive patients in a prospective stroke registry were included. Patients were followed for a median of 7.7 years (interquartile range, 5.6-9.7). The degree of WMH was assessed by Fazekas grade on fluid-attenuated inversion recovery images. Total WMH burden was calculated by summation of Fazekas scores in periventricular and deep white matter. Severe WMH was defined as total burden score ≥ 3.Among 2529 patients, 639 patients (25.3%) were classified with the LAA subtype. After applying exclusion criteria, the data from 538 patients were analyzed. The mean patient age was 65.7 ± 10.3 years. Severe WMHs were found in 243 patients (45.2%). During follow-up, 200 patients (37.2%) died. Cox regression analysis showed that LAA patients with severe WMH had a 1.50-fold (95% CI, 1.12-2.00, p = 0.007) higher death rate compared to those without. In the older age group (≥65 years), Cox regression revealed that patients with severe WMH had a 1.75-fold (95% CI, 1.15-2.65, p = 0.008) higher 5-year death rate, whereas the younger age group did not have this association.The degree of WMH might be a surrogate marker for long-term outcome in patients with LAA. Atherosclerotic burdens in both small and large arteries might impact long-term prognosis in ischemic stroke patients.

BACKGROUND:Stent retriever has a distinct ability to restore blood flow temporarily before achieving final reperfusion. There has been a limited report regarding the clinical impact of it. We investigated if temporary opening of occluded vessels using a stent retriever before final reperfusion might improve clinical outcome in acute ischemic stroke patients who received the endovascular reperfusion treatment. METHODS:We enrolled consecutive ischemic stroke patients who had an initial occlusive lesion in the anterior circulation and achieved final reperfusion (Thrombolysis In Cerebral Infarction [TICI] ≥2) by endovascular treatment. Temporary opening was defined as the presence of ante grade flow (TICI≥2) during deployment of a stent retriever. Favorable outcome was defined as a modified Rankin scale score≤2 at 90 day. RESULTS:A total of 98 patients were included in the study and temporary opening was achieved in 49 (50%). Temporary opening was associated with favorable outcome (odds ratio, 7.825; 95% confidence interval, 1.592-38.461; p = 0.011) in the multivariate analysis. The probability of having a favorable outcome tended to decrease as time from onset to final reperfusion increased in patients without temporary opening. However, this trend was not evident in the patient with temporary opening. The beneficial effect of temporary opening on clinical outcome seemed to be present in patients with good collaterals but not in patients with poor collaterals. CONCLUSIONS:Temporary opening of occluded vessel using a stent retriever may be beneficial for improving clinical outcome in acute ischemic stroke patients.

Introduction Stent-assisted coil embolisation (SACE) for the treatment of unruptured cerebral aneurysms has been increasingly used. Long-term advantages of antiplatelet therapy (APT) post-SACE treatment are still not well understood. We investigated the long-term effects of APT on clinical prognosis after SACE.Patients and methods We conducted a retrospective study using nationwide health insurance claims data from South Korea, including patients with cerebral aneurysm treated with SACE from January 2009 to December 2020. The study outcomes consisted of the occurrence of cerebral infarction and major haemorrhage. To evaluate the impact of APT, we employed a multivariable time-dependent Cox proportional hazards regression model for each of the three distinct periods: 1–12 months, 12–24 months and >24 months after SACE.Results This study included 17 692 unruptured cerebral aneurysm patients treated with SACE. During the mean follow-up of 4.2 years, there were 379 (2.1%) patients with cerebral infarction and 190 (1.1%) patients with major haemorrhage. The percentage of patients receiving APT was 79.5% at 1 year, which gradually decreased to 58.3% at 2 years after SACE. APT was beneficial in preventing cerebral infarction within 12 months after SACE (adjusted HR (aHR) 0.56; 95% CI, 0.35 to 0.89; p=0.014). After 12 months, this association was not evident. APT increased the risk of haemorrhage after 24 months (aHR 1.76; 95% CI 1.11 to 2.87; p=0.016).Discussion and conclusion Our findings suggest that in patients with unruptured cerebral aneurysm treated with SACE, the reasonable duration of APT for preventing cerebral infarction might be 1 year after SACE.

Background and objective Knowledge regarding the pharmacological treatment for moyamoya disease (MMD), a chronic and progressive cerebrovascular disease conferring greater stroke risk, is limited. In the present study, whether statin therapy is associated with a reduced risk of stroke in patients with MMD was investigated.Methods This was a retrospective cohort study in which the occurrence of stroke in patients with newly diagnosed MMD was investigated using the nationwide health insurance database in Korea from January 2007 to March 2021. A multivariable Cox proportional hazards regression model was constructed for stroke, in which statin therapy after MMD diagnosis was treated as a time-dependent variable. Adjustment was done for sex, age, presence of comorbidities, concurrent stroke, revascularisation surgery and treatment with antiplatelets.Results The present study included 13 373 newly diagnosed patients with MMD; 40.8% had a concurrent stroke at the time of MMD diagnosis. During the mean follow-up of 5.1±3.3 years, 631 patients (4.7%) suffered a stroke event (haemorrhagic stroke: 458 patients, ischaemic stroke: 173 patients). Statin therapy after MMD diagnosis was significantly associated with a reduced risk of stroke (adjusted HR 0.74; 95% CI 0.60 to 0.91, p=0.004). In the secondary outcome analysis, the risk of haemorrhagic stroke (adjusted HR 0.74; 95% CI 0.58 to 0.95, p=0.018) and ischaemic stroke (adjusted HR 0.75; 95% CI 0.52 to 1.08, p=0.124) were reduced with the statin treatment. Taking statins was also associated with a lower risk of all-cause mortality (adjusted HR 0.47; 95% CI 0.33 to 0.67, p