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Introduction: Visual field defects (VFDs) represent a debilitating poststroke complication, characterized by unseen parts of the visual field. Visual perceptual learning (VPL), involving repetitive visual training in blind visual fields, may effectively restore visual field sensitivity in cortical blindness. This current multicenter, double-blind, randomized, controlled clinical trial investigated the efficacy and safety of VPL-based digital therapeutics (Nunap Vision [NV]) for treating poststroke VFDs., Methods: Stroke outpatients with VFDs (>6 months after stroke onset) were randomized into NV (defective field training) or Nunap Vision-Control (NV-C, central field training) groups. Both interventions provided visual perceptual training, consisting of orientation, rotation, and depth discrimination, through a virtual reality head-mounted display device 5 days a week for 12 weeks. The two groups received VFD assessments using Humphrey visual field (HVF) tests at baseline and 12-week follow-up. The final analysis included those completed the study (NV, n = 40; NV-C, n = 35). Efficacy measures included improved visual area (sensitivity ≥6 dB) and changes in the HVF scores during the 12-week period., Results: With a high compliance rate, NV and NV-C training improved the visual areas in the defective hemifield (>72 degrees 2 ) and the whole field (>108 degrees 2 ), which are clinically meaningful improvements despite no significant between-group differences. According to within-group analyses, mean total deviation scores in the defective hemifield improved after NV training (p = .03) but not after NV-C training (p = .12)., Conclusions: The current trial suggests that VPL-based digital therapeutics may induce clinically meaningful visual improvements in patients with poststroke VFDs. Yet, between-group differences in therapeutic efficacy were not found as NV-C training exhibited unexpected improvement comparable to NV training, possibly due to learning transfer effects., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery., (© 2024. The Author(s).)

Early neurological deterioration (END) in lenticulostriate artery (LSA) infarction is associated with perforating artery hypoperfusion. As middle cerebral artery (MCA) tortuosity may alter hemodynamics, we investigated the association between MCA tortuosity and END in LSA infarction. We reviewed patients with acute LSA infarction without significant MCA stenosis. END was defined as an increase of ≥ 2 or ≥ 1 in the National Institutes of Health Stroke Scale (NIHSS) total or motor score, respectively, within first 72 h. The MCA tortuosity index (actual /straight length) was measured. Stroke mechanisms were categorized as branch atheromatous disease (BAD; lesions > 10 mm and 4 axial slices) and lipohyalinotic degeneration (LD; lesion smaller than BAD). Factors associated with END in LD and BAD were investigated. END occurred in 104/390 (26.7%) patients. A high MCA tortuosity index (adjusted odds ratio, aOR 10.63, 95% confidence interval [2.57-44.08], p = 0.001) was independently associated with END. In patients with BAD, high initial NIHSS score (aOR 1.40 [1.03-1.89], p = 0.031) and presence of parental artery disease (stenosis < 50%; aOR 10.38 [1.85-58.08], p = 0.008) were associated with END. In patients with LD, high MCA tortuosity (aOR 41.78 [7.37-237.04], p < 0.001) was associated with END. The mechanism causing END in patients with LD and BAD may differ., (© 2023. The Author(s).)

Two different stroke mechanisms are involved in small vessel disease: branch atheromatous disease (BAD) and lipohyalinotic degeneration (LD). We compared mechanisms of stroke in lenticulostriate arteries (LSA) vs. anterior pontine arteries (APA) and verified factors associated with stroke mechanisms, including shape of middle cerebral artery (MCA) and basilar artery (BA). We retrospectively reviewed patients with acute ischemic stroke with penetrating artery territory confirmed by MRI. The mechanisms of stroke were categorized based on diffusion-weighted imaging; BAD was defined as lesion larger than 10 mm in LSA and lesions involving basal pontine in APA. Other lesions were classified as LD. The shapes of MCA and BA were classified as straight, with one angle, or with two angles (U, C or S shape, respectively) using anterior-posterior view. The study included 221 patients. LD was more common in LSA infarcts, but BAD was more common in APA infarcts (p < 0.001). Low initial National Institutes of Health Stroke Scale [Adjusted Odds ratio (aOR) = 0.78; p < 0.001], absence of hyperlipidemia [aOR = 0.31; p = 0.002], previous statin use [aOR = 4.35; p = 0.028] LSA infarcts [reference = APA territory; aOR = 11.07; p < 0.001], and S-shaped vessels (reference = straight shaped vessels; aOR = 3.51; p = 0.004) were independently associated with LD. Angulations in the mother vessels may be more associated with true small vessel disease more with LD than BAD., (© 2022. The Author(s).)

Objective: Chronic kidney disease (CKD) increases blood pressure variability (BPV) and affects stroke outcomes. However, the effect of BPV on early neurological deterioration (END) may be different according to the renal function., Methods: We enrolled ischemic stroke patients with a National Institutes of Health Stroke Scale of ≤5. END was defined as worsening of ≥1 point in motor power or ≥2 points in total score. BPV was calculated with BP measured during the first 5 days and presented as standard deviation (SD) and coefficient of variation (CoV). Renal function was classified using the Kidney Disease Improving Global Outcomes (KDIGO) classification of CKD. Variables were compared between those with (KDIGO classification: moderate- to very-high-risk) and without renal impairment (KDIGO classification: low-risk) and factors associated with END were investigated., Results: Among the 290 patients (136 [46.9%] renal impairment), END was observed in 59 (20.3%) patients. BPV parameters and the risk of END increased as renal function was impaired. Renal function and systolic BP (SBP) mean, SD, CoV, and diastolic BP (DBP) mean, SD were independently associated with END. We found no association between BPV parameters and END in normal renal function patients; however, among impaired renal function patients, SBP SD (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.09-1.32, P<0.001) and CoV (1.30 [1.12-1.50], P<0.001) were associated with END., Conclusions: The association between END and BPV parameters differs according to renal function in minor ischemic stroke; BPV was associated with END in patients with renal impairment, but less in those with normal renal function., Competing Interests: The authors have declared that no competing interests exist.

Background Which type of recurrent stroke is associated with pulse pressure (PP) remains uncertain in ischemic stroke with cerebral microbleeds or intracerebral hemorrhage. Methods and Results The PICASSO (Prevention of Cardiovascular Events in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage) database involving 1454 subjects was analyzed. Subjects were stratified into quartiles according to the distribution of mean PP (mm Hg) during follow-up (mean, 1.9 years): <47 (first quartile), 48 to 53 (second quartile), 54 to 59 (third quartile), and ≥60 mm Hg (fourth quartile). The primary end point was hemorrhagic stroke, and the secondary end points were ischemic stroke, stroke of any type, and major adverse cardiovascular events. Adjusted time-dependent area under the receiver operating characteristic curve analysis was performed to assess the prediction accuracy of mean PP. The mean frequency of visit for blood pressure checkup was 9.4±5.5 times. The stroke incidence rate per 100 person-years was 3.14, 2.24, 5.52, and 6.22, respectively in increasing quartile of mean PP, and the rate of major adverse cardiovascular events was 3.82, 2.84, 6.37, and 7.14, respectively. In the presence of mean arterial pressure, hemorrhagic stroke risk was higher in the highest quartile (adjusted hazard ratio, 6.03; 95% CI, 1.04-34.99) versus the lowest quartile, which was evident at higher mean systolic blood pressure. Higher mean PP as a continuous variable was also a predictor of hemorrhagic stroke (1.09, 1.03-1.15). The time-dependent area under the receiver operating characteristic curve for hemorrhagic stroke was 0.79. Conclusions Long-term elevated PP with higher systolic blood pressure confers a greater risk of subsequent hemorrhagic stroke among stroke patients with cerebral microbleeds or intracerebral hemorrhage. Registration URL: https://www.clinicaltrials.gov; Unique identifier, NCT01013532.

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.

Background and Purpose- We aimed to investigate the ability of machine learning (ML) techniques analyzing diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging to identify patients within the recommended time window for thrombolysis. Methods- We analyzed DWI and FLAIR images of consecutive patients with acute ischemic stroke within 24 hours of clear symptom onset by applying automatic image processing approaches. These processes included infarct segmentation, DWI, and FLAIR imaging registration and image feature extraction. A total of 89 vector features from each image sequence were captured and used in the ML. Three ML models were developed to estimate stroke onset time for binary classification (≤4.5 hours): logistic regression, support vector machine, and random forest. To evaluate the performance of ML models, the sensitivity and specificity for identifying patients within 4.5 hours were compared with the sensitivity and specificity of human readings of DWI-FLAIR mismatch. Results- Data from a total of 355 patients were analyzed. DWI-FLAIR mismatch from human readings identified patients within 4.5 hours of symptom onset with 48.5% sensitivity and 91.3% specificity. ML algorithms had significantly greater sensitivities than human readers (75.8% for logistic regression, P =0.020; 72.7% for support vector machine, P =0.033; 75.8% for random forest, P =0.013) in detecting patients within 4.5 hours, but their specificities were comparable (82.6% for logistic regression, P =0.157; 82.6% for support vector machine, P =0.157; 82.6% for random forest, P =0.157). Conclusions- ML algorithms using multiple magnetic resonance imaging features were feasible even more sensitive than human readings in identifying patients with stroke within the time window for acute thrombolysis.

Multimodal magnetic resonance imaging (MRI) has emerged as a promising tool for diagnosing ischemic stroke and for determining treatment strategies in the acute phase. The detection and quantification of the penumbra and the infarct core regions aid the assessment of the potential risks and benefits of thrombolysis by providing information on salvageable tissue or ischemic lesion age. In this study, we proposed a fully automated and real-time algorithm to compute parameter maps of perfusion-weighted images (PWIs) and to identify an infarct core from diffusion-weighted images (DWIs). DWI and PWI were obtained using a 1.5 Tesla MRI scanner for 15 patients with acute ischemic stroke. Parameter maps of PWI were computed using restricted gamma-variate curve fitting and Fourier-based deconvolution. The ischemic penumbra was identified using time-to-maximum (T max ) > 6 s as the mutual optimal threshold, while the infarct core was segmented using an adaptive thresholding on DWI. When the penumbra on PWI was compared with that generated using commercial software Pearson's linear correlation coefficient between penumbra volumes was 0.601 (p = 0.030), and the Dice coefficient was 0.51 ± 0.15. The infarct core on DWI was compared with the manually segmented gold standard. Dice coefficient between the manually drawn and automated segmented infarct cores was 0.62 ± 0.18. The processing times for PWI and DWI were 222.9 ± 16.4 and 53.4 ± 4.8 s, respectively. In conclusion, we demonstrate a fully automated and real-time algorithm to segment the penumbra and the infarct core regions based on PWI and DWI.

Background: Recent reports showing the favorable role of patent foramen ovale (PFO) closure in patients with cryptogenic stroke have raised the issue of selecting optimal candidates., Objectives: This study, DEFENSE-PFO (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale), evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO, as evaluated by transesophageal echocardiography., Methods: Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group. High-risk PFO included PFO with atrial septal aneurysm, hypermobility (phasic septal excursion into either atrium ≥10 mm), or PFO size (maximum separation of the septum primum from the secundum) ≥2 mm. The primary endpoint was a composite of stroke, vascular death, or Thrombolysis In Myocardial Infarction-defined major bleeding during 2 years of follow-up., Results: From September 2011 until October 2017, 120 patients (mean age: 51.8 years) underwent randomization. PFO size, frequency of septal aneurysm (13.3% vs. 8.3%; p = 0.56), and hypermobility (45.0% vs. 46.7%; p > 0.99) were similar between the groups. All PFO closures were successful. The primary endpoint occurred exclusively in the medication-only group (6 of 60 patients; 2-year event rate: 12.9% [log-rank p = 0.013]; 2-year rate of ischemic stroke: 10.5% [p = 0.023]). The events in the medication-only group included ischemic stroke (n = 5), cerebral hemorrhage (n = 1), Thrombolysis In Myocardial Infarction-defined major bleeding (n = 2), and transient ischemic attack (n = 1). Nonfatal procedural complications included development of atrial fibrillation (n = 2), pericardial effusion (n = 1), and pseudoaneurysm (n = 1)., Conclusions: PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence. (Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Troponin elevation with electrocardiography changes is not uncommon in patients with acute ischemic stroke; however, it is still unclear whether the mechanism of these changes is due to cardiac problems or neurally mediated myocytic damage. Thus, we investigated cardiac and neurological predictors of troponin elevation in those patients., Methods and Results: We retrospectively analyzed medical data of the prospectively registered ischemic stroke patients on stroke registry who were admitted and underwent a serum cardiac troponin I and 12-lead electrocardiography within 24 hours of symptom onset. However, patients with well-known troponin-elevating comorbidities were excluded from the analysis. Among 1404 ischemic stroke patients, 121 (8.7%) had elevated troponin, which was defined as more than 0.04 mg/mL. Multivariable analysis identified electrocardiography abnormalities such as QTc-prolongation (odds ratio [OR]: 1.52, 95% CI: 1.02-2.28), left ventricular hypertrophy (OR: 2.14, 95% CI 1.43-3.19), Q-wave (OR: 2.53, 95% CI: 1.48-4.32), and ST elevation (OR: 2.74, 95% CI: 1.12-6.72) as cardiac variables associated with troponin elevation, and higher National Institutes of Health Stroke Scale score (OR: 1.04, 95% CI: 1.01-1.07) and insular cortical lesions (OR: 2.78, 95% CI: 1.85-4.19) as neurological variables associated with troponin elevation. Incidence of troponin elevation as well as QTc-prolongation was increased further in combination with cardiac and neurological factors., Conclusions: Certain cardiac and neurological conditions in acute ischemic stroke may contribute to troponin elevation. The proposed concept of cardiac vulnerability to cerebrogenic stress can be a practical interpretation of troponin elevation and electrocardiography abnormalities in stroke patients., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Hemodynamic tandem intracranial lesions (TILs) on intracranial magnetic resonance angiography, which develop flow dependently, have been overlooked clinically in patients undergoing carotid endarterectomy. As they represent severe baseline hemodynamic compromise at the segment, they may be associated with distinctive clinical outcomes., Methods and Results: We assessed 304 consecutive carotid endarterectomy cases treated over 3 years. Included cases had both preoperative and postoperative intracranial 3-dimensional time-of-flight magnetic resonance angiography, of which signal intensities are flow dependent, and postoperative diffusion-weighted imaging (≤3 days following carotid endarterectomy). Preoperative TILs in the ipsilateral intracranial arteries were evaluated by the presence of nonexclusive components: focal stenosis (>50%), diffuse stenosis (>50%), and decreased signal intensities (>50%). The components showing postoperative normalization were considered hemodynamic. TILs with hemodynamic components were defined as hemodynamic TILs, while others as consistent TILs. Baseline characteristics and postoperative outcomes were analyzed among 3 groups: no TILs, consistent TILs, and hemodynamic TILs. Preoperative TILs were identified in 104 (34.2%) cases; 54 (17.8%) had hemodynamic components. Diffuse stenosis and decreased signal intensities were usually reversed postoperatively. Patients with hemodynamic TILs tended to have severe proximal carotid stenosis and recent strokes (≤14 days). For the outcome, hemodynamic TILs were independently associated with the advent of postoperative ischemic lesions on diffusion-weighted imaging (odds ratio: 2.50; 95% CI, 1.20-5.20)., Conclusions: In patients undergoing carotid endarterectomy, a significant number of preoperative TILs demonstrated hemodynamic components, which were reversed postoperatively. The presence of such components was distinctively associated with the postoperative incidence of new ischemic lesions., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background and Purpose: Dissection is an increasingly recognized cause of ischemic stroke, which occurs spontaneously or after trauma, in relatively young patients. We hypothesized that there might be a predisposing factor weakening the vascular wall and that arterial tortuosity might be higher in patients with dissection., Methods: We consecutively enrolled cervical artery dissection (CerAD) patients who had undergone magnetic resonance angiography. Age- and sex-matched healthy subjects who underwent magnetic resonance angiography in a routine health examination were used as controls. The tortuosity was measured semiautomatically from the carotid artery and vertebral artery (VA) arteries. Tortuosity index was defined as: [(arc/chord)-1×100] in each arteries. Independent risk factors associated with CerAD were investigated using multivariable analysis. Subgroup analysis according to the dissected artery was performed., Results: There were no differences in vascular risk factors between the 75 CerAD patients and the 75 controls. The tortuosity indexes of the contralesional VA (16.3±6.8 versus 12.1±4.5, respectively; P<0.001) and carotid artery (8.8±4.0 versus 7.3±2.9, respectively; P=0.01) were higher in patients with CerAD compared with those of control subjects. VA tortuosity (odds ratio, 1.175; P=0.001) was independently associated with the presence of CerAD. In subgroup analysis, VA tortuosity was significantly higher in 57 patients with VA dissection than in controls (P<0.001), and carotid artery tortuosity was marginally higher in 18 patients with carotid artery dissection (P=0.05)., Conclusions: CerAD is associated with tortuous cervical arteries, which may implicate weakened cervical vascular structure in these patients., (© 2016 American Heart Association, Inc.)

Background and Purpose: In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence., Methods: In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding., Results: Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group., Conclusions: Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268., (© 2016 American Heart Association, Inc.)

Background and Purpose: Right-to-left shunt (RLS) via the patent foramen ovale is an important cause of cryptogenic stroke. The Valsalva maneuver provokes or enhances RLS, but RLS can also occur during normal respiration. This study examined whether the ischemic lesion pattern differs depending on the character of RLS., Methods: All consecutive patients with a patent foramen ovale (diagnosed by transesophageal echocardiography) who had a cryptogenic stroke and underwent transcranial Doppler-patent foramen ovale test (monitoring of microbubbles in the right middle cerebral artery by transcranial Doppler after hand-agitated saline injection) were divided according to whether RLS was constant (microbubbles detected both at baseline and after the Valsalva maneuver) or provoked (microbubbles detected only after the Valsalva maneuver). The groups were compared in terms of clinical and imaging characteristics., Results: Seventy-six patients met the eligibility criteria: 50 had constant RLS and 26 had provoked RLS. Provoked RLS patients were significantly younger. The ischemic lesions in provoked RLS patients were located predominantly in the vertebro-basilar circulation (73.1% versus 28.0%; P=0.002), whereas constant RLS patients were more likely to have multicirculatory lesions (16.0% versus 0.0%; P=0.045). After adjusting for confounders, provoked RLS associated independently with a vertebro-basilar lesion location (OR=3.306; P=0.03)., Conclusions: The predominance of posterior-circulatory infarction in provoked RLS patients suggests that the Valsalva maneuver may promote RLS and paradoxical embolization to the posterior circulation., (© 2014 American Heart Association, Inc.)

Background and Purpose: Diffusion-weighted image fluid-attenuated inversion recovery (FLAIR) mismatch has been considered to represent ischemic lesion age. However, the inter-rater agreement of diffusion-weighted image FLAIR mismatch is low. We hypothesized that color-coded images would increase its inter-rater agreement., Methods: Patients with ischemic stroke <24 hours of a clear onset were retrospectively studied. FLAIR signal change was rated as negative, subtle, or obvious on conventional and color-coded FLAIR images based on visual inspection. Inter-rater agreement was evaluated using κ and percent agreement. The predictive value of diffusion-weighted image FLAIR mismatch for identification of patients <4.5 hours of symptom onset was evaluated., Results: One hundred and thirteen patients were enrolled. The inter-rater agreement of FLAIR signal change improved from 69.9% (k=0.538) with conventional images to 85.8% (k=0.754) with color-coded images (P=0.004). Discrepantly rated patients on conventional, but not on color-coded images, had a higher prevalence of cardioembolic stroke (P=0.02) and cortical infarction (P=0.04). The positive predictive value for patients <4.5 hours of onset was 85.3% and 71.9% with conventional and 95.7% and 82.1% with color-coded images, by each rater., Conclusions: Color-coded FLAIR images increased the inter-rater agreement of diffusion-weighted image FLAIR recovery mismatch and may ultimately help identify unknown-onset stroke patients appropriate for thrombolysis., (© 2014 American Heart Association, Inc.)

Background and Purpose: Hyperhomocysteinemia is a well-known risk factor for vascular disease. However, its action, mechanism, and role in the acute phase of stroke have not been determined. We tried to determine whether an association existed between elevated serum homocysteine levels and early neurological deterioration (END) in patients with acute ischemic stroke., Methods: We performed a secondary analysis from the Cilostazol in Acute Ischemic Stroke Treatment (CAIST) trial, which was a double-blinded, randomized, multicenter trial, assessing the noninferiority of cilostazol over aspirin within 48 hours of an acute ischemic stroke. END was defined as an increase of ≥1 point in motor power or an increase of ≥2 points in the total National Institute of Health Stroke Scale score within 7 days., Results: The mean (±SD) serum homocysteine level was 11.4±4.7 μmol/L. Of the 396 patients studied, 57 (14.4%) patients worsened during the 7 days after inclusion. Most (68%) of the END cases occurred within the first 24 hours after treatment. High levels (>10.3 μmol/L) of serum homocysteine were independent predictors for END (third quartile odds ratio, 3.45; 95% confidence intervals, 1.25-9.50; P=0.016; fourth quartile odds ratio, 3.36; 95% confidence intervals 1.18-9.52; P=0.023) in multivariate analysis., Conclusions: Patients with acute stroke with elevated serum homocysteine levels are at an increased risk for END.

Background and Purpose: Mismatch in lesion visibility between diffusion-weighted image and fluid-attenuated inversion recovery image (DWI-FLAIR mismatch) has been proposed as a biomarker for the estimation of ischemic lesion age. The actual onset in some patients with unclear-onset stroke (UnCOS) may be close to the first-found abnormal time. We hypothesized that patients with UnCOS within a particular time window might have a similar DWI-FLAIR mismatch profile with patients with clear-onset stroke (COS)., Methods: Patients who underwent MRI within 6 hours from first-found abnormal time were recruited retrospectively. Clinical characteristics and the proportion of DWI-FLAIR and perfusion-weighted image-DWI mismatch in each time window were compared between UnCOS and COS., Results: The final analysis included 259 patients (114 with UnCOS and 145 with COS). Patients with UnCOS were older and had more severe stroke at baseline. Risk factors, stroke subtypes, and perfusion-weighted image-DWI mismatch did not differ between the 2 groups. The proportion of patients with DWI-FLAIR mismatch in UnCOS did not differ from COS within 2 hours of first-found abnormal time (50.0% versus 51.5%; P=0.92), but it was significantly lower in UnCOS than in COS at 2 to 3 hours (16.1% versus 44.4%; P=0.02), 3 to 4 hours (13.8% versus 36.4%; P=0.04), and 4 to 5 hours (5.6% versus 29.6%; P=0.05)., Conclusions: The proportion of DWI-FLAIR mismatch in UnCOS within the first 2 hours from first-found abnormal time was similar with COS, but it sharply decreased beyond 2 hours. These data suggest that patients with UnCOS within 2 hours of symptom detection may be good candidates for multimodal imaging-based thrombolysis.

Background and Purpose: Subclinical atrial fibrillation (AF) and patent foramen ovale (PFO) are the major causes of cryptogenic stroke, and neuroimaging may help distinguish the cause. We compared the imaging characteristics of ischemic stroke caused by PFO (PFO-stroke) and AF (AF-stroke)., Methods: We recruited 117 patients with PFO-stroke and 358 patients with AF-stroke after excluding other causes. The lesion patterns were classified according to number, location, size, and pertinent vascular territory and were compared between the 2 groups. Occlusion of the corresponding artery and its recanalization rate were also investigated., Results: The lesion pattern of a PFO-stroke was more frequently observed as a single cortical infarction (34.2% versus 3.1%; P<0.001) or multiple small (<15 mm) scattered lesions (23.1% versus 5.9%; P<0.001) and in the vertebrobasilar artery territory (44.4% versus 22.9%; P<0.001). By contrast, AF-stroke was more frequently observed as a large cortico-subcortical infarction or confluent lesion (>15 mm) with additional lesions in multicirculatory territories. For a PFO-stroke, occlusion of the corresponding vessel on angiography was less frequent (34.2% versus 71.5%; P<0.001), and the neurological deficit evaluated by the National Institutes of Health Stroke Scale was mild (3.48±4.16 versus 9.15±7.35; P<0.001). The recanalization rate was also lower (57.1% versus 78.3%; P=0.007)., Conclusions: A PFO-stroke usually appears as a single cortical or multiple small ischemic lesions in the vertebrobasilar circulation without any visible vessel occlusion on angiography. The recanalization rate is significantly lower than in AF-stroke. These imaging characteristics of PFO-stroke may help to diagnose the mechanism and determine the treatment strategy.

In acute stroke magnetic resonance imaging, a 'mismatch' between visibility of an ischemic lesion on diffusion-weighted imaging (DWI) and missing corresponding parenchymal hyperintensities on fluid-attenuated inversion recovery (FLAIR) data sets was shown to identify patients with time from symptom onset ≤4.5 hours with high specificity. However, moderate sensitivity and suboptimal interpreter agreement are limitations of a visual rating of FLAIR lesion visibility. We tested refined image analysis methods in patients included in the previously published PREFLAIR study using refined visual analysis and quantitative measurements of relative FLAIR signal intensity (rSI) from a three-dimensional, segmented stroke lesion volume. A total of 399 patients were included. The rSI of FLAIR lesions showed a moderate correlation with time from symptom onset (r=0.382, P<0.001). A FLAIR rSI threshold of <1.0721 predicted symptom onset ≤4.5 hours with slightly increased specificity (0.85 versus 0.78) but also slightly decreased sensitivity (0.47 versus 0.58) as compared with visual analysis. Refined visual analysis differentiating between 'subtle' and 'obvious' FLAIR hyperintensities and classification and regression tree algorithms combining information from visual and quantitative analysis also did not improve diagnostic accuracy. Our results raise doubts whether the prediction of stroke onset time by visual image judgment can be improved by quantitative rSI measurements.

Background and Purpose: The aim of this study was to investigate differences in risk factors and stroke mechanisms between intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) and between anterior and posterior circulation atherosclerosis., Methods: A multicenter, prospective, Web-based registry was performed on atherosclerotic strokes using diffusionweighted magnetic resonance imaging and magnetic resonance angiography. Stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombo-occlusion, local branch occlusion, or hemodynamic impairment., Results: Onethousand patients were enrolled from 9 university hospitals. Age (odds ratio [OR], 1.033; 95% confidence interval [CI], 1.018-1.049), male gender (OR, 3.399; 95% CI, 2.335-4.949), and hyperlipidemia (OR, 1.502; 95% CI, 1.117-2.018) were factors favoring ECAS (vs ICAS), whereas hypertension (OR, 1.826; 95% CI, 1.274-2.618; P=0.001) and diabetes mellitus (OR, 1.490; 95% CI, 1.105-2.010; P=0.009) were related to posterior (vs anterior) circulation diseases. Metabolic syndrome was a factor related to ICAS (vs ECAS) only in posterior circulation strokes (OR, 2.433; 95% CI, 1.005-5.890; P=0.007). Stroke mechanisms included arterytoartery embolism (59.7%), local branch occlusion (14.9%), in situ thrombo-occlusion (13.7%), hemodynamic impairment (0.9%), and mixed (10.8%). Anterior ICAS was more often associated with artery-to-artery embolism (51.8% vs 34.0%) and less often associated with local branch occlusion (12.3% vs 40.4%) than posterior ICAS (P<0.001)., Conclusions: The prevalence of risk factors and stroke mechanisms differ between ICAS and ECAS, and between anterior and posterior circulation atherosclerosis. Posterior ICAS seems to be closely associated with metabolic derangement and local branch occlusion. Prevention and management strategies may have to consider these differences.

Background and Purpose: Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke., Methods: This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch>20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries., Results: Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5±10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14-4.49)., Conclusions: In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.

Background and Purpose: Hyperintense vessels (HVs) have been observed in fluid-attenuated inversion recovery imaging of patients with acute ischemic stroke and been linked to slow flow in collateral arterial circulation. Given the potential importance of HV, we used a large, multicenter data set of patients with stroke to clarify which clinical and imaging factors play a role in HV., Methods: We analyzed data of 516 patients from the previously published PRE-FLAIR study (PREdictive value of FLAIR and DWI for the identification of acute ischemic stroke patients≤3 and ≤4.5 hours of symptom onset-a multicenter study) study. Patients were studied by MRI within 12 hours of symptom onset. HV were defined as hyperintensities in fluid-attenuated inversion recovery corresponding to the typical course of a blood vessel that was not considered the proximal, occluded main artery ipsilateral to the diffusion restriction. Presence of HV was rated by 2 observers and related to clinical and imaging findings., Results: Presence of HV was identified in 240 of all 516 patients (47%). Patients with HV showed larger initial ischemic lesion volumes (median, 12.3 versus 4.9 mL; P<0.001) and a more severe clinical impairment (median National Institutes of Health Stroke Scale 10.5 versus 6; P<0.001). In 198 patients with MR angiography, HVs were found in 80% of patients with vessel occlusion and in 17% without vessel occlusion. In a multivariable logistic regression model, vessel occlusion was associated with HV (OR, 21.7%; 95% CI, 9.6-49.9; P<0.001). HV detected vessel occlusion with a specificity of 0.86 (95% CI, 0.80-0.90) and sensitivity of 0.76 (95% CI, 0.69-0.83)., Conclusions: HVs are a common finding associated with proximal arterial occlusions and more severe strokes. HVs predict arterial occlusion with high diagnostic accuracy.

Background and Purpose: Our goal was to investigate whether initial ischemic lesion pattern can predict stroke recurrence in patients with symptomatic intracranial arterial stenosis., Methods: Of the Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis (TOSS)-2 trial participants, we included patients who underwent diffusion-weighted imaging and fluid attenuation inversion recovery imaging at baseline with a follow-up fluid attenuation inversion recovery imaging at 7 months. Based on the diffusion-weighted imaging findings, we classified the initial ischemic lesion patterns according to location (subcortical versus cortical versus subcorticocortical) and multiplicity (single versus multiple). We also evaluated the occurrence of new ischemic lesions on follow-up fluid attenuation inversion recovery as well as clinical stroke in the symptomatic intracranial arterial stenosis territory., Results: Of 353 patients included in this study, 44 (12.5%) and 13 (3.7%) patients had new ischemic lesions and clinical recurrent stroke in the initial symptomatic intracranial arterial stenosis territory, respectively. On multivariable analysis, the initial lesion patterns of subcorticocortical and multiple lesions were independent predictors of new ischemic lesions in the symptomatic intracranial arterial stenosis territory (OR, 3.01; 95% CI, 1.33-7.01; P=0.03; OR, 2.81; 95% CI, 1.34-5.9; P=0.006). These patterns also predicted clinical recurrent stroke., Conclusions: Subcorticocortical lesions and multiple lesions are radiological predictors of recurrent ischemic stroke in symptomatic patients with intracranial arterial stenosis. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT00130039.

Background and Purpose: Based on thrombus location and nature and anatomic features of aorta and cerebral arteries, we hypothesized that cardiogenic embolisms (CE) and aortogenic embolisms (AE) might have different right-left propensity and lesion patterns., Methods: We retrospectively reviewed patients with acute ischemic stroke with high-risk CE sources or moderate-or-severe aortic atherosclerotic plaques on transesophageal echocardiography. Lesion side and patterns on diffusion-weighted imaging were compared between CE and AE., Results: CE was identified in 123 and AE in 63. In multivariate analysis, right-sided lesions and corticosubcortical infarcts were independently associated with CE, and left-sided lesions and pial infarcts were independently associated with AE., Conclusions: CE and AE have different radiological characteristics, as shown by the right-left propensity and lesions patterns of cerebral infarcts.

Objectives: We aimed to define the relationship between cerebral atherosclerosis and stroke after coronary artery bypass grafting (CABG)., Background: Although cerebral atherosclerosis may play a crucial role in the advent of post-CABG stroke, only extracranial carotid artery disease has been extensively studied, and the effects of atherosclerosis on the mechanisms underlying post-CABG stroke remain unclear., Methods: Pre-operative magnetic resonance angiography was performed on 1,367 consecutive CABG patients to assess intracranial and extracranial cerebral atherosclerosis. Disease severity was evaluated by atherosclerosis score, as determined by the number of steno-occlusions of cerebral arteries and the degree thereof. Post-CABG strokes (within 14 days) were classified as atherosclerotic (strokes attributable to pre-defined atherosclerosis) or other (strokes caused by other mechanisms). Associations between post-CABG stroke and each type of atherosclerotic disease (extracranial carotid artery disease, intracranial, extracranial, or extracranial and/or intracranial cerebral atherosclerosis), differentiated according to the involved arteries, were analyzed., Results: Stroke occurred in 33 patients, and the atherosclerosis score was independently associated with stroke development (odds ratio: 1.35; 95% confidence interval: 1.16 to 1.56). Atherosclerotic stroke was defined in 15 (45%), and constituted >40% of both immediate (within 24 h) and delayed strokes. Intracranial, extracranial, and extracranial and/or intracranial cerebral atherosclerosis were significantly associated with stroke., Conclusions: Cerebral atherosclerosis was closely related to the occurrence of post-CABG stroke, being both an independent risk factor for and the cause of a significant proportion of strokes. Pre-operative evaluation of intracranial and extracranial cerebral arteries, apart from the extracranial carotid artery, may be useful to predict the likelihood of post-CABG stroke., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Complications after stroke increase disability or death. The disability-adjusted life-year (DALY) metric, developed by the World Health Organization to measure the global burden of disease, integrates both mortality and disability. Widely used in population-level data analyses, it has not been applied to individual patient-level data captured in outcome registries., Methods: We analyzed patient-level data from the outcome registry of 1254 consecutive patients with acute ischemic stroke enrolled between September 1, 2004, and August 31, 2005, in South Korea. For each subject, we calculated DALY lost due to the qualifying stroke and then analyzed additional DALY lost due to complications after stroke., Results: For 1233 patients with available 3-month outcomes, the average DALY lost due to the index stroke was 3.82 (95% CI, 3.68 to 3.96). Any complications, neurological complications, and medical complications occurred in 34.0%, 20.8%, and 24.0%, respectively. The additional DALYs lost associated with any, neurological, and medical complications were 2.11 (95% CI, 1.78 to 2.44), 2.15 (95% CI, 1.72 to 2.59), and 1.99 (95% CI, 1.59 to 2.40), respectively. Patients with 1 complication had 1.52 (95% CI, 1.15 to 1.89) additional DALY lost, and those with >or=2 complications had 2.69 (95% CI, 2.18 to 3.20) additional DALY lost., Conclusions: Early poststroke complications deprive patients of approximately 2 years of optimum health. Greater numbers of complications are associated with greater loss of healthy life-years. DALY analysis quantifies the burden of poststroke complications with a uniform metric potentially useful for health system planners.

Background and Purpose: Early recurrent ischemic lesions (ERILs) on diffusion-weighted imaging after acute ischemic stroke have been suggested as a potential marker of early recurrent stroke. We hypothesized that biomarkers of inflammation or coagulation may be associated with the pathogenesis of ERILs and sought to investigate whether these biomarkers provide prognostic information on the risk of development of ERILs independently of clinical and imaging variables., Methods: This prospective study enrolled 153 consecutive patients with acute ischemic stroke who underwent diffusion-weighted imaging within 24 hours and subsequently at 5 days after onset and whose plasma or serum for biomarkers (C-reactive protein, fibrinogen, d-dimer, tissue plasminogen activator, and plasminogen activator inhibitor-1) were collected within 24 hours of onset. Those receiving thrombolysis or interventional therapy were excluded. ERILs were defined as new ischemic lesions on 5-day diffusion-weighted imaging separate from the index stroke lesions, which were not accompanied by subsequent recanalization., Results: ERILs were observed in 37 patients (24.2%). In univariate analysis, shorter time from onset to initial MRI (P=0.013), initial acute multiple infarcts (P<0.001), initial larger infarct volume (P=0.005), stroke subtype (P<0.001), elevated d-dimer (P=0.028), and anticoagulation after admission (P=0.001) were associated with ERILs. In multivariate analysis, initial acute multiple infarcts (OR, 16.60; 95% CI, 5.73 to 48.08), large artery atherosclerosis (OR, 4.62; 95% CI, 1.51 to 14.11), and log d-dimer (OR, 3.20; 95% CI, 1.14 to 9.00) remained independent predictors of ERILs., Conclusions: These data suggest that elevated d-dimer level reflecting increase of thrombin generation and fibrin turnover may be an independent factor predicting ERILs.

Background and Purpose: The efficacy and safety of the selective serotonin reuptake inhibitor fluoxetine have rarely been studied in the treatment of poststroke emotional disturbances., Methods: Stroke patients (152) who had poststroke depression (PSD), emotional incontinence (PSEI), or anger proneness (PSAP) were studied. PSD was evaluated by Beck Depression Inventory and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PSEI by Kim's criteria, and PSAP was assessed by Spielberger Trait Anger Scale. Subjects were randomly given either fluoxetine 20 mg/day (n=76) or placebo (n=76) for 3 months. Follow-up evaluations were done 1, 3, and 6 months after the beginning of the treatment. The primary outcome measurement was the scores of emotional disturbances at each follow-up assessment. The secondary outcome measurements were the percentage changes of the scores and the subjective responses of the patients., Results: Although patients in the fluoxetine group more often dropped out because of adverse effects, fluoxetine administration was generally safe. Fluoxetine significantly improved PSEI and PSAP, whereas no definitive improvement of PSD was found. Improvement of PSAP was noted even at 3 months after the discontinuation of the treatment., Conclusions: Fluoxetine is efficacious in the treatment of PSEI and PSAP. Its effect on PSD is not solidly confirmed.

Background and Purpose: In contrast to platelet-rich white thrombi, red thrombi in the heart are rich in fibrin and trapped erythrocytes. The magnetic susceptibility effect of deoxygenated hemoglobin in red thrombi may result in hypointense signals on T2*-weighted gradient echo imaging (GRE). We tested the hypothesis that a GRE susceptibility vessel sign (SVS) is specific for cardioembolic stroke., Methods: This retrospective study examined data from acute ischemic stroke patients who underwent diffusion-weighted imaging, GRE and magnetic resonance angiography (MRA) within 24 hours of stroke onset and who had symptomatic occlusion of large intracranial arteries in the circle of Willis. Hypointense signals within vascular cisterns on GRE corresponding to symptomatic vascular occlusion were termed "GRE SVS." Recanalization was assessed on follow-up MRA performed within 7 days of onset. The relationships between GRE SVS and stroke subtypes and subsequent recanalization were explored., Results: Of the 95 patients who met the inclusion criteria, GRE SVS was observed in 45 (47.4%). GRE SVS was more commonly associated with cardioembolic stroke patients (31 of 40, 77.5%) than with other stroke subtypes (14 of 55, 25.5%; P<0.001). In 66 patients who underwent follow-up MRA, GRE SVS was associated with subsequent recanalization (P<0.001). Multivariate analysis showed that GRE SVS was an independent predictor of cardioembolic stroke and subsequent recanalization (odds ratio, 10.75 and 4.26; 95% CI, 3.68 to 31.47 and 1.12 to 16.30)., Conclusions: GRE SVS may predict cardioembolic stroke and subsequent recanalization. Identifying clot composition may be important in choosing the optimal treatment based on clot characteristics.

Background and Purpose: MRI screening for thrombolytic therapy may improve patient selection. Alternatively, it may excessively delay treatment and thereby lead to worse outcomes. We hypothesized that times to treatment and outcomes in a stroke center with immediate MRI access and interpretation would not differ from those of the typical clinical practice., Methods: We compared the results of 120 consecutive patients treated with intravenous tissue plasminogen activator (tPA) within 3 hours of onset at our center with those of the 2 largest multicenter registries of tPA use. In addition to standard criteria, MRI specific eligibility criteria were applied in 97 patients. MRI was not performed in 23 patients because of contraindications to MRI or late patient arrival (>2.5 hours). Outcomes were the modified Rankin Scale (mRS) obtained at 3 months., Results: Times to treatment (median door-to-needle time 81.5 minutes; median onset-to-needle time 135 minutes) and outcomes (mRS 0 to 1, 40.8%; mRS 0 to 2, 47.5%) were not inferior to those of the typical clinical practice. Door-to-needle time was shorter in computed tomography (CT) screening (67.5+/-22.5 minutes; n=23) than in MRI screening (86.8+/-21.5 minutes; n=97; P<0.001). However, outcomes were not different between MRI screening (mRS 0 to 1, 42.3%; mRS 0 to 2, 49.5%) and CT screening (mRS 0 to 1, 34.8%; mRS 0 to 2, 39.1%). Neither times to treatment nor MRI screening was predictive of outcomes., Conclusions: These data demonstrate that MRI screening before tPA therapy is feasible and not associated with unacceptable times to treatment or outcomes.

One of the main reasons for the soaring interest in acute ischemic stroke among radiologists is the advent of new magnetic resonance techniques such as diffusion-weighted imaging. This new modality has prompted us to seek a better understanding of the pathophysiologic mechanisms of cerebral ischemia/infarction. The ischemic penumbra is an important concept and tissue region because this is the target of various recanalization treatments during the acute phase of stroke. In this context, it is high time for a thorough review of the concept, especially from the imaging point of view.

Background and Purpose: Analogous to the CT hyperattenuated vessel sign (HMCAS), MR imaging may show hypo- or hyperintense vessels in acute ischemic stroke (AIS) patients. We assessed the diagnostic and prognostic strength of early MR imaging vessel signs in AIS patients treated with intravenous thrombolysis (IVT) within 3 hours of the onset of symptoms., Methods: We studied AIS patients both treated with IVT and stroke MR imaged within 3 hours of the onset of symptoms and at 2 hours and 24 hours after treatment. We assessed the presence or absence of early vessel signs (hyperintense fluid-attenuated inversion recovery sign [FLAIR HVS]; gradient-echo susceptibility vessel sign [GRE SVS]) compared with a combined MR angiography/perfusion-weighted imaging reference and their strength for predicting clinical outcome (favorable vs. poor, independent vs. dependent, or dead, death), recanalization (by clot composition and flow), and hemorrhage in uni- and multivariate analysis., Results: Fifty-six patients (age range, 76 years +/- 13 years; median National Institutes of Health stroke scale score [NIHSSS], 11) met the inclusion criteria. Forty-four patients (78.6%) had a vessel occlusion at baseline; 22 of them (50%) recanalized. Nineteen patients (33.9%) suffered some form of intracranial hemorrhage (ICH), 24 patients (42.9%) had an independent outcome, 18 patients (32.1%) a favorable outcome, and 14 patients died. Compared with our combined reference for vessel status PWI/MRA, the sensitivities of CT HMCAS, FLAIR HVS, and GRE SVS were 40%, 66%, and 34%, respectively, and improved during the hours that followed. Localization was accurately reflected by FLAIR HVS but not by GRE SVS. Only NIHSSS and age were independent predictors for recanalization and all clinical outcomes in multiple logistic regression analysis., Conclusion: Although early vessel signs can be helpful in the diagnosis of intravascular disease, they do not independently predict recanalization, ICH, or any of the three clinical outcomes in a multivariate logistic regression model. Thrombus composition as reflected by signal intensity characteristics on GRE and FLAIR does not predict the therapeutic effect of IVT.

Background and aims:Assessment of ischemic lesions on computed tomography or MRI diffusion-weighted imaging (DWI) using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to guide acute stroke treatment. However, it has never been defined how many voxels need to be affected to label a DWI-ASPECTS region ischemic. We aimed to assess the effect of various lesion load thresholds on DWI-ASPECTS and compare this automated analysis with visual rating. Materials and methods:We analyzed overlap of individual DWI lesions of 315 patients from the previously published predictive value of fluid-attenuated inversion recovery study with a probabilistic ASPECTS template derived from 221 CT images. We applied multiple lesion load thresholds per DWI-ASPECTS region (>0, >1, >10, and >20% in each DWI-ASPECTS region) to compute DWI-ASPECTS for each patient and compared the results to visual reading by an experienced stroke neurologist. Results:By visual rating, median ASPECTS was 9, 84 patients had a DWI-ASPECTS score ≤7. Mean DWI lesion volume was 22.1 (±35) ml. In contrast, by use of >0, >1-, >10-, and >20%-thresholds, median DWI-ASPECTS was 1, 5, 8, and 10; 97.1% (306), 72.7% (229), 41% (129), and 25.7% (81) had DWI-ASPECTS ≤7, respectively. Overall agreement between automated assessment and visual rating was low for every threshold used (>0%: κw = 0.020 1%: κw = 0.151; 10%: κw = 0.386; 20% κw = 0.381). Agreement for dichotomized DWI-ASPECTS ranged from fair to substantial (≤7: >10% κ = 0.48; >20% κ = 0.45; ≤5: >10% κ = 0.528; and >20% κ = 0.695). Conclusion:Overall agreement between automated and the standard used visual scoring is low regardless of the lesion load threshold used. However, dichotomized scoring achieved more comparable results. Varying lesion load thresholds had a critical impact on patient selection by ASPECTS. Of note, the relatively low lesion volume and lack of patients with large artery occlusion in our cohort may limit generalizability of these findings.

Background and purposeAlberta Stroke Program Early Computed Tomographic Score (ASPECTS) has been used to estimate diffusion-weighted imaging (DWI) lesion volume in acute stroke. We aimed to assess correlations of DWI-ASPECTS with lesion volume in different middle cerebral artery (MCA) subregions and reproduce existing ASPECTS thresholds of a malignant profile defined by lesion volume ≥100 mL.MethodsWe analyzed data of patients with MCA stroke from a prospective observational study of DWI and fluid-attenuated inversion recovery in acute stroke. DWI-ASPECTS and lesion volume were calculated. The population was divided into subgroups based on lesion localization (superficial MCA territory, deep MCA territory, or both). Correlation of ASPECTS and infarct volume was calculated, and receiver-operating characteristics curve analysis was performed to identify the optimal ASPECTS threshold for ≥100-mL lesion volume.ResultsA total of 496 patients were included. There was a significant negative correlation between ASPECTS and DWI lesion volume (r=-0.78; P

Background: Acute dizziness is a common symptom among patients visiting emergency medical centers. Extensive neurological examinations aimed at delineating the cause of dizziness often require experience and specialized training. We tried to diagnose central dizziness by machine learning using only basic clinical information. Methods: Patients were enrolled who had visited an emergency medical center with acute dizziness and underwent diffusion-weighted imaging. The enrolled patients were dichotomized as either having central (with a corresponding central lesion) or non-central dizziness. We obtained patient demographics, risk factors, vital signs, and presentation (non-whirling type dizziness or vertigo). Various machine learning algorithms were used to predict central dizziness. The area under the receiver operating characteristic curve (AUROC) was measured to evaluate diagnostic accuracy. The SHapley Additive exPlanations (SHAP) value was used to explain the importance of each factor. Results: Of the 4,481 visits, 414 (9.2%) were determined as central dizziness. Central dizziness patients were more often older and male and had more risk factors and higher systolic blood pressure. They also presented more frequently with non-whirling type dizziness (79 vs. 54.4%) than non-central dizziness. Catboost model showed the highest AUROC (0.738) with a 94.4% sensitivity and 31.9% specificity in the test set (n = 1,317). The SHAP value was highest for previous stroke presence (mean; 0.74), followed by male (0.33), presentation as non-whirling type dizziness (0.30), and age (0.25). Conclusions: Machine learning is feasible for classifying central dizziness using demographics, risk factors, vital signs, and clinical dizziness presentation, which are obtainable at the triage. [ABSTRACT FROM AUTHOR]