Association of CYP2C19 Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke.

BACKGROUND: CYP2C19variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect ofCYP2C19variants on clinical outcomes in the chronic phase.Methods and Results:In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according toCYP2C19genotype: extensive metabolizer (EM:*1/*1), intermediate metabolizer (IM:*1/*2or*1/*3), and poor metabolizer (PM:*2/*2,*2/*3, or*3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups. CONCLUSIONS: Despite associations betweenCYP2C19variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups ofCYP2C19variants.

Amyloid ß deposition in subcortical stroke patients and effects of educational achievement: A pilot study.

OBJECTIVE: A direct causal relationship of cerebrovascular risk factors/stroke to amyloid ß (Aß) deposition has yet to be shown. We conducted [11 C] Pittsburgh compound B (PiB)-positron emission tomography (PET) analysis on subacute ischemic stroke patients and healthy controls. We hypothesized that subacute ischemic stroke patients would show focal Aß accumulation in cortical regions, which would increase and extend over time during the chronic phase after stroke onset. METHODS: Patients were recruited 14 to 28 days after acute subcortical ischemic stroke and examined with [11 C]PiB-PET scans. Regional time-activity data were analyzed with the Logan graphical method. Whole brain voxel-based analysis was conducted to compare stroke patients with healthy controls. We also performed longitudinal comparison of patients with successive [11 C]PiB-PET scans 1 year after stroke. RESULTS: Voxel-based analysis revealed a significant increase of [11 C]PiB-BPND of the precuneus/posterior cingulate cortex (PCu/PCC) in stroke patients at the subacute stage. Based on stepwise multiple regression analysis of [11 C]PiB-BP changes during follow-up as the dependent variable, years of education was the best independent correlate. There was a significant negative relationship between changes in [11 C]PiB-BP and years of education. CONCLUSIONS: Our results suggest that processes before and after the onset of ischemic stroke may trigger Aß deposition in the PCu/PCC, whereby amyloid deposition begins at an early stage of Alzheimer's disease (AD). Our findings support the existence of a cooperative association between vascular risk factors/stroke and AD progression. Further, educational achievement had a protective effect against the increase in Aß accumulation.

Detection of brain amyloid-ß deposits due to the repetitive head trauma in a former karate player.

Head trauma is a well-established epidemiological risk factor for Alzheimer's disease, but a study of early detection of its pathology has not yet been performed in human patients in vivo. To address this issue, we performed 11 C-labelled Pittsburgh compound B-positron emission tomography on a right-handed 30-year-old man with cognitive deterioration after repetitive head trauma during karate matches. Structural magnetic resonance imaging was also performed on this patient. The same positron emission tomography analysis was performed on elderly healthy controls (15 men, mean age: 70.7 ± 6.2 years). To analyze grey matter volume, structural magnetic resonance imaging was performed on age-matched healthy controls (15 men, mean age: 28.5 ± 3.6 years). The cognitive deterioration in our patient was fixed and partially improved in the 10 years after the repetitive head trauma. However, Pittsburgh compound B-non-displaceable binding potential was significantly elevated in the patient. Volume reduction was shown in the medial temporal region, cerebellum, and the basal frontal cortex, while amyloid-ß increase was shown in the bilateral prefrontal cortex. This is the first study to show an early degenerative process due to head trauma in the prefrontal cortex, where structural damage is not yet visible. Early recognition of the degenerative pathology due to repetitive head trauma by amyloid and possibly tau imaging would help clinicians determine how to treat those with early symptoms.

Flip-Flop Phenomenon: Swallowing-Induced Arterial Displacement as an Indicator of Carotid Artery Disease.

BACKGROUND AND PURPOSE: The dynamic displacement of the carotid arteries with interference of the hyoid bone during swallowing, named as "flip-flop" phenomenon (FFP), may be associated with ischemic stroke. However, the extent to which FFP is prevalent in carotid artery disease remains unknown. We aimed to investigate its exact prevalence to explore the relationship between FFP and carotid artery disease. METHODS: We examined 202 consecutive patients who were affected by neurological diseases including cerebrovascular diseases. Using carotid ultrasound, we evaluated carotid intima-media thickness, internal carotid artery stenosis (ICS), and FFP during swallowing with neck rotation. RESULTS: FFP was observed in 39 of the 202 patients (19.3%). Patients with FFP showed significantly higher prevalence of ICS than those without FFP (12/39 [30.8] vs. 21/163 [12.9%]; p = 0.007). Among those with ICS (n = 33; 36 vessels), FFP was associated with symptomatic ICS more frequently than with asymptomatic ICS (6/11 [54.5] vs. 5/25 [20.0%]; p = 0.038). Among those with unilateral FFP (n = 37), the prevalence of ipsilateral ICS was higher than that of contralateral ICS (9/37 [24.3] vs. 2/37 [5.4%]; p = 0.035). CONCLUSIONS: FFP accompanies the swallowing movement in some neurological patients, and more frequently in patients with ICS. FFP may thus be a novel indicator of stroke.

Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study.

BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

Seasonal Variations in Neurological Severity and Outcomes of Ischemic Stroke　- 5-Year Single-Center Observational Study.

BACKGROUND: Seasonal variations in the severity and outcomes of stroke remain unclarified.Methods and Results:A total of 2,965 acute ischemic stroke patients from a single-center prospective registry were studied. Among the total patients, stroke onset did not vary by season, though it varied with a peak in winter when limited to patients >75 years old (P=0.026), when limited to patients with moderate-to-severe initial neurological deficits (National Institutes of Health Stroke Scale Score ≥10, P=0.014), and when limited to those with cardioembolic stroke (n=1,031, P=0.010). In 1,934 patients with noncardioembolic stroke, stroke onset did not vary by season. After multivariable adjustment, moderate-to-severe neurological deficits were more common in winter (odds ratio 1.37, 95% confidence interval 1.10-1.72) and spring (1.27, 1.01-1.60), and death at 1 year was more common in summer than in fall (1.55, 1.03-2.36); death or dependency (modified Rankin Scale score 3-6) and death or bedridden (score of 5-6) were not differently common among the seasons. CONCLUSIONS: Overall ischemic stroke showed a fairly even distribution among the 4 seasons. Cardioembolic stroke was more common in winter. Ischemic stroke patients had more moderate-to-severe initial neurological deficits in winter and spring. Poor clinical outcomes at 1 year were generally similar among the seasons. Ischemic stroke is not necessarily a winter-dominant disease.

Risk Factors for Nonconvulsive Status Epilepticus after Stroke.

BACKGROUND: Status epilepticus (SE) sometimes occurs after stroke. SE is classified as convulsive SE (CSE) and nonconvulsive SE (NCSE). Clinical characteristics, outcomes, mortality, and recurrences of post-stroke NCSE are yet to be clarified. METHODS: We retrospectively identified post-stroke SE patients between April 2010 and September 2015, with follow-ups continued until March 2016. We compared baseline clinical characteristics (age, sex, past history of epilepsy, early seizure, stroke type, and localization) between the CSE and NCSE groups. We determined the Glasgow Outcome Scale (GOS) at discharge, along with the mortality and seizure recurrence rates for the two groups. RESULTS: We identified 300 consecutive post-stroke seizure patients admitted to our department. A total of 50 post-stroke SE patients (33 men; mean age, 71.6 ± 14.2 years; 38 CSE; 12 NCSE; 20 ischemic strokes; 23 intracerebral hemorrhages; 7 subarachnoid hemorrhages) were included. Multivariable analysis showed that cardioembolic stroke and frontal lesion were significant risk factors of NCSE after stroke. GOS (Scale 1/2/3/4/5) results at patient discharge showed there was no significant difference between the groups (CSE; 8/26.3/18.4/26.3/21%, NCSE; 0/25/33/25/17%). Follow-up in 31 patients (21 CSE, 10 NCSE, median 815 days, interquartile range 538-1,327 days), revealed that seizure recurred in 15 CSE patients (71%) and in 4 NCSE patients (40%). During the follow-up, 3 CSE patients (14%) and 2 NCSE patients (20%) died. Seizure recurrence and mortality were not significantly different between the 2 groups. CONCLUSION: Cardioembolic stroke and frontal lesion were significant risk factors of NCSE after stroke.

Management of pregnancy complicated with intracranial arteriovenous malformation.

AIM: To clarify the perinatal outcomes in pregnancy complicated with intracranial arteriovenous malformation (i-AVM). METHODS: A retrospective study was performed in 36 pregnancies complicated by i-AVM from 1981 to 2013 at one institution. RESULTS: In total, 6 women miscarried, and 30 had live births. The median (range) gestational age at delivery was 38 (24-40) weeks; 11 cases experienced initial i-AVM rupture during pregnancy (first, second and third trimester: 18%, 64% and 18%, respectively). At onset, 4 cases had a Glasgow Coma Scale ≤10, 10 cases needed emergency maternal transport, 4 underwent neurosurgery with the fetus in utero and 4 had termination of pregnancy in the second trimester for emergent treatment for i-AVM. Two cases delivered vaginally. Another 25 cases had already been diagnosed as i-AVM at conception. Of these, as an indication for epidural birth, 18 cases had either residual lesion of i-AVM or neurological symptoms, although 18 cases had received treatments of i-AVM before conception. Without rupture of i-AVM and worsening of symptoms, 15 cases succeeded in epidural birth. One case was delivered by cesarean section for residual i-AVM with indication of treatment. Another case who had refused treatment of i-AVM experienced rupture of i-AVM 1 year after delivery. CONCLUSION: Most of the cases with residual i-AVM lesion and neurological symptoms could deliver vaginally without worsening of symptoms. However, pregnancy with i-AVM can be complicated by rupture of i-AVM. In cases with a residual lesion with indication of treatment and rupture of i-AVM during pregnancy, meticulous care is required during pregnancy and after delivery.

Urgent Detection of Acute Type A Aortic Dissection in Hyperacute Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Urgent diagnosis of acute Stanford type A aortic dissection (AAD) in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) is sometimes challenging. We assessed predictive values for markers of AAD in patients with AIS or TIA. METHODS: Consecutive patients with AIS or TIA with AAD who presented to our emergency room within 4.5 hours of symptom onset between 2007 and 2014 were compared with patients without AAD seen between 2012 and 2014. RESULTS: Data were obtained for 24 patients with AIS or TIA with AAD (15 women; mean age, 75 ± 12 years) and 812 patients without AAD (305 women; mean age, 73 ± 12 years). Compared with patients without AAD, patients with AAD displayed significantly higher systolic blood pressure (SBP) laterality (30 ± 20 mm Hg versus 12 ± 11 mm Hg), initial D-dimer concentration (median 38.1 µg/mL versus 1.3 µg/mL), and mediastinal width-to-chest width (M/C) ratio on x-ray (.35 ± .05 versus .29 ± .05), and more frequently showed common carotid artery (CCA) dissection on carotid ultrasonography (84% versus 1%) and pericardial effusion on echocardiography (43% versus 0%). Sensitivity and specificity to identify AAD were 80% and 75% for SBP laterality 17 mm Hg or greater; 100% and 86% for D-dimer concentration 4.1 µg/mL or greater; 75% and 76% for M/C ratio .32 or greater; 84% and 99% for CCA dissection; and 43% and 100% for pericardial effusion, respectively. CONCLUSIONS: High D-dimer level may provide the most reliable screening test for AAD in patients with AIS or TIA. CCA dissection on ultrasonography appears to represent the most disease-specific finding and shows acceptable sensitivity.

Detection of Left Ventricular Thrombus by Cardiac Magnetic Resonance in Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: We aimed to use contrast-enhanced cardiac magnetic resonance (CE-CMR) imaging to elucidate the prevalence of left ventricular (LV) thrombus in patients suspected of embolic stroke of undetermined source (ESUS) with previous myocardial infarction or LV dysfunction (LV ejection fraction [LVEF] <50%). METHODS: We prospectively investigated 797 consecutive patients who presented to our hospital with acute ischemic stroke between 2014 and 2015. Patients with myocardial infarction or LVEF<50% underwent CE-CMR imaging. ESUS was diagnosed according to proposal criteria based on transthoracic echocardiography findings. RESULTS: The prevalence of ESUS was 22% (178 of 797) on initial diagnosis. Among 60 patients with myocardial infarction or LVEF<50%, the stroke subtypes were as follows: small artery disease, 17% (10 of 60); large artery atherosclerosis, 5% (3 of 60); cardioembolic stroke, 49% (29 of 60); ESUS, 23% (14 of 60); and undetermined causes other than ESUS, 6% (4 of 60). Of 60 patients examined via CE-CMR, LV thrombus was confirmed in 12 patients, whereas only 1 had been detected on transthoracic echocardiography (P=0.04). Importantly, 29% (4 of 14) of patients with ESUS had LV thrombus. A prediction model based on CE-CMR findings showed higher performance in LV thrombus detection, permitting a net improvement of 0.46 (95% confidence interval, 0.08-0.82; P=0.016) in cardioembolic stroke reclassification. Compared with patients without LV thrombus, those with LV thrombus had lower LVEF (median: 26% versus 40%; P=0.003). Notably, 42% (5 of 12) of patients with LV thrombus had LVEF≥30%. CONCLUSIONS: When ESUS-suspected patients have myocardial infarction or LV dysfunction, CE-CMR may help improve detection of cardioembolic stroke and provide relevant information for anticoagulation therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665.

A Novel Evaluation for Predicting Aortic Complicated Lesions Using Calcification on Chest X-ray.

BACKGROUND: The aorta is a significant source of cerebral thromboembolisms. Aortic complicated lesions (ACLs) are key findings on transesophageal echocardiography (TEE) for assessing aortic sources of emboli to the brain. TEE is sometimes avoided due to its invasiveness. However, few reports have examined alternative methods for predicting ACLs. We investigated relationships between aortic arch calcification (AAC) on chest X-ray and ACLs. METHODS: Participants comprised 300 patients with acute ischemic stroke or transient ischemic attack who underwent TEE for the evaluation of the aortic arch and heart. A postero-anterior plain chest X-ray in the recumbent position was evaluated on admission for each patient. AAC was evaluated using 4 grades (0-3) and "AAC thickness" defined as the distance from the inner margin of the most distant AAC to the outer margin of the aortic vessel wall. ACLs were defined by intima-media thickness (IMT) ≥4.0 mm or presence of ulcerated or mobile plaques. Carotid maximum IMT on ultrasonography was also evaluated. Comparison of the diagnostic ability to predict ACL was performed between AAC grades and AAC thickness or AAC thickness and carotid maximum IMT using the Delong method. RESULTS: ACLs were identified in 71 patients (23.7%), including ACLs with ulcerated plaques in 24 (8.0%) and ACLs with mobile plaques in 9 (3.0%). Plaque thickness was greater in higher AAC grades or higher quartiles of AAC thickness (p for trend <0.001 each). The Cochran-Armitage test showed that both higher AAC grade and higher quartile of AAC thickness were significantly associated with the presence of ACLs, as well as the presence of ulcerated or mobile plaques (p for trend < 0.001 each). Receiver-operating characteristic (ROC) analysis showed optimal cut-off values for AAC thickness of 5.6 mm for ACLs and 6.0 mm for ulcerated or mobile plaques. Multivariate logistic regression revealed a higher grade of AAC (grades 2-3) and AAC thickness (≥6 mm) as significantly associated with ACLs and ulcerated or mobile plaques (p < 0.001 each). ROC curve comparisons showed that AAC thickness offered a better marker of ACLs than AAC grade (p = 0.019), although no significant difference was evident between AAC thickness and carotid maximum IMT (p = 0.567). CONCLUSIONS: AAC on chest X-ray, evaluated by both AAC grade and AAC thickness to the outer aortic vessel wall, was significantly associated with ACLs on TEE. AAC thickness was suggested as more useful than AAC grade and equivalent to carotid IMT in predicting ACLs.

Mutual effect of cerebral amyloid ß and peripheral lymphocytes in cognitively normal older individuals.

OBJECTIVE: We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre-dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro-inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects. METHODS: We applied [11 C] Pittsburgh compound B (PiB)-positron emission tomography to 36 cognitively normal older individuals, and Aß deposition was quantified by cortical binding potential (PiB-BPND ). Blood samples were obtained, and lymphocyte subsets were evaluated. We examined differences between low and high PiB-BPND groups in the percentage of B cells, T cells, helper T cells, cytotoxic T cells, regulatory T cells, and natural killer cells. RESULTS: Subjects with high PiB-BPND showed significantly higher percentage of cytotoxic T cells (%CD3+ ). Correlation analysis revealed a significant relationship between the percentage of cytotoxic T cells and global cortical mean PiB-BPND . Hierarchical regression analyses showed that cytotoxic T cells were significantly related to the value of global cortical mean PiB-BPND and vice versa. CONCLUSIONS: Our results indicated that a specific peripheral immune response, reflected in the increased ratio of cytotoxic T cells, could be regarded as a preclinical sign of AD and could be attributed to the Aß neuropathological mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

A novel mouse model of subcortical infarcts with dementia.

Subcortical white matter (WM) is a frequent target of ischemic injury and extensive WM lesions are important substrates of vascular cognitive impairment (VCI) in humans. However, ischemic stroke rodent models have been shown to mainly induce cerebral infarcts in the gray matter, while cerebral hypoperfusion models show only WM rarefaction without infarcts. The lack of animal models consistently replicating WM infarct damage may partially explain why many neuroprotective drugs for ischemic stroke or VCI have failed clinically, despite earlier success in preclinical experiments. Here, we report a novel animal model of WM infarct damage with cognitive impairment can be generated by surgical implantation of different devices to the right and left common carotid artery (CCA) in C57BL/6J mice. Implantation of an ameroid constrictor to the right CCA resulted in gradual occlusion of the vessel over 28 d, whereas placement of a microcoil to the left CCA induced ∼50% arterial stenosis. Arterial spin labeling showed a gradual reduction of cerebral blood flow over 28 d post operation. Such reductions were more marked in the right, compared with the left, hemisphere and in subcortical, rather than the cortical, areas. Histopathological analysis showed multiple infarct damage in right subcortical regions, including the corpus callosum, internal capsule, hippocampal fimbria, and caudoputamen, in 81% of mice. Mice displaying such damage performed significantly poorer in locomotor and cognitive tests. The current mouse model replicates the phenotypes of human subcortical VCI, including multiple WM infarcts with motor and cognitive impairment.

Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism.

BACKGROUND: Coronary artery embolism (CE) is recognized as an important nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical features, and prognosis remain insufficiently characterized. METHODS AND RESULTS: We screened 1776 consecutive patients who presented with de novo acute myocardial infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing histological, angiographic, and other diagnostic imaging findings. The prevalence, clinical characteristics, treatment strategies, in-hospital outcomes, and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and the median international normalized ratio was 1.42 (range, 0.95-1.80). Eighteen of the 30 CE patients with nonvalvular atrial fibrillation had a CHADS2 score of 0 or 1. When those patients were reevaluated using CHA2DS2-VASc, 61% were reassigned to a higher risk category. During a median follow-up of 49 months, CE and thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of major adverse cardiac and cerebrovascular events was 27.1%. In the propensity score-matched cohorts (n=45 each), Kaplan-Meier analysis showed a significantly higher incidence of cardiac death in the CE group than in the non-CE group (hazard ratio, 9.29; 95% confidence interval, 1.13-76.5; P<0.001). CONCLUSIONS: Atrial fibrillation is the most frequent cause of CE. Patients with CE represent a high-risk subgroup of patients with acute myocardial infarction and require close follow-up.

Histopathologic Analysis of Retrieved Thrombi Associated With Successful Reperfusion After Acute Stroke Thrombectomy.

BACKGROUND AND PURPOSE: Histopathologic evaluation of occlusive thrombi retrieved from cerebral arteries using endovascular therapy is possible. We investigated the relationship between successful reperfusion after thrombectomy and histopathologic characteristics of retrieved thrombi. METHODS: Among consecutive patients with acute ischemic stroke treated with endovascular therapy at our institute from December 2010 to July 2015, we retrospectively reviewed those with acute major arterial occlusion from which retrieved thrombi were evaluated histopathologically. Obtained thrombi were assessed for the existence of atheromatous gruel, organization, and the ratios of erythrocyte and fibrin/platelet components. Successful reperfusion was defined as the modified Treatment in Cerebral Ischemia grade of 2b to 3. RESULTS: Of 83 patients studied, 58 (70%) underwent successful reperfusion. Atheromatous gruel was less frequently identified (3% versus 20%; P=0.024), and the proportion of erythrocyte components was higher (57±23% versus 47±24%; P=0.042) in thrombi retrieved from the reperfused than the unreperfused group. On multivariate logistic regression analysis, atheromatous gruel was inversely related (odds ratio, 0.062; 95% confidence interval, 0.002-0.864), and >64% erythrocyte components (cutoff obtained from receiver operating characteristic curve) were positively related (odds ratio, 4.352; 95% confidence interval, 1.185-19.363) to successful reperfusion. CONCLUSIONS: Successful reperfusion could be associated with the histopathology of occlusive thrombi, including the existence of atheromatous gruel and proportion of erythrocyte components. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665.

Frequency and Detection of Stanford Type A Aortic Dissection in Hyperacute Stroke Management.

BACKGROUND AND PURPOSE: Acute Stanford type A aortic dissection (AAD) is a devastating aortic disease, and prompt diagnosis is sometimes difficult to make. Identification of AAD in suspected acute stroke patients is especially challenging. Nevertheless, the frequencies and predictive factors of AAD in suspected acute stroke patients have not been well investigated. The aim of this study was to elucidate the prevalence of and predictors for AAD in patients with suspected acute stroke. METHODS: From January 2012 through January 2013, consecutive patients who visited our emergency department (ED) due to suspected acute (<24 h from onset) stroke were retrospectively enrolled. Clinical parameters including systolic blood pressure (SBP) and laboratory data were collected. Frequency of AAD in suspected acute stroke patients and acute ischemic stroke (AIS) subjects were assessed, and factors associated with AAD among AIS patients were investigated. RESULTS: A total of 1,637 patients were included in this study. Five patients (0.31%, 95% CI 0.04-0.57) were diagnosed as having AAD. The prevalence of AAD in all AIS individuals during the study period was 1.09% (95% CI 0.14-2.05), and AAD accounted for 1.70% (95% CI 0.05-3.36) of AIS patients who appeared at the hospital within 4 h from onset. Most AAD patients presented with disturbed consciousness, and none of the AAD patients complained of chest pain. Neck ultrasonography detected an intimal flap in AAD patients. Two AAD cases died soon after ED arrival. The remaining 3 were promptly diagnosed as having AAD in the ED and underwent emergency surgery; all were discharged with only mild neurological symptoms. Low SBP in the right arm (cut-off value ≤110 mm Hg, sensitivity 100%, specificity 94.4%) and high D-dimer level (cut-off value ≥5.0 µg/ml, sensitivity 100%, specificity 91.7%) had high predictive values for detecting AAD in patients with AIS presenting within 4 h from onset. CONCLUSIONS: AAD was seen in 0.31% of suspected acute stroke patients and 1.70% of AIS patients presenting within 4 h from onset. AAD patients who were initially suspected as having acute stroke had severe neurological symptoms, including disturbance of consciousness, did not complain of typical chest pain, and when emergency surgery was performed, favorable neurological and survival outcomes were achieved. Low SBP in the right arm and high D-dimer level could predict AAD.

High amyloid-ß deposition related to depressive symptoms in older individuals with normal cognition: a pilot study.

OBJECTIVE: Previous studies have reported depressive symptoms in the preclinical stages of Alzheimer's disease (AD). The objective of this study was to determine whether depressive symptoms are associated with cortical amyloid burden. In order to do this, we measured cortical amyloid via (11) C-labeled Pittsburgh Compound B ([(11) C]PIB) uptake using positron emission tomography (PET) in cognitively normal subjects. METHODS: We performed [(11) C]PIB-PET in 29 cognitively normal, older participants. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS). Aß deposition was quantified by binding potential (BPND ), and the association between cortical mean BPND values and GDS scores was evaluated. Analysis of parametric BPND images was performed to examine the relationship between regional BPND and GDS scores. RESULTS: We found a positive correlation between depressive symptoms and mean cortical PIB-BPND in groups of subjects with middle to high PIB-BPND . There was little change in GDS-depression score between subjects with low and middle PIB-BPND levels, while an increase in GDS was shown in the high PIB-BPND group. The main BPND increase was localized to the precuneus/posterior cingulate cortex (PCu/PCC) in subjects with high PIB-BPND , and we found a significant positive relationship between PIB-BPND in this area and depressive symptoms. CONCLUSIONS: Emotional dysregulation because of Aß neuropathology in the PCu/PCC may relate to depressive symptoms. More specifically, we found that older, cognitively normal patients with depressive episodes were more likely to have underlying AD pathology. Thus, depressive symptoms may increase the predictive ability of the identification of future AD cases. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was not uncommon and was associated with more frequent adverse events including major bleeding in NVAF patients with anticoagulation therapy. CHADS2, CHA2DS2-VASc, and HAS-BLED scores may be useful as an index of predicting renal function deterioration.

How Commonly Is Stroke Found in Patients with Isolated Vertigo or Dizziness Attack?

BACKGROUND: The sudden development of vertigo or dizziness without focal neurological symptoms is generally attributable to vestibular diseases such as benign paroxysmal positional vertigo. Isolated vertigo or dizziness attack needs more attention than vestibular diseases. This retrospective study was performed to elucidate the frequency of strokes in patients with isolated vertigo or dizziness attack. SUBJECTS AND METHODS: We enrolled 221 patients (men, 119; women, 102; mean age, 68.4 ± 10.3 years) who were admitted to our hospital over the last 10 years because of sudden isolated vertigo or dizziness attack without other neurological symptoms except for nystagmus, deafness, or tinnitus. We investigated the clinical features, final diagnosis, neuroimaging findings, and short- or long-term outcome of these patients. RESULTS: One hundred eighteen patients had vertigo whereas the other 103 had dizziness. Brain computed tomography or magnetic resonance imaging revealed recent stroke lesions in 25 patients (11.3%) (ischemic, 21; hemorrhagic, 4).The lesions were generally small and localized in the cerebellum (n = 21), pons (n = 1), medulla oblongata (n = 1), or corona radiata (n = 1). Of the 25 patients, 19 (76%) had dizzy-type spells; none had neurological dysfunction at the time of discharge. In the remaining 196 patients, no stroke was detected on computed tomography or magnetic resonance imaging. CONCLUSIONS: Stroke was found in 11% of patients with isolated vertigo or dizziness attack. The posterior inferior cerebellar artery area was the most frequently implicated for isolated vertigo or dizziness.

Peak Systolic Velocity Measured by Continuous-Wave Doppler Ultrasonography without Angle Correction in Patients with Internal Carotid Artery Stenosis.

BACKGROUND: Peak systolic velocity (PSV) is measured with pulse-wave (PW) Doppler with angle correction in patients with internal carotid artery stenosis (ICAS). However, the correlation between conventional angiography and PSV shows considerable scattering. We hypothesized that measuring PSV without angle correction would lead to better inter-rater reliability. This hypothesis was tested using a sector probe and continuous-wave (CW) Doppler without angle correction. METHODS: Consecutive patients with more than 50% ICAS were enrolled from a prospective database. PSV was measured with PW Doppler with angle correction (PW PSV) and CW Doppler without angle correction (CW PSV) by 2 examiners. The inter-rater reliabilities of PW PSV and CW PSV were analyzed by Spearman's rank correlation test. RESULTS: A total of 37 ICAS sites (median 67 [interquartile range 57-78] % stenosis) were enrolled. Measuring PSV using a sector probe insonating nearly parallel to the flow was feasible in all cases. Inter-rater reproducibility of CW PSV (Spearman's ρ = .810) was similar to that of PW PSV (Spearman's ρ = .796). When limited to patients with a PSV greater than 200 cm/s with both PW Doppler examinations (25 ICAS sites), inter-rater reliability was relatively higher for CW PSV (Spearman's ρ = .674) than for PW PSV (Spearman's ρ = .423). CONCLUSIONS: Measuring PSV with CW Doppler using a sector probe was feasible. Inter-rater reliability was similar between PW Doppler with angle correction and CW Doppler without angle correction in evaluating PSV in patients with ICAS. CW Doppler appears to have better inter-rater reproducibility than PW Doppler in assessing high PSV.