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Cumulative evidence regarding the use of brain magnetic resonance imaging (MRI) for predicting prognosis of unconscious out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM) is available. Theoretically, these patients are at a high risk of developing cerebral infarction. However, there is a paucity of reports regarding the characteristics of cerebral infarction in this population. Thus, we performed a pilot study to identify the characteristics and risk factors of cerebral infarction and to evaluate whether this infarction is associated with clinical outcomes.A single-center, retrospective, registry-based cohort study was conducted at Severance Hospital, a tertiary center. Unconscious OHCA survivors were registered and treated with TTM between September 2011 and December 2015. We included patients who underwent brain MRI in the first week after the return of spontaneous circulation. We excluded patients who underwent any endovascular interventions to focus on "procedure-unrelated" cerebral infarctions. We assessed hypoxic-ischemic encephalopathy (HIE) and procedure-unrelated cerebral infarction separately on MRI. Patients were categorized into the following groups based on MRI findings: HIE (-)/infarction (-), infarction-only, and HIE (+) groups. Conventional vascular risk factors showing p 0.05 in univariate analyses were entered into multivariate logistic regression. We also evaluated if the presence of this procedure-unrelated cerebral infarction lesion or HIE was associated with a poor clinical outcome at discharge, defined as a cerebral performance category of 3-5.Among 71 unconscious OHCA survivors who completed TTM, underwent MRI, and who did not undergo endovascular interventions, 14 (19.7%) patients had procedure-unrelated cerebral infarction based on MRI. Advancing age [odds ratio (OR) 1.11] and atrial fibrillation (OR 5.78) were independently associated with the occurrence of procedure-unrelated cerebral infarction (both p 0.05). There were more patients with poor clinical outcomes at discharge in the HIE (+) group (88.1%) than in the infarction-only (30.0%) or HIE (-)/infarction (-) group (15.8%) (p 0.001). HIE (+) (OR 38.69, p 0.001) was independently associated with poor clinical outcomes at discharge, whereas infarction-only was not (p 0.05), compared to HIE (-)/infarction (-).In this pilot study, procedure-unrelated cerebral infarction was noted in approximately one-fifth of unconscious OHCA survivors who were treated with TTM and underwent MRI. Older age and atrial fibrillation might be associated with the occurrence of procedure-unrelated cerebral infarction, and cerebral infarction was not considered to be associated with clinical outcomes at discharge. Considering that the strict exclusion criteria in this pilot study resulted in a highly selected sample with a relatively small size, further work is needed to verify our findings.

Background and Purpose— We investigated whether measuring the volume and density of a thrombus could predict nonrecanalization after intravenous thrombolysis. Methods— This study included a retrospective cohort to develop a computed tomography marker of thrombus for predicting nonrecanalization after intravenous thrombolysis and a prospective multicenter cohort for validation of this marker. The volume and density of thrombus were measured semiautomatically using 3-dimensional software on a baseline thin-section noncontrast computed tomography (1 or 1.25 mm). Recanalization was assessed on computed tomography angiography or magnetic resonance angiography immediately after intravenous thrombolysis or conventional angiography in patients who underwent further intra-arterial treatment. Nonrecanalization was defined as a modified Thrombolysis in Cerebral Infarction grade 0, 1, 2a. Results— In the retrospective cohort, 162 of 214 patients (76.7%) failed to achieve recanalization. The thrombus volume was significantly larger in patients with nonrecanalization than in those with successful recanalization (149.5±127.6 versus 65.3±58.3 mm 3 ; P P 3 . In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm 3 among 78 enrolled patients achieved successful recanalization. The positive and negative predictive values were 95.5 and 29.4 in the retrospective cohort 100 and 23.3 in the prospective validation cohort, respectively. The thrombus density was not associated with nonrecanalization. Conclusions— Thrombus volume was predictive of nonrecanalization after intravenous thrombolysis. Measurement of thrombus volume may help in determining the recanalization strategy and perhaps identify patients suitable for direct endovascular thrombectomy.

Aortic atheroma is a known cause of ischemic stroke. However, it is unclear whether ischemic stroke is caused by emboli from aortic atheroma or by accompanying atherosclerosis. In this study, we evaluated lesion patterns of patients with complex aortic plaque (CAP) to assume the underlying pathophysiology. Acute ischemic stroke patients who underwent transesophageal echocardiography were included. CAP was defined as a plaque in the proximal aorta ≥ 4 mm thick or with a mobile component. The diffusion-weighted imaging lesion patterns of patients with CAP were compared to those with large arterial atherosclerosis (LAA) or cardioembolism (CE). A total of 64 CAP patients, 127 LAA patients, and 80 CE patients were included. Small cortical pattern was more common in the CAP group (45.3%) than in the LAA (7.9%, p < 0.001) or the CE group (23.8%, p = 0.018). A large cortical pattern was more common in the CE group than in the CAP group (p < 0.001), whereas subcortical only pattern tended to be more common in the CAP group than in the CE group (p = 0.057). In multinominal analysis, the CAP group was more likely to have a small cortical lesion than the LAA group [odds ratio (OR) 14.63; 95% confidence interval (CI) 4.67–45.85] or the CE (OR 3.69, 95% CI 1.19–11.39) group. In conclusion, patients with CAP frequently had small cortical lesions or subcortical single lesion. These findings imply that ischemic stroke in aortic atheroma patients is associated with either small emboli or small artery disease.

Background and Purpose— The presence of intracranial artery calcification is associated with an increased risk for stroke. However, calcified atherosclerotic plaques are also known to be less vulnerable to rupture. Given this discrepancy, we investigated whether the vulnerability of intracranial arterial atherosclerosis differed based on the presence or absence of calcification. Methods— We considered consecutive patients with acute stroke in the unilateral middle cerebral artery (MCA) territory. Patients with any stenotic MCAs were included in this study. Symptomatic MCA was defined as the occurrence of infarctions relevant to the stenotic MCA. The presence of calcification in the MCA was evaluated on noncontrast thin-section computed tomography images using a 3dimensional software package. Generalized estimating equations were used to compare the frequency of calcification between symptomatic and asymptomatic stenosis. Results— Of the 1066 MCAs examined in 533 patients, 645 MCAs were stenotic and were included in the study. Among the 645 stenotic MCAs, 406 MCAs (62.9%) were symptomatic. Calcification was observed in 36 MCAs (5.6%). Calcification in the MCA was more frequently observed in the asymptomatic group (7.9% versus 4.2%; P =0.032). On multivariable analysis, the presence of calcification in MCA atherosclerosis was less frequent in the symptomatic group (odds ratio, 0.46; 95% confidence interval, 0.23–0.92; P =0.027). Conclusions— This study showed that calcified atherosclerosis in the MCA was less frequently symptomatic.

The relationship between liver fibrosis and the occurrence of ischemic stroke is unknown. We investigated the correlation between liver fibrosis assessed with transient elastography (TE) and the risk of ischemic stroke.Between April 2013 and August 2014, patients with acute ischemic stroke and subjects who underwent a health check-up were included in the study. Liver fibrotic burden was assessed with TE in all participants. The degree of liver fibrosis was compared between groups by using various multiple logistic regression models and propensity-score matched analyses.Two hundred ninety-five patients with ischemic stroke (stroke group) and 1942 subjects with health check-up (control group) were included. The mean liver stiffness (LS) on TE (5.6 vs. 4.1 kPa) and the proportion of significant fibrosis (8 kPa) (9.2% vs. 1.8%) were significantly higher in the stroke than in the control group (all p0.05). These trends were observed regardless of body mass index, the degree of hepatic steatosis, and metabolic syndrome (all p0.05). The adjusted odds ratio (OR) for ischemic stroke was 1.268 (95% confidence intervals [CI] 1.183-1.358) per 1 kPa increase and 12.033 (95% CI 5.180-27.948) for significant fibrosis, compared with no fibrosis (all p 0.05). Propensity-score matched analysis also confirmed that liver fibrosis was independently associated with the risk of ischemic stroke (OR 1.804 [95% CI 1.461-2.230] per 1 kPa increase, 13.184 [95% CI 3.127-55.645] for significant fibrosis, compared with no fibrosis; all p0.001).The degree of liver fibrosis, assessed with TE, was significantly associated with the risk of ischemic stroke.

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 Acute superior mesenteric artery occlusion is a life-threatening disease that often has nonspecific symptoms. However, it should be suspected in those with known risk factors such as atrial fibrillation, cardiac thrombus or cardiac valvular disease. Case Report We reported two cases of acute thromboembolic occlusions of superior mesenteric artery that developed in acute cerebral infarction patients with confirmed atrial fibrillation. Conclusions Nonspecific symptoms of acute superior mesenteric artery occlusion should be closely monitored in acute cerebral infarction patients with atrial fibrillation, considering significance of early management of both vascular disease entities.

Background: Central sleep apnea is characterized by loss of automatic respiration during sleep. There are only a few reports which document that medullary infarction resulted in central sleep apnea and failure in early recognition of this condition could be catastrophic. We report a case of central sleep apnea following lateral medullary infarction. Case Report: A 49-year-old woman with an unknown past history presented with sudden onset of dizziness, loss of balance, and dysarthria for 1-hour duration. Diffusion-weighted imaging confirmed right lateral medullary infarction. She had episodes of hypercapnia and respiratory arrest due to central sleep apnea, which was confirmed by polysomnography. Tracheostomy was performed and she was put on a home ventilator. After 3 months, follow-up polysomnography showed disappearance of central sleep apnea. Conclusion: Patients with lateral medullary infarction need to be monitored closely with respect to the respiratory pattern.

Although early neurological deterioration (END) during the acute stroke period is known to be directly associated with poor short- and long-term outcomes, few studies have investigated the ability to predict END. The aim of this study was to investigate whether there are differences in the occurrence of END according to the ischemic stroke predictive risk score (iScore), which was developed to predict short- and long-term mortality.We collected data from 2150 consecutive ischemic stroke patients who were admitted to 3 study hospitals between January 2012 and June 2014. END was defined as an increase (≥4) in the National Institutes of Health Stroke Scale score within the first 72 hours of stroke onset. We calculated the 30-day iScore for each patient to determine the relationship between the iScore and occurrence of END.Among 2150 patients, END was observed in 146 patients (6.8%). There was a positive correlation between the iScore and occurrence of END. After adjusting for potential confounders, the iScore was independently associated with END (odds ratio: 1.217 per 20-point increase in iScore, 95% confidence interval: 1.121-1.321, P .001). There was good correlation between observed and expected outcomes predicted by the iScore (Pearson correlation coefficient: r = .950, P .001).The iScore can predict the risk of END development within the acute stroke stage.

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-naive 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 mm(3) vs. placebo: 0.3±1.3 mm(3); 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.

Background and Purpose— We investigated the relationship between the degree of thrombus resolution and the time from stroke onset or thrombus formation to intravenous tissue-type plasminogen activator (tPA) treatment. Methods— In patients with stroke, we measured thrombus volume on thin-section noncontrast brain computed tomographic scans taken at baseline and 1 hour after tPA administration. We determined the association between the time from symptom onset to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model of FeCl 3 -induced carotid artery thrombosis, we investigated the effect of tPA administered at different time intervals after thrombus formation, using Doppler-based blood flow measurement. Results— Of 249 patients enrolled, 171 showed thrombus on baseline computed tomography. Thrombus was resolved by ≥50% in 43 patients (25.1%, good volume reduction) and by P =0.006) and the frequency of final recanalization decreased ( P for trends=0.006). Conclusions— Early administration of tPA after stroke onset is associated with better thrombus resolution.

Background and Purpose— Spontaneous echo contrast (SEC) is frequently detected in patients with atrial fibrillation (AF). Coexisting SEC in patients with AF may be associated with heightened thrombogenicity, which affects stroke outcomes. Methods— Consecutive stroke patients with nonvalvular AF who underwent transesophageal echocardiography were included in this study. We compared initial stroke severity and functional outcome at 3 months between the patients with and those without SEC. Results— Of 440 patients with nonvalvular AF who underwent transesophageal echocardiography during a 7-year period, 193 (43.9%) patients had SEC. Stroke was more severe in the patients with SEC than in those without SEC (National Institute of Health Stroke Scale score: median [interquartile range], 5 [2–12] versus 3 [1–8]; P =0.004). The patients with SEC more frequently had poor functional outcomes (modified Rankin scale score of >2) at 3 months than those without SEC (32.3% versus 16.1%; P Conclusions— In the ischemic stroke patients with nonvalvular AF, coexisting SEC was associated with more severe stroke and was predictive of poor long-term functional outcome.

Background and purpose: Many patients with ischemic stroke have concomitant coronary artery disease (CAD). Coronary screening is recommended in patients with high risks for CAD. It remains uncertain which group of stroke patients need evaluation for asymptomatic CAD, and which evaluation tool is appropriate for stroke patients. We investigated whether the coronary artery calcium (CAC) scores could predict significant CAD in patients with acute stroke and which stroke patients need a screening test for significant CAD. Methods: Among consecutive stroke patients between September 2011 and August 2013, a total of 1143 patients who underwent multiple detector CT coronary angiography and cerebral angiography were included. Atherosclerotic stenosis ≥ 50% or obstruction was classified as significant stenosis in coronary and cerebral arteries. Patients were grouped into four subgroups on the basis of CAC score: 0, 0.1-99.9, 100-399.9, and ≥ 400. Presence of hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking were considered as risk factors. Results: Of 1143 patients, significant stenosis was detected in 164 patients (14.3%) in the internal carotid artery (ICA), 279 (24.4%) in the vertebrobasilar artery (VBA), and 81 (7.1%) in the both ICA and VBA. Significant coronary artery stenosis in at least one coronary artery was detected in the 398 patients (34.8%). Two or more risk factors and one or more significant stenosis in the ICA or VBA were considered as screening criteria for choosing potential CAD patients according to AUC analysis. As the CAC score increased, odd ratio for significant CAD remarkably increased (2.1678, CI 1.0152 to 4.6290 for CAC score 0, 5.7193 ,CI 2.9192 to 11.2051 for 0 Conclusion: Two or more risk factors and one or more significant stenosis in the ICA or VBA can be used to choose patients with stroke who need to perform a screening test predicting significant CAD. CAC score also can be used as a screening to perform coronary artery evaluation even in the patients without documented cerebral atherosclerosis.

SummaryPatent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648–17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

Background: Patients may experience stroke while being admitted to the hospital (in-hospital stroke (IHS)) and they may be important candidates for reperfusion therapy. IHS patients may have various comorbidities and show worse outcomes compared with patients with an out-of-hospital stroke (OHS). On the other hand, the time from onset to treatment may be shorter in IHS patients than OHS patients. Most outcome studies of reperfusion therapy have been based on findings in OHS patients, and little information is currently available regarding outcomes of IHS, whether the outcomes differ between patients with IHS and those with OHS who receive reperfusion therapy. Methods: This is a retrospective observational study using prospectively registered data. Consecutive patients who underwent the reperfusion therapy (intravenous (IV), intra-arterial (IA), or combined IV and IA) between July 2002 and June 2014 in a university hospital were included for this study. We compared the demographics, time interval from symptom onset to treatment, and outcomes between IHS and OHS patients and analyzed the factors associated with in-hospital mortality. Results: A total of 686 patients received the reperfusion therapy during the study period. Of them, 256 (37.3%) patients received the IV tissue plasminogen activator (t-PA) therapy only, 243 (35.4%) patients received the IA therapy only, and 187 (27.3%) patients received the combined IV and IA therapy. Among these, 104 (15.2%) were IHS patients. The time intervals from symptom onset to IV t-PA administration (87.5 ± 48.4 vs. 113.4 ± 38.3 min, p < 0.001) and IA puncture (221.8 ± 195.0 vs. 343.6 ± 155.4 min, p < 0.001) were shorter for IHS than OHS. The rates of successful recanalization and symptomatic intracerebral hemorrhage, and the favorable functional outcome at 3 months were similar between the groups. In-hospital all-cause mortality was higher in IHS than OHS (16.3 vs. 8.4%, p = 0.019), but after adjustment, IHS was not an independent factor. The stroke mortality did not differ between the groups (9.6 vs. 6.9%, p = 0.432). Conclusions: Although IHS patients more frequently had comorbid diseases and higher overall in-hospital mortality, the standard outcomes of the reperfusion therapy were similar between IHS and OHS patients, which might be, in part, ascribed to the shorter interval from symptom onset to treatment in IHS. Considering a substantial portion of IHS patients, we should pay more attention to these patients.

Objectives: We investigated the association of cerebral microbleeds (CMBs) with long-term mortality in patients with nonvalvular atrial fibrillation (NVAF) according to burden and distribution of CMBs. Methods: This was a retrospective, hospital-based, observational study. In total, 504 consecutive ischemic stroke patients with NVAF who underwent brain T2-weighted, gradient-recalled echo MRI were included. Data for the date and causes of death were based on the death certificates from the Korean National Statistical Office. We determined the association of the presence, burden, and distribution of CMBs with mortality from all-cause, ischemic heart disease, ischemic stroke, and hemorrhagic stroke. Results: CMBs were found in 30.7% of patients (155/504). During a median follow-up of 2.5 years, 176 patients (34.9%) died (ischemic stroke, 81; hemorrhagic stroke, 12; ischemic heart disease, 32). Patients with CMBs died more frequently than those without (41.9% vs 31.8%, p = 0.028). After adjusting for age, sex, and other significant variables, the presence of multiple (≥5) CMBs was as an independent predictor for all-cause (hazard ratio [HR]: 1.99) and ischemic stroke (HR: 3.39) mortality. Patients with strictly lobar CMBs had an increased risk of hemorrhagic stroke mortality (HR: 5.91). Conclusions: The presence and burden of CMBs were associated with increased mortality in stroke patients with NVAF. Patients with lobar CMBs were at increased risk of death due to hemorrhagic stroke. The diagnosis of CMBs is of value in predicting long-term prognosis in stroke patients with NVAF.

Brachial-ankle pulse wave velocity (baPWV) has been proposed as a simple, noninvasive method for estimating arterial stiffness. Although high baPWV was predictive of cardiovascular mortality and morbidity among general population, its predictive value for mortality in patients with acute stroke is unknown. We evaluated the prognostic value of baPWV in 1765 patients who had been admitted for acute ischemic stroke and had completed measurement of baPWV during admission. Primary outcomes were all-cause mortality and vascular mortality (death because of heart diseases, cerebrovascular diseases, or diseases of arteries, arterioles, and capillaries, determined according to the International Classification of Diseases ) after stroke. During a mean follow-up period of 3.33±1.57 years, there were 228 all-cause deaths, including 143 vascular deaths. In multivariate Cox hazard regression, patients in the highest tertile of baPWV (>22.63 m/s) were at an increased risk for both all-cause death (adjusted hazard ratio, 1.97; 95% confidence interval, 1.25–3.08) and vascular death (adjusted hazard ratio, 2.39; 95% confidence interval, 1.33–4.29) compared with the lowest tertile (

Background and Purpose— Identifying occult coronary artery stenosis may improve secondary prevention of stroke patients. The aim of this study was to derive and validate a simple score to predict severe occult coronary artery stenosis in stroke patients. Methods— We derived a score from a French hospital–based cohort of consecutive patients (n=300) who had an ischemic stroke or a transient ischemic attack and no previous history of coronary heart disease (Predicting Asymptomatic Coronary Artery Disease in Patients With Ischemic Stroke and Transient Ischemic Attack [PRECORIS] score) and validated the score in a similar Korean cohort (n=1602). In both cohorts, severe coronary artery stenosis was defined by the presence of at least 1 ≥50% coronary artery stenosis as detected by 64-section CT coronary angiography. Results— A 5-point score (Framingham Risk Score–predicted 10-year coronary heart disease risk [≥20%=3; 10–19%=1; Conclusions— The PRECORIS score can identify a population of stroke or transient ischemic attack patients with a high prevalence of occult severe coronary artery stenosis.

a Neurology, b Biostatistics, and Background and Purpose Widespread use of thrombolytic treatments, along with improved chances of survival after an initial ischemic stroke, increases the possibility of repeated thrombolysis. There are few reports, however, regarding repeated thrombolysis in patients who have suffered acute ischemic stroke. We explored the number and outcome of patients with repeated thrombolytic therapy in the era of multimodal thrombolytic treatments. Methods We investigated patients with acute ischemic stroke who had received thrombo- lytic treatments for a period of 10 years. Number of thrombolysis was determined in each patient. Recanalization was defined as Thrombolysis in Cerebral Infarction grading ≥ 2a. Symptomatic hemorrhagic transformation was defined as any increase in the National Insti- tutes of Health Stroke Scale score that could be attributed to intracerebral hemorrhage. A good outcome was defined as a modified Rankin scale score ≤ 2. Results Of the 437 patients who received thrombolytic treatments, only 7 underwent re- peated thrombolysis (1.6%). The median age at the time of repeated thrombolytic therapy was 71 years old; 4 of the patients were female. All patients had 1 or more potential sources of cardiac embolism. Recanalization was achieved in all patients, in both the first and the second thrombolysis. No symptomatic intracranial hemorrhage occurred after repeated thrombolytic treatments. Five patients (71.4%) showed good outcomes at 3 months. Conclusions Repeated thrombolysis for recurrent acute ischemic stroke appears to be safe and feasible. Among patients who experience recurrent acute ischemic stroke, thrombolytic therapy could be considered even if the patient has had previous thrombolytic treatments.

BACKGROUND AND PURPOSE The recently developed total cerebral small-vessel disease (CSVD) score might appropriately reflect the total burden or severity of CSVD. We investigated whether the total CSVD score is associated with long-term outcomes during follow-up in patients with acute ischemic stroke. METHODS In total, 1,096 consecutive patients with acute ischemic stroke who underwent brain magnetic resonance imaging were enrolled. We calculated the total CSVD score for each patient after determining the burden of cerebral microbleeds (CMBs), high-grade white-matter hyperintensities (HWHs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and cause of death for all of the patients using data from the Korean National Statistical Office. We compared the long-term mortality rate with the total CSVD score using Cox proportional-hazards models. RESULTS CMBs were found in 26.8% of the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096), and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that were significant at p

Background and aims Proteinuria is a marker of kidney disease and a strong risk factor for cardiovascular diseases including stroke. This study was aimed at investigating the prognostic value of proteinuria measured by urine dipstick in patients with acute ischemic stroke. Methods This post-hoc analysis of a prospective cohort study included 3404 consecutive patients who had been admitted for acute ischemic stroke between November 2005 and June 2013. Proteinuria was defined as a trace or more of protein on a urine dipstick test routinely performed at admission. Date and cause of death until December 31, 2013 were collected. We investigated the association of proteinuria with all-cause mortality, cardiovascular mortality (defined as ICD-10 codes I00–I99), and non-cardiovascular mortality. Results Proteinuria was present in 12.8% of the 3404 patients. During the mean follow-up period of 3.56 ± 2.22 years, there were 681 cases of all-cause mortality (460 cardiovascular deaths and 221 non-cardiovascular deaths). Multivariate Cox regression analysis showed that the presence of proteinuria was an independent risk factor for all-cause mortality (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.40–2.04), cardiovascular mortality (adjusted HR 1.65, 95% CI 1.31–2.08), and non-cardiovascular mortality (adjusted HR 1.59, 95% CI 1.13–2.23). Adding proteinuria to the multivariate Cox models moderately improved the model performance for all-cause mortality (integrated area under curve [95% CI]: from 0.800 [0.784–0.816] to 0.803 [0.788–0.818], p = 0.026). Conclusions Proteinuria, which was detected on a urine dipstick test, was a significant predictor of mortality after acute ischemic stroke.

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.

Objective: To investigate whether angiographically defined occlusion type could predict of the etiology of acute intracranial large artery occlusion and the stentriever response. Methods: We reviewed consecutive patients with acute intracranial large artery occlusion who underwent endovascular treatment and examined their workups for embolic sources. Patient demographics, laboratory findings, hyperdense artery sign, and angiographic occlusion type (truncal-type or branching-site occlusion) were compared between embolic sources (+) and (−) groups. These variables were also compared between stentriever failure and success groups. Details of endovascular procedures were also compared according to occlusion type. Results: A total of 259 patients (mean age 70.3 years; M:F = 132:127) were finally included. Of these patients, 216 (83.4%) were assigned to the embolic sources (+) group after thorough evaluation. Young age, no coronary artery disease, and truncal-type occlusion (odds ratio [OR] 9.07; 95% confidence interval [CI] 3.74–22.0) were independently associated with the embolic source (−) group. Of the overall group, 224 patients (86.5%) underwent stentriever-based endovascular treatment. Hypertension, diabetes, high C-reactive protein level, and truncal-type occlusion (OR 32.2; 95% CI 7.78–133.0) were independent predictors of stentriever failure. Truncal-type occlusion was associated with more reocclusion (77.3% vs 5.0%), resulting in recanalization failure by the stentriever (81.8% vs 20.3%), a longer puncture-to-recanalization time (118.0 vs 49.5 minutes), and more rescue treatment for final successful recanalization (78.9% vs 7.0%). Conclusions: Angiographic occlusion type is an independent predictor of stentriever refractoriness and of the underlying stroke mechanism.

Background and Purpose— Higher serum alkaline phosphatase (ALP) and phosphate levels are associated with atherosclerotic disease and an increased risk of cardiovascular events. However, the association of ALP/phosphate with cerebral atherosclerosis and prognosis in patients with acute stroke is not well known. Methods— In 1034 patients with first-ever acute cerebral infarction, levels of ALP and phosphate were compared with (1) cerebral atherosclerosis and (2) poor long-term functional outcomes as defined by the modified Rankin Scale >2 at 3 months after stroke onset. Results— ALP levels were not associated with cerebral atherosclerosis. However, higher levels of ALP were associated with a poor functional outcome (adjusted odds ratio per 1 SD, 1.25; 95% confidence interval, 1.04–1.50). Phosphate was associated with neither cerebral atherosclerosis nor functional outcome. Conclusions— A higher level of ALP was not associated with cerebral atherosclerosis but was an independent prognostic factor for long-term functional outcome after acute cerebral infarction.

PURPOSE In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA₂DS₂-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS₂ score or ≥3 points of other components of CHA₂DS₂-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION NVAF patients with high CHADS₂/CHA₂DS₂-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of 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.

Background Alberta Stroke Program Early CT Score (ASPECTS) represents the extent of irreversibly damaged tissue; while CT angiography collateral score (CTA-CS) denotes the degree of collaterals. Aims We investigated whether there is cumulative value in using both ASPECTS and CTA-CS for outcome prediction and attempted to determine the specific subgroup of patients who could benefit from successful reperfusion using these scores. Methods This is a retrospective observational study of stroke patients treated with intra-arterial reperfusion therapy for unilateral arterial occlusion in the anterior circulation. A favorable outcome was defined as modified Rankin Scale ≤ 2 at three-months. Receiver operating characteristic comparison analysis was performed to decide whether outcome predictability increases when ASPECTS and CTA-CS are used together. Classification and regression tree (CART) analysis was done to identify the variables that best predict outcome and define the specific subgroup of patients who could benefit from successful reperfusion. Results A total of 91 consecutive patients were included. Outcome predictability of ASPECTS with CTA-CS was better than that of ASPECTS ( P = 0·088) or that of CTA-CS ( P = 0·049). CART analysis revealed that ASPECTS > 5 was the primary determinant of favorable outcome, followed by CTA-CS > 1. Among 19 patients with ASPECTS ≤ 5, none had a favorable outcome. Successful reperfusion was associated significantly with favorable outcome in the 51 patients with ASPECTS > 5 and CTA-CS > 1, but not in the 21 patients with ASPECTS > 5 and CTA-CS ≤ 1. Conclusions Outcome predictability improves when using ASPECTS and CTA-CS together.

Background and Purpose— We investigated whether the brachial-ankle pulse wave velocity (baPWV) has prognostic value for predicting functional outcome after acute cerebral infarction and whether the prognostic value differs between stroke subtypes. Methods— We included 1091 consecutive patients with first-ever acute cerebral infarction who underwent baPWV measurements. Stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Poor functional outcomes were defined as modified Rankin Scale score >2 at 3 months after stroke onset. Results— We noted that 181 (16.59%) patients had a poor functional outcome. In multivariate logistic regression, patients in the highest tertile of baPWV (>22.25 m/s) were found to be at increased risk for poor functional outcome (adjusted odds ratio, 1.88; 95% confidence interval, 1.06–3.40) compared with those in the lowest tertile ( Conclusions— baPWV has an independent prognostic value for predicting functional outcome after acute cerebral infarction. The prognostic value did not differ according to the stroke subtype.

SummaryThere has been little information regarding the impact of unrecognised brain infarctions (UBIs) on stroke outcome in patients with nonvalvular atrial fibrillation (NVAF). By using volumetric analysis of ischaemic lesions, we evaluated the potential impact of UBIs on clinical outcome according to their presence and categorised type. This study enrolled 631 patients with NVAF having no clinical stroke history. UBIs were categorised into three types as territorial, lacunar, or subcortical. We collected stroke severity, functional outcome at three months, and the total volume of UBIs and acute infarction lesions. We investigated the association between clinical outcome and the type or volume of UBI, using a linear mixed model and logistic regression analysis. UBIs were detected in 285 (45.2 %) patients; territorial UBIs were observed in 24.4 % of patients (154/631), lacunar UBIs in 25 % (158/631), and subcortical UBIs in 15.7 % (99/631). Although initial stroke severity was not different between patients with UBIs and those without, those with UBIs had less improvement during hospitalisation, leading to poorer outcome at three months. Among the three types of UBIs, only territorial UBIs were associated with poor outcome, especially in patients with relatively smaller acute infarction volume. UBIs, in particular, territorial UBIs, may be considered as predictors for poor outcome after ischaemic stroke in patients with NVAF. Our results suggest that the impact of UBIs on clinical outcome differs according to the type of UBIs and the acute stroke severity.

Background: Cerebral microbleeds (CMBs) were predictive of mortality in elderly and considered as a putative marker for risk of intracranial hemorrhage. Stroke patients with non valvular atrial fibrillation (NVAF) require anticoagulation, which increases the risk of hemorrhages. We investigated association of CMBs with the long term mortality in acute ischemic stroke patients with NVAF. Methods: During 6 years , consecutive ischemic stroke patients who had NVAF and who had undergone brain MRI with a gradient-recalled echo sequence were enrolled. Long-term mortality and causes of death were identified using data from Korean National Statistical Office. Survival analysis was performed whether the presence, number and location of CMBs were related with all causes, cardiovascular, and cerebrovascular mortality during follow-up. Results: Total 506 patients were enrolled during the study period and were followed up for median 2.5 years. CMBs were found in 30.8% of patients (156/506). Oral anticoagulation with warfarin was prescribed at discharge in 477 (82.7%) patients. During follow up, 177 (35%) patients died and cerebrovascular death was noted in 93 patients (81 ischemic stroke and 12 hemorrhagic stroke). After adjusting age, sex and significant variables in univariate analysis (p Conclusions: Multiple CMBs were the independent predictor for the long term mortality in stroke patients with NVAF. Among them, patients with strictly lobar CMBs had a high risk of death due to hemorrhagic stroke. Our findings suggest that detection of CMBs in stroke patients with NVAF are of clinical relevance for predicting long term outcome and that particular concern is necessary in those with strictly lobar CMBs for their increased risk of death due to hemorrhagic stroke. Figure 1.

Background and purpose Although the stent retriever (SR) has shown a better reperfusion rate and clinical outcome than the older generation mechanical clot retrieval device, it is uncertain whether the SR is superior to intra-arterial fibrinolysis (IAF). Methods Ischaemic stroke patients who were treated with SR or IAF as initial endovascular treatment modality for unilateral arterial occlusion in the anterior circulation were included. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction grade ≥2b. A favourable clinical outcome was defined as a modified Rankin Score ≤2 at 3 months. Results Between January 2009 and May 2012, 55 patients were treated with SR and 50 patients were treated with IAF. The baseline characteristics were similar between the two groups except for the occlusion site and rescue treatment. In binary logistic regression analysis adjusted for the occlusion site and rescue treatment, SR was independently associated with increased successful reperfusion [82.0% vs. 47.3%; odds ratio (OR) 5.21; 95% confidence interval (CI) 1.92–14.14) and a more favourable clinical outcome at 3 months (54.0% vs. 43.6%; OR 3.40; 95% CI 1.31–8.84). The frequency of symptomatic intracranial haemorrhage and mortality at 3 months was not different between the two groups. Conclusions Stent retriever was as safe as and more effective than IAF. Our findings suggest that SR may be considered as an initial modality rather than IAF in acute stroke patients who undergo endovascular treatment.

Background and Purpose— We investigated whether the presence of nonrelevant cerebral atherosclerosis (NRCA) had prognostic value in patients with acute stroke. Methods— We compared prognosis in 780 consecutive patients with first-ever acute cerebral infarction who underwent cerebral angiography and diffusion-weighted MRI. Results— NRCA was present in 267 patients (34.2%). Multivariate analysis demonstrated that the presence of NRCA was independently associated with less improvement in National Institute of Health Stroke Scale score during the first 7 days ( P =0.004), and a poor functional outcome (modified Rankin Scale score >2) after 3 months (odds ratio, 2.51; 95% confidence interval, 1.55–4.07). An increase in burden count of NRCA was also associated with poor outcomes. Conclusions— The presence and burden count of NRCA were associated with poor neurological outcomes in patients with acute cerebral infarction.

Objective: The objective of this study was to assess the prognostic value of interarm difference of blood pressure (IAD) measured in acute ischemic stroke and to investigate its association with systemic atherosclerosis. Methods: This was a hospital-based retrospective observational study. Survival data and systolic/diastolic IAD were collected in patients with acute ischemic stroke. Systemic atherosclerosis was determined based on coronary CT angiography, transesophageal echocardiography, ankle-brachial index examination, and cerebral angiography covering both intracranial and extracranial cerebral arteries. Results: Of 834 patients, 10.3% had a systolic IAD ≥10 mm Hg, and 6.0% had a diastolic IAD ≥10 mm Hg. During a mean follow-up period of 2.96 ± 0.95 years, 92 patients died (including 68 cardiovascular deaths). In multivariate Cox regression adjusted for cardiovascular risk factors and initial stroke severity, the presence of systolic IAD ≥10 mm Hg was associated with increased risk of all-cause mortality (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.16–3.35) and cardiovascular mortality (HR 2.49, 95% CI 1.39–4.46). Patients with diastolic IAD ≥10 mm Hg also had increased risk of all-cause mortality (HR 3.43, 95% CI 1.94–6.08) and cardiovascular mortality (HR 3.51, 95% CI 1.83–6.74). The presence of systolic or diastolic IAD ≥10 mm Hg was associated with peripheral artery disease in the lower limbs, but not with atherosclerosis in the cerebral artery, coronary artery, or the aorta. Conclusions: The presence of interarm systolic or diastolic blood pressure difference ≥10 mm Hg is a strong independent prognostic marker in acute ischemic stroke.

Purpose Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not. Materials and methods This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (-) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses. Results During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (-) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (-) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172-8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (-) group seemed to also have a higher risk of recurrent stroke. Conclusion Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up.

Purpose Patients with superficial middle cerebral artery (MCA) territory infarction may have concomitant lenticulostriate artery (LSA) territory infarction. We investigated the mechanisms thereof and the outcomes of patients with superficial MCA territory infarction according to the presence or absence of LSA involvement. Materials and Methods Consecutive patients with first-ever infarction in the unilateral superficial MCA territory were included in this study. They were divided into the superficial MCA only (SM) group and the superficial MCA plus LSA (SM+L) group. Results Of the 398 patients, 84 patients (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had significant stenosis of the proximal MCA or carotid artery and high-risk cardioembolic sources. Stroke severity and outcomes were remarkably different between the groups. The SM+L group showed more severe neurologic deficits (National Institute of Health Stroke Scale score 10.8±7.1 vs. 4.0±5.0, p2) at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p

Background & Aims Liver fibrosis is a multifactorial disease that can affect the development of cerebral small vessel diseases (SVDs) including cerebral microbleeds (CMBs), leukoaraiosis, and silent infarctions. Transient elastography can accurately assess the degree of liver fibrosis by measuring liver stiffness (LS). In the present study, we investigated the association between SVDs and LS values. Methods We recruited 300 participants (mean age 56 years, 170 men) who underwent a comprehensive medical health check-up between January 2011 and December 2012. Transient elastography was taken on the right lobe of the liver through intercostal space with patients lying in the dorsal decubitus position with the right arm in maximal abduction. Mild and significant fibrosis were defined as LS values >5.6 and >8.0 kPa, respectively. The presence of each SVD was determined using the FLAIR, GRE MR imaging as well as T1-, T2-weighted MR images. We tested whether the presence and burden of each type of SVD were different by LS values. Results Of the different types of SVDs, only the presence (p = 0.001) and number of CMBs (p8.0 kPa) was an independent predictor of CMBs (odds ratio 6.079, 95% confidence interval 1.489–24.819, p = 0.012). However, leukoaraiosis and silent infarctions were not associated with LS values (all p>0.05). Conclusions The degree of liver fibrosis, as assessed using transient elastography, was independently associated with the presence and burden of CMBs in healthy, asymptomatic participants. Understanding the link between the brain and liver may advance future research on the pathomechanisms of CMBs.

Purpose: Although early neurological deterioration (END) during the acute stroke period is known to be associated with poor functional outcomes, there is little data regarding the impact of END on long-term outcomes according to the characteristics of END. The aim of this study was to investigate whether there are differences in long-term mortality according to the characteristics of END among acute ischemic stroke or transient ischemic attack patients. Materials and Methods: END was defined as any increase (≥1) in National Institute of Health Stroke Scale score within 7 days after admission. We assessed the characteristics of END, such as the etiology and severity of END, as well as recovery after END. The relationship between 30-day or long-term mortality and each characteristic of END was investigated using multiple logistic analysis or Cox regression model. Results: Among 2820 patients, END was observed in 344 patients (12.2%). After adjustment for age, sex, underlying cardiovascular diseases, stroke severity, and stroke subtypes, END was associated with long-term mortality, whether it was mild or severe and whether or not it was followed by recovery. However, 30-day mortality was strongly related to the severity of END or the absence of recovery after END. Among the causes of END, recurrent stroke and medical illness were related to 30-day mortality, as well as long-term mortality, while brain herniation and intracranial hemorrhagic complications were only associated with 30-day mortality. Conclusion: The results of the present study demonstrated that END is associated with higher mortality and the effects of END on short-term and long-term mortality depend on END characteristics.