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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).)

Background: Therapeutic-induced hypertension treatment (iHTN) is helpful for alleviating early neurological deterioration (END) in acute small vessel occlusive stroke. We examined the time parameters related to iHTN effectiveness in these patients., Methods: We retrospectively reviewed patients with acute small vessel occlusive stroke who underwent iHTN for END, defined as an increase of ≥2 points in total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 point in motor items of NIHSS. The primary outcome was an early neurological improvement (ENI; a decrease of ≥2 points in total NIHSS score or ≥1 point in motor items of NIHSS), and the secondary outcome was any neurological improvement (a decrease of ≥1 point in the total NIHSS score). We conducted a multivariable logistic regression analysis, adjusting for demographics, risk factors, baseline clinical status, and intervention-related variables. We also generated a restricted cubic spline curve for the END-to-iHTN time cutoff., Results: Among the 1062 patients with small vessel occlusive stroke screened between 2017 and 2021, 136 patients who received iHTN within 24 hours from END were included. The mean age was 65.1 (±12.0) years, and 61.0% were male. Sixty-five (47.8%) patients showed ENI and 77 (56.6%) patients showed any neurological improvement. END-to-iHTN time was significantly shorter in patients with ENI (150 [49-322] versus 290 [97-545] minutes; P =0.018) or any neurological improvement (150 [50-315] versus 300 [130-573] minutes; P =0.002). A 10-minute increase in the time between END and iHTN decreased the odds of achieving ENI (odds ratio, 0.984 [95% CI, 0.970-0.997]; P =0.019) or any neurological improvement (odds ratio, 0.978 [95% CI, 0.964-0.992]; P =0.002). The restricted cubic spline curve showed that the odds ratio of ENI reached its minimum at ≈3 hours., Conclusions: Among patients with small vessel occlusive stroke with END, a shorter interval between END and the initiation of iHTN was associated with increased odds of achieving neurological improvement. The efficacy of iHTN may be limited to induction within the first 3 hours of END., Competing Interests: Disclosures None.

Introduction: Patients with atrial fibrillation-related stroke (AF-stroke) are prone to developing rapid ventricular response (RVR). We investigated whether RVR is associated with initial stroke severity, early neurological deterioration (END) and poor outcome at 3 months., Methods: We reviewed patients who had AF-stroke between January 2017 and March 2022. RVR was defined as having heart rate >100 beats per minute on initial electrocardiogram. Neurological deficit was evaluated with National Institutes of Health Stroke Scale (NIHSS) score at admission. END was defined as increase of ≥2 in total NIHSS score or ≥1 in motor NIHSS score within first 72 h. Functional outcome was score on modified Rankin Scale at 3 months. Mediation analysis was performed to examine potential causal chain in which initial stroke severity may mediate relationship between RVR and functional outcome., Results: We studied 568 AF-stroke patients, among whom 86 (15.1%) had RVR. Patients with RVR had higher initial NIHSS score (p < 0.001) and poor outcome at 3 months (p = 0.004) than those without RVR. The presence of RVR [adjusted odds ratio (aOR) = 2.13; p = 0.013] was associated with initial stroke severity, but not with END and functional outcome. Otherwise, initial stroke severity [aOR = 1.27; p = <0.001] was significantly associated with functional outcome. Initial stroke severity as a mediator explained 58% of relationship between RVR and poor outcome at 3 months., Conclusion: In patients with AF-stroke, RVR was independently associated with initial stroke severity but not with END and functional outcome. Initial stroke severity mediated considerable proportion of association between RVR and functional outcome., (© 2023 S. Karger AG, Basel.)

Background:  We investigated the association between the reaction time (R), a thromboelastography (TEG) parameter for hypercoagulability, and functional outcomes based on the occurrence of hemorrhagic transformation (HT) and early neurological deterioration (END)., Methods:  We enrolled ischemic stroke patients and performed TEG immediately after the patients' arrival. The baseline characteristics, occurrence of HT and END, stroke severity, and etiology were compared according to the R. END was defined as an increase of ≥1 point in motor or ≥2 points in the total National Institute of Health Stroke Scale within 3 days after admission. The outcome was the achievement of functional independence (modified Rankin scale [mRS]: 0-2) at 3 months after stroke. Logistic regression analyses were performed to verify the association between R and outcome., Results:  HT and END were frequently observed in patients with an R of <5 minutes compared with the group with an R of ≥5 minutes (15 [8.1%] vs. 56 [21.0%], p  < 0.001; 16 [8.6%] vs. 65 [24.3%], p  = 0.001, respectively). In multivariable analysis, an R of <5 minutes was associated with decreased odds of achieving functional independence (0.58 [0.34-0.97], p  = 0.038). This association was maintained when the outcome was changed to disability free (mRS 0-1) and when mRS was analyzed as an ordinal variable., Conclusion:  Hypercoagulability on TEG (R <5 minutes) may be a negative predictor for functional outcome of stroke after 3 months, with more frequent HT, END, and different stroke etiologies. This study highlights the potential of TEG parameters as biomarkers for predicting functional outcomes in ischemic stroke patients., Competing Interests: None declared., (Thieme. All rights reserved.)

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).)

Background and Purpose: Stenting is an important treatment for preventing stroke. However, the effect of vertebrobasilar stenting (VBS) might be limited because of relatively high periprocedural risks. Silent brain infarcts (SBIs) are known as a predictor for future stroke. Because of anatomical differences, factors for SBIs might be different between carotid artery stenting (CAS) and VBS. We compared the characteristics of SBIs between VBS and CAS., Methods: We included patients who underwent elective VBS or CAS. Diffusion-weighted imaging was performed pre- and post-procedure to detect new SBIs. Clinical variables, occurrence of SBIs, and procedure-related factors were compared between CAS and VBS. Moreover, we investigated predictors of SBIs in each group separately., Results: Ninety-two (34.2%) out of 269 patients had SBIs. SBIs were more frequently observed in VBS (29 [56.6%] vs. 63 [28.9%], p<.001). The risk of SBIs outside the stent-inserted vascular territory was higher in VBS compared to CAS (14 [48.3%] vs. 8 [12.7%], p<.001). Larger-diameter stents (odds ratio: 1.28, 95% confidence interval: 1.06-1.54, p = .012) and prolonged procedure time (1.01, [1.00-1.03], p = .026) increased the risk of SBIs in CAS, whereas only age increased the risk of SBIs in VBS (1.08 [1.01-1.16], p = .036)., Conclusions: Compared to CAS, VBS was associated with longer procedure time, more residual stenosis, and more SBIs, especially outside the stent-inserted vascular territory. The risk of SBIs after CAS was associated with stent size and procedural difficulty. Only age was associated with SBIs in VBS. The pathomechanism of SBIs after VBS and CAS may be different., (© 2023 American Society of Neuroimaging.)

Background: Thromboelastography (TEG) is a useful for predicting hemorrhagic transformation, early neurological deterioration, and functional outcome after stroke. We aimed to investigate whether TEG value could also be useful in predicting functional outcome via various intraprocedural and postprocedural factors in patients with acute large vessel occlusive stroke who underwent intraarterial thrombectomy (IAT)., Methods: Patients with ischemic stroke who underwent IAT between March 2018 and March 2020 at two tertiary hospitals were included. The association between reaction time (R) and functional outcome was evaluated. The primary outcome was the achievement of functional independence defined as the achievement of a modified Rankin Scale (mRS) score of 0-2 at 3 months after the index stroke., Results: Among a total of 160 patients (mean age, 70.6 ± 12.3 years; 103 [64.4 %] men), 79 (49.3 %) achieved functional independence at 3 months. R, both as a continuous (odds ratio [OR]: 1.45, 95 % confidence interval [95 % CI]: 1.09-1.92, P = 0.011) and dichotomized parameters (R < 5 min [OR: 0.37, 95 % CI: 0.16-0.82, P = 0.014]), were inversely associated with increased odds of achieving functional independence (mRS score 0-2) after multivariable analysis. The association was still consistent when the outcome was the achievement of disability free (mRS score 0-1) or mRS score analyzed as an ordinal variable., Conclusions: Decreased R, especially R < 5 min, was inversely associated with functional outcome pf stroke after EVT., Competing Interests: Declaration of competing interest The authors have no financial conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Propensity for lesion lateralization in atrial fibrillation-related cardiac embolic stroke (AF-stroke) remains controversial. In this study, we compared the hemispheric differences among patients with AF-stroke and identified factors associated with lesion laterality., Methods: We retrospectively reviewed patients with acute AF-stroke admitted from January, 2017 to March, 2022. Patients were grouped based on whether lesions were right or left hemispheric in the anterior circulation territory, based on diffusion-weighted imaging. Factors associated with right-side propensity were analyzed., Results: Among 385 patients, the mean age was 74±11 years and 52.5 % were male. Right and left hemispheric lesions were observed in 189 (49.1 %) and 196 (50.9%) patients, respectively. In the multivariate analysis, enlarged left atrium (LA) (adjusted odds ratio [aOR]=1.03, 95% confidential interval [CI], 1.007-1.061; p=0.013) and single confluent lesion pattern (aOR= 1.55, 95% CI, 1.012-2.381; p=0.044) were associated with right hemispheric lesions., Conclusions: Enlarged LA and single confluent lesion pattern were strongly related to right-sided propensity in patients with AF-stroke., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Endovascular thrombectomy (EVT) has benefits in selected patients 6-24 h after stroke onset. However, the response to EVT >24 h after stroke onset is still unclear. We compared the early response to EVT in patients with different time windows., Methods: Patients who underwent EVT in an emergency setting were enrolled and categorized according to when EVT was performed: within 6 (early), 6-24 (late), and >24 h (very late) after stroke onset. Early neurological improvement (ENI) and deterioration (END) were defined as improvement and worsening, respectively, of National Institutes of Health Stroke Scale (NIHSS) score by ≥4 points after EVT. The three groups' clinical characteristics and response to EVT were compared. We also investigated factors associated with ENI and END., Results: During study period, 274 patients underwent EVT (109 early, 104 late, and 61 very late). Patients who underwent EVT very late were younger (p = 0.007), had smaller ischemic cores, and had lower initial NIHSS scores (8 ± 5) than those who underwent EVT early (14 ± 6) and late (13 ± 7; p < 0.001). Stroke mechanisms also differed according to the time window (p < 0.001): cardioembolism was more common after early EVT, whereas large-artery atherosclerosis was more prevalent among patients who underwent EVT very late. ENI was significantly more common after early (60.6%) and late EVT (51.0%) than after very late EVT (29.5%; p = 0.001); however, rates of END did not differ (11.0%, 13.5%, and 4.9%, respectively). ENI was independently associated with male, higher NIHSS score, and early and late EVT. END was associated with failure of recanalization., Conclusions: ENI was more observed and associated with early and late EVT. Highly selected patients receiving very late EVT may not benefit from ENI but may still have a chance to prevent END. The occurrence of END was associated not with time window but with failure of recanalization., (© 2022 S. Karger AG, Basel.)

Background and Purpose: Treatment of acute ischemic stroke is heavily contingent upon time, as there is a strong relationship between time clock and tissue progression. Work has established imaging biomarker assessments as surrogates for time since stroke (TSS), namely, by comparing signal mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging. Our goal was to develop an automatic technique for determining TSS from imaging that does not require subspecialist radiology expertise., Methods: Using 772 patients (66 ± 9 years, 319 women), we developed and externally evaluated a deep learning network for classifying TSS from MR images and compared algorithm predictions to neuroradiologist assessments of DWI-FLAIR mismatch. Models were trained to classify TSS within 4.5 hours and performance metrics with confidence intervals were reported on both internal and external evaluation sets., Results: Three board-certified neuroradiologists' DWI-FLAIR mismatch assessments, based on majority vote, yielded a sensitivity of .62, a specificity of .86, and a Fleiss' kappa of .46 when used to classify TSS. The deep learning method performed similarly to radiologists and outperformed previously reported methods, with the best model achieving an average evaluation accuracy, sensitivity, and specificity of .726, .712, and .741, respectively, on an internal cohort and .724, .757, and .679, respectively, on an external cohort., Conclusion: Our model achieved higher generalization performance on external evaluation datasets than the current state-of-the-art for TSS classification. These results demonstrate the potential of automatic assessment of onset time from imaging without the need for expertly trained radiologists., (© 2022 American Society of Neuroimaging.)

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).)

Background: The effect of cholesterol on the functional outcome after endovascular thrombectomy (EVT) is still controversial. This study aimed to investigate whether the lipid profile is associated with the EVT prognosis., Methods: We retrospectively analyzed patients with emergent large vessel occlusion who underwent EVT. The blood lipid levels were measured in the fasting state, 1 day after admission. We divided patients into terciles of serum total cholesterol (TC) levels and compared the clinical characteristics among the groups. The factors associated with a good outcome at 3 months (modified Rankin scale 0-2) were investigated, considering the stroke mechanism and recanalization status., Results: Among 274 patients, good outcomes were observed in 108 (39.4%) patients. Low initial severity (odds ratio (OR), 0.91, 95% confidence interval (CI), 0.858-0.954; p < 0.001) and high TC level (1.35, 1.034-1.758; p = 0.041) were associated with good outcomes. In patients with cardioembolism, young age (0.95, 0.915-0.991; p = 0.021), low initial severity (0.92, 0.857-0.988; p = 0.024), and high TC level (1.60, 1.019-2.499; p = 0.036) were associated with good outcomes. The lipid profile was not associated with a functional outcome in those with large artery atherosclerosis. In patients with complete recanalization, young age (0.97, 0.941-0.994; p = 0.016), low initial severity (0.91, 0.864-0.961; p = 0.001), absence of diabetes (0.45, 0.218-0.947; p = 0.035) or any hemorrhage (0.33, 0.142-0.760; p = 0.009), and high TC level (1.40, 1.031-1.879; p = 0.031) were associated with good outcomes., Conclusions: A high TC level was associated with favorable outcomes after EVT, especially in patients with cardioembolism and complete recanalization., (© 2022. Fondazione Società Italiana di Neurologia.)

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: Clinical-diffusion mismatch (CDM) and perfusion-diffusion mismatch (PDM) are used to select patients for endovascular thrombectomy (EVT) in the late-window period. As CDM well reflects true penumbra, we hypothesized that patients with CDM and PDM would respond better to EVT than those with PDM only at the late-window period., Methods: Acute ischemic stroke patients who received EVT 6-24 h after stroke onset were included. PDM (perfusion-/diffusion-weighted image (DWI) lesion volume >1.8) was used to select candidates for EVT in this time-period in our center. CDM was defined according to the DAWN trial criteria. Response to EVT was compared between patients with and without CDM. Early neurological improvement (ENI) was defined as improvement >4 points on National Institutes of Health Stroke Scale (NIHSS) score 1 day after EVT. Multivariable analysis was performed to investigate independent factors associated with ENI. The correlation between DWI lesion volume and NIHSS score was investigated in those with and without CDM., Results: Among 94 patients enrolled, all patients had PDM and 44 (46.3%) had CDM. Forty-eight patients (51.1%) showed ENI. The prevalence of hypertension, initial NIHSS score, improvement in NIHSS score after EVT, and prevalence of ENI were greater in patients with CDM than those without. ENI was independently associated with onset-to-door time (odds ratio [95% confidence interval]: 0.998 [0.997-1.000]; p = 0.042), complete recanalization (23.912 [2.238-255.489]; p = 0.009), initial NIHSS score (1.180 [1.012-1.377]; p = 0.034), and the presence of CDM (5.160 [1.448-18.386]; p = 0.011). The correlation between DWI lesion volume and initial NIHSS score was strong in patients without CDM (r = 0.731) but only moderate in patients with CDM (r = 0.355)., Conclusion: Patients with both CDM and PDM had a better response to late-window EVT than those with PDM only., (© 2021 S. Karger AG, Basel.)

Treating acute ischemic stroke (AIS) patients is a time-sensitive endeavor, as therapies target areas experiencing ischemia to prevent irreversible damage to brain tissue. Depending on how an AIS is progressing, thrombolytics such as tissue-plasminogen activator (tPA) may be administered within a short therapeutic window. The underlying conditions for optimal treatment are varied. While previous clinical guidelines only permitted tPA to be administered to patients with a known onset within 4.5 hours, clinical trials demonstrated that patients with signal intensity differences between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences in an MRI study can benefit from thrombolytic therapy. This intensity difference, known as DWI-FLAIR mismatch, is prone to high inter-reader variability. Thus, a paradigm exists where onset time serves as a weak proxy for DWI-FLAIR mismatch. In this study, we sought to detect DWI-FLAIR mismatch in an automated fashion, and we compared this to assessments done by three expert neuroradiologists. Our approach involved training a deep learning model on MRI to classify tissue clock and leveraging time clock as a weak proxy label to supplement training in a semi-supervised learning (SSL) framework. We evaluate our deep learning model by testing it on an unseen dataset from an external institution. In total, our proposed framework was able to improve detection of DWI-FLAIR mismatch, achieving a top ROC-AUC of 74.30%. Our study illustrated that incorporating clinical proxy information into SSL can improve model optimization by increasing the fidelity of unlabeled samples included in the training process.

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: To devise appropriate preventive strategies after stroke, knowledge of the association between post-stroke cognitive impairment (PSCI) and prognosis of stroke patients is important. We investigated the association between PSCI and the vascular outcomes in patients with ischemic stroke with best medical care considering their risk factors and adherence to medications., Methods: Of the 1534 ischemic stroke patients who randomly assigned to aspirin or cilostazol treatment with best medical therapy by the PICASSO (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage) trial, 1240 with baseline mini-mental state examination (MMSE) scores were analysed retrospectively. The patients were classified into three groups based on MMSE scores. Recurrence of ischemic stroke, stroke of any type and composite of major vascular events were compared among them., Results: Of the 1240 patients, 376 had MMSE scores of 28-30 (highest tertile), 419 had scores of 24-27 (middle tertile) and 445 had scores of 0-23 (lowest tertile). The average time from stroke onset to MMSE examination was 31.8 days. By trend analysis, lower tertile of MMSE score was significantly associated with recurrent ischemic stroke (p = 0.0017), stroke of any type (p = 0.0053) and composite vascular outcome (p = 0.0122). After adjustment for covariates, PSCI was independently associated with risk of recurrent ischemic stroke (HR 2.40, 95% confidence interval 1.12-5.14)., Conclusions: Cognitive impairment was associated with recurrence of ischemic stroke in high risk patients during adequate medical therapy including antiplatelet therapy. However, the other vascular events were not.

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.

Objectives: To investigate whether clinical condition, imaging session, and locations affect repeatability of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) in the brain., Materials and Methods: Three APTw MRI data sets were acquired, involving two intrasession scans and one intersession scan for 19 healthy, 15 glioma, and 12 acute stroke adult participants (mean age 53.8, 54.6, and 68.5, respectively) on a 3T MR scanner. The mean APTw signals from five locations in healthy brain (supratentorial and infratentorial locations) and from entire tumor and stroke lesions (supratentorial location) were calculated. The within-subject coefficient of variation (wCV) and intraclass correlation coefficient (ICC) were calculated for each clinical conditions, image sessions, and anatomic locations. Differences in APTw signals between sessions were analyzed using repeated-measures analysis of variance., Results: The ICC and wCV were 0.96 (95% confidence interval [CI], 0.91-0.99) and 16.1 (12.6-21.3) in glioma, 0.93 (0.82-0.98) and 15.0 (11.4-20.6) in stroke, and 0.84 (0.72-0.91) and 34.0 (28.7-41.0) in healthy brain. There were no significant differences in APTw signal between three sessions, irrespective of disease condition and location. The ICC and wCV were 0.85 (0.68-0.94) and 27.4 (21.8-35.6) in supratentorial, and 0.44 (- 0.18 to 0.76) and 32.7 (25.9 to 42.9) in infratentorial locations. There were significant differences in APTw signal between supra- (mean, 0.49%; 95% CI, 0.38-0.61) and infratentorial locations (1.09%, 0.98-1.20; p < 0.001)., Conclusion: The repeatability of APTw signal was excellent in supratentorial locations, while it was poor in infratentorial locations due to severe B0 inhomogeneity and susceptibility which affects MTR asymmetry., Key Points: • In supratentorial locations, APTw MRI showed excellent intrasession and intersession repeatability in brains of healthy controls and patients with glioma, as well as in stroke-affected regions. • APTw MRI showed excellent repeatability in supratentorial locations, but poor repeatability in infratentorial locations. • Considering poor repeatability in the infratentorial locations, the use of APTw MRI in longitudinal assessment in infratentorial locations is not indicated.

Background: Genetic variants may play a role in determining the location of cerebral atherosclerosis. We aimed to investigate the association between RNF213, MMP2, and genetic polymorphisms linked to vascular tortuosity with the location of cerebral arterial atherosclerosis., Methods: A prospective case-control study was conducted on patients with ischemic stroke and age- and sex-matched stroke-free controls. The stroke patients were categorized into those with intracranial artery atherosclerosis (ICAS), extracranial artery atherosclerosis (ECAS), and small vessel occlusion (SVO). Six single nucleotide polymorphisms (SNPs) including rs2118181 (FBN1), rs2179357 (SLC2A10), rs1036095 (TGFBR2), rs243865 (MMP2), rs1800470 (TGFB1), and rs112735431 (RNF213) were analyzed with the TaqMan Genotyping Assay, and the distribution of genotypes across groups was compared., Results: None of the 6 SNPs were associated with stroke on comparing the 449 stroke patients (71 with ECAS, 169 with ICAS, and 209 with SVO) to the 447 controls. In the subgroup analysis, the adjusted odds ratios (aORs) for age and sex indicated a significant association between rs112735431 and ICAS in the allele comparison analysis and in the additive and dominant model analyses. rs112735431 was associated with anterior circulation involvement and increased burden of cerebral atherosclerosis. rs2179357 was significantly associated with ICAS in the recessive model analysis, and rs1800470 was significantly associated with ECAS in the recessive model analysis when compared to controls., Conclusion: rs112735431 was associated with ICAS and increased atherosclerosis burden in Korean stroke patients. Further studies are needed to elucidate the role of rs112735431 and to confirm the association of rs2179357 and rs1800470 with cerebral atherosclerosis., (© 2020 S. Karger AG, Basel.)

Background and Purpose: This study aimed to evaluate the efficacy of intra-arterial thrombectomy (IAT) and prognosis for acute ischaemic stroke patients with active cancer., Methods: We retrospectively reviewed 253 patients who underwent IAT within 24 h after stroke onset between January 2012 and August 2017. We classified the patients into active cancer (n = 26) and control groups (n = 227) and compared clinical data. Primary outcome was a modified Rankin scale score at 3 months with ordinal logistic regression (shift analysis)., Results: Initial National Institutes of Health Stroke Scale (NIHSS) and rate of successful recanalisation did not differ between groups, but the active cancer group showed poor outcomes at 3 months on shift analysis (P = 0.001). The independent predictors of poor prognosis were age [adjusted common odds ratio (aOR) 1.03, 95% confidence interval (CI) 1.01-1.05], baseline NIHSS (aOR 1.14, 95% CI 1.09-1.19), baseline C-reactive protein level (aOR 1.14, 95% CI 1.03-1.25), any cerebral haemorrhage (aOR 1.92, 95% CI 1.21-3.06), and active cancer (aOR 2.35, 95% CI 1.05-5.25). Mortality at 90 days was 30.8% in the cancer group and 8.8% in the control group (P = 0.003)., Conclusions: Although baseline characteristics and recanalisation rate after IAT up to 24 h after stroke onset were similar between acute ischaemic stroke patients with active cancer and without any cancer, stroke-related death and short-term outcome were significantly poorer in patients with active cancer than the controls. Post-procedural haemorrhage and active cancer itself were independent predictors of a decrease in functional independence at 3 months.

Background: High blood pressure variability (BPV) is associated with recurrent stroke. We investigated the association between BPV, new ischemic lesions (NILs), and white matter lesion (WML) growth in patients with ischemic stroke due to intracranial atherosclerosis (ICAS)., Methods: This study was performed as a post-hoc analysis of the STABLE-ICAS trial, which enrolled subacute ischemic stroke patients with symptomatic ICAS (>50% stenosis) and hypertension. BPV was measured at the office (visit by visit) and at home (day by day). Patients were divided into 3 groups (tertiles) according to their home BPV. WML growth and the occurrence of NILs were compared among the 3 groups. Multivariable analyses were performed to identify the independent risk factors of WML growth and NILs., Results: Of the 111 enrolled patients, 69 patients (67.6%) demonstrated WML growth and 15 patients (13.7%) had NILs. Patients with higher BPV demonstrated a more WML growth (50% vs. 61.8% vs. 83.8; P = 0.02, by tertiles) and more NILs (5.4% vs. 5.4% vs. 29.7%; P = 0.002, by tertiles). In multivariable analyses, old age [odds ratio (OR) = 1.052 (95% confidence interval (CI) = 1.005-1.101); P = 0.03] and home BPV [OR = 1.149 (95% CI = 1.013-1.304); P = 0.02] were independently associated with WML growth. Low mean diastolic blood pressure [OR = 0.913 (95% CI = 0.874-0.984); P = 0.02] and high home BPV [OR = 1.287 (95% CI = 1.086-1.526); P = 0.004] were independently associated with NILs at follow-up., Conclusions: High BPV is associated with WML growth and NIL in ischemic stroke patients with symptomatic ICAS. BPV monitoring at home may be helpful., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the predictors of hemorrhagic transformation (HT) in patients with mild atrial fibrillation-related stroke who were treated with early anticoagulation. We conducted a post-hoc subgroup analysis from Acute Cerebral Infarction Patients with Non-valvular Atrial Fibrillation (Triple AXEL) study., Patients and Methods: The Triple AXEL study was a randomized, multicenter, open-label, blinded end-point evaluation, comparative phase 2 trial. To identify the relationship between the type of HT and risk factors. We analyzed various factors using data from the Triple AXEL study, such as sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, initial infarction volume, initial infarction location, and new intracranial hemorrhage on follow-up gradient recalled echo or susceptibility-weighted imaging., Results: We analyzed various factors by dividing patients into a new HT group and a no HT group. No correlation was found between HT and risk factors that were significantly associated with HT, including age, sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, and initial infarction volume. When the initial infarction was classified into anterior circulation infarction (ACI) and posterior circulation infarction (PCI), the occurrence of new HT was significantly more associated with PCI than with ACI (57.6% vs 24.0%, P = 0.001). Multivariate logistic regression analysis was performed using HT as a response variable. Only the location of initial infarction according to the vascular territory contributed to the increased risk of HT (OR2.3, 95%CI1.33-3.91, P = 0.003)., Conclusion: PCI is a very important independent risk factor for HT in patients with mild AF-related stroke treated with early anticoagulation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients., Methods: In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532., Findings: Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation., Interpretation: In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events., Funding: Korea Otsuka Pharmaceutical., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.)

Although stroke is a leading cause of disability, the quantitative relationship between baseline clinical and imaging characteristics and long-term disability outcomes has rarely been studied. Prospectively collected clinical data from 405 patients with acute ischemic stroke including brain magnetic resonance images (MRIs) and disability outcomes assessed using the modified Rankin Scale (mRS) 3 month after the onset of disease were analyzed using a proportional odds cumulative logit model implemented in NONMEM. The relationship between the difference in lesion volume (DLV) - lesion volume measured by brain MRI 5 days later - lesion volume at the onset of the disease, and the mRS measured at 3 months (mRS3) was modeled first, and the potential covariates were tested. The E max model best described the relationship between DLV and the logit probability of each mRS3. DLV, baseline stroke severity, age, and diabetes mellitus were identified as significant predictors of the probabilities of mRS3. The quantitative model constructed in the current analysis will enable us to predict the long-term disabilities of the patients with acute ischemic stroke using the patient-specific MRI and other clinical information, which will be useful for individualizing therapies and for making the clinical development of a novel drug more efficient., (© 2017, The American College of Clinical Pharmacology.)

Importance: In atrial fibrillation (AF)-related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear., Objective: To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke., Design, Setting, and Participants: A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis., Interventions: Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks., Main Outcomes and Measures: The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length., Results: Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001)., Conclusions and Relevance: In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy., Trial Registration: clinicaltrials.gov Identifier: NCT02042534.

Background: It is still controversial whether early fluid-attenuated inversion recovery (FLAIR) hyperintensity within acute ischemic lesions carries the risk of hemorrhagic transformation (HT) after reperfusion therapy. Furthermore, the association between the location of FLAIR hyperintensity and HT has not been investigated., Methods: We retrospectively reviewed patients who underwent reperfusion therapy within 6 hours of stroke onset and magnetic resonance imaging including a FLAIR sequence before completing reperfusion therapy. FLAIR hyperintensity within the diffusion-weighted imaging (DWI) lesion was rated qualitatively, and HT was assessed on follow-up gradient echo imaging. The location of the FLAIR change and HT was classified as subcortical, cortical, or cortico-subcortical., Results: Of 134 patients with acute ischemic stroke included in this study, early FLAIR changes within DWI lesions were identified in 56 (41.8%) patients, and HT was noted in 51 (38.1%) patients. FLAIR change was independently associated with HT (odds ratio: 4.37, 95% confidence interval: 1.72-11.12). Geographically, 48.2% of the patients with a FLAIR change developed a matched HT (restricted to the region with the FLAIR change), and the risk of HT was further increased in patients with a FLAIR change in the cortico-subcortical region (68.8%)., Conclusions: In patients in the acute stage of stroke, an early FLAIR change is associated with the risk of HT following reperfusion therapy with a highly matched geographic relationship and common risk factors. Thus, identification of FLAIR change may be a useful surrogate marker to assess the likelihood of subsequent HT in patients treated with reperfusion therapy., (Copyright © 2017 National Stroke Association. 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: The onset of wake-up stroke and daytime-unwitnessed stroke is unclear. Though the clinical importance is similar by both being excluded from reperfusion therapy, the characteristics of daytime-unwitnessed stroke are less known than that of wake-up stroke. Here, we compared the characteristics between daytime-unwitnessed stroke and wake-up stroke., Methods: Unclear-onset (i.e., last-known normal time ≠ first-found abnormal time) stroke patients admitted within 24 h of recognition of stroke between February 2011 and October 2013 were reviewed. Demographics and clinical and imaging variables were compared between patients with daytime-unwitnessed stroke and those with wake-up stroke., Results: Among the 762 ischemic stroke patients, 276 (36.2%) had unclear-onset stroke (104 daytime-unwitnessed stroke and 172 wake-up stroke). Compared to wake-up stroke, daytime-unwitnessed stroke patients had a higher prevalence of cardioembolic stroke and more frequently presented altered mental status (p < 0.001) and/or aphasia (p < 0.001) with more severe neurological deficit (p < 0.001). However, the time from symptom recognition to hospital arrival was shorter (p < 0.001), and diffusion-weighted image-fluid-attenuated inversion recovery image mismatch (p = 0.02) and perfusion-diffusion mismatch (p = 0.001) were also more frequently observed in daytime-unwitnessed stroke. Finally, the proportion of patients eligible for thrombolysis (p < 0.001) was higher in daytime-unwitnessed stroke patients., Conclusions: Clinical and imaging characteristics of daytime-unwitnessed stroke significantly differ from those of wake-up stroke. Daytime-unwitnessed stroke patients are more likely to receive reperfusion therapy, as they arrive at the hospital earlier after symptom recognition, compared to wake-up stroke patients., (© 2016 World Stroke Organization.)

Objective: To test whether a silent new ischemic lesion (SNIL) on MRI after stroke predicted future recurrent ischemic stroke or vascular events., Methods: In this prospective study, we analyzed data from patients presenting with acute ischemic stroke who underwent MRI <24 hours and 5 and 30 days after symptom onset. The presence of a SNIL at 5 (5D-SNIL) and 30 (30D-SNIL) days was determined on diffusion-weighted and fluid-attenuated inversion recovery images. Patients were contacted every 3-6 months to identify recurrent clinical events. The log-rank test and Cox proportional hazard model were used to estimate the hazard ratio of recurrent ischemic stroke and composites of recurrent ischemic stroke, transient ischemic attack, acute coronary syndrome, and vascular death., Results: The 5D- and 30D-SNILs were found in 24.4% (66/270) and 7.4% (19/256) of patients. During the 5-year follow-up, clinical events were observed in 42 patients (15.6%). The 5D- and 30D-SNIL independently predicted recurrent ischemic stroke (hazard ratio [95% confidence interval] 2.9 [1.3-6.4] and 9.6 [4.1-22.1], respectively) and composite vascular events (2.4 [1.3-4.5] and 6.1 [3.1-12.4], respectively)., Conclusions: Patients with a SNIL within the first few weeks after index stroke have an increased risk of recurrent ischemic stroke or vascular events. The presence of a SNIL on MRI could serve as a surrogate endpoint for clinical recurrence in secondary prevention clinical trials., (© 2015 American Academy of Neurology.)

Background and Purpose: (18) F-fluoromisonidazole (FMISO) positron emission tomography (PET) is used to image metabolically compromised but viable hypoxic tissue. We hypothesized that FMISO PET might predict early infarct growth in acute ischemic stroke patients with perfusion-diffusion mismatch in magnetic resonance imaging (MRI)., Methods: We prospectively enrolled acute ischemic stroke patients who visited the emergency room within 48 hours after stroke onset and had perfusion-diffusion mismatch (>20%), as shown MRI. Infarct growth was defined as >20% increase of initial infarct volume or >5 mL in follow-up diffusion-weighted image 5 ± 2 days after stroke. The association between FMISO uptake and infarct growth was explored., Results: Of 19 enrolled patients, 10 (52.6%) showed increased FMISO uptake, with 8 of the latter showing infarct growth. None of the 9 patients who did not show FMISO uptake had infarct growth. FMISO uptake was significantly associated with infarct growth (Fisher's exact test; P < .01). FMISO PET scan had a sensitivity of 100% and a specificity of 82% (AUC = .909) in predicting infarct growth., Conclusions: FMISO PET scan can predict early infarct growth in acute ischemic stroke patients with perfusion-diffusion mismatch in MRI., (Copyright © 2014 by the American Society of Neuroimaging.)

Background and Aims: To assess the efficacy and safety of modest blood pressure (BP) reduction with valsartan within 48 h after symptom onset in patients with acute ischemic stroke and high BP., Methods: This was a multicenter, prospective, randomized, open-label, blinded-end-point trial. A total of 393 subjects were recruited at 28 centers and then randomly assigned in a 1:1 ratio to receive valsartan (n = 195) or no treatment (n = 198) for seven-days after presentation. The primary outcome was death or dependency, defined as a score of 3-6 on the modified Rankin Scale (mRS) at 90 days after symptom onset. Early neurological deterioration (END) within seven-days and 90-day major vascular events were also assessed., Results: There were 372 patients who completed the 90-day follow-up. The valsartan group had 46 of 187 patients (24·6%) with a 90-day mRS 3-6, compared with 42 of 185 patients (22·6%) in the control group (odds ratio [OR], 1·11; 95% confidence interval [CI], 0·69-1·79; P = 0·667). The rate of major vascular events did not differ between groups (OR, 1·41; 95% CI, 0·44-4·49; P = 0·771). There was a significant increase of END in the valsartan group (OR, 2·43; 95% CI, 1·25-4·73; P = 0·008)., Conclusions: Early reduction of BP with valsartan did not reduce death or dependency and major vascular events at 90 days, but increased the risk of END., (© 2015 World Stroke Organization.)

Background: Early recurrent ischemic lesions detected on diffusion-weighted imaging (DWI) have been proposed as a surrogate marker for clinical recurrence. We hypothesized that cytochrome P450 2C19 (CYP2C19) genotype influences the incidence of early recurrence on DWI in acute stroke patients treated with clopidogrel., Methods: We enrolled 76 Korean patients with acute ischemic stroke due to large artery atherosclerosis who were treated with clopidogrel. Early ischemic lesion recurrence was defined as new lesions separate from the index lesion. We compared the rates of early ischemic lesion recurrence on DWI based on the CYP2C19 genotypes., Results: Early recurrence on DWI was observed in 36 patients (47.4%). A total of 76 patients were classified into 3 phenotypic groups: extensive metabolizers (EMs; n = 27, 35.5%), intermediate metabolizers (IMs; n = 36, 47.4%), and poor metabolizers (PMs; n = 13, 17.1%). Early recurrence on DWI was more common in PMs (84.6%), followed by IMs (50.0%), and EMs (25.9%; P < .001). PMs had a significantly higher recurrence rate than EMs (P < .001). In multivariate analysis, CYP2C19 genotypes were independently associated with early DWI recurrence (for PMs: odds ratio, 19.3; 95% confidence interval, 3.15-117.56)., Conclusions: CYP2C19 genotypes are significantly associated with early lesion recurrence in Korean acute stroke patients treated with clopidogrel., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Ischemic lesions dynamically evolve during the acute phase of stroke. Although the ischemic lesion volume has been considered as a predictor of clinical outcome, it is still controversial whether early changes in ischemic lesion have prognostic information in addition to clinical variables. We hypothesized that early infarct growth on diffusion-weighted imaging (DWI) might be independently associated with long-term outcome in acute ischemic stroke patients., Methods: This was a prospective study for acute ischemic stroke patients admitted to the Stroke Unit of Asan Medical Center. The patients underwent DWI at baseline (within 24h) and subsequently at 5 days after stroke onset. Early infarct growth was defined as the absolute difference between follow-up and baseline infarct volumes. Poor outcome was a modified Rankin Scale (mRS) at 3 months of 2-6 or 3-6. The association between infarct growth on DWI and clinical outcome was explored using multivariate analysis adjusting for demographics, risk factors for stroke, and other clinical variables. The cut-off values of early infarct growth predicting long-term outcomes were estimated using receiver operating characteristic analysis., Results: Of 409 patients enrolled, 345 (84.4%) showed any infarct growth (median, 0.63 cm(3); interquartile range [IQR], 0.11-6.33 cm(3); mean ± standard deviation, 9.55 ± 25.54 cm(3)). At the 3-month follow-up, the good outcomes were observed in 217 patients (53.1%) for mRS 0-1 and 303 patients (74.1%) for mRS 0-2. The larger infarct growth was associated with poor clinical outcome (for mRS 2-6, 0.29 cm(3) [IQR 0.04-2.19] vs. 2.16 cm(3) [IQR 0.26-17.68], p<0.001; and for mRS 3-6, 0.39 cm(3) [IQR 0.05-3.25] vs. 7.36 cm(3) [IQR 0.57-26.48], p<0.001). After adjusting age, diabetes, baseline National Institutes of Health Stroke Scale, and baseline infarct volume by multivariate logistic regression analysis, infarct growth was an independent predictor of poor clinical outcomes (for mRS 2-6, odds ratio [OR], 1.03, 95% confidence interval [CI], 1.004-1.06, p=0.03; and for mRS 3-6, OR, 1.03, 95% CI, 1.01-1.05, p=0.01). The cut-off values of infarct growth discriminating between good and poor outcomes were 0.99 cm(3) for mRS 0-1 vs. 2-6 (area under curve, 0.685; P<0.001) and 8.86 cm(3) for mRS 0-2 vs. 3-6 (area under curve, 0.736; P<0.001)., Conclusions: Our present study findings show that infarct growth within a week of onset independently predicts 3-month clinical outcomes. This suggests that short-term changes in infarct volume may serve as a surrogate marker of long-term clinical outcomes after ischemic stroke., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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: Neuron-specific enolase (NSE) is a surrogate marker for the extent of brain damage after ischemic stroke and affords a good predictor of stroke prognosis. We hypothesized that the pattern of NSE level changes in the peripheral blood during the acute period of ischemic stroke is dependent on stroke mechanism and is associated with hemorrhagic transformation., Methods: Acute ischemic stroke patients visiting our center within 24 hours of symptom onset were recruited into the study. NSE levels were obtained serially at various time points after stroke, and the pattern of change was categorized into no significant change, continuously increasing, continuously decreasing, with 1 peak and with 2 peaks. Clinical, laboratory, and imaging variables were compared among the patient groups. Multivariate analysis was performed to verify the independent association between the second NSE peak and hemorrhagic transformation after adjusting for potential confounders., Results: Among 83 patients, NSE levels were stationary in 22 (26.5%) of the patients, increased in 9 (10.8%), decreased in 18 (21.7%), and showed 1 peak in 17 (20.5%) and 2 peaks in 17 (20.5%) patients. The incidence of atrial fibrillation and hemorrhagic transformation was significantly elevated (P = .02) in patients with 2 NSE peaks. Furthermore, the second NSE peak and the initial lesion volume were associated independently with hemorrhagic transformation after we adjusted for potential confounders (odds ratio = 6.844 and 1.024, P = .04 and .02, respectively)., Conclusions: Serial NSE analysis during the acute period of ischemic stroke is useful for monitoring hemorrhagic transformation and the blood-brain barrier disruption status., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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.)

Objective: We evaluated the relationship between hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and small-vessel disease (SVD) and atherosclerotic large-vessel disease (LVD) in stroke patients., Methods: A total of 825 noncardioembolic ischemic stroke patients whose plasma concentrations of total homocysteine were measured and whose MTHFR C677T polymorphism status was identified were included in this retrospective study. MRI of the brain and magnetic resonance angiography of the intracranial and extracranial cerebral arteries had been performed. SVD and LVD were assessed by the Scheltens scale (the SVD score) and by the number of atherosclerotic steno-occlusive arteries (the LVD score), respectively., Results: The TT genotype of the MTHFR C677T polymorphism was associated with hyperhomocysteinemia (p < 0.001), but not with SVD (p = 0.182) or LVD (p = 0.988) scores. Multiple logistic regression analysis showed that hyperhomocysteinemia was associated with SVD (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01-1.07; p = 0.005) and LVD (OR 1.02; 95% CI 1.00-1.05; p = 0.041) scores. Hyperhomocysteinemia was related to the LVD score of extracranial arteries (p = 0.008), but not to the LVD score of intracranial arteries (p = 0.730). In multiple logistic regression analysis, however, hyperhomocysteinemia was not related to the LVD score of extracranial arteries (p = 0.255)., Conclusions: Hyperhomocysteinemia was associated with SVD of the brain and LVD of cerebral arteries. The MTHFR C677T polymorphism was not related to SVD and LVD, although the TT genotype was an important determinant of hyperhomocysteinemia., (© 2014 American Academy of Neurology.)

Background: It remains unclear whether the characteristics of ischemic stroke in patients with cancer (ISC) differ from usual ischemic strokes (non-ISC). Although a small number of studies have been conducted to characterize ISC, the status of cancer has rarely been considered seriously., Aims: We aimed to investigate the features of ISC according to the status of cancer, and compare their characteristics with those of non-ISC., Methods: We assessed and classified 204 ISC patients into two groups: 104 with active (ISC-active) and 100 with inactive (ISC-inactive) cancer. For each ISC patient, two age- and gender-matched ischemic stroke patients without history of cancer were selected as non-ISC control subjects. We compared the clinical/laboratory data, stroke mechanisms, and diffusion weighted imaging (DWI) lesion patterns between ISC-active and non-ISC patients, and between ISC-inactive and non-ISC patients., Results: ISC-active patients demonstrated higher C-reactive protein (CRP) and D-dimer, more frequent cryptogenic stroke and patterns of multiple DWI lesions (in bilateral anterior or in anterior and posterior circulations), and less prevalent conventional risk factors than non-ISC patients, while ISC-inactive patients revealed no such marked differences. Among ISC-active patients, both elevated CRP and D-dimer levels were associated with cryptogenic mechanism and multiple lesion patterns. Furthermore, ISC-active patients with cryptogenic strokes tended to have multiple lesion patterns and metastasis., Conclusions: ISC-active, but not ISC-inactive, is distinct in terms of risk factors, stroke mechanisms, and lesion patterns. Chronic inflammation and an activated coagulation system may contribute to the pathogenic mechanism of strokes, the extent of each depending on the activity and severity of cancer., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Background: The progression of carotid intima-media thickness (CIMT) is closely associated with ischemic stroke recurrence. However, the efficacy of cilostazol on preventing CIMT progression in stroke patients has never been investigated properly by a prospective trial., Methods: This study is a part of "Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis-2." Six centers that are available to measure CIMT according to the protocol participated in this substudy. After 7 months of randomization, the changes of CIMT were compared between cilostazol group and clopidogrel group. CIMT was measured by a semiautomated software (Intimascope) and was presented as the mean of maximum (CIMT-max) and average (CIMT-ave) of both common carotid arteries. Linear logistic regression analysis and analysis of covariance were performed to verify the independent factors associated with CIMT progression., Results: Among the 85 patients, 39 subjects were assigned to cilostazol group and 46 subjects to clopidogrel group. Follow-up CIMT significantly decreased in cilostazol group (CIMT-max: -.03 ± .11 and CIMT-ave: -.02 ± .08) compared with the increase in clopidogrel group (CIMT-max: .04 ± .20 and CIMT-ave: .04 ± .11; P = .05 and P = .04, respectively). Female, diabetes, and smoking were independently associated with the progression of CIMT, whereas the use of cilostazol was against CIMT progression from the results of linear regression analysis (P = .03 for both CIMT-max and CIMT-ave). The use of cilostazol also well predicted less progression of CIMT at follow-up after adjusting for baseline CIMT values and conventional risk factors (CIMT-max: P = .04 and CIMT-ave: P = .03)., Conclusion: Cilostazol has a beneficial effect in preventing the progression of CIMT in ischemic stroke patients., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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.