Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial.

BACKGROUND: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 µg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. METHODS: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. RESULTS: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2-2.6). Median time from baseline CT to study drug was 62.5 (55-80) minutes, and from study drug to early post-dose CT was 19 (14.5-30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (-0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8-8.3) in the placebo arm (P=0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (-2.6 to 8.3) in the rFVIIa arm and 0.7 mL (-1.6 to 2.1) in the placebo arm (P=0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71-1.43]; P=0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994-1.003]; P=0.50; Table 3). CONCLUSIONS: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01359202.

Cerebral Infarction Observed on Brain MRI in Unconscious Out-of-Hospital Cardiac Arrest Survivors: A Pilot Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (-). CONCLUSIONS: 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.

Thrombus Volume as a Predictor of Nonrecanalization After Intravenous Thrombolysis in Acute Stroke.

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 mm3; P<0.001). In the multivariate analysis, thrombus volume was independently associated with nonrecanalization ( P<0.001). The cutoff for predicting nonrecanalization was calculated as 200 mm3. In the prospective multicenter validation study, none of the patients with a thrombus volume ≥200 mm3 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.

The Protective Effect of Middle Cerebral Artery Calcification on Symptomatic Middle Cerebral Artery Infarction.

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.

Poor Outcome of Stroke Patients With Atrial Fibrillation in the Presence of Coexisting Spontaneous Echo Contrast.

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<0.001). On multivariate analysis, the presence of SEC was an independent factor of poor outcome (odds ratio, 2.09; 95% confidence interval, 1.24-3.53). 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.

Thrombus length discrepancy on dual-phase CT can predict clinical outcome in acute ischemic stroke.

OBJECTIVES: The thrombus length may be overestimated on early arterial computed tomography angiography (CTA) depending on the collateral status. We evaluated the value of a grading system based on the thrombus length discrepancy on dual-phase CT in outcome prediction. METHODS: Forty-eight acute ischemic stroke patients with M1 occlusion were included. Dual-phase CT protocol encompassed non-contrast enhanced CT, CTA with a bolus tracking technique, and delayed contrast enhanced CT (CECT) performed 40s after contrast injection. The thrombus length discrepancy between CTA and CECT was graded by using a three-point scale: G0 = no difference; G1 = no difference in thrombus length, but in attenuation distal to thrombus; G2 = difference in thrombus length. Univariate and multivariate analyses were performed to define independent predictors of poor clinical outcome at 3 months. RESULTS: The thrombus discrepancy grade showed significant linear relationships with both the collateral status (P = 0.008) and the presence of antegrade flow on DSA (P = 0.010) with good interobserver agreement (κ = 0.868). In a multivariate model, the presence of thrombus length discrepancy (G2) was an independent predictor of poor clinical outcome [odds ratio = 11.474 (1.350-97.547); P =0.025]. CONCLUSIONS: The presence of thrombus length discrepancy on dual-phase CT may be a useful predictor of unfavourable clinical outcome in acute M1 occlusion patients. KEY POINTS: • Early arterial phase CTA may underestimate thrombus length. • Thrombus length discrepancy grade reflects collateral status or presence of antegrade flow. • Outcome prediction may be better with thrombus length grade than collateral score.

The Ischemic Stroke Predictive Risk Score Predicts Early Neurological Deterioration.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: The iScore can predict the risk of END development within the acute stroke stage.

Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in Patients With Stroke and Mice.

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 FeCl3-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 <50% in 94 patients (55.0%, moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%, nonvolume reduction; either no change or thrombus volume increased), overall thrombus volume increased. The probability of thrombus resolution decreased as the time interval from symptom onset to treatment increased. On multivariate analysis, good volume reduction was independently related with shorter time intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute saved; 95% confidence interval, 0.974-0.999). In the mouse model, as the interval between thrombus formation and tPA treatment increased, the initiation of recanalization was delayed (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.

Comparison of Outcomes after Reperfusion Therapy between In-Hospital and Out-of-Hospital Stroke Patients.

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.

Incidence and risk factors for diffusion-weighted imaging (+) lesions after intracranial stenting and its relationship with symptomatic ischemic complications.

BACKGROUND AND PURPOSE: Little is known about high-signal lesions in magnetic resonance diffusion-weighted imaging (DWI [+]) after stenting for intracranial atherosclerotic stenosis. This study aimed to evaluate the incidence, distribution, risk factors, and clinical implications of DWI (+) after intracranial stenting. METHODS: A total of 123 patients (male:female=88:35, mean age, 64.1 years) with symptomatic intracranial atherosclerotic stenosis (mean stenosis, 76.1±7.7%) underwent both stenting and poststenting DWI. The incidence, distribution (embolic-alone versus stenosis-associated perforator/mixed), and risk factors of DWI (+) and its relationship with symptomatic ischemic complications (SIC, including stroke or transient ischemic attack) were retrospectively evaluated. RESULTS: Forty-three patients (35.0%) had DWI (+). Middle cerebral artery, smaller distal parent artery, and treatment-related dissection were independent risk factors for DWI (+) (P<0.05). SIC occurred in 4 patients (3.3%), all of whom had DWI (+). Of the patients with DWI (+), neither the number nor the volume of DWI (+) differed significantly between SIC and asymptomatic patients: median number/patient, 3.5 (range, 2-11) versus 2.0 (range, 1-11) and median volume/patient, 329.8 mm(3) (range, 76-883.5 mm(3)) versus 119.5 mm(3) (range, 32.5-873.0 mm(3)). However, SIC occurred more frequently in the stenosis-associated perforator/mixed type (3/11, 27.3%) than in the embolic-alone type (1/32, 3.1%; P<0.05). CONCLUSIONS: The incidence of DWI (+) after intracranial stenting for intracranial atherosclerotic stenosis was 35.0%. Middle cerebral artery, smaller distal parent artery, and treatment-related dissection were independent risk factors for DWI (+). SIC occurred more frequently in the stenosis-associated perforator/mixed type than in the embolic-alone type.

Predicting asymptomatic coronary artery disease in patients with ischemic stroke and transient ischemic attack: the PRECORIS score.

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; <10%=0] and cervicocephalic artery stenosis [≥50%=2; <50%=1; none=0]) was predictive of occult≥50% coronary artery stenosis risk in the derivation cohort (C-statistic=0.77 [0.70-0.84]) and in the validation cohort (C-statistic=0.66 [0.63-0.68]). The predictive ability of the score was even stronger when only ≥50% left main trunk disease or 3-vessel disease were considered (C-statistic=0.83 [0.74-0.92] and 0.70 [0.66-0.74] in derivation and validation cohorts, respectively). The prevalence of occult≥50% coronary artery stenosis and ≥50% left main trunk or 3-vessel disease increased gradually with the PRECORIS score, reaching 44.2% and 13.5% in derivation cohort and 49.8% and 12.8% in validation cohort in patients with a PRECORIS score≥4. 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.

Brachial-ankle pulse wave velocity for predicting functional outcome in acute stroke.

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 (<17.55 m/s). No significant interaction between baPWV and stroke subtype was noted. Receiver operating characteristic curve analysis indicated that the addition of baPWV to the prediction model significantly improved the discrimination ability for poor functional outcome. 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.

Serum alkaline phosphatase and phosphate in cerebral atherosclerosis and functional outcomes after cerebral infarction.

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.

Nonrelevant cerebral atherosclerosis is a strong prognostic factor in acute cerebral infarction.

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.

Coronary Calcium Score for the Prediction of Asymptomatic Coronary Artery Disease in Patients With 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.

Infarct Core Expansion on Computed Tomography before and after Intravenous Thrombolysis.

PURPOSE: Infarct core can expand rapidly in acute stroke patients receiving intravenous tissue plasminogen activator (IV t-PA). We investigated changes in the extent of infarct core during IV t-PA treatment, and explored the associative factors of this infarct core expansion in patients with proximal artery occlusion. MATERIALS AND METHODS: We included patients who were considered for sequential intra-arterial therapy (IAT) due to occlusion of intracranial proximal artery after IV t-PA. Patients who had a baseline Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) ≥6 and who underwent two consecutive CT scans before and shortly after IV t-PA infusion were enrolled. Patients were classified into no, moderate, and marked expansion groups based on decreases in ASPECTS (0-1, 2-3, and ≥4, respectively) on follow-up CT. Collateral status was graded using CT angiography. RESULTS: Of the 104 patients, 16 (15.4%) patients showed moderate and 13 (12.5%) patients showed marked infarct core expansion on follow-up CT scans obtained at 71.1±19.1 min after baseline CT scan. Sixteen (15.4%) patients had an ASPECTS value <6 on the follow-up CT. None of the patients with marked expansion were independent at 3 months. Univariate analysis and ordinal logistic regression analysis demonstrated that the infarct core expansion was significantly associated with collateral status (p<0.001). CONCLUSION: Among patients who were considered for IAT after IV t-PA treatment, one out of every seven patients exhibited marked expansion of infarct core on follow-up CT before IAT. These patients tend to have poor collaterals and poor outcomes despite rescue IAT.

Different infarction patterns in patients with aortic atheroma compared to those with cardioembolism or large artery atherosclerosis.

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.

Poor long-term outcomes in stroke patients with asymptomatic coronary artery disease in heart CT.

BACKGROUND AND AIMS: Although stroke patients have a high risk of ischemic heart disease, little information is available on the risk of coronary events in stroke patients with asymptomatic coronary artery disease (CAD). We investigated the long-term vascular outcomes in stroke patients with asymptomatic CAD diagnosed with multi-detector coronary computed tomography (MDCT). METHODS: This study was a retrospective analysis using a prospective cohort of ischemic stroke patients. We included consecutive stroke patients without history or symptoms of CAD who underwent MDCT. We investigated the long-term risk of major adverse cardiovascular events (MACE: cardiovascular mortality, ischemic stroke, myocardial infarction, unstable angina, and urgent coronary revascularization) and composite of MACE/all-cause mortality/elective coronary revascularization. We further investigated the value of MDCT for MACE prediction. RESULTS: Among the 1893 included patients, 1349 (71.3%) patients had some degree of CAD and 654 patients (34.5%) had significant (≥50%) CAD. At follow-up (median, 4.4 years), MACE occurred in 230 patients (12.2%). Event rates of MACE increased with the increasing extent of CAD. After adjustment for age, sex, and risk factors, the hazard ratios for MACE in mild CAD, 1-VD, 2-VD, and 3-VD or left main coronary disease were 1.28 (95% confidence interval [CI]: 0.88-1.87), 1.39 (95% CI: 0.90-2.16), 2.22 (95% CI: 1.39-3.55), and 2.91 (95% CI: 1.82-4.65), respectively (no CAD as a reference). Diagnosis of asymptomatic CAD significantly improved the prediction of MACE. CONCLUSIONS: Asymptomatic CAD detected on MDCT was associated with increased risks of vascular events or deaths in acute stroke patients.

Predictive value of thrombus volume for recanalization in stent retriever thrombectomy.

This retrospective study investigated whether the volume or density of the thrombus is predictive of recanalization in stent retriever (SR) treatment. Consecutive patients treated with SR thrombectomy as the first endovascular modality were enrolled. The thrombus volume and density were measured on thin-section noncontrast computed tomography using 3-dimensional software. The patients were grouped by recanalization status and the number of SR passes. Among 165 patients, recanalization was achieved with the first pass in 68 (50.0%), 2-3 passes in 43 (31.6%), and ≥4 passes in 25 (18.4%) patients. The thrombus volume was smaller in patients with (107.5 mm3) than without (173.7 mm3, p = 0.025) recanalization, and tended to be larger with increasing number of passes (p for trend = 0.001). The thrombus volume was an independent predictor of first-pass recanalization (odds ratio 0.93 per 10 mm3, 95% confidence interval 0.89-0.97). However, the thrombus density was not associated with recanalization success. Recanalization within 3 passes was associated with a favorable outcome. In conclusion, the thrombus volume was significantly related to recanalization in SR thrombectomy. Measuring the thrombus volume was particularly predictive of first-pass recanalization, which was associated with a higher likelihood of a favorable outcome.

Total Cerebral Small-Vessel Disease Score is Associated with Mortality during Follow-Up after Acute Ischemic Stroke.

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<0.1 in the univariate analysis, the total CSVD score was independently associated with long-term death from all causes [hazard ratio (HR)=1.18 per point, 95% confidence interval (CI)=1.07-1.30], ischemic stroke (HR=1.20 per point, 95% CI=1.01-1.42), and hemorrhagic stroke (HR=2.05 per point, 95% CI=1.30-3.22), but not with fatal cardiovascular events (HR=1.17 per point, 95% CI=0.82-1.67). CONCLUSIONS: The total CSVD score is a potential imaging biomarker for predicting mortality during follow-up in patients with acute ischemic stroke.