Body mass index and waist circumference as predictors of recurrent vascular events after a recent ischemic stroke.

OBJECTIVES: Although elevated body mass index (BMI) is a risk factor for stroke, it appears to protect against recurrent vascular events. We tried to evaluate BMI and waist circumference (WC) as predictors of recurrent stroke and vascular events in a cohort of stroke survivors who were followed for 12 months. MATERIALS AND METHODS: We analyzed the stroke registry database of 6 hospitals and recruited patients with a first-ever stroke who were admitted from January 2011 to November 2019 and had their BMI and WC measured. Cox proportional hazards models were used to compare risks of recurrent stroke and major vascular events (a composite of stroke, myocardial infarction, or vascular death) between different BMI and WC quintiles. Reference categories were patients in the lowest quintiles. RESULTS: A total of 14 781 patients were analyzed. Patients in the second quintile of BMI had the lowest risk of recurrent stroke (adjusted hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.58-0.91); patients in the highest quintile had the lowest risk or a major vascular event (adjusted HR 0.71; 95% CI 0.58-0.86). Patients in the fourth quintile of WC had the lowest risk of recurrent stroke (adjusted HR 0.73; 95% CI 0.59-0.91) and a major vascular event (adjusted HR 0.72; 95 % CI 0.60-0.86). CONCLUSIONS: Our results show favorable effects of excess body weight and intra-abdominal fat on avoidance of vascular events after stroke and a favorable effect of intra-abdominal fat on avoidance of recurrent stroke.

Biological Mechanism of Sex Difference in Stroke Manifestation and Outcomes.

BACKGROUND AND OBJECTIVES: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location. METHODS: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations. RESULTS: The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, p = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, p < 0.001) and had more frequent END (adjusted difference 3.5%; p = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, p = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, p = 0.06) and cerebellar (9.1% vs. 11.1%, p = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; p < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; p < 0.001) and vertebral artery (6.5% vs 4.7%; p = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; p < 0.001). DISCUSSION: Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients.

The usefulness of global longitudinal peak strain and left atrial volume index in predicting atrial fibrillation in patients with ischemic stroke.

Introduction: Detection of atrial fibrillation (AF) is crucial for preventing recurrence in patients with ischemic stroke. We aimed to examine whether the left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) are associated with AF in patients with ischemic stroke. Methods: We prospectively analyzed 678 consecutive patients with ischemic stroke. LAVI and GLPS were assessed using three-dimensional transthoracic echocardiography with speckle-tracking imaging. Multiple logistic regression was used to evaluate the association of AF with LAVI and GLPS. To evaluate the predictive value of LAVI and GLPS for the presence of AF, we used optimism-corrected c-statistics calculated by 100 bootstrap repetitions and the net reclassification improvement (NRI). Results: The mean patient age was 68 ± 13 years (men, 60%). Patients with AF (18%) were a higher LAVI (41.7 ml/m2 vs. 74.9 ml/m2, P < 0.001) and a higher GLPS than those without AF (-14.0 vs. -17.3, P < 0.001). Among the 89 patients classified with embolic stroke of unknown source, the probable cardioembolic group had higher GLPS (n= 17, -14.6 vs. -18.6, respectively; P= 0.014) than the other groups (n= 72). Adding GLPS to age, hypertension, and the LAVI significantly improved the NRI, with an overall NRI improvement of 6.1% (P= 0.03). Discussion: The LAVI andGLPS with speckle-tracking imaging echocardiography may help identify patients with AF.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

BACKGROUND: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. METHODS AND FINDINGS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. CONCLUSIONS: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Hyperintense Vessel Sign in Large-Vessel Occlusion Stroke of Mild-to-Moderate Severity Ineligible for Recanalization.

BACKGROUND AND PURPOSE: The impact of fluid-attenuated inversion recovery hyperintense vessels (FHVs) on outcomes in patients ineligible for recanalization therapy with large-vessel occlusion (LVO) is unclear. We investigated the impact of FHVs determined using the FHV- Alberta Stroke Program Early CT Score (ASPECTS) on clinical outcomes in patients with LVO stroke of mild-to-moderate severity ineligible for recanalization therapy. METHODS: Sixty-eight consecutive patients with M1-middle cerebral artery occlusion who underwent magnetic resonance imaging within 24 hours of symptom onset and were ineligible for recanalization were included. Patients were dichotomized into a severe-FHV group (FHV-ASPECTS ≤4; n=33) and a mild-FHV group (FHV-ASPECTS >4; n=35), and multiple logistic regression analysis was used to examine the relationships of FHV scores with early neurological deterioration (END) and an unfavorable 3-month outcome (modified Rankin Scale score ≥3). RESULTS: Mean age was 66.2±13.5 years (mean±SD), and 30 (44%) were female. The severe-FHV group had a larger infarct volume (median, 5.5 mL vs. 3 mL) and more frequently exhibited the susceptibility vessel sign (30% vs. 3%) than the mild-FHV group. Ipsilateral old nonlacunar infarct was more frequent in the mild-FHV group than in the severe-FHV group (37% vs. 15%). The severe-FHV group had a fivefold higher risk of END (odds ratio [OR] 5.02, 95% confidence interval [CI] 1.36-18.45) and unfavorable outcome (OR 5.97, 95% CI 1.18-33.31, p=0.03) compared with the mild-FHV group. CONCLUSIONS: Greater FHV extent was associated with higher risk of END and unfavorable outcome in patients with LVO stroke of mild-to-moderate severity.

Relation of Pre-Stroke Aspirin Use With Cerebral Infarct Volume and Functional Outcomes.

OBJECTIVE: We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke. METHODS: This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use. RESULTS: The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score < 3), particularly in large artery atherosclerosis stroke and cardioembolic stroke (adjusted difference = 7.2%, 95% CI = 1.8 to 12.5 and adjusted difference = 6.4%, 95% CI = 1.7 to 11.1, respectively). Pre-stroke aspirin use (vs nonuse) was associated with 85% less frequent cerebral thrombus-related susceptibility vessel sign (SVS) in large artery atherosclerosis stroke (adjusted difference = -1.4%, 95% CI = -2.1 to -0.8, p < 0.001) and was associated with ~40% lower SVS volumes, particularly in cardioembolic stroke (adjusted difference = -0.16 cm3 , 95% CI = -0.29 to -0.02, p = 0.03). Moreover, pre-stroke aspirin use was not significantly associated with hemorrhagic transformation (adjusted difference = -1.1%, p = 0.09). INTERPRETATION: Pre-stroke aspirin use associates with improved functional independence in patients with first-ever ischemic large arterial stroke by reducing infarct volume and/or END, likely by decreasing thrombus burden, without increased risk of hemorrhagic transformation. ANN NEUROL 2021;90:763-776.

Platelet-Derived Growth Factor Is Associated with Progression of Symptomatic Intracranial Atherosclerotic Stenosis.

BACKGROUND AND PURPOSE: We aimed to determine the relationships of 33 biomarkers of inflammation, oxidation, and adipokines with the risk of progression of symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS: Fifty-two of 409 patients who participated in the TOSS-2 (Trial of Cilostazol in Symptomatic Intracranial Stenosis-2) showed progression of symptomatic ICAS in magnetic resonance angiography at 7 months after an index stroke. We randomly selected 20 patients with progression as well as 40 age- and sex-matched control patients. We serially collected blood samples at baseline, 1 month, and 7 months after an index stroke. Multiplex analysis of biomarkers was then performed. RESULTS: Demographic features and risk factors such as hypertension, diabetes, and smoking history were comparable between the two groups. Univariate analyses revealed that the levels of platelet-derived growth factor (PDGF)-AA [median (interquartile range)=1.64 (0.76-4.57) vs. 0.77 (0.51-1.71) ng/mL], PDGF-AB/BB [10.31 (2.60-25.90) vs. 2.35 (0.74-6.70) ng/mL], and myeloperoxidase [10.5 (7.5-22.3) vs. 7.8 (5.5-12.2) ng/mL] at 7 months were higher in the progression group. In the multivariate analysis using logistic regression, the PDGF AB/BB level at 7 months was independently associated with the progression of ICAS (p=0.02). CONCLUSIONS: The PDGF-AB/BB level is associated with the progression of ICAS, and so may play a significant role in the progression of human ICAS.

Total small vessel disease burden and functional outcome in patients with ischemic stroke.

BACKGROUND: Cerebral small vessel disease (SVD) is comprised of lacunes, cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and enlarged perivascular space (EPVS). We investigated the cumulative effect of SVD on 3-month functional outcome following ischemic stroke using the total SVD score. METHODS: The total SVD score of 477 acute ischemic stroke patients with adequate brain MRI was analyzed. We used multivariable ordinal logistic regression analysis to investigate the independent impact of total SVD score on ordinal modified Rankin Scale (mRS) score at 3-month after ischemic stroke. RESULTS: Mean age was 66±14 years, and 61% were men. The distribution of the total SVD score from 0 to 4 was 27%, 24%, 26%, 16%, and 7%, respectively. The proportion of mRS scores 2 or greater was 16% and 47% in total SVD score 0 and 4, respectively. Multivariable ordinal logistic regression analysis results showed that compared with the total SVD score of 0, total SVD scores of 2, 3, and 4 were independently associated with higher mRS scores with adjusted odds ratios (95% confidence intervals) of 1.68 (1.02-2.76), 2.24 (1.25-4.00), and 2.00 (1.02-4.29). Lacunes, CMBs, WMHs but not EPVS were associated with mRS scores at 3 months. However, the impact of each SVD marker on stroke outcome was smaller than that of the total SVD score. CONCLUSION: We found an independent association between total SVD scores and functional outcome at 3 months following ischemic stroke. The total SVD score may be useful for stratification of patients who are at a high-risk of unfavorable outcomes.

White matter hyperintensity load on stroke recurrence and mortality at 1 year after ischemic stroke.

OBJECTIVE: To define the role and risks associated with white matter hyperintensity (WMH) load in a stroke population with respect to recurrent stroke and mortality after ischemic stroke. METHODS: A total of 7,101 patients at a network of university hospitals presenting with ischemic strokes were followed up for 1 year. Multivariable Cox proportional hazards model and competing risk analysis were used to examine the independent association between quartiles of WMH load and stroke recurrence and mortality at 1 year. RESULTS: Overall recurrent stroke risk at 1 year was 6.7%/y, divided between 5.6%/y for recurrent ischemic and 0.5%/y for recurrent hemorrhagic strokes. There was a stronger association between WMH volume and recurrent hemorrhagic stroke by quartile (hazard ratio [HR] 7.32, 14.12, and 33.52, respectively) than for ischemic recurrence (HR 1.03, 1.37, and 1.61, respectively), but the absolute incidence of ischemic recurrence by quartile was higher (3.8%/y, 4.5%/y, 6.3%/y, and 8.2%/y by quartiles) vs hemorrhagic recurrence (0.1%/y, 0.4%/y, 0.6%/y, and 1.3%/y). All-cause mortality (10.5%) showed a marked association with WMH volume (HR 1.06, 1.46, and 1.60), but this was attributable to nonvascular rather than vascular causes. CONCLUSIONS: There is an association between WMH volume load and stroke recurrence, and this association is stronger for hemorrhagic than for ischemic stroke, although the absolute risk of ischemic recurrence remains higher. These data should be helpful to practitioners seeking to find the optimal preventive/treatment regimen for poststroke patients and to individualize risk-benefit ratios.

Association between electroencephalogram changes and plasma clozapine levels in clozapine-treated patients.

This retrospective observational study was performed to investigate electroencephalogram abnormalities in clozapine-treated patients with refractory schizophrenia or bipolar disorder. The electroencephalogram and plasma clozapine and norclozapine levels in 71 patients were measured on the same day. Fifty-nine patients (85.9%) had a diagnosis of schizophrenia, and 12 patients (14.1%) had a diagnosis of bipolar disorder. The mean daily clozapine dose was 242.9 ± 105.5 mg (range 25-500 mg), and the mean plasma clozapine and norclozapine levels were 429.4 ± 264.1 and 197.8 ± 132.6 ng/ml, respectively. Twenty-five patients (35.2%) were taking valproate in combination with clozapine. electroencephalogram abnormalities were found in 51 (71.8%) patients. No patient reported clinical seizures. Plasma clozapine level was significantly associated with electroencephalogram abnormalities and was identified as a significant predictor of electroencephalogram abnormalities in a logistic regression analysis. The plasma norclozapine levels of patients taking both clozapine and valproic acid were significantly lower than those of patients treated with clozapine alone. These results demonstrate that electroencephalogram abnormalities are closely correlated with plasma clozapine levels. Valproate reduced plasma norclozapine levels. Simultaneous monitoring of electroencephalogram and plasma clozapine levels was useful for adjusting clozapine doses, improving clinical efficacy, and preventing the side effects of clozapine treatment.

Estimation of Acute Infarct Volume with Reference Maps: A Simple Visual Tool for Decision Making in Thrombectomy Cases.

BACKGROUND AND PURPOSE: Thrombectomy within 24 hours can improve outcomes in selected patients with a clinical-infarct mismatch. We devised an easy-to-use visual estimation tool that allows infarct volume estimation in centers with limited resources. METHODS: We identified 1,031 patients with cardioembolic or large-artery atherosclerosis infarction on diffusion-weighted images (DWIs) obtained before recanalization therapy and within 24 hours of onset, and occlusion of the internal carotid or middle cerebral artery. Acute DWIs were mapped onto a standard template and used to create visual reference maps with known lesion volumes, which were then used in a validation study (with 130 cases) against software estimates of infarct volume. RESULTS: The DWI reference map chart comprises 144 maps corresponding to 12 different infarct volumes (0.5, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mL) in each of 12 template slices (Montreal Neurological Institute z-axis -15 to 51 mm). Infarct volume in a patient is estimated by selecting a slice with a similar infarct size at the corresponding z-axis level on the reference maps and then adding up over all slices. The method yielded good correlations to software volumetrics and was easily learned by both experienced and junior physicians, with approximately 1 to 2 minutes spent per case. The sensitivity, specificity, and accuracy for detecting threshold infarct volumes (<21, <31, and <51 mL) were very high (all about >90%). CONCLUSION: s We developed easy-to-use reference maps that allow prompt and reliable visual estimation of infarct volumes for triaging patients to thrombectomy in acute stroke.

Mapping the Supratentorial Cerebral Arterial Territories Using 1160 Large Artery Infarcts.

Importance: Cerebral vascular territories are of key clinical importance in patients with stroke, but available maps are highly variable and based on prior studies with small sample sizes. Objective: To update and improve the state of knowledge on the supratentorial vascular supply to the brain by using the natural experiment of large artery infarcts and to map out the variable anatomy of the anterior, middle, and posterior cerebral artery (ACA, MCA, and PCA) territories. Design, Setting, and Participants: In this cross-sectional study, digital maps of supratentorial infarcts were generated using diffusion-weighted magnetic resonance imaging (MRI) of 1160 patients with acute (<1-week) stroke recruited (May 2011 to February 2013) consecutively from 11 Korean stroke centers. All had supratentorial infarction associated with significant stenosis or occlusion of 1 of 3 large supratentorial cerebral arteries but with patent intracranial or extracranial carotid arteries. Data were analyzed between February 2016 and August 2017. Main Outcomes and Measures: The 3 vascular territories were mapped individually by affected vessel, generating 3 data sets for which infarct frequency is defined for each voxel in the data set. By mapping these 3 vascular territories collectively, we generated data sets showing the Certainty Index (CI) to reflect the likelihood of a voxel being a member of a specific vascular territory, calculated as either ACA, MCA, or PCA infarct frequency divided by total infarct frequency in that voxel. Results: Of the 1160 patients (mean [SD] age, 67.0 [13.3] years old), 623 were men (53.7%). When the cutoff CI was set as 90%, the volume of the MCA territory (approximately 54% of the supratentorial parenchymal brain volume) was about 4-fold bigger than the volumes of the ACA and PCA territories (each approximately 13%). Quantitative studies showed that the medial frontal gyrus, superior frontal gyrus, and anterior cingulate were involved mostly in ACA infarcts, whereas the middle frontal gyrus and caudate were involved mostly by MCA infarcts. The PCA infarct territory was smaller and narrower than traditionally shown. Border-zone maps could be defined by using either relative infarct frequencies or CI differences. Conclusions and Relevance: We have generated statistically rigorous maps to delineate territorial border zones and lines. The new topographic brain atlas can be used in clinical care and in research to objectively define the supratentorial arterial territories and their borders.

Hemispheric Asymmetry of White Matter Hyperintensity in Association With Lacunar Infarction.

Background White matter hyperintensities ( WMHs ) are commonly asymmetric between hemispheres but for unknown reasons. We investigated asymmetric WMHs associated with lacunar infarcts. Methods and Results A total of 267 consecutive patients with small first-ever supratentorial infarcts (≤20 mm) were included. None had a relevant vascular stenosis. WMH asymmetry was measured based on the hemispheric difference of a modified Scheltens scale score (≥3 defined as asymmetric). We analyzed the association of the hemispheric WMH asymmetry with old silent lacunar infarcts or acute lacunar infarcts. We compared lesion frequency maps between groups and generated t-statistics maps. The mean age of patients was 64 years, and 63% were men. Asymmetric WMH was more than 3-fold as frequent ( P<0.001) in the group with old silent lacunar infarcts (42%, 43/102) than in the group without old silent lacunar infarcts (15%, 24/165). In patients with left hemispheric dominance of WMHs , an acute lacunar infarct was more likely to be located in the left (versus right) hemisphere (74% versus 26%, P<0.001). In patients with right hemispheric dominance of WMHs , an acute lacunar infarct was more likely to be located on the right (versus left) hemisphere (81% versus 19%, P<0.001). Mapping studies showed that the side of hemispheric dominance of WMHs was associated with acute and silent lacunes on the same side. Conclusions These are the first data to show that asymmetric WMH s are associated with both old silent lacunar infarcts and acute lacunar infarcts ipsilateral to the greatest WMH burden. This suggests that the hemisphere with relatively large WMHs is more vulnerable to ischemia.

Increased Left Ventricular Filling Pressure and Arterial Occlusion in Stroke Related to Atrial Fibrillation.

BACKGROUND: We investigated whether left ventricular filling pressure is associated with arterial occlusion in patients with ischemic stroke related to atrial fibrillation (AF). METHODS: Ninety-nine patients with AF-related stroke were included. Left ventricular filling pressure was assessed by E (early mitral inflow velocity)/e' (early diastolic velocity of the mitral valve annulus velocity) ratio based on tissue Doppler echocardiography. Arterial occlusion was evaluated by computed tomography or magnetic resonance angiography. In addition, the presence of a hyperdense middle cerebral artery sign (HMCAS) on noncontrast brain computed tomography, a marker of acute thrombus burden, was assessed. Multiple logistic regression was used to evaluate the association of E/e' with arterial occlusion and the HMCAS. RESULTS: The mean age was 73.2 (±10.2), and 56% were men. Thirty-six (36.4%) patients had arterial occlusion on imaging. E/e' ratios were independently associated with arterial occlusion with an odds ratio of 1.24 (per 1 increase, 95% confidence interval 1.11-1.38). The receiver operating characteristics curve demonstrated that E/e' ratios have an excellent discriminatory capacity in predicting arterial occlusion with an area under the curve of .77 (P < .001). In addition, E/e' ratios were higher in patients with HMCAS than in those without (19.1 versus 14.0, P < .001). CONCLUSION: E/e' ratios were associated with arterial occlusion in AF-related stroke and may play a role in identifying patients at high risk of severe stroke.

Stroke outcomes are worse with larger leukoaraiosis volumes.

Leukoaraiosis or white matter hyperintensities are frequently observed on magnetic resonance imaging of stroke patients. We investigated how white matter hyperintensity volumes affect stroke outcomes, generally and by subtype. In total, 5035 acute ischaemic stroke patients were enrolled. Strokes were classified as large artery atherosclerosis, small vessel occlusion, or cardioembolism. White matter hyperintensity volumes were stratified into quintiles. Mean age (± standard deviation) was 66.3 ± 12.8, 59.6% male. Median (interquartile range) modified Rankin Scale score was 2 (1-3) at discharge and 1 (0-3) at 3 months; 16.5% experienced early neurological deterioration, and 3.3% recurrent stroke. The Cochran-Mantel-Haenszel test with adjustment for age, stroke severity, sex, and thrombolysis status showed that the distributions of 3-month modified Rankin Scale scores differed across white matter hyperintensity quintiles (P < 0.001). Multiple ordinal logistic regression analysis showed that higher white matter hyperintensity quintiles were independently associated with worse 3-month modified Rankin Scale scores; adjusted odds ratios (95% confidence interval) for the second to fifth quintiles versus the first quintile were 1.29 (1.10-1.52), 1.40 (1.18-1.66), 1.69 (1.42-2.02) and 2.03 (1.69-2.43), respectively. For large artery atherosclerosis (39.0%), outcomes varied by white matter hyperintensity volume (P = 0.01, Cochran-Mantel-Haenszel test), and the upper three white matter hyperintensity quintiles (versus the first quintile) had worse 3-month modified Rankin Scale scores; adjusted odds ratios were 1.45 (1.10-1.90), 1.86 (1.41-2.47), and 1.89 (1.41-2.54), respectively. Patients with large artery atherosclerosis were vulnerable to early neurological deterioration (19.4%), and the top two white matter hyperintensity quintiles were more vulnerable still: 23.5% and 22.3%. Moreover, higher white matter hyperintensities were associated with poor modified Rankin Scale improvement: adjusted odds ratios for the upper two quintiles versus the first quintile were 0.66 (0.47-0.94) and 0.62 (0.43-0.89), respectively. For small vessel occlusion (17.8%), outcomes tended to vary by white matter hyperintensitiy volume (P = 0.10, Cochran-Mantel-Haenszel test), and the highest quintile was associated with worse 3-month modified Rankin Scale scores: adjusted odds ratio for the fifth quintile versus first quintile, 1.98 (1.23-3.18). In this subtype, worse white matter hyperintensities were associated with worse National Institute of Health Stroke Scale scores at presentation. For cardioembolism (20.6%), outcomes did not vary significantly by white matter hyperintensity volume (P = 0.19, Cochran-Mantel-Haenszel test); however, the adjusted odds ratio for the highest versus lowest quintiles was 1.62 (1.09-2.40). Regardless of stroke subtype, white matter hyperintensities were not associated with stroke recurrence within 3 months of follow-up. In conclusion, white matter hyperintensity volume independently correlates with stroke outcomes in acute ischaemic stroke. There are some suggestions that stroke outcomes may be affected by leukoaraiosis differentially depending on stroke subtypes, to be confirmed in future investigations.

Grading and interpretation of white matter hyperintensities using statistical maps.

BACKGROUND AND PURPOSE: We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke. METHODS: We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.0 years) enrolled consecutively from 11 nationwide stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a standard brain template set. Using multivariable analyses, we assessed the impact of major (age/hypertension) and minor risk factors on WMH variability. RESULTS: We have produced a large reference data library showing the location and quantity of WMHs as topographical frequency-volume maps. This easy-to-use graphical reference data set allows the quantitative estimation of the severity of WMH as a percentile rank score. For all patients (median age=69 years), multivariable analysis showed that age, hypertension, atrial fibrillation, and left ventricular hypertrophy were independently associated with increasing WMH (0-9.4%, median=0.6%, of the measured brain volume). For younger (≤69) hypertensives (n=819), age and left ventricular hypertrophy were positively associated with WMH. For older (≥70) hypertensives (n=944), age and cholesterol had positive relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial fibrillation had negative relationships with WMH. For younger nonhypertensives (n=578), age and diabetes mellitus were positively related to WMH. For older nonhypertensives (n=328), only age was positively associated with WMH. CONCLUSIONS: We have generated a novel graphical WMH grading (Kim statistical WMH scoring) system, correlated to risk factors and adjusted for age/hypertension. Further studies are required to confirm whether the combined data set allows grading of WMH burden in individual patients and a tailored patient-specific interpretation in ischemic stroke-related clinical practice.

Complementarity between (18)F-FDG PET/CT and Ultrasonography or Angiography in Carotid Plaque Characterization.

BACKGROUND AND PURPOSE: To estimate clinical roles of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus angiography and ultrasonography in carotid plaque characterization. METHODS: We characterized two groups of patients with recently (<1 month) symptomatic (n=14; age=71.8±8.6 years, mean±SD) or chronic (n=13, age=68.9±9.0 years) carotid stenosis using a battery of imaging tests: diffusion magnetic resonance (MR) imaging, MR or transfemoral angiography, duplex ultrasonography (DUS), and carotid FDG-PET/computed tomography. RESULTS: The degree of angiographic stenosis was greater in patients with recently symptomatic carotid plaques (67.5±21.5%) than in patients with chronic carotid plaques (32.4±26.8%, p=0.001). Despite the significant difference in the degree of stenosis, lesional maximum standardized uptake values (maxSUVs) on the carotid FDG-PET did not differ between the recently symptomatic (1.56±0.53) and chronic (1.56±0.34, p=0.65) stenosis groups. However, lesional-to-contralesional maxSUV ratios were higher in the recently symptomatic stenosis group (113±17%) than in the chronic stenosis group (98±10%, p=0.017). The grayscale median value of the lesional DUS echodensities was lower in the recently symptomatic stenosis group (28.2±10.0, n=9) than in the chronic stenosis group (53.9±14.0, n=8; p=0.001). Overall, there were no significant correlations between angiographic stenosis, DUS echodensity, and FDG-PET maxSUV. Case/subgroup analyses suggested complementarity between imaging modalities. CONCLUSIONS: There were both correspondences and discrepancies between the carotid FDG-PET images and DUS or angiography data. Further studies are required to determine whether FDG-PET could improve the clinical management of carotid stenosis.

Association between changes in lipid profiles and progression of symptomatic intracranial atherosclerotic stenosis: a prospective multicenter study.

BACKGROUND AND PURPOSE: Predictors of progression of intracranial atherosclerotic stenosis have not been clearly identified. We investigated whether poststroke changes in lipid profiles would affect the prognosis of symptomatic intracranial atherosclerotic stenosis. METHODS: This is a substudy of Trial of cilOstazol in Symptomatic intracranial Stenosis 2 (TOSS-2). From 10 centers we enrolled 230 subjects with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or basilar artery. At baseline and 7 months after stroke, subjects underwent MR angiogram and assessment of cardiovascular risk factors including lipoprotein levels. Progression of intracranial atherosclerotic stenosis was determined by comparing stenosis on the baseline and follow-up MR angiograms. RESULTS: Cilostazol treatment was more frequently seen in the nonprogression group (109 of 198 [55.1%]) than in the progression group (11 of 32 [34.4%]). At 7 months after stroke when compared with baseline, low-density lipoprotein cholesterol and total cholesterol levels decreased in both groups. However, only nonprogressors showed increase in high-density lipoprotein cholesterol levels between baseline and follow-up. Changes in apolipoprotein B/apolipoprotein A-I levels were not different between the groups, although apolipoprotein B/A-I at 7 months was higher in progressors than in nonprogressors. Remnant lipoprotein cholesterol levels decreased in nonprogressors, whereas they did not change in progressors. In multivariable analyses, after adjusting for cilostazol treatment and remnant lipoprotein cholesterol reduction or apolipoprotein B/A-I at 7 months, high-density lipoprotein cholesterol elevation remained as a significant predictor for the nonprogression. CONCLUSIONS: This is the first prospective multicenter study to demonstrate that high-density lipoprotein cholesterol elevation, along with remnant lipoprotein cholesterol reduction and low apolipoprotein B/A-I, is associated with prevention of angiographic progression of symptomatic intracranial atherosclerotic stenosis. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00130039.