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Patent foramen ovale (PFO) is often found in stroke patients with determined etiologies. PFO may be the actual cause of stroke in some of them. We determined whether the risk of recurrent ischemic stroke differs with PFO status in stroke patients with determined etiologies.This study included consecutive patients with stroke of determined etiology who underwent transesophageal echocardiography. We compared the rates of recurrent cerebral infarction in patients with versus without PFO, and according to PFO-Associated Stroke Causal Likelihood (PASCAL) classification.Of 2,314 included patients, 827 (35.7%) had PFO. During a median follow-up of 4.4 years, cerebral infarction recurred in 202 (8.7%). In multivariate modified Cox regression analyses, recurrence of infarction did not significantly differ between patients with PFO and those without PFO (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.64-1.17, p = 0.339). Interaction analysis showed a significant effect of PFO in patients aged65 years (adjusted p for interaction = 0.090). PFO was independently associated with a decreased risk of recurrent infarction in patients younger than 65 years (HR = 0.41, 95% CI = 0.20-0.85, adjusted p = 0.016). Patients with probable PFO-associated stroke on the PASCAL classification had a significantly lower risk of recurrent infarction than those without PFO (HR = 0.31, 95% CI = 0.10-0.97, p = 0.044).Considering the generally low risk of recurrence in PFO-associated stroke, PFO may be the actual cause of stroke in some patients with determined etiologies, especially younger patients or those with PFO features of probable PFO-associated stroke. ANN NEUROL 2022;92:596-606.

Background and ObjectivesA machine learning technique for identifying hidden coronary artery disease (CAD) might be useful. We developed and validated machine learning models to predict patients with hidden CAD and to assess long-term outcomes in patients with acute ischemic stroke.MethodsMultidetector coronary CT was performed for patients without a known history of CAD. Primary outcomes were defined as having any degree of CAD and having obstructive CAD (≥50% stenosis). Demographic variables, risk factors, laboratory results, Trial of ORG 10172 in Acute Stroke Treatment classification, NIH Stroke Scale score, blood pressure, and carotid artery stenosis were used to develop and validate machine learning models to predict CAD. Area under the receiver operating characteristic curves (AUC) was calculated for performance analysis, and Kaplan-Meier and Cox survival analyses of long-term outcomes were performed. Major adverse cardiovascular events (MACEs) were defined as ischemic stroke, myocardial infarction, unstable angina, urgent coronary revascularization, and cardiovascular mortality.ResultsOverall, 1,710 patients were included for the training dataset and 348 patients for the validation dataset. An extreme gradient boosting model was developed to predict any degree of CAD, which showed an AUC of 0.763 (95% CI 0.711–0.814) on validation. A logistic regression model was used to predict obstructive CAD and had an AUC of 0.714 (95% CI 0.692–0.799). During the first 5 years of follow-up, MACEs occurred more frequently with predictions of any CAD (p = 0.022) or obstructive CAD (p < 0.001). Cox proportional analysis showed that the hazard ratio of MACE was 1.5 (95% CI 1.1–2.2; p = 0.016) with prediction of any CAD, whereas it was 1.9 (95% CI 1.3–2.6; p < 0.001) for obstructive CAD.DiscussionWe demonstrated that machine learning may help identify hidden CAD in patients with acute ischemic stroke. Long-term outcomes were also associated with prediction results.Classification of EvidenceThis study provides Class II evidence that in patients with acute ischemic stroke with CAD risk factors but no known history of CAD, a machine learning model predicts CAD on multidetector coronary CT with an AUC of 0.763 (95% CI 0.711–0.814).

Background: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. Methods: This prospective registry–based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. Results: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P P =0.001) and low eGFR (HR, 2.29 [95% CI, 1.41–3.72]; P =0.001). These associations persisted regardless of treatment modality or various baseline characteristics. Conclusions: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528–6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Background and Purpose: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

ObjectiveWe investigated whether interankle blood pressure difference (IAND) can predict major adverse cardiovascular events (MACEs) in patients with cryptogenic stroke (CS) without peripheral artery disease (PAD).DesignA retrospective cohort study.SettingRetrospective medical record data of patients with first-ever acute cerebral infarction who were admitted between 1 January 2007 and 31 July 2013.ParticipantsCS patients admitted within 7 days of symptom onset were included.Outcome measuresMACEs were defined as stroke recurrence, myocardial infarction occurrence, or death. Survival analyses were conducted using the Kaplan-Meier method and Cox regression analysis.MethodsConsecutive CS patients without PAD who underwent ankle–brachial index (ABI) measurements were enrolled. PAD was defined if a patient had an ABI of ResultsA total of 612 patients were enrolled and followed up for a median 2.6 (interquartile range, 1.0–4.3) years. In the Cox regression analysis, systolic and diastolic IANDs ≥15 mm Hg were independently associated with MACEs in CS patients without PAD (hazard ratio (HR) 2.115, 95% confidence interval (CI) 1.230 to 3.635 and HR 2.523, 95% CI 1.086 to 5.863, respectively). In the subgroup analysis, systolic IAND ≥15 mm Hg was independently associated with MACEs in older patients (age ≥65 years) (HR 2.242, 95% CI 1.170 to 4.298) but not in younger patients (age ConclusionsLarge IAND is independently associated with the long-term occurrence of MACEs in patients with CS without PAD. In particular, the association between IAND and MACEs is only valid in elderly patients.

Background The purpose of the RAFAS (Risk and Benefits of Urgent Rhythm Control of Atrial Fibrillation in Patients With Acute Stroke) trial was to explore the risks and benefits of early rhythm control in patients with newly documented atrial fibrillation (AF) during an acute ischemic stroke (IS). Method and Results An open‐label, randomized, multicenter trial design was used. If AF was diagnosed, the patients in the early rhythm control group started rhythm control within 2 months after the occurrence of an IS, unlikely the usual care. The primary end points were recurrent IS within 3 and 12 months. The secondary end points were a composite of all deaths, unplanned hospitalizations from any cause, and adverse arrhythmia events. Patients (n=300) with AF and an acute IS (63.0% men, aged 69.6±8.5 years; 51.2% with paroxysmal AF) were randomized 2:1 to early rhythm control (n=194) or usual care (n=106). A total of 273 patients excluding those lost to follow‐up (n=27) were analyzed. The IS recurrences did not differ between the groups within 3 months of the index stroke (2 [1.1%] versus 4 [4.2%]; hazard ratio [HR], 0.257 [log‐rank P =0.091]) but were significantly lower in the early rhythm control group at 12 months (3 [1.7%] versus 6 [6.3%]; HR, 0.251 [log‐rank P =0.034]). Although the rates of overall mortality, any cause of hospitalizations (25 [14.0%] versus 16 [16.8%]; HR, 0.808 [log‐rank P =0.504]), and arrhythmia‐related adverse events (5 [2.8%] versus 1 [1.1%]; HR, 2.565 [log‐rank P =0.372]) did not differ, the proportion of sustained AF was lower in the early rhythm control group than the usual care group (60 [34.1%] versus 59 [62.8%], P Conclusions The early rhythm control strategy of an acute IS decreased the sustained AF and recurrent IS within 12 months without an increase in the composite adverse outcomes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 02285387.

BACKGROUND AND PURPOSE The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS Patients were categorized on the basis of their BMI into underweight (BMI

Background and Purpose— Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods— Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results— Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke ( P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01–0.61]; P =0.01). A marginal interaction between treatment group and white matter change on any stroke ( P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13–0.97]; P =0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29–0.92]; P =0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions— Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01013532.

Introduction: There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA). Objective: We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA. Methods: This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of >3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used. Results: There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40–6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59–12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05–3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037). Conclusions: The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA.

Even after extensive standard evaluation, the probable cause of stroke in some patients remains unclear; this condition is defined as cryptogenic stroke (CS). The prognosis of patients with CS is largely undetermined. We investigated whether higher brachial-ankle pulse wave velocities (baPWVs) can predict poor functional outcomes at 3 months after stroke onset in these patients. We investigated patients with CS with first-ever acute cerebral infarction who underwent baPWV measurements. The stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment classification. Poor functional outcomes were defined as modified Rankin Scale scores of2 at 3 months after stroke onset. In total, 595 patients with CS were included; among them, 360 were men (60.5%). Their mean age was 65.0 ± 12.4 years. One-hundred-eleven patients (18.7%) had poor functional outcomes. In the multivariable logistic regression analysis, the cutoff baPWV value based on the receiver-operating characteristic curve was1968 cm/s, which was determined as a strong independent predictor (OR 3.159, 95% CI 1.487-6.715, p = 0.003). The OR of the cutoff value was higher in the patients with CS with initial National Institutes of Health Stroke Scale (NIHSS) scores of ≥5 (OR 4.252, 95% CI 1.596-11.324, p = 0.004); that in the patients with initial NIHSS scores of5 was not significant (OR 1.671, 95% CI 0.620-4.505, p = 0.310). baPWV measurement during the acute stroke phase might be useful in identifying patients with CS at high risks of having a poor neurological prognosis.

BackgroundMechanical thrombectomy (MT) is a primary endovascular modality for acute intracranial large vessel occlusion. However, further treatment, such as rescue stenting, is occasionally necessary for refractory cases. We aimed to investigate the efficacy and safety of rescue stenting in first-line MT failure and to identify the clinical factors affecting its clinical outcome.MethodsA multicenter prospective registry was designed for this study. We enrolled consecutive patients who underwent rescue stenting for first-line MT failure. Endovascular details and outcomes, follow-up patency of the stented artery, and clinical outcomes were summarized and compared between the favorable and unfavorable outcome groups.ResultsA total of 78 patients were included. Intracranial atherosclerotic stenosis was the most common etiology for rescue stenting (97.4%). Seventy-seven patients (98.7%) were successfully recanalized by rescue stenting. A favorable outcome was observed in 66.7% of patients. Symptomatic intracranial hemorrhage and mortality were observed in 5.1% and 4.0% of patients, respectively. The stented artery was patent in 82.1% of patients on follow-up angiography. In a multivariable analysis, a patent stent on follow-up angiography was an independent factor for a favorable outcome (OR 87.6; 95% CI 4.77 to 1608.9; p=0.003). Postprocedural intravenous maintenance of glycoprotein IIb/IIIa inhibitor was significantly associated with the follow-up patency of the stented artery (OR 5.72; 95% CI 1.45 to 22.6; p=0.013).ConclusionsIn this multicenter prospective registry, rescue stenting for first-line MT failure was effective and safe. For a favorable outcome, follow-up patency of the stented artery was important, which was significantly associated with postprocedural maintenance of glycoprotein IIb/IIIa inhibitors.

Intracranial atherosclerotic stroke occurs through various mechanisms, mainly by artery-to-artery embolism (AA) or branch occlusive disease (BOD). This study evaluated the spatial relationship between middle cerebral artery (MCA) plaques and perforating arteries among different MCA territory infarction types using vessel wall magnetic resonance imaging (VW-MRI).We retrospectively enrolled patients with acute MCA infarction who underwent VW-MRI. Thirty-four patients were divided into three groups according to infarction pattern: 1) BOD, 2) both BOD and AA (BOD-AA), and 3) AA. To determine the factors related to BOD, the BOD and BOD-AA groups were combined into one group (with striatocapsular infarction [BOD+]) and compared with the AA group. To determine the factors related to AA, the BOD-AA and AA groups were combined into another group (with cortical infarction [AA+]) and compared with the BOD group. Plaque morphology and the spatial relationship between the perforating artery orifice and plaque were evaluated both quantitatively and qualitatively.The plaque margin in the BOD+ group was closer to the perforating artery orifice than that in the AA group (The spatial relationship between the perforating artery orifice and plaque varied among different types of MCA territory infarctions. In patients with BOD, the plaque margin was closer and blocked the perforating artery orifice, and stenosis degree and enhancement were less than those in patients with AA.

Background and Purpose— The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of 4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods— One thousand seventy-three French patients were assigned to Results— After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57–0.94]; P =0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% ( P =0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% ( P =0.023). The primary outcome or intracranial hemorrhage was reduced by 25% ( P =0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53–2.62]; P =0.70). Conclusions— After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875.

Background and Purpose— Automatic segmentation of cerebral infarction on diffusion-weighted imaging (DWI) is typically performed based on a fixed apparent diffusion coefficient (ADC) threshold. Fixed ADC threshold methods may not be accurate because ADC values vary over time after stroke onset. Deep learning has the potential to improve the accuracy, provided that a large set of correctly annotated lesion data is used for training. The purpose of this study was to evaluate deep learning–based methods and compare them with commercial software in terms of lesion volume measurements. Methods— U-net, an encoder-decoder convolutional neural network, was adopted to train segmentation models. Two U-net models were developed: a U-net (DWI+ADC) model, trained on DWI and ADC data, and a U-net (DWI) model, trained on DWI data only. A total of 296 subjects were used for training and 134 for external validation. An expert neurologist manually delineated the stroke lesions on DWI images, which were used as the ground-truth reference. Lesion volume measurements from the U-net methods were compared against the expert’s manual segmentation and Rapid Processing of Perfusion and Diffusion (RAPID; iSchemaView Inc) analysis. Results— In external validation, U-net (DWI+ADC) showed the highest intraclass correlation coefficient with manual segmentation (intraclass correlation coefficient, 1.0; 95% CI, 0.99–1.00) and sufficiently high correlation with the RAPID results (intraclass correlation coefficient, 0.99; 95% CI, 0.98–0.99). U-net (DWI+ADC) and manual segmentation resulted in the smallest 95% Bland-Altman limits of agreement (−5.31 to 4.93 mL) with a mean difference of −0.19 mL. Conclusions— The presented deep learning–based method is fully automatic and shows a high correlation of diffusion lesion volume measurements with manual segmentation and commercial software. The method has the potential to be used in patient selection for endovascular reperfusion therapy in the late time window of acute stroke.

Background and Purpose— Based on its mechanism, the use of balloon guide catheters (BGCs) may be beneficial during endovascular treatment, regardless of the type of mechanical recanalization modality used—stent retriever thrombectomy or thrombaspiration. We evaluated whether the use of BGCs can be beneficial regardless of the first-line mechanical endovascular modality used. Methods— We retrospectively reviewed consecutive acute stroke patients who underwent stent retriever thrombectomy or thrombaspiration from the prospectively maintained registries of 17 stroke centers nationwide. Patients were assigned to the BGC or non-BGC group based on the use of BGCs during procedures. Endovascular and clinical outcomes were compared between the BGC and non-BGC groups. To adjust the influence of the type of first-line endovascular modality on successful recanalization and favorable outcome, multivariable analyses were also performed. Results— This study included a total of 955 patients. Stent retriever thrombectomy was used as the first-line modality in 526 patients (55.1%) and thrombaspiration in 429 (44.9%). BGC was used in 516 patients (54.0%; 61.2% of stent retriever thrombectomy patients; 45.2% of thrombaspiration patients). The successful recanalization rate was significantly higher in the BGC group compared with the non-BGC group (86.8% versus 74.7%, respectively; P P P P P P =0.038) irrespective of the type of first-line endovascular modality used. Conclusions— Regardless of the first-line mechanical endovascular modality used, the use of BGC in endovascular treatment was beneficial in terms of both recanalization success and functional outcome.

BACKGROUND It remains controversial whether carotid artery stenting (CAS) is needed in cases of tandem cervical internal carotid artery occlusion (cICAO) and intracranial large vessel occlusion (LVO). OBJECTIVE To investigate the efficacy and safety of CAS in combination with endovascular thrombectomy (CAS-EVT) in cICAO-LVO patients and to compare its outcomes with those of EVT without CAS (EVT-alone). METHODS We identified all patients who underwent EVT for tandem cICAO-LVO from the prospectively maintained registries of 17 stroke centers. Patients were classified into 2 groups: CAS-EVT and EVT-alone. Clinical characteristics and procedural and clinical outcomes were compared between 2 groups. We tested whether CAS-EVT strategy was independently associated with recanalization success. RESULTS Of the 955 patients who underwent EVT, 75 patients (7.9%) had cICAO-LVO. Fifty-six patients underwent CAS-EVT (74.6%), and the remaining 19 patients underwent EVT-alone (25.4%). The recanalization (94.6% vs 63.2%, P = .002) and good outcome rates (64.3% vs 26.3%, P = .007) were significantly higher in the CAS-EVT than in the EVT-alone. Mortality was significantly lower in the CAS-EVT (7.1% vs 21.6%, P = .014). There was no significant difference in the rate of symptomatic intracranial hemorrhage between 2 groups (10.7 vs 15.8%; P = .684) and according to the use of glycoprotein IIb/IIIa inhibitor (10.0% vs 12.3%; P = .999) or antiplatelet medications (10.2% vs 18.8%; P = .392). CAS-EVT strategy remained independently associated with recanalization success (odds ratio: 24.844; 95% confidence interval: 1.445-427.187). CONCLUSION CAS-EVT strategy seemed to be effective and safe in cases of tandem cICAO-LVO. CAS-EVT strategy was associated with recanalization success, resulting in better clinical outcome.

Background: To investigate whether there are differences in long-term all-cause and cardiovascular mortality according to the burden of liver fibrosis or steatosis in patients with ischaemic stroke or transient ischaemic attack (TIA). ­Methods: Consecutive patients with acute ischaemic stroke or TIA who underwent transient elastography (TE) from January 2014 to December 2014 were considered eligible. The influence of liver fibrosis or steatosis, assessed via TE, on long-term outcomes was investigated using Cox proportional hazard models. Results: Among 395 patients included in this study, there were 37 (9%) patients with significant fibrosis (> 8.0 kPa) and 164 (41.5%) patients with fatty liver (> 250 dB/m). During the follow-up period (median 2.7 years), all-cause and cardiovascular mortality occurred in 28 (7.1%) and 20 (5.1%) patients. On multivariate analyses, significant liver fibrosis was independently associated with increased risk of all-cause (hazard ratio [HR] 8.14, 95% CI 3.03–21.90, p p = 0.036) mortality, whereas fatty liver was not (all p > 0.05). Conclusions: This study found that the burden of liver fibrosis but not that of steatosis, assessed via TE, was an independent predictor of all-cause and cardiovascular mortality during long-term follow-up in patients with ischaemic stroke.

Background The stroke severity or functional outcomes could differ because the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) could be different according to the dose. We investigated whether there was any difference in the stroke outcomes in patients with non-valvular atrial fibrillation (NVAF) by their prior medication status, including standard-dosed versus under-dosed NOACs. Materials and Methods We enrolled 858 patients with acute ischaemic stroke with chronic NVAF admitted at six hospitals in Korea. We categorized their prior medication status as follows: (1) no anti-thrombotics (n = 219), (2) only anti-platelet (n = 347), (3) warfarin with a sub-therapeutic intensity (n = 185), (4) warfarin with a therapeutic intensity (n = 37), (5) under-dosed NOAC (n = 27) and (6) standard-dosed NOAC (n = 43). We compared the initial stroke severity between groups. Results Among the 858 patients, the patients on standard-dosed NOACs had the lowest initial National Institute of Health Stroke Scale (NIHSS) score, followed by those on warfarin with a therapeutic intensity and those on only anti-platelet (p Conclusion Use of warfarin with a therapeutic intensity or standard-dosed NOACs was associated with a relatively mild stroke in the patients with NVAF.

We explored the hypothesis that the diagnostic performance of cardiac computed tomography (CT) throughout the full cardiac cycle would be superior to single-phase CT and comparable to transesophageal echocardiography (TEE) in diagnosing patent foramen ovale (PFO). From May 2011 to April 2015, 978 patients with stroke were diagnosed with PFO by TEE. In patients with stroke, cardiac CT was performed if the patients had more than two cardiovascular risk factors. We prospectively enrolled 70 patients with an indication for cardiac CT. Cardiac CT images were reconstructed at 10% increments of the R-R interval. The sensitivity of cardiac CT throughout the full cardiac cycle in diagnosing PFO was compared to that for TEE and single-phase cardiac CT. To evaluate the specificity of cardiac CT, we analyzed patients without PFO confirmed by TEE who underwent cardiac CT within 1 month of pre-cardiac surgery. Sixty-six patients with cardiac CT and TEE were included in the final analysis. Throughout the full cardiac cycle, cardiac CT had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing PFO, compared to TEE as a reference. PFO was primarily detected in the 60% and 70% intervals in 10-phase reconstructed images. The sensitivity of PFO diagnosis with cardiac CT was 81.8% when analyzing both the 60% and 70% intervals instead of the full cardiac cycle. Cardiac CT throughout the full cardiac cycle outperforms single-phase cardiac CT in detecting PFO. Cardiac CT can be used as an alternative method to TEE for detecting PFO in stroke patients. • Throughout the full cardiac cycle, cardiac computed tomography (CT) had a sensitivity of 89.4% and a specificity of 92.3% in diagnosing patent foramen ovale (PFO), compared to transesophageal echocardiography. • The sensitivity of diagnosing patent foramen ovale with cardiac CT was 81.8% when analyzing 60% and 70% R-R intervals instead of the full cardiac cycle. • Cardiac CT with retrospective electrocardiographic gating throughout the full cardiac cycle can increase the detectability of PFO, compared to single-phase cardiac CT.

Interleukin (IL)-17A has been suggested to play a role in the growth and organization of thrombi. We examined whether IL-17A plays a role in the early stages of thrombosis and whether there are sex differences in the effects of IL-17A.We performed a blinded, randomized, placebo-controlled study to compare time to thrombotic occlusion and sex differences therein between mice treated with IL-17A and those treated with saline using a ferric chloride-induced model. We also assessed thrombus histology, blood coagulation, and plasma levels of coagulation factors.Time to occlusion values did not differ between the IL-17A group and the control group (94.6±86.9 sec vs. 121.0±84.4 sec,IL-17A plays a role in the initial st ages of arterial thrombosis in mice. Coagulation factors and monocyte chemoattractant protein-1 may be associated with IL-17A-mediated thrombosis.

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

Background Sex hormones may be associated with a higher incidence of ischemic stroke or stroke-related events. In observational studies, lower testosterone concentrations are associated with infirmity, vascular disease, and adverse cardiovascular risk factors. Currently, female sexual hormones are considered neuroprotective agents. The purpose of this study was to assess the role of sex hormones and the ratio of estradiol/testosterone (E/T) in patients with acute ischemic stroke (AIS). Methods Between January 2011 and December 2016, 146 male patients with AIS and 152 age- and sex-matched control subjects were included in this study. Sex hormones, including estradiol, progesterone, and testosterone, were evaluated in the AIS patient and control groups. We analyzed the clinical and physiological levels of sex hormones and hormone ratios in these patients. Results The E/T ratio was significantly elevated among patients in the stroke group compared to those in the control group (P = 0.001). Categorization of data into tertiles revealed that patients with the highest E/T ratio were more likely to have AIS [odds ratio (OR) 3.084; 95% Confidence interval (CI): 1.616-5.886; P < 0.001) compared with those in the first tertile. The E/T ratio was also an independent unfavorable outcome predictor with an adjusted OR of 1.167 (95% CI: 1.053-1.294; P = 0.003). Conclusions These findings support the hypothesis that increased estradiol and reduced testosterone levels are associated with AIS in men.

To evaluate the clinical significance of hyperattenuating lesions on CT after mechanical thrombectomy for acute ischaemic stroke, and to identify imaging factors that predict symptomatic haemorrhage and unfavourable outcomes.Seventy-eight patients with acute ischaemic stroke in the anterior circulation who underwent mechanical thrombectomy were evaluated. All patients underwent post-interventional unenhanced computed tomography (CT) within 24 h and follow-up CT or magnetic resonance imaging (MRI) within 7 days. Baseline characteristics and clinical outcomes were compared between patients with and without hyperattenuating lesions. In patients with hyperattenuating lesions, clinical and imaging factors that predict symptomatic haemorrhage and unfavourable outcomes were determined.Fifty-six of 78 patients (71.8%) demonstrated hyperattenuating lesions on post-interventional CT. Patients with hyperattenuating lesions showed lower Alberta Stroke Program Early CT score (ASPECTS), persistent/symptomatic haemorrhage, and unfavourable outcomes than those without. In patients with hyperattenuating lesions, larger hyperattenuating lesion volume (21.3 ml; OR, 55.60, p0.001) and perilesional oedema (OR, 46.04, p=0.015) were independent factors predicting symptomatic haemorrhage. Older age (OR, 1.2, p=0.006) and lower ASPECTS (OR, 0.45, p=0.046) were independent factors predicting unfavourable outcomes in patients with hyperattenuating lesions. Adding the volume of the hyperattenuating lesion to age and ASPECTS increased the predictive performance of unfavourable outcomes (area under the curve 0.874 versus 0.934, p=0.043).Hyperattenuating lesions on post-interventional CT are associated with increased risk of symptomatic haemorrhage and unfavourable outcomes. Larger hyperattenuating lesion volume is an independent factor of symptomatic haemorrhage and it has added predictive value for unfavourable outcomes.

IntroductionPrior use of direct oral anticoagulants has been associated with reduced stroke severity in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to investigate the impact of prothrombin time (PT) and activated partial thromboplastin time (aPTT) on stroke severity in patients who were receiving dabigatran or rivaroxaban at the time of stroke onset.Materials and methodsWe enrolled 107 patients with NVAF who developed acute ischemic stroke while on dabigatran or rivaroxaban and presented within 24 hours to nine hospitals between January 2014 and December 2018. The results of PT and aPTT assays were obtained within 24 hours of stroke onset in all patients. We analyzed PT and aPTT in relation to stroke severity and ischemic lesion volume using correlation and multivariable regression analyses.ResultsOf the 107 patients included, 46 (43.0%) were on dabigatran and 61 (57.0%) were on rivaroxaban. In patients with prior dabigatran use, while aPTT was inversely correlated with admission National Institutes of Health Stroke Scale (NIHSS) score (r = -0.369, p = 0.012) and ischemic lesion volume (r = -0.480, p = 0.005), there was no correlation between PT and either of these variables. Multivariable analysis confirmed the existence of a significant independent inverse relationship between aPTT and NIHSS score at admission (B, -0.201; 95% confidence interval [CI], -0.370 to -0.032; p = 0.005) and between aPTT and ischemic lesion volume (B, -0.076; 95% CI, -0.130 to -0.023; p = 0.007). In patients with prior rivaroxaban use, neither PT nor aPTT was associated with admission NIHSS score or ischemic lesion volume in the correlation and multivariable analyses.ConclusionsIn patients with NVAF who were receiving dabigatran, prolonged aPTT was associated with reduced stroke severity.

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.

Background and Purpose— Stent retriever (SR) thrombectomy has become the mainstay of treatment of acute intracranial large artery occlusion. However, it is still not much known about the optimal limit of SR attempts for favorable outcome. We evaluated whether a specific number of SR passes for futile recanalization can be determined. Methods— Patients who were treated with a SR as the first endovascular modality for their intracranial large artery occlusion in anterior circulation were retrospectively reviewed. The recanalization rate for each SR pass was calculated. The association between the number of SR passes and a patient’s functional outcome was analyzed. Results— A total of 467 patients were included. Successful recanalization by SR alone was achieved in 82.2% of patients. Recanalization rates got sequentially lower as the number of passes increased, and the recanalization rate achievable by ≥5 passes of the SR was 5.5%. In a multivariable analysis, functional outcomes were more favorable in patients with 1 to 4 passes of the SR than in patients without recanalization (odds ratio [OR] was 8.06 for 1 pass; OR 7.78 for 2 passes; OR 6.10 for 3 passes; OR 6.57 for 4 passes; all P P =0.455; OR 0.33 with 0.02–5.70, P =0.445 for ≥6 passes). Conclusions— The likelihood of successful recanalization got sequentially lower as the number of SR passes increased. Five or more passes of the SR became futile in terms of the recanalization rate and functional outcomes.

Background and Purpose— Perfusion-based triage has proven to be effective and safe for selecting patients who are likely to benefit from endovascular thrombectomy (EVT) in a late time window. We investigated collateral-based triage for EVT in patients presenting beyond 6 hours, in terms of interrater reliability and efficacy in predicting clinical outcome, in comparison to perfusion-based triage. Methods— One hundred and thirty-two patients who underwent both computed tomographic angiography and computed tomography perfusion for anterior circulation large artery occlusion 6 to 24 hours after last seen well were enrolled. Patients were classified into EVT-eligible and EVT-ineligible groups according to perfusion- and collateral-based triages. We evaluated the interrater reliability of collateral-based triage and differences in good outcome rates of patients who received EVT in the EVT-eligible groups based on perfusion- and collateral-based triages. Results— Both computed tomographic angiography and computed tomography perfusion were assessable in 93 patients. Seventy-six patients were eligible for EVT according to perfusion-based triage. Among them, EVT was performed in 58, of whom 32 (55.1%) had good outcome. Sixty-nine patients were eligible for EVT based on collateral-based triage. Among them, EVT was performed in 50 patients, of whom 31 (62.0%) had good outcome. Interrater reliability of collateral-based triage was good (generalized κ=0.73 [95% CI, 0.59–0.84]). Agreement on EVT eligibility between perfusion- and collateral-based triages was moderate (κ=0.41 [95% CI, 0.16–0.61]). There was no difference in good outcome rates of patients who underwent EVT in the EVT-eligible groups based on perfusion- and collateral-based triages (55.1% versus 62.0%; P =0.0675). Conclusions— Collateral-based triage showed good interrater reliability and comparable efficacy to that of perfusion-based triage in predicting clinical outcome after EVT in patients presenting beyond 6 hours. Collateral-based triage is a reliable approach for selecting patients for EVT in the extended therapeutic time window.

BACKGROUND Although several outcome prediction scores incorporated with pretreatment variables have been developed for acute ischemic stroke (AIS) patients, there is not currently a prediction score that includes pretreatment imaging that can show salvageable brain tissue. OBJECTIVE To evaluate whether addition of the collateral grade on computed tomography angiography to previously published prediction scores could increase accuracy of clinical outcome prediction in endovascular thrombectomy (EVT) for AIS. METHODS This study used a retrospective multicenter registry for patients undergoing EVT for anterior circulation large vessel occlusion. Three previously published outcome prediction scores (Houston intra-arterial therapy 2, HIAT2; totaled health risks in vascular events, THRIVE; and Pittsburgh response to endovascular therapy, PRE scores) were tested in this study. Using 482 deprivation cohorts, areas under the receiver operating characteristic curves (AUC-ROCs) were compared between prediction scores with/without collateral grades in predicting the poor outcomes (modified Rankin Scale 4-6 at 3-mo follow-up) after EVT. We developed modified prediction scores by adding the collateral grade, and their advancement of outcome prediction was validated using 208 independent validation cohorts. RESULTS AUC-ROCs of HIAT2, THRIVE, and PRE scores that incorporated with collateral grade were superior in predicting poor outcomes when compared to that of the unmodified scores (P

Background and Purpose— Effective rescue treatment has not yet been suggested in patients with mechanical thrombectomy (MT) failure. This study aimed to test whether rescue stenting (RS) improved clinical outcomes in MT-failed patients. Methods— This is a retrospective analysis of the cohorts of the 16 comprehensive stroke centers between September 2010 and December 2015. We identified the patients who underwent MT but failed to recanalize intracranial internal carotid artery or middle cerebral artery M1 occlusion. Patients were dichotomized into 2 groups: patients with RS and without RS after MT failure. Clinical and laboratory findings and outcomes were compared between the 2 groups. It was tested whether RS is associated with functional outcome. Results— MT failed in 148 (25.0%) of the 591 patients with internal carotid artery or middle cerebral artery M1 occlusion. Of these 148 patients, 48 received RS (RS group) and 100 were left without further treatment (no stenting group). Recanalization was successful in 64.6% (31 of 48 patients) of RS group. Compared with no stenting group, RS group showed a significantly higher rate of good outcome (modified Rankin Scale score, 0–2; 39.6% versus 22.0%; P =0.031) without increasing symptomatic intracranial hemorrhage (16.7% versus 20.0%; P =0.823) or mortality (12.5% versus 19.0%; P =0.360). Of the RS group, patients who had recanalization success had 54.8% of good outcome, which is comparable to that (55.4%) of recanalization success group with MT. RS remained independently associated with good outcome after adjustment of other factors (odds ratio, 3.393; 95% confidence interval, 1.192–9.655; P =0.022). Follow-up vascular imaging was available in the 23 (74.2%) of 31 patients with recanalization success with RS. The stent was patent in 20 (87.0%) of the 23 patients. Glycoprotein IIb/IIIa inhibitor was significantly associated with stent patency but not with symptomatic intracranial hemorrhage. Conclusions— RS was independently associated with good outcomes without increasing symptomatic intracranial hemorrhage or mortality. RS seemed considered in MT-failed internal carotid artery or middle cerebral artery M1 occlusion.

ObjectiveTo characterise the time window in which endovascular thrombectomy (EVT) is associated with good outcome, and to test the differential relationship between functional outcome and onset-to-reperfusion time (ORT), depending on collateral status.MethodsThis was a retrospective analysis of clinical and imaging data of 554 consecutive patients, who had recanalisation success by EVT for anterior circulation large artery occlusion, from the prospectively maintained registries of 16 comprehensive stroke centres between September 2010 and December 2015. The patients were dichotomised into good and poor collateral groups, based on CT angiography. We tested whether the likelihood of good outcome (modified Rankin Scale, 0–2) by ORT was different between two groups.ResultsORT was 298 min±113 min (range, 81–665 min), and 84.5% of patients had good collaterals. Age, diabetes mellitus, previous infarction, National Institutes of Health Stroke Scale, good collaterals (OR 40.766; 95% CI 10.668 to 155.78; pConclusionsEarlier successful recanalisation was strongly associated with good outcome in poor collateral group; however, this association was weak during the tested time window in good collateral group. This suggests that the ORT window for good outcome can be adjusted according to collateral status.

Background: The actions and responses of the hospital personnel during acute stroke care in the emergency department (ED) may differ according to the severity of a patient’s stroke symptoms. We investigated whether the time from arrival at ED to various care steps differed between patients with minor and non-minor stroke who were treated with intravenous tissue plasminogen activator (IV tPA). Methods: We included consecutive patients who received IV tPA during a 1.5 year-period in 5 hospitals. Minor stroke was defined as a National Institutes of Health Stroke Scale (NIHSS) score < 5. We compared various intervals from arrival at the ED to treatment between patients with minor stroke and those with non-minor stroke (NIHSS score ≥5). Delayed treatment was defined as a door-to-needle time > 40 min. Results: During the study period, 356 patients received IV tPA treatment. The median door-to-needle time was significantly longer in the minor stroke group than it was in the non-minor stroke group (43 min [interquartile range [IQR] 35.5–55.5] vs. 37 min [IQR 30–46], p < 0.001). The minor stroke group had a significantly longer door-to-notification time (7 min [IQR 4.5–12] vs. 5 min [IQR 3–8], p < 0.001) and door-to-imaging time (20 min [IQR 15–26.5] vs. 16 min [IQR 11–21], p < 0.001) than did the non-minor stroke group. However, the imaging-to-needle time was not different between the groups. Multivariable analyses revealed that minor stroke was associated with delayed treatment (OR 2.54 [95% CI 1.52–4.30], p = 0.001). Conclusions: Our findings show that the door-to-needle time was longer in patients with minor stroke than it was in those with non-minor stroke, mainly owing to delayed action in the initial steps of neurology notification and imaging. Our findings suggest that some quality improvement initiatives are necessary for patients with suspected stroke with minor symptoms.

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.

Background and Purpose— We investigated whether occlusion type identified with computed tomography angiography (CTA-determined occlusion type) could predict endovascular treatment success using stent retriever (SR) thrombectomy. Methods— Consecutive patients with stroke who underwent CTA and then endovascular treatment for intracranial large artery occlusion were retrospectively reviewed. CTA-determined occlusion type was classified into truncal-type occlusion or branching-site occlusion and compared with digital subtraction angiography–determined occlusion type during endovascular treatment. Three rapidly- and readily-assessable pre-procedural findings (CTA-determined occlusion type, atrial fibrillation, and hyperdense artery sign), which may infer occlusion pathomechanism (embolic versus nonembolic) before endovascular treatment, were evaluated for association with SR success along with stroke risk factors and laboratory results. In addition, the predictive power of the 3 pre-procedural findings for SR success was compared with receiver operating characteristic curve analyses. Results— A total of 238 patients (mean age, 70.0 years; male patients, 52.9%) were included in this study. CTA-determined occlusion type corresponded adequately with digital subtraction angiography–determined occlusion type ( P =0.453). Atrial fibrillation (odds ratio, 2.66; 95% confidence interval, 1.25–5.66) and CTA-determined branching-site occlusion (odds ratio, 8.20; confidence interval, 3.45–19.5) were independent predictors for SR success. For predicting SR success, the area under the receiver operating characteristic curve value for CTA-determined branching-site occlusion (0.695) was significantly greater than atrial fibrillation (0.594; P =0.038) and hyperdense artery sign (0.603; P =0.023). Conclusions— CTA-determined branching-site occlusion was significantly associated with SR success. Furthermore, among the 3 rapidly- and readily-assessable pre-procedural findings, CTA-determined branching-site occlusion had the greatest predictive power for SR success.

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

BackgroundFirst pass recanalization (FPR, defined as achieving a modified Thrombolysis in Cerebral Ischemia (mTICI) grade 2c/3 with a single pass of a thrombectomy device) effect has not yet been evaluated in contact aspiration thrombectomy (CAT). We evaluated FPR effect on clinical outcomes and FPR predictors in CAT.MethodsAll consecutive patients who underwent frontline CAT for anterior circulation large vessel occlusion with recanalization (mTICI 2b–3) were identified from registries at six stroke centers. The patients were dichotomized into FPR and non-FPR groups. Clinical features and outcomes were compared between the groups. Multivariate analyses were performed to determine whether FPR was independently associated with clinical outcomes and to identify predictors of FPR.ResultsOf the 429 patients who underwent frontline CAT, recanalization was successful in 344 patients (80.2%; mean age 68.7±11.0 years; M:F ratio 179:165). The FPR group had a higher rate of good outcome (modified Rankin Scale score 0–2) than the non-FPR group. Furthermore, the good outcome rate was higher in the FPR group than in patients who achieved mTICI 2c/3 with multiple passes or rescue treatment. FPR (OR 2.587; 95% CI 1.237 to 5.413) remained independently associated with good outcomes, in addition to age, baseline National Institute Health Stroke Scale, and coronary artery disease. The use of a balloon guide catheter (OR 3.071; 95% CI 1.699 to 5.550) was the only predictor of FPR.ConclusionsPatients in the FPR group had better clinical outcomes than the non-FPR group in CAT. FPR was independently associated with a good outcome. The use of a balloon guide catheter was the only predictor of FPR.

Background and Purpose— The effect of endovascular thrombectomy (EVT) cumulative case volume (EVT-CCV) on outcomes of acute stroke patients has not been studied. This study investigated whether EVT-CCV was associated with outcomes. Methods— We identified all patients who underwent EVT for anterior circulation large vessel occlusion. Patients who met enrollment criteria were grouped into 5 based on the number of previous cases at each hospital. The number of cases that were recruited from each hospital and then assigned to each group (n) was designed to increase by the function of 10×2 (n-1) ; group 1 consisted of cases 1 to 10 at each hospital, group 2 was cases 11 to 30, group 3 was cases 31 to 70, group 4 was cases 71 to 150, and group 5 was cases ≥151. We tested whether EVT-CCV group was associated with procedural and clinical outcomes. Results— Nine hundred fifty-five patients fulfilled the enrollment criteria. Recanalization and good outcome positively correlated with EVT-CCV group ( P r =0.122] for recanalization; P =0.002 [ r =0.099] for good outcome), whereas symptomatic intracranial hemorrhage and mortality negatively correlated ( P =0.039 [ r =–0.067] for symptomatic intracranial hemorrhage; P =0.016 [ r =–0.078] for mortality). EVT-CCV group was independently associated with recanalization (odds ratio, 1.182; 95% CI, 1.029–1.358) and good outcome (odds ratio, 1.187; 95% CI, 1.053–1.337). Conclusions— With increased EVT-CCV, recanalization and good outcome increased, whereas symptomatic intracranial hemorrhage and mortality decreased. Increased EVT-CCV was independently associated with recanalization and good outcome.

Background and Purpose— The prediction of long-term outcomes in ischemic stroke patients may be useful in treatment decisions. Machine learning techniques are being increasingly adapted for use in the medical field because of their high accuracy. This study investigated the applicability of machine learning techniques to predict long-term outcomes in ischemic stroke patients. Methods— This was a retrospective study using a prospective cohort that enrolled patients with acute ischemic stroke. Favorable outcome was defined as modified Rankin Scale score 0, 1, or 2 at 3 months. We developed 3 machine learning models (deep neural network, random forest, and logistic regression) and compared their predictability. To evaluate the accuracy of the machine learning models, we also compared them to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score. Results— A total of 2604 patients were included in this study, and 2043 (78%) of them had favorable outcomes. The area under the curve for the deep neural network model was significantly higher than that of the ASTRAL score (0.888 versus 0.839; P P =0.136) and logistic regression (0.849; P =0.413) models were not significantly higher than that of the ASTRAL score. Using only the 6 variables that are used for the ASTRAL score, the performance of the machine learning models did not significantly differ from that of the ASTRAL score. Conclusions— Machine learning algorithms, particularly the deep neural network, can improve the prediction of long-term outcomes in ischemic stroke patients.

Comorbidities are prevalent among stroke patients. The current study assesses the variations in cost and stroke prognosis by concurrent comorbidities in patients with acute ischemic stroke. The Charlson comorbidity index was used as the composite comorbidity level (0 none, 1 mild, 2 moderate, and ≥ 3 severe). Outcomes included modified Rankin Scale (mRS) at 3 months and 1-year mortality and stroke recurrence. We utilized a multivariate log-normal model for cost, a proportional Cox hazards model for outcomes, and a decision analytic model for the excess cost per unit change in outcome probability compared with the no-comorbidity group. A total of 3605 consecutive patients were enrolled. At 3 months, the severe comorbidity group was 0.32 times less likely to have mRS ≤ 2, and were 4.86 times more likely to die from stroke than the no-comorbidity group. Within 1 year, the severe comorbidity group showed 10.36 and 3.38 times higher likelihoods of death from stroke and stroke recurrence than the no-comorbidity group. The incremental cost was 4376 in 3 months and 7074 USD in 1 year for the severe comorbidity group, and 985 in 3 months and 1265 USD in 1 year for the mild comorbidity group compared to the no-comorbidity group. The excess cost per unit increase of a short-term good prognosis was largest for the severe comorbidity group. Patients with severe comorbidities showed poor prognosis and large health expenditure. Assessing comorbidity level is crucial for better prediction of outcomes and excess cost.

Background and Purpose— Recent guidelines have suggested the potential benefit of intravenous thrombolysis in stroke patients with systemic malignancy who have a reasonable life expectancy of >6 months. However, it is difficult to determine which patients with cancer will have a life expectancy of >6 months. Therefore, we identified the factors associated with 6-month mortality in patients with acute ischemic stroke and systemic malignancy. Methods— Consecutive stroke patients with systemic malignancy were retrospectively analyzed. We classified the patients into 3 groups: the nonactive cancer, active nonmetastatic cancer, and metastatic cancer groups. We compared the baseline characteristics and 6-month survival rates. Results— Of the 468 ischemic stroke patients with systemic malignancy during an 8-year period, 223 patients had nonactive cancer, 105 patients had active nonmetastatic cancer, and 140 patients had metastasis. During the 6-month follow-up, 122 patients (26.1%) died (nonactive cancer group [7.2%, 16/223], active nonmetastatic cancer group [11.4%, 12/105], and metastatic cancer group [67.1%, 94/140]). Multivariate Cox regression analysis revealed that the presence of metastasis (hazard ratio, 4.527; 95% CI, 2.175–9.422) was independently associated with 6-month mortality. However, the active nonmetastatic cancer group exhibited similar 6-month mortality to the nonactive cancer group (hazard ratio, 0.711; 95% CI, 0.282–1.795). Gastric/esophageal cancer and pancreatic cancer were also independently associated with 6-month mortality (hazard ratio, 2.068 and 2.389, respectively). Conclusions— In stroke patients with active cancer, the presence of metastasis and the cancer type were crucial factors associated with 6-month mortality.

BackgroudThe need for rescue treatment (RT) may differ depending on first-line modality (stent retriever (SR) or contact aspiration (CA)) in endovascular thrombectomy (EVT). We aimed to investigate whether the type of first-line modality in EVT was associated with the need for RT.MethodsWe identified all patients who underwent EVT for anterior circulation large-vessel occlusion from prospectively maintained registries of 17 stroke centers. Patients were dichotomized into SR-first and CA-first. RT involved switching to the other device, balloon angioplasty, permanent stenting, thrombolytics, glycoprotein IIb/IIIa antagonist, or any combination of these. We compared clinical characteristics, procedural details, and final recanalization rate between the two groups and assessed whether first-line modality type was associated with RT requirement and if this affected clinical outcome.ResultsA total of 955 patients underwent EVT using either SR-first (n=526) or CA-first (n=429). No difference occurred in the final recanalization rate between SR-first (82.1%) and CA-first (80.2%). However, recanalization with the first-line modality alone and first-pass recanalization rates were significantly higher in SR-first than in CA-first. CA-first had more device passes and higher RT rate. The RT group had significantly longer puncture-to-recanalization time (93±48 min versus 53±28 min). After adjustment, CA-first remained associated with RT (OR, 1.367; 95% CI, 1.019 to 1.834). RT was negatively associated with good outcome (OR, 0.597; 95% CI, 0.410 to 0.870).ConclusionCA was associated with requiring RT, while recanalization with first-line modality alone and first-pass recanalization rates were higher with SR. RT was negatively associated with good outcome.

The histological features of thrombus in stroke patients with cancer are not well known. Using immunohistochemical staining of thrombi retrieved during mechanical thrombectomy in stroke patients, thrombus compositions were compared between 16 patients with active cancer, 16 patients with inactive cancer, and 16 patients without any history of cancer. The active cancer group showed higher platelet and lower erythrocyte fractions than the inactive cancer or the control group. Four patients with vegetation showed very high platelet and low erythrocyte fractions. Patients with cryptogenic etiology in the active cancer group showed a similar pattern to those with vegetation. These findings may aid the determination of treatment strategies in cancer-associated stroke. ANN NEUROL 2019.

Background and Purpose— Endovascular treatment for acute intracranial atherosclerosis–related large vessel occlusion (ICAS [+]-LVO) is one of the challenging issues in modern mechanical thrombectomy era. We evaluated procedural and clinical outcomes of endovascular treatment for the ICAS (+)-LVO. We also compared their outcomes with those of large vessel occlusion not associated with intracranial atherosclerosis (ICAS [−]-LVO). Methods— We retrospectively reviewed consecutive patients with acute stroke who underwent endovascular treatment for LVO. Patients were assigned to the ICAS (+)-LVO group or the ICAS (−)-LVO group primarily based on catheter angiogram. Procedural and clinical outcomes were compared between the ICAS (+)-LVO and ICAS (−)-LVO groups. Results— The present study included 318 patients. Fifty-six patients (17.6%) had an ICAS (+)-LVO. Recanalization was achieved in 45 patients in the ICAS (+)-LVO group (80.4%), which was comparable with the ICAS (−)-LVO group (88.5%; P =0.097). However, recanalization using a stent retriever was less successful in the ICAS (+)-LVO (28.9%) than the ICAS (−)-LVO group (93.5%). Of the remaining patients in the ICAS (+)-LVO group, 84.3% of patients required specific rescue treatments appropriate for ICAS, including balloon angioplasty, stenting, and intra-arterial glycoprotein IIb/IIIa inhibitor infusion. The rates of favorable outcomes (46.4% versus 46.9%), death, and symptomatic intracranial hemorrhage were not significantly different between the 2 groups. Glycoprotein IIb/IIIa inhibitor use was not significantly associated with symptomatic intracranial hemorrhage. Conclusions— ICAS (+)-LVO was often refractory to mechanical thrombectomy. With specific rescue treatments appropriate for ICAS, patients in the ICAS (+)-LVO group had a recanalization rate comparable with patients in the ICAS (−)-LVO. With comparable recanalization rate, the clinical outcomes did not differ between patients with ICAS (+)-LVO and ICAS (−)-LVO.

Background and Purpose— We hypothesized that permanent stenting may be a rescue treatment for stentriever-failed anterior circulation large artery occlusion. We compared the outcomes among patients with permanent stenting and those without stenting after stentriever failure. Methods— We retrospectively evaluated 208 patients who underwent stentriever thrombectomy for anterior circulation large artery occlusion between September 2010 and September 2015. Modified thrombolysis in cerebral ischemia 2b-3 recanalization was achieved with stentriever alone or in combination with Penumbra device in 155 patients (74.5%). An additional 8 patients (3.8%) obtained modified thrombolysis in cerebral ischemia 2b-3 with urokinase or glycoprotein IIb/IIIa inhibitor infusion. Of the remaining 45 patients (21.6%), 17 underwent stenting (stenting group; mean age, 68 years), whereas 28 did not undergo stenting (nonstenting group; mean age, 72 years). The rate of modified thrombolysis in cerebral ischemia 2b-3 in stenting group was assessed, and clinical outcomes were compared between groups. Results— There were no differences in clinical and laboratory findings, initial National Institute of Health Stroke Scale score, location of anterior circulation large artery occlusion, and onset-to-puncture time between groups. Modified thrombolysis in cerebral ischemia 2b-3 was achieved in 14 members (83.3%) of the stenting group. Stenting group had more favorable outcomes (modified Rankin Scale score 0–2, 35.3%) and less cerebral herniation (11.8%) than nonstenting group (modified Rankin Scale score 0–2, 7.1%; cerebral herniation, 42.9%; P Conclusions— Permanent stenting may be a rescue modality for stentriever-failed anterior circulation large artery occlusion. A large prospective study is necessary for confirmation because of the small sample size of this study.

Background The histologic features of thrombus may differ according to the stroke subtypes. However, in acute reperfusion therapy, fibrin-specific thrombolytics are used based on the assumption that all thrombi are alike. Aims The histologic characteristics of thrombi were compared between patients with different stroke etiologies. Methods Between April 2010 and March 2012, we analyzed thrombi retrieved from acute stroke patients during mechanical thrombectomy. All thrombi were analyzed using component-specific stains such as Martius scarlet blue for fibrins and immunostaining with CD42b antibody for platelets. The stroke subtypes were determined based on the Trial of ORG 10172 in Acute Stroke Treatment classification. Results Among 36 patients, 22 were diagnosed with cardioembolism, 8 with atherothrombosis, and 6 with undetermined etiology. In arteriogenic thrombi, red blood cells were most abundant (56.9 ± 12.2%), and the platelets covered the fibrin layers or were localized at the edge or periphery of the thrombus. In cardiogenic thrombi, fibrin was most abundant (39.5 ± 13.5%), and platelets were clustered within the rich fibrin. Red blood cells proportion was greater in arteriogenic thrombi than in cardiogenic thrombi ( p Conclusions Acute thrombi showed different histologic features according to the stroke etiology. The distribution of platelets and proportion of red blood cells and fibrin were major distinguishing factors between stroke subtypes.

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 Subtle abnormal motor signs are indications of serious neurological diseases. Although neurological deficits require fast initiation of treatment in a restricted time, it is difficult for nonspecialists to detect and objectively assess the symptoms. In the clinical environment, diagnoses and decisions are based on clinical grading methods, including the National Institutes of Health Stroke Scale (NIHSS) score or the Medical Research Council (MRC) score, which have been used to measure motor weakness. Objective grading in various environments is necessitated for consistent agreement among patients, caregivers, paramedics, and medical staff to facilitate rapid diagnoses and dispatches to appropriate medical centers. Objective In this study, we aimed to develop an autonomous grading system for stroke patients. We investigated the feasibility of our new system to assess motor weakness and grade NIHSS and MRC scores of 4 limbs, similar to the clinical examinations performed by medical staff. Methods We implemented an automatic grading system composed of a measuring unit with wearable sensors and a grading unit with optimized machine learning. Inertial sensors were attached to measure subtle weaknesses caused by paralysis of upper and lower limbs. We collected 60 instances of data with kinematic features of motor disorders from neurological examination and demographic information of stroke patients with NIHSS 0 or 1 and MRC 7, 8, or 9 grades in a stroke unit. Training data with 240 instances were generated using a synthetic minority oversampling technique to complement the imbalanced number of data between classes and low number of training data. We trained 2 representative machine learning algorithms, an ensemble and a support vector machine (SVM), to implement auto-NIHSS and auto-MRC grading. The optimized algorithms performed a 5-fold cross-validation and were searched by Bayes optimization in 30 trials. The trained model was tested with the 60 original hold-out instances for performance evaluation in accuracy, sensitivity, specificity, and area under the receiver operating characteristics curve (AUC). Results The proposed system can grade NIHSS scores with an accuracy of 83.3% and an AUC of 0.912 using an optimized ensemble algorithm, and it can grade with an accuracy of 80.0% and an AUC of 0.860 using an optimized SVM algorithm. The auto-MRC grading achieved an accuracy of 76.7% and a mean AUC of 0.870 in SVM classification and an accuracy of 78.3% and a mean AUC of 0.877 in ensemble classification. Conclusions The automatic grading system quantifies proximal weakness in real time and assesses symptoms through automatic grading. The pilot outcomes demonstrated the feasibility of remote monitoring of motor weakness caused by stroke. The system can facilitate consistent grading with instant assessment and expedite dispatches to appropriate hospitals and treatment initiation by sharing auto-MRC and auto-NIHSS scores between prehospital and hospital responses as an objective observation.

Purpose There are various patterns in determining the choice of the first-line antithrombotic agent for acute stroke with non-valvular atrial fibrillation. We investigated the efficacy and safety of non-vitamin K oral anticoagulants as first-line antithrombotics for patients with acute stroke and non-valvular atrial fibrillation. Materials and Methods Patients with non-valvular atrial fibrillation and ischemic stroke or transient ischemic attack within 24 h from stroke onset were included. On the basis of the first regimen used and the regimen within 7 days after admission, the study population was divided into three groups: 1) antiplatelet switched to warfarin (A-W), 2) antiplatelet switched to NOAC (A-N), and 3) NOAC only (N only). We compared the occurrence of early neurologic deterioration, symptomatic intracranial hemorrhage, systemic bleeding, and poor functional outcome at 90 days. Results Of 314 included patients, 164, 53, and 97 were classified into the A-W, A-N, and N only groups, respectively. Early neurologic deterioration was most frequently observed in the A-W group (9.1%), followed by the A-N (5.7%) and N only (1.0%) groups (p = 0.017). Multivariable analysis adjusting for potential confounders demonstrated that the N only group was independently associated with a lower rate of early neurologic deterioration (odds ratio [OR] 0.104, 95% CI 0.013-0.831) or poor functional outcome at 90 days (OR 0.450, 95% CI 0.215-0.940) than the A-W group. However, the rate of symptomatic intracranial hemorrhage or any systemic bleeding event did not differ among the groups. Conclusion Using non-vitamin K oral anticoagulants as the first-line regimen for acute ischemic stroke may help prevent early neurologic deterioration without increasing the bleeding risk.

Objective Compressed sensing (CS) has gained wide interest since it accelerates MRI acquisition. We aimed to compare the 3D post-contrast T1-weighted volumetric isotropic turbo spin echo acquisition (VISTA) with CS (VISTA-CS) and without CS (VISTA-nonCS) in intracranial vessel wall MRIs (VW-MRI). Materials and methods From April 2017 to July 2018, 72 patients who underwent VW-MRI, including both VISTA-CS and VISTA-nonCS, were retrospectively enrolled. Wall and lumen volumes, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured from normal and lesion sites. Two neuroradiologists independently evaluated overall image quality and degree of normal and lesion wall delineation with a four-point scale (scores ≥ 3 defined as acceptable). Results Scan coverage was increased in VISTA-CS to cover both anterior and posterior circulations with a slightly shorter scan time compared to VISTA-nonCS (approximately 7 minutes vs. 8 minutes). Wall and lumen volumes were not significantly different with VISTA-CS or VISTA-nonCS (interclass correlation coefficient = 0.964-0.997). SNR was or trended towards significantly higher values in VISTA-CS than in VISTA-nonCS. At normal sites, CNR was not significantly different between two sequences (p = 0.907), whereas VISTA-CS provided lower CNR in lesion sites compared with VISTA-nonCS (p = 0.003). Subjective wall delineation was superior with VISTA-nonCS than with VISTA-CS (p = 0.019), although overall image quality did not differ (p = 0.297). The proportions of images with acceptable quality were not significantly different between VISTA-CS (83.3-97.8%) and VISTA-nonCS (75-100%). Conclusion CS may be useful for intracranial VW-MRI as it allows for larger scan coverage with slightly shorter scan time without compromising image quality.