Real-Time Imaging Assessment of Stress-Induced Vascular Inflammation Using Heartbeat-Synchronized Motion Compensation.

BACKGROUND: Chronic mental stress accelerates atherosclerosis through complicated neuroimmune pathways, needing for advanced imaging techniques to delineate underlying cellular mechanisms. While histopathology, ex vivo imaging, and snapshots of in vivo images offer promising evidence, they lack the ability to capture real-time visualization of blood cell dynamics within pulsatile arteries in longitudinal studies. METHODS: An electrically tunable lens was implemented in intravital optical microscopy, synchronizing the focal plane with heartbeats to follow artery movements. ApoE-/- mice underwent 2 weeks of restraint stress before baseline imaging followed by 2 weeks of stress exposure in the longitudinal imaging, while nonstressed mice remained undisturbed. The progression of vascular inflammation was assessed in the carotid arteries through intravital imaging and histological analyses. RESULTS: A 4-fold reduction of motion artifact, assessed by interframe SD, and an effective temporal resolution of 25.2 Hz were achieved in beating murine carotid arteries. Longitudinal intravital imaging showed chronic stress led to a 6.09-fold (P=0.017) increase in myeloid cell infiltration compared with nonstressed mice. After 3 weeks, we observed that chronic stress intensified vascular inflammation, increasing adhered myeloid cells by 2.45-fold (P=0.031), while no significant changes were noted in nonstressed mice. Microcirculation imaging revealed increased circulating, rolling, and adhered cells in stressed mice's venules. Histological analysis of the carotid arteries confirmed the in vivo findings that stress augmented plaque area, myeloid cell and macrophage accumulation, and necrotic core volume while reducing fibrous cap thickness indicating accelerated plaque formation. We visualized the 3-dimensional structure of the carotid artery and 4-dimensional dynamics of the venules in the cremaster muscle. CONCLUSIONS: Dynamic focusing motion compensation intravital microscopy enabled subcellular resolution in vivo imaging of blood cell dynamics in beating arteries under chronic restraint stress in real time. This novel technique emphasizes the importance of advanced in vivo imaging for understanding cardiovascular disease.

Automated Prediction of Proximal Middle Cerebral Artery Occlusions in Noncontrast Brain Computed Tomography.

BACKGROUND: Early identification of large vessel occlusion (LVO) in patients with ischemic stroke is crucial for timely interventions. We propose a machine learning-based algorithm (JLK-CTL) that uses handcrafted features from noncontrast computed tomography to predict LVO. METHODS: We included patients with ischemic stroke who underwent concurrent noncontrast computed tomography and computed tomography angiography in seven hospitals. Patients from 5 of these hospitals, admitted between May 2011 and March 2015, were randomly divided into training and internal validation (9:1 ratio). Those from the remaining 2 hospitals, admitted between March 2021 and September 2021, were designated for external validation. From each noncontrast computed tomography scan, we extracted differences in volume, tissue density, and Hounsfield unit distribution between bihemispheric regions (striatocapsular, insula, M1-M3, and M4-M6, modified from the Alberta Stroke Program Early Computed Tomography Score). A deep learning algorithm was used to incorporate clot signs as an additional feature. Machine learning models, including ExtraTrees, random forest, extreme gradient boosting, support vector machine, and multilayer perceptron, as well as a deep learning model, were trained and evaluated. Additionally, we assessed the models' performance after incorporating the National Institutes of Health Stroke Scale scores as an additional feature. RESULTS: Among 2919 patients, 83 were excluded. Across the training (n=2463), internal validation (n=275), and external validation (n=95) datasets, the mean ages were 68.5±12.4, 67.6±13.8, and 67.9±13.6 years, respectively. The proportions of men were 57%, 53%, and 59%, with LVO prevalences of 17.0%, 16.4%, and 26.3%, respectively. In the external validation, the ExtraTrees model achieved a robust area under the curve of 0.888 (95% CI, 0.850-0.925), with a sensitivity of 80.1% (95% CI, 72.0-88.1) and a specificity of 88.6% (95% CI, 84.7-92.5). Adding the National Institutes of Health Stroke Scale score to the ExtraTrees model increased sensitivity (from 80.1% to 92.1%) while maintaining specificity. CONCLUSIONS: Our algorithm provides reliable predictions of LVO using noncontrast computed tomography. By enabling early LVO identification, our algorithm has the potential to expedite the stroke workflow.

The 2022 FASEB Virtual Catalyst Conference on the Cardiac Interatrial Septum and Stroke Risk, December 7, 2022.

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022. During this conference, many aspects of the cardiac interatrial septum were discussed. Among these were the embryogenesis of the interatrial septum and development of anatomic variants such as patent foramen ovale and left atrial septal pouch. Also addressed were various mechanisms of injury such as shunting physiologies and the consequences that can result from anatomic variants, as well as imaging considerations in echocardiography, computed tomography, and magnetic resonance imaging. Treatment options including anticoagulation and closure were addressed, as well as an in-depth discussion on whether the left atrial septal pouch is a stroke risk factor. These issues were discussed and debated by multiple experts from neurology, cardiology, and radiology.

High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). METHODS: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). RESULTS: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. CONCLUSIONS: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Adults.

OBJECTIVE: Vagus nerve stimulation (VNS) has recently been reported to exert additional benefits for functional recovery in patients with brain injury. However, the mechanisms underlying these effects have not yet been elucidated. This study examined the effects of transcutaneous auricular VNS (taVNS) on cortical excitability in healthy adults. MATERIALS AND METHODS: We recorded subthreshold and suprathreshold single- and paired-pulse motor-evoked potentials (MEPs) in the right-hand muscles of 16 healthy adults by stimulating the left primary motor cortex. Interstimulus intervals were set at 2 milliseconds and 3 milliseconds for intracortical inhibition (ICI), and 10 milliseconds and 15 milliseconds for intracortical facilitation (ICF). taVNS was applied to the cymba conchae of both ears for 30 minutes. The intensity of taVNS was set to a maximum tolerable level of 1.95 mA. MEPs were measured before stimulation, 20 minutes after the beginning of the stimulation, and 10 minutes after the cessation of stimulation. RESULTS: The participants' age was 33.25 ± 7.08 years, and nine of 16 were male. No statistically significant changes were observed in the mean values of the single-pulse MEPs before, during, or after stimulation. Although the ICF showed an increasing trend after stimulation, the changes in ICI and ICF were not significant, primarily because of the substantial interindividual variability. CONCLUSIONS: The effect of taVNS on cortical excitability varied in healthy adults. An increase in ICF was observed after taVNS, although the difference was not statistically significant. Our findings contribute to the understanding of the mechanisms by which taVNS is effective in patients with brain disorders.

Independent effect of cardiometabolic syndromes and depression on dementia in Parkinson's disease: A 12-year longitudinal follow-up study of a nationwide cohort.

BACKGROUND: We aimed to investigate the incidence rate of Parkinson's disease dementia (PDD) according to age and disease duration by sex. Furthermore, we explored the effect of each cardiometabolic syndrome and depression on the incidence of PDD. METHODS: Using data from the Korean National Health Insurance Service, 79,622 patients with de novo Parkinson's disease (PD) aged ≥40 years between January 2002 and December 2010 were followed to December 2019. We analyzed the incidence of PDD according to age at PD diagnosis and disease duration. To determine cardiometabolic syndromes and depression that affected PDD, we used Fine and Gray competing regression after controlling for age and sex. RESULTS: During the 12.5-year follow-up period, the incidence of PDD increased with age at PD diagnosis (0.81-45.31 per 1000 person-years among those aged 40-44 and over 80 years, respectively) and longer disease duration (22.68 per 1000 person-years in 1-2 years to 34.16 per 1000 person-years in 15-16 years). Hypertension (subdistribution hazard ratio [SHR] = 1.11; 95% confidence interval [CI] 1.07-1.16), diabetes (SHR = 1.09; 95% CI 1.05-1.14), dyslipidemia (SHR = 1.15; 95% CI 1.11-1.20), and depression (SHR = 1.36; 95% CI 1.30-1.41) independently increased the risk for PDD. CONCLUSIONS: Our findings provide insights into cardiometabolic syndromes as modifiable risk factors for incident PDD. Furthermore, our results will help in designing public health policies with respect to controlling cardiometabolic syndromes and depression to prevent incident PDD in patients with PD.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Headaches during pregnancy and the risk of subsequent stroke.

BACKGROUND: Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women. METHODS: Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes. RESULTS: Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30-1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12-2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23-2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19-2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke. CONCLUSIONS: We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.

Stress-associated neurobiological activity is linked with acute plaque instability via enhanced macrophage activity: a prospective serial 18F-FDG-PET/CT imaging assessment.

AIMS: Emotional stress is associated with future cardiovascular events. However, the mechanistic linkage of brain emotional neural activity with acute plaque instability is not fully elucidated. We aimed to prospectively estimate the relationship between brain amygdalar activity (AmygA), arterial inflammation (AI), and macrophage haematopoiesis (HEMA) in acute myocardial infarction (AMI) as compared with controls. METHODS AND RESULTS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) imaging was performed within 45 days of the index episode in 62 patients (45 with AMI, mean 60.0 years, 84.4% male; 17 controls, mean 59.6 years, 76.4% male). In 10 patients of the AMI group, serial 18F-FDG-PET/CT imaging was performed after 6 months to estimate the temporal changes. The signals were compared using a customized 3D-rendered PET reconstruction. AmygA [target-to-background ratio (TBR), mean ± standard deviation: 0.65 ± 0.05 vs. 0.60 ± 0.05; P = 0.004], carotid AI (TBR: 2.04 ± 0.39 vs. 1.81 ± 0.25; P = 0.026), and HEMA (TBR: 2.60 ± 0.38 vs. 2.22 ± 0.28; P < 0.001) were significantly higher in AMI patients compared with controls. AmygA correlated significantly with those of the carotid artery (r = 0.350; P = 0.005), aorta (r = 0.471; P < 0.001), and bone marrow (r = 0.356; P = 0.005). Psychological stress scales (PHQ-9 and PSS-10) and AmygA assessed by PET/CT imaging correlated well (P < 0.001). Six-month after AMI, AmygA, carotid AI, and HEMA decreased to a level comparable with the controls. CONCLUSION: AmygA, AI, and HEMA were concordantly enhanced in patients with AMI, showing concurrent dynamic changes over time. These results raise the possibility that stress-associated neurobiological activity is linked with acute plaque instability via augmented macrophage activity and could be a potential therapeutic target for plaque inflammation in AMI.

Atherosclerotic Burden and Vascular Risk in Stroke Patients With Atrial Fibrillation.

Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events. Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 3­4). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed. Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA2DS2-VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.00­1.56) for ASVD 1, 1.34 (95% CI, 1.02­1.76) for ASVD 2, and 1.93 (95% CI, 1.24­2.99) for ASVD 3­4. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.01­1.74), 1.47 (1.06­2.03), and 2.39 (1.47­3.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.05­1.54]) and all-cause death (1.45 [1.17­1.81]). Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.

Efficacy and Safety of Timely Urgent Superficial Temporal Artery-to-Middle Cerebral Artery Bypass Surgery in Patients with Acute Ischemic Stroke: A Single-Institutional Prospective Study and a Pooled Analysis.

BACKGROUND: Clinical outcome in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) is not satisfactory if reperfusion treatment fails or is not tried. AIMS: We aimed to assess the efficacy and safety of urgent superficial temporal-to-middle cerebral artery (STA-MCA) bypass surgery in selected patients. METHODS: Patients who were diagnosed with LVO-induced AIS in the anterior circulation but had a failed intra-arterial thrombectomy (IAT) or were not tried due to IAT contraindications were prospectively enrolled. Timely urgent STA-MCA bypass surgery was performed if they showed perfusion-diffusion mismatch or symptom-diffusion mismatch in the acute phase of disease. Clinical and radiological data of these patients were assessed to demonstrate the safety and efficacy of urgent bypass procedures. A pooled analysis of published data on urgent bypass surgery in acute stroke patients was conducted and analyzed. RESULTS: In 18 patients who underwent timely bypass, the National Institutes of Health Stroke Scale (NIHSS) score improved from 12.11 ± 4.84 to 9.89 ± 6.52, 1 week after surgery. Three-month and long-term (9.72 ± 5.00 months) favorable outcomes (modified Rankin Scale [mRS] scores 0-2) were achieved in 50 and 75% of the patients, respectively. The pooled analysis (117 patients from 10 articles, including ours) identified favorable mRS scores in 71.79% patients at 3 months. A significant NIHSS score improvement from 11.51 ± 4.89 to 7.59 ± 5.50 was observed after surgery with significance. Major complications occurred in 3 patients (2.6%, 3/117) without mortality. CONCLUSIONS: Urgent STA-MCA bypass surgery can be regarded as a safe optional treatment to prevent cerebral infarct expansion and to improve clinical and radiological outcomes in highly selected patients.

Pre-Admission CHADS2 and CHA2DS2-VASc Scores on Early Neurological Worsening.

BACKGROUND: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. OBJECTIVE: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. METHODS: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. RESULTS: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. CONCLUSIONS: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.

Regional Arterial Spin Labeling Perfusion Defect Is Associated With Early Ischemic Recurrence in Patients With a Transient Ischemic Attack.

Background and Purpose- With the lack of confirmatory examinations, the distinction of a transient ischemic attack (TIA) from various TIA-mimicking diseases is difficult, particularly in diffusion-weighted imaging (DWI)-negative TIAs. In this study, we aimed to evaluate the relationship between arterial spin labeling (ASL) perfusion defects and early ischemic recurrence (FU-DWI [+]) in patients with DWI-negative TIAs. Methods- We assessed consecutive patients with a DWI-negative TIA within 24 hours of symptom onset, who underwent both ASL images and follow-up magnetic resonance imaging during the acute period. As markers of the ASL images, we evaluated the ASL perfusion defects in each hemisphere. Arterial transit artifact (ATA) and intraarterial high-intensity signal (IAS) were also rated as markers of collateral status and blood stagnation due to large vessel occlusion, respectively. Results- Among the 136 patients with a DWI-negative TIA, 33 patients had FU-DWI (+) lesions in 36 hemispheres. In the multivariable analysis, ASL defects remained an independent predictor of FU-DWI (+) (adjusted odds ratio, 13.94 [95% CI, 5.77-33.70], P<0.001). In the evaluation of the interactive relationship between ASL defects and ATA/IAS, the (ASL [+] ATA [-]) group showed the highest frequencies of FU-DWI (+) events (55.6%) with the highest adjusted odds ratio values (adjusted odds ratio, 14.86 [95% CI, 5.63-39.24], P<0.001), indicating a negative synergistic effect between the ASL defects and ATA. Meanwhile, the (ASL [+] IAS [+]) group showed higher frequencies of FU-DWI (+) and higher adjusted odds ratio values than those of the (ASL [+] IAS [-]) and (ASL [-] IAS [-]) groups, indicating a positive synergistic effect. Conclusions- We demonstrated that ASL perfusion defects were associated with ipsilateral FU-DWI (+) in patients with a DWI-negative TIA. Furthermore, this association was enhanced with IASs and attenuated with ATAs.

Impact of Sleep-Disordered Breathing on Functional Outcomes in Ischemic Stroke: A Cardiopulmonary Coupling Analysis.

BACKGROUND AND PURPOSE: Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up. METHODS: A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort. CPC analysis was conducted, and SDB was defined by the presence of narrow-band coupling during sleep time. We investigated the association between SDB and functional impairment at 3 months as measured by the modified Rankin Scale. RESULT: Narrow-band coupling was present in 191 (31.1%) of 615 patients (mean age 64.5±12.6 years). The narrow-band group showed a significantly higher rate of severe functional impairment (modified Rankin Scale score >2; 45.5% versus 12.9%, P<0.001) and persistent disability (Δmodified Rankin Scale score ≤0; 53.9% versus 39.8%, P<0.001) at the 3-month follow-up. In multivariate analysis, narrow-band coupling was an independent predictor of higher risk of severe and persistent functional impairment at 3 months (odds ratio, 3.98 [95% CI, 2.34-6.78]; P<0.001; and odds ratio, 1.81 [95% CI, 1.23-2.66]; P<0.001, respectively). The results remained consistent after propensity-score matched analysis with 157 patient pairs (C-statistic=0.770). CONCLUSIONS: SDB assessed by CPC analysis at the early stage of ischemic stroke could predict severe and prolonged functional impairment at 3 months. CPC analysis using Holter monitoring can help predicting functional impairment in acute ischemic stroke.

Gamma-glutamyl transferase predicts future stroke: A Korean nationwide study.

OBJECTIVE: Although gamma-glutamyl transferase (GGT) is generally regarded as an alternative biomarker for alcohol consumption, its independent role in vascular diseases emerged recently. However, its role in stroke remains unknown. The aim of this study is to clarify the impact of GGT on stroke in a large-sized, national, standardized population cohort in Korea. METHODS: In Korea, the National Health Insurance Service (NHIS) provides full-coverage health insurance service for all citizens. Using data from the NHIS, the NHIS-National Sample Cohort was designed by randomly selecting 2% of Koreans, carefully considering demographic characteristics. We analyzed eligible individuals from this standardized cohort. The Cox proportional hazards model was used for the study investigating the relationship between GGT and stroke. RESULTS: Among the 456,100 eligible participants, 7,459 patients (1.64%) developed stroke as follows: 5,789 ischemic strokes, 1,046 intracerebral hemorrhages (ICHs), and 624 subarachnoid hemorrhages. GGT was independently correlated with increased risk of stroke after adjustment for alcohol consumption and stroke risk factors (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.29-1.51). The risks of both ischemic stroke (HR = 1.45, 95% CI = 1.32-1.58) and ICH (HR = 1.46, 95% CI = 1.18-1.80) were significantly elevated with increasing GGT. Despite some effect modifications by sex, age, and alcohol, the risk of total stroke and ischemic stroke in association with GGT remained significant in all subgroups. INTERPRETATION: In a standard Korean population, GGT was a novel biomarker predicting stroke risk, independently from alcohol consumption and other risk factors. Ann Neurol 2018;83:375-386.

Relationship between the Angle of the Posterior Inferior Cerebellar Artery and Cardioembolic Stroke.

BACKGROUND: In patients with unilateral posterior inferior cerebellar artery (PICA) territory infarction, the absence of relevant vessel stenosis may make it difficult to determine the etiology of the infarction. The incidence of cardioembolic (CE) infarction and the factors associated with infarction in such patients remains largely unknown. We hypothesized that the PICA angle would affect the flow direction of embolic sources. Thus, we analyzed the association between high-risk CE sources and the PICA angle. METHODS: Patients with an isolated unilateral PICA territory infarction without relevant vessel stenosis who were admitted between 2014 and 2017 were included from the Korea University Stroke Registry, which includes data from 3 university hospitals. We classified patients according to the presence of CE sources. For each case, we measured the angle between the vertebral artery (VA) and the proximal PICA. RESULTS: In all, 71 patients met the final study entry criteria. Multivariable analysis showed that the PICA angle was independently associated with the risk of a CE source. The optimal cut-off value using Youden's index was 89°. We classified the PICA shape based on the optimal cut-off value. A CE source was identified in 83.3% of cases in which the PICA angle exceeded 89°. CONCLUSIONS: The angle between the PICA and VA was an independent predictor of unilateral PICA stroke with high-risk CE sources without relevant artery stenosis, suggesting that an angle greater than 89° could be a new image marker for determining the stroke subtype.

Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage.

Background and Purpose- Despite early aneurysm repair and aggressive management for complications, subarachnoid hemorrhage (SAH) results in at least 25% mortality rate and 50% persistent neurological deficit. We investigated whether ceria nanoparticles which have potent antioxidative activities can protect against subarachnoid hemorrhage via attenuating fatal brain injuries. Methods- Uniform, 3 nm, water-dispersed ceria nanoparticles were prepared from short sol-gel reaction of cerium (III) ions with aminocaproic acid in aqueous phase. SAH was induced by endovascular perforation of middle cerebral artery of rats. A single dose of ceria nanoparticles (0.5 mg Ce/kg) or saline control was randomly administered intravenously at an hour post-SAH. Neuronal death, macrophage infiltration, SAH grade, and brain edema were evaluated at 72 hours. Mortality and neurological function were assessed for 14 days. Results- The obtained ceria nanoparticles with high Ce3+ to Ce4+ ratio demonstrated potent antioxidative, cytoprotective, and anti-inflammatory activities in vitro. In rodent SAH models, the severity of hemorrhage was comparable between the ceria nanoparticles- and saline-treated groups. However, ceria nanoparticles significantly reduced neuronal death, macrophage infiltration, and brain edema after SAH. Ceria nanoparticles successfully improved survival rates (88.2% in the ceria nanoparticles group versus 21.1% in the control group; P<0.001) and neurological outcomes (modified Garcia score: 12.1±0.5 in the ceria nanoparticles group versus 4.4±0.5 in the control group; P<0.001) of the animals with SAH. Conclusions- Ceria nanoparticles, totally synthesized in aqueous phase using aminocaproic acid, demonstrated promising results against SAH via potent antioxidative, neuroprotective and anti-inflammatory activities. Given the obvious limitations of current therapies for SAH, ceria nanoparticles can be a potential therapeutic agent which might result in a paradigm shift in SAH treatment.

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion.

In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting 20 to 23 seconds and cerebral blood flow <5 to 7 ml/min-1/(100 g)-1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.

Treatment of Cryptogenic Stroke with Active Cancer with a New Oral Anticoagulant.

BACKGROUND: Low-molecular weight heparin (LMWH) was shown to be effective and safe in treating venous thromboembolism, and generally used for stroke in cancer patients, but its effects on stroke are unclear. We compared clinical outcomes between LMWH and new oral anticoagulant (NOAC) in patients with cancer-related stroke. METHODS: We enrolled patients with cryptogenic ischemic stroke with active cancer who were treated with LMWH or NOAC between May 2012 and June 2015. The clinical outcomes, including early neurologic deterioration, early radiologic recurrence, 3-month modified Rankin scale score, 90-day mortality, cardio-cerebrovascular recurrence, and bleeding complications, were compared. RESULTS: Among 48 patients, 7 patients were treated with NOAC, and the remaining 41 patients with LMWH. Overall, the participants presented poor outcomes, including 20 (42%) early neurologic deteriorations, 28 (58%) early radiologic recurrences, 34 (71%) poor modified Rankin scale scores, 27 (56%) 90-day mortality events, 24 (50%) cardio-cerebrovascular recurrences, and 18 (38%) bleeding complications, that led to a change or temporary hold in medication in 12 cases. No statistical differences were found between the 2 groups in terms of demographic, clinical, or cardiovascular risk factors and clinical outcomes. CONCLUSIONS: NOAC showed the similar clinical outcomes and safety compared with LMWH in the treatment of cryptogenic ischemic stroke in active cancer patients.

Ceria-Zirconia Nanoparticles as an Enhanced Multi-Antioxidant for Sepsis Treatment.

The two oxidation states of ceria nanoparticles, Ce3+ and Ce4+ , play a pivotal role in scavenging reactive oxygen species (ROS). In particular, Ce3+ is largely responsible for removing O2- and . OH that are associated with inflammatory response and cell death. The synthesis is reported of 2 nm ceria-zirconia nanoparticles (CZ NPs) that possess a higher Ce3+ /Ce4+ ratio and faster conversion from Ce4+ to Ce3+ than those exhibited by ceria nanoparticles. The obtained Ce0.7 Zr0.3 O2 (7CZ) NPs greatly improve ROS scavenging performance, thus regulating inflammatory cells in a very low dose. Moreover, 7CZ NPs are demonstrated to be effective in reducing mortality and systemic inflammation in two representative sepsis models. These findings suggest that 7CZ NPs have the potential as a therapeutic nanomedicine for treating ROS-related inflammatory diseases.