Publications by authors named "Shuhei Okazaki"

62 Publications

Regional Differences in the Response to Acute Blood Pressure Lowering After Cerebral Hemorrhage.

Neurology 2021 02 20;96(5):e740-e751. Epub 2020 Nov 20.

From the Department of Cerebrovascular Medicine (K. Toyoda, M.K., S.Y., K. Tanaka, K.M.), Center for Advancing Clinical and Translational Sciences (H.Y., M.F.-D., S.O.), and Department of Neurology (M.I.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Public Health Sciences (Y.Y.P., L.F.), Medical University of South Carolina, Charleston; Department of Neurology (Y.H.), St. Marianna University School of Medicine, Kawasaki; Department of Neurosurgery and Stroke Center (Y.S.), Kyorin University School of Medicine, Mitaka; Department of Neurosurgery (T.I.), Gifu University Graduate School of Medicine; Department of Neurosurgery (K.K.), Nakamura Memorial Hospital, Sapporo; Department of Neurology (H.H.), Tokyo Saiseikai Central Hospital, Japan; Department of Neurology (T.S.), Klinikum Frankfurt Höchst, Germany; Department of Neurology (B.-W.Y.), Seoul National University Hospital, South Korea; Beijing Tiantan Hospital (Y.W.), China; China Medical University (C.Y.H.), Taichung, Taiwan; and Zeenat Qureshi Stroke Research Center (A.I.Q.), University of Minnesota, Minneapolis.

Objective: To compare the impact of intensive blood pressure (BP) lowering right after intracerebral hemorrhage (ICH) on clinical and hematoma outcomes among patients from different geographic locations, we performed a prespecified subanalysis of a randomized, multinational, 2-group, open-label trial to determine the efficacy of rapidly lowering BP in hyperacute ICH (Antihypertensive Treatment of Acute Cerebral Hemorrhage [ATACH]-2), involving 537 patients from East Asia and 463 recruited outside of Asia.

Methods: Eligible patients were randomly assigned to a systolic BP target of 110 to 139 mm Hg (intensive treatment) or 140 to 179 mm Hg (standard treatment). Predefined outcomes were poor functional outcome (modified Rankin Scale score 4-6 at 90 days), death within 90 days, hematoma expansion at 24 hours, and cardiorenal adverse events within 7 days.

Results: Poor functional outcomes (32.0% vs 45.9%), death (1.9% vs 13.3%), and cardiorenal adverse events (3.9% vs 11.2%) occurred significantly less frequently in patients from Asia than those outside of Asia. The treatment-by-cohort interaction was not significant for any outcomes. Only patients from Asia showed a lower incidence of hematoma expansion with intensive treatment (adjusted relative risk [RR] 0.56, 95% confidence interval [CI] 0.38-0.83). Both Asian (RR 3.53, 95% CI 1.28-9.64) and non-Asian (RR 1.71, 95% CI 1.00-2.93) cohorts showed a higher incidence of cardiorenal adverse events with intensive treatment.

Conclusions: Poor functional outcomes and death 90 days after ICH were less common in patients from East Asia than those outside of Asia. Hematoma expansion, a potential predictor for poor clinical outcome, was attenuated by intensive BP lowering only in the Asian cohort.

Clinicaltrialsgov Identifier: NCT01176565.

Classification Of Evidence: This study provides Class II evidence that, for patients from East Asia with ICH, intensive blood pressure lowering significantly reduces the risk of hematoma expansion.
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http://dx.doi.org/10.1212/WNL.0000000000011229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884997PMC
February 2021

CREB Coactivator CRTC2 Plays a Crucial Role in Endothelial Function.

J Neurosci 2020 12 30;40(49):9533-9546. Epub 2020 Oct 30.

Department of Neurology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.

The cAMP pathway is known to stabilize endothelial barrier function and maintain vascular physiology. The family of cAMP-response element binding (CREB)-regulated transcription coactivators (CRTC)1-3 activate transcription by targeting the basic leucine zipper domain of CREB. CRTC2 is a master regulator of glucose metabolism in liver and adipose tissue. However, the role of CRTC2 in endothelium remains unknown. The aim of this study was to evaluate the effect of CRTC2 on endothelial function. We focused the effect of CRTC2 in endothelial cells and its relationship with p190RhoGAP-A. We examined the effect of CRTC2 on endothelial function using a mouse aorta ring assay and with photothrombotic stroke in endothelial cell-specific CRTC2-knock-out male mice CRTC2 was highly expressed in endothelial cells and related to angiogenesis. Among CRTC1-3, only CRTC2 was activated under ischemic conditions at endothelial cells, and CRTC2 maintained endothelial barrier function through p190RhoGAP-A expression. Ser was a pivotal regulatory site for CRTC2 intracellular localization, and Ser functioned as a crucial phosphorylation site. Endothelial cell-specific CRTC2-knock-out mice showed reduced angiogenesis , exacerbated stroke via endothelial dysfunction, and impaired neurologic recovery via reduced vascular beds These findings suggest that CRTC2 plays a crucial protective role in vascular integrity of the endothelium via p190RhoGAP-A under ischemic conditions. Previously, the role of CRTC2 in endothelial cells was unknown. In this study, we firstly clarified that CRTC2 was expressed in endothelial cells and among CRTC1-3, only CRTC2 was related to endothelial function. Most importantly, only CRTC2 was activated under ischemic conditions at endothelial cells and maintained endothelial barrier function through p190RhoGAP-A expression. Ser in CRTC2 functioned as a crucial phosphorylation site. Endothelial cell-specific CRTC2-knock-out mice showed reduced angiogenesis , exacerbated stroke via endothelial dysfunction, and impaired neurologic recovery via reduced vascular beds These results suggested that CRTC2 maybe a potential therapeutic target for reducing blood-brain barrier (BBB) damage and improving recovery.
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http://dx.doi.org/10.1523/JNEUROSCI.0407-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724130PMC
December 2020

Mechanical thrombectomy in acute ischemic stroke patients with left ventricular assist device.

J Neurol Sci 2020 Nov 17;418:117142. Epub 2020 Sep 17.

Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address:

Objectives: As the number of patients with left ventricular assist device (LVAD) implantation has been increasing, treatment of LVAD-related ischemic stroke is becoming a critical issue. We sought to clarify the features of mechanical thrombectomy in LVAD-related stroke with large vessel occlusion.

Methods: In a multi-center, retrospective case-control study, we compared 20 LVAD-related strokes with 33 non-LVAD strokes, all of which had large vessel occlusion in the anterior circulation treated with mechanical thrombectomy. A comparative histopathological examination of the retrieved thrombi was also performed.

Results: Successful reperfusion was achieved in 75% of the LVAD-related strokes. The time from onset to reperfusion was similar to that of non-LVAD strokes, but the total number of device passes required for reperfusion (median, 2.5 versus 1, P = 0.01) and the incidences of post-procedural parenchymal and subarachnoid hemorrhage (25% versus 3%, P = 0.02 and 55% versus 15%, P = 0.01, respectively) were higher in LVAD-related strokes. Symptomatic intracranial hemorrhage occurred in 4 patients (20%) with LVAD-related strokes. The histopathological analysis revealed that the ratio of erythrocyte components was significantly lower in thrombi retrieved from patients with LVAD-related stroke than in those with non-LVAD stroke (19 ± 6% versus 41 ± 17%, P = 0.01).

Conclusions: Mechanical thrombectomy is feasible in patients with LVAD-related stroke. However, repetitive device passes are needed to achieve successful reperfusion mainly because of the structurally organized thrombi, and the higher risk of hemorrhagic complications should be considered, while offering this therapeutic alternative.
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http://dx.doi.org/10.1016/j.jns.2020.117142DOI Listing
November 2020

Sex Differences in Blood Pressure-Lowering Therapy and Outcomes Following Intracerebral Hemorrhage: Results From ATACH-2.

Stroke 2020 08 6;51(8):2282-2286. Epub 2020 Jul 6.

Department of Cerebrovascular Medicine (M.F.-D., M.K., S.Y., K.M., K.T.), National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Purpose: Evidence regarding sex differences in clinical outcomes and treatment effect following intracerebral hemorrhage is limited. Using the ATACH-2 trial (Antihypertensive Treatment in Intracerebral Hemorrhage-2) data, we explored whether sex disparities exist in outcomes and response to intensive blood pressure (BP)-lowering therapy.

Methods: Eligible intracerebral hemorrhage subjects were randomly assigned to intensive (target systolic BP, 110-139 mm Hg) or standard (140-179 mm Hg) BP-lowering therapy within 4.5 hours after onset. Relative risk of death or disability corresponding to the modified Rankin Scale score of 4 to 6 was calculated, and interaction between sex and treatment was explored.

Results: In total, 380 women and 620 men were included. Women were older, more prescribed antihypertensive drugs before onset, and had more lobar intracerebral hemorrhage than men. Hematoma expansion was observed less in women. After multivariable adjustment, the relative risk of death or disability in women was 1.19 (95% CI, 1.02-1.37, =0.023). The relative risk of death or disability between intensive versus standard BP-lowering therapy was 0.91 (95% CI, 0.74-1.13) in women versus 1.13 (95% CI, 0.92-1.39) in men ( for interaction=0.11), with inconclusive Gail-Simmon test (=0.16).

Conclusions: Women had a higher risk of death or disability following intracerebral hemorrhage. The benefit of intensive BP-lowering therapy in women is inconclusive, consistent with the overall results of ATACH-2. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565.
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http://dx.doi.org/10.1161/STROKEAHA.120.029770DOI Listing
August 2020

The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale.

Gerontology 2020 1;66(5):447-459. Epub 2020 Jul 1.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria,

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, -ankle-brachial index, pulse wave velocity, and coronary -artery calcium. The Prospective Studies of Atherosclerosis -(Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences.
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http://dx.doi.org/10.1159/000508498DOI Listing
July 2020

Prevalence and Atypical Clinical Characteristics of Mutations Among Patients Admitted for Acute Lacunar Infarctions.

Front Aging Neurosci 2020 14;12:130. Epub 2020 May 14.

Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary small vessel disease, with reported frequencies of 2-5/100,000 individuals. Recently, it has been reported that some patients with gene mutations show atypical clinical symptoms of CADASIL. Assuming that CADASIL is underdiagnosed in some cases of lacunar infarction, this study was designed to examine the prevalence of gene mutations in the patients at highest risk who were admitted for lacunar infarctions. From January 2011 to April 2018, 1,094 patients with lacunar infarctions were admitted to our hospital, of whom 31 patients without hypertension but with white matter disease (Fazekas scale 2 or 3) were selected and genetically analyzed for gene mutations (Phase 1). Furthermore, 54 patients, who were 60 years or younger, were analyzed for mutations (Phase 2). exons 2-24, which encode the epidermal growth factor-like repeat domain of the receptor, were analyzed for mutations by direct sequencing of genomic DNA. Three patients presented p.R75P mutations: two in the Phase 1 and one in the Phase 2 cohort. Among patients aged 60 years or younger and those without hypertension but with moderate-to-severe white matter lesions, the carrier frequency of p.R75P was 3.5% (3/85), which was significantly higher than that in the Japanese general population (4.7KJPN) (odds ratio [95% CI] = 58.2 [11.6-292.5]). All three patients with mutations had family histories of stroke, and the average patient age was 51.3 years. All three patients also showed white matter lesions in the external capsule but not in the temporal pole. The CADASIL and CADASIL scale-J scores of the three patients were 6, 17, 7 (mean, 10.0) and 13, 20, 10 (mean, 14.3), respectively. Among patients hospitalized for lacunar infarctions, the p.R75P prevalence may be higher than previously estimated. The p.R75P mutation may be underdiagnosed in patients with early-onset lacunar infarctions due to the atypical clinical and neuroimaging features of CADASIL. Early-onset, presence of family history of stroke, external capsule lesions, and absence of hypertension may help predict underlying mutations despite no temporal white matter lesions.
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http://dx.doi.org/10.3389/fnagi.2020.00130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240022PMC
May 2020

The Effect of Chemotherapy on Stroke Risk in Cancer Patients.

Thromb Haemost 2020 Apr 14;120(4):714-723. Epub 2020 Apr 14.

Department of Neurology, Graduate School of Medicine, Osaka University, Osaka, Japan.

Background:  Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We investigated how chemotherapy affects stroke risk in cancer patients.

Methods:  Of 27,932 patients in a hospital-based cancer registry (which contains clinical data on all patients treated for cancer at Osaka University Hospital) screened between 2007 and 2015, medical records of 19,006 patients with complete data were investigated. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression.

Results:  Of 19,006 patients, 5,887 (31%) were in the chemotherapy group. Stroke occurred in 44 (0.75%) and 51 (0.39%) patients in the chemotherapy and nonchemotherapy group, respectively. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than those in the nonchemotherapy group (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.75). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03).

Conclusion:  In our study, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.
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http://dx.doi.org/10.1055/s-0040-1708484DOI Listing
April 2020

Late Neurological Deterioration after Acute Intracerebral Hemorrhage: A post hoc Analysis of the ATACH-2 Trial.

Cerebrovasc Dis 2020 11;49(1):26-31. Epub 2020 Feb 11.

Department of Neurology, University of Missouri, Columbia, Missouri, USA.

Background: Neurological deterioration (ND) has a major influence on the prognosis of intracerebral hemorrhage (ICH); however, factors associated with ND occurring after 24 h of ICH onset are unknown.

Methods: We performed exploratory analyses of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial, which compared intensive and standard blood pressure lowering treatment in ICH. NDs were captured on the adverse event case report form. Logistic regression analysis was performed to examine the independent predictors of late ND.

Results: Among 1,000 participants with acute ICH, 82 patients (8.2%) developed early ND (≤24 h), and 64 (6.4%) had late ND. Baseline hematoma volume (adjusted OR [aOR] per 1-cm3 increase 1.04, 95% CI 1.02-1.06, p < 0.0001), hematoma volume increase in 24 h (aOR 2.24, 95% CI 1.23-4.07, p = 0.008), and the presence of intraventricular hemorrhage (IVH; aOR 2.38, 95% CI 1.32-4.29, p = 0.004) were independent predictors of late ND (vs. no late ND). Late ND was a significant risk factor for poor 90-day outcome (OR 3.46, 95% CI 1.82-6.56). No statistically significant difference in the incidence of late ND was noted between the 2 treatment groups.

Conclusions: Initial hematoma volume, early hematoma volume expansion, and IVH are independent predictors of late ND after ICH. Intensive reduction in the systolic blood pressure level does not prevent the development of late ND.
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http://dx.doi.org/10.1159/000506117DOI Listing
September 2020

Frequent Premature Atrial Contractions in Cryptogenic Stroke Predict Atrial Fibrillation Detection with Insertable Cardiac Monitoring.

Cerebrovasc Dis 2020 5;49(2):144-150. Epub 2020 Feb 5.

Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.

Objective: To determine whether frequent premature atrial contractions (PAC) predict atrial fibrillation (AF) in cryptogenic stroke patients, we analyzed the association between frequent PACs in 24-h Holter electrocardiogram recording and AF detected by insertable cardiac monitoring (ICM).

Methods: We retrospectively analyzed a database of 66 consecutive patients with cryptogenic stroke who received ICM implantation between October 2016 and March 2018 at 5 stroke centers. We included the follow-up data until June 2018 in this analysis. We defined frequent PACs as the upper quartile of the 66 patients. We analyzed the association of frequent PACs with AF detected by ICM.

Results: Frequent PACs were defined as >222 PACs per a 24-h period. The proportion of patients with newly detected AF by ICM was higher in patients with frequent PACs than those without (50% [8/16] vs. 22% [11/50], p < 0.05). Frequent PACs were associated with AF detection and time to the first AF after adjustment for CHADS2 score after index stroke, high plasma -B-type natriuretic peptide (BNP; >100 pg/mL) or serum -N-terminal pro-BNP levels (>300 pg/mL), and large left atrial diameter (≥45 mm).

Conclusion: High frequency of PACs in cryptogenic stroke may be a strong predictor of AF detected by ICM.
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http://dx.doi.org/10.1159/000505958DOI Listing
September 2020

Abnormalities of brain imaging in patients after left ventricular assist device support following explantation.

J Heart Lung Transplant 2020 03 29;39(3):220-227. Epub 2019 Nov 29.

Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Background: The potential impact of long-term left ventricular assist device (LVAD) support on the brain remains unclear. This study aimed to investigate cerebral microvascular damage in patients after long-term LVAD implantation using magnetic resonance imaging (MRI).

Methods: We reviewed the medical records of patients after continuous-flow LVAD implantation in our hospital from 2006 to 2016, who underwent brain MRI after LVAD explantation for either transplantation or recovery. Age- and sex-matched healthy controls and patients with chronic heart failure (CHF) were collected from our pooled MRI database. The presence of cerebral microbleeds (CMBs) and cortical superficial siderosis and the severity of white matter hyperintensity (WMH) and cerebral atrophy were compared between patients with prior LVAD and 2 control groups.

Results: This study included 49 patients with prior LVAD, 49 healthy controls, and 45 patients with CHF. CMBs and cortical superficial siderosis were detected in 98% (p < 0.001) and 31% (p < 0.001) of patients with prior LVAD, respectively. The number of CMBs was higher in patients with prior LVAD than in the 2 control groups. The severity of the WMH was higher in patients with prior LVAD than in healthy controls but similar to that in patients with CHF. Quantitative analyses of cerebral atrophy revealed a significantly higher bicaudate ratio and cella media index in patients with prior LVAD than in the 2 control groups.

Conclusions: Patients after long-term LVAD support showed a higher prevalence of CMBs and cortical superficial siderosis and more severe cerebral atrophy than did controls. These findings may indicate cerebral microvascular damages in long-term LVAD support patients.
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http://dx.doi.org/10.1016/j.healun.2019.11.019DOI Listing
March 2020

[Reliability of modified Rankin Scale assessment with a Japanese version of simplified modified Rankin Scale Questionnaire (J-RASQ)].

Rinsho Shinkeigaku 2019 Jul 27;59(7):399-404. Epub 2019 Jun 27.

Department of Neurology, National Cerebral and Cardiovascular Center.

Modified Rankin Scale (mRS) is widely used as an indicator of physical disability after the onset of stroke and a main evaluation scale in clinical stroke trials but sometimes has discrepancies among raters. We designed a Japanese version of simplified mRS questionnaire (J-RASQ) to evaluate mRS using closed question to assess the difference from the original. Currently there are no Japanese version of mRS questionnaire and its validity and reliability assessment has been warranted. Patients with planned visit to our hospital between 60 and 120 days after the onset of cerebral hemorrhage or infarction between August 2017 and March 2018 were recruited. J-RASQ was distributed before the outpatient visit to stroke patients, families or caregivers, and response was obtained. Thereafter, outpatient attending physicians qualified as stroke or neurological specialists evaluated mRS according to the Japanese version of guidance scheme for mRS. Subsequently, 130 patients (mean age, 72 ± 12 years old) were enrolled, and the difference between the two scale scores (mRS vs. J-RASQ) were statistically examined by the κ statistic and the weighted κ statistic. The κ statistic was 0.42 (95% CI, 0.31-0.52), and the weighted κ statistic calculated taking into account the extent of disagreement was 0.78 (95% CI, 0.70-0.86). We conclude that the J-RASQ appears to have decent reliability and is similar to the existing mRS.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001295DOI Listing
July 2019

Prevalence of RNF213 p.R4810K Variant in Early-Onset Stroke With Intracranial Arterial Stenosis.

Stroke 2019 06 7;50(6):1561-1563. Epub 2019 May 7.

From the Department of Neurology (T.K., S.O., T.Y., M.I.), National Cerebral and Cardiovascular Center, Osaka, Japan.

Background and Purpose- The ring finger protein 213 gene ( RNF213) is a susceptibility gene for moyamoya disease and large-artery ischemic stroke in East Asia. We examined the prevalence and correlates of the RNF213 p.R4810K variant in patients with early-onset ischemic stroke in a Japanese single-center cohort. Methods- We analyzed 70 early-onset stroke patients with intracranial arterial stenosis who developed a noncardioembolic stroke or transient ischemic attack from 20 to 60 years of age. Patients with moyamoya disease were excluded. Results- The RNF213 p.R4810K variant was found in 17 patients (24%), and more often in women than men (38% versus 16%, odds ratio 3.3; 95% CI, 1.1-10.2, P=0.04). The variant was identified in 35% of patients with stenosis in the M1 segment of the middle cerebral artery or the A1 segment of the anterior cerebral artery (odds ratio, 25.0; 95% CI, 1.4-438; P<0.01) but in only one patient (9%) with intracranial posterior circulation stenosis. Conventional atherosclerotic risk factors did not differ between variant carriers and noncarriers. Conclusions- The RNF213 p.R4810K variant is common in early-onset ischemic stroke with anterior circulation stenosis in Japan. Further investigation of the RNF213 gene will provide new insights into pathogenetic mechanisms of early-onset stroke.
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http://dx.doi.org/10.1161/STROKEAHA.118.024712DOI Listing
June 2019

Cortical Cerebral Microinfarcts on 3T Magnetic Resonance Imaging in Patients With Carotid Artery Stenosis.

Stroke 2019 03;50(3):639-644

From the Department of Neurology (J.T., K.M., S.O., K.T., T.S., M.S., H.M.), Osaka University Graduate School of Medicine, Japan.

Background and Purpose- Carotid artery stenosis is common in the elderly and contributes to cognitive impairment and dementia. Cortical cerebral microinfarcts (CMIs) play an important role in vascular cognitive impairment and dementia. We aimed to investigate the association between CMIs on 3T magnetic resonance imaging and clinical and radiological features, including plaque morphology, and cognitive function in patients with carotid stenosis. Methods- Eighty-nine patients with >30% carotid stenosis on ultrasound were prospectively enrolled, and underwent brain and carotid artery magnetic resonance imaging. CMIs were rated according to predetermined criteria based on 3D-double inversion recovery and fluid-attenuated inversion recovery images. Results- CMIs were identified in 26 patients (29%; median number 0, range 0-9). Poisson regression models adjusted for age and sex revealed that CMIs were associated with intraplaque hemorrhage (rate ratio, 1.95; 95% CI, 1.26-3.18), lacunar infarcts (rate ratio, 1.54; 95% CI, 1.00-2.44), and cortical infarcts (rate ratio, 3.22; 95% CI, 2.20-5.00). These associations were also observed in asymptomatic patients (n=64). Of 81 patients with unilateral carotid stenosis, the prevalence and number of CMIs were significantly higher in the hemisphere ipsilateral to the carotid stenosis than in the contralateral hemisphere ( P=0.005 and P<0.001, respectively). The presence of CMIs was associated with poor cognitive function. Conclusions- Our results indicate that vulnerable carotid plaque increases the risk of CMIs and subsequent cognitive impairment. Carotid atherosclerosis could be a potential therapeutic target for cognitive impairment.
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http://dx.doi.org/10.1161/STROKEAHA.118.023781DOI Listing
March 2019

Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

PLoS One 2018 20;13(9):e0204633. Epub 2018 Sep 20.

[This corrects the article DOI: 10.1371/journal.pone.0191172.].
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204633PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147579PMC
September 2018

Rolling stones sign as hard and fast evidence of calcified cerebral emboli.

Neurology 2018 07 30;91(1):41-43. Epub 2018 May 30.

From the National Cerebral and Cardiovascular Center, Suita, Japan.

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http://dx.doi.org/10.1212/WNL.0000000000005731DOI Listing
July 2018

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

PLoS One 2018 12;13(4):e0191172. Epub 2018 Apr 12.

Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.

Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

Methods And Results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C.

Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191172PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896895PMC
July 2018

Arterial Spin Labeling Cerebral Perfusion Magnetic Resonance Imaging in Migraine Aura: An Observational Study.

J Stroke Cerebrovasc Dis 2018 May 10;27(5):1262-1266. Epub 2018 Jan 10.

Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany; Department of Neurology, Klinikum Kempten, Kempten, Germany.

Background: Changes in cerebral perfusion during migraine with aura (MA) have been assessed mainly using dynamic susceptibility contrast (DSC) magnetic resonance perfusion imaging. A contrast agent-free method to assess these changes would be desirable. We assessed changes in cerebral perfusion during MA using arterial spin labeling (ASL) perfusion magnetic resonance imaging.

Methods: We investigated 4 patients with a standardized protocol including ASL perfusion imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow-up. Semiquantitative evaluation was done using a region of interest (ROI) within hypoperfused or hyperperfused areas and corresponding ROIs in the contralateral hemisphere. Relative ratios of mean perfusion in the corresponding ROIs were calculated. DSC imaging was done at initial time points and compared visually with ASL findings.

Results: In all patients, regional perfusion changes were detected in the acute phase. These abnormalities did not respect the boundaries of major cerebral vascular territories but overlapped onto adjoining regions. During MA, adjacent hypoperfused and hyperperfused areas were found, whereas during headache, regional hyperperfusion only was observed. Perfusion abnormalities normalized on follow-up.

Conclusions: ASL perfusion imaging is a contrast agent-free method suitable for assessment of reversible perfusion changes during or immediately after MA.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.12.002DOI Listing
May 2018

[Progressive dysarthria and bilateral sensory disturbance in a case of bilateral ventrolateral pontine infarction].

Rinsho Shinkeigaku 2017 Dec 28;57(12):764-768. Epub 2017 Nov 28.

Department of Neurology, National Cerebral and Cardiovascular Center, Osaka.

A rare case of bilateral ventrolateral pontine infarction in a 70-year-old man who developed progressive dysarthria and bilateral sensory disturbance is reported with literature review. He had been diagnosed with hypertension, dyslipidemia, and impaired glucose tolerance 10 years earlier. Ten days before admission, he was aware of the difficulty in walking and speaking, which gradually worsened. On admission he showed bilateral thermal hypoalgesia of face and lower extremities, dysarthria, dysphagia, and ataxic gait. High resolution three-dimensional MRI revealed bilateral ventrolateral pontine infarction with a large atherosclerotic plaque in the ventral side of the basilar artery, which led to a diagnosis of atherothrombotic brain infarction. The atherosclerotic plaque in the basilar artery was thought to be responsible for simultaneous occlusion of the bilateral short circumflex arteries of the pons.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001090DOI Listing
December 2017

Relationship Between Bacteremia and Hemorrhagic Stroke in Patients With Continuous-Flow Left Ventricular Assist Device.

Circ J 2018 01 23;82(2):448-456. Epub 2017 Sep 23.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine.

Background: Blood stream infection is thought to increase the risk of hemorrhagic stroke, a major adverse event with devastating outcome, in patients with continuous-flow left ventricular assist devices (LVADs). We analyzed the risk factors of hemorrhagic stroke in LVAD patients, as well as the time relationship between systemic bacteremia and hemorrhagic stroke.Methods and Results:We evaluated the incidence of systemic bacteremia and stroke in 164 patients who underwent continuous-flow LVAD implantation between 2005 and 2016. At 1 and 2 years after implantation, the incidence of bacteremia was 29% and 36%, and the incidence of hemorrhagic stroke was 22% and 22% in patients without bacteremia, and 32% and 44% in those with bacteremia, respectively (P=0.035). This higher prevalence of hemorrhagic stroke in patients with bacteremia was notable particularly in the chronic phase (>90 days after implantation). Multivariate analysis revealed that bacteremia was an independent risk factor of hemorrhagic stroke in the chronic phase [hazard ratio, 2.36 (1.02-5.62); P=0.044]. The hazard rate was the highest immediately after the onset of bacteremia, and the risk steadily declined by 90 days after the last episode of bacteremia and flattened thereafter.

Conclusions: Bacteremia was an independent risk factor of hemorrhagic stroke in patients in the chronic phase, with the highest risk seen in the early phase following an episode of bacteremia.
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http://dx.doi.org/10.1253/circj.CJ-17-0541DOI Listing
January 2018

Prevalence of Cerebral Microbleeds in Patients With Continuous-Flow Left Ventricular Assist Devices.

J Am Heart Assoc 2017 Sep 11;6(9). Epub 2017 Sep 11.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Background: The prevalence of cerebral microbleeds (CMBs) in gradient echo T2*-weighted brain MRI has a positive correlation with hemorrhagic stroke incidence. However, the prevalence of CMBs in patients with left ventricular assist devices (LVADs) has not been evaluated. We evaluated the prevalence of CMBs and the relationship with hemorrhagic stroke incidence in patients with LVADs.

Method And Results: We analyzed results from brain MRI in prospective examinations of 35 consecutive patients who had undergone LVAD explantation for heart transplantation or recovery since 2011. The number and distribution of CMBs were counted, then the relationship between baseline characteristics and adverse events during LVAD support were analyzed. The mean age was 37.7±12.4 years and the mean LVAD duration was 2.43±1.08 years. Thirty-four (97%) patients had at least one CMB. Nine (26%) developed hemorrhagic stroke during LVAD support, and patients with hemorrhagic stroke had a significantly greater number of CMBs compared with patients without hemorrhagic stroke (5 [interquartile range (IQR), 4-7] versus 9 [IQR, 5-23]; odds ratio 1.14 [95% Confidence Interval (CI), 1.02-1.32], =0.05). There was no significant relationship between age, LVAD support duration, or systolic blood pressure during LVAD. However, patients who had at least one episode of bacteremia (9 [IQR, 4-16] versus 5 [IQR, 3-7], =0.06) and pump pocket infection (14 [IQR, 4-27] versus 5 [IQR, 3-7], =0.08) showed a trend toward a greater number of CMBs than patients without bacteremia.

Conclusions: Thirty-four (97%) patients with continuous-flow LVAD had at least one CMB, and the number of CMBs were more prevalent in patients with hemorrhagic stroke and in patients with LVAD-related infection.
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http://dx.doi.org/10.1161/JAHA.117.005955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634264PMC
September 2017

Cerebral hyperperfusion on arterial spin labeling MRI after reperfusion therapy is related to hemorrhagic transformation.

J Cereb Blood Flow Metab 2017 Sep 30;37(9):3087-3090. Epub 2017 Jun 30.

1 Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

Early detection of hemorrhagic transformation after reperfusion therapy is crucial in acute stroke treatment. Here, we evaluated the relationship between hemorrhagic transformation and post-reperfusion hyperperfusion using pulsed arterial spin labeling (ASL) perfusion MRI and I-iodoamphetamine single-photon emission-computed tomography. Patients who developed hemorrhagic transformation showed significantly higher cerebral blood flow in the affected lesion after thrombolysis and/or endovascular intervention. Focal hyperperfusion (ipsilateral to contralateral ratio >1.5) was associated with hemorrhagic transformation after reperfusion (odds ratio, 9.3; 95% confidence interval, 1.4-64.0). Our findings suggest that post-reperfusion hyperperfusion on ASL could represent a reliable marker of hemorrhagic transformation.
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http://dx.doi.org/10.1177/0271678X17718099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584703PMC
September 2017

Clustering of cardiovascular risk factors and carotid intima-media thickness: The USE-IMT study.

PLoS One 2017 21;12(3):e0173393. Epub 2017 Mar 21.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht,Utrecht, the Netherlands.

Background: The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation.

Methods: Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group.

Results: Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women.

Conclusion: Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173393PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360240PMC
August 2017

Relationship Between Infarct Volume and Prothrombin Time-International Normalized Ratio in Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation.

Circ J 2017 Feb 31;81(3):391-396. Epub 2017 Jan 31.

Stroke Center, Kindai University Faculty of Medicine.

Background: In Japan, warfarin treatment at prothrombin time-international normalized ratio (PT-INR) of 1.60-2.60 is recommended for elderly patients with nonvalvular atrial fibrillation (NVAF). But it remains unknown whether PT-INR 1.60-1.99 has a similar effect on stroke severity as a value >2.0. The purpose of this study was to clarify the association between infarct volume and PT-INR levels.Methods and Results:The 180 patients (mean age, 76 years [SD, 10 years], 53% male) selected from 429 consecutive ischemic stroke patients admitted within 48 h of onset between 2004 and 2014 with NVAF were included. We classified them into 4 groups according to their PT-INR values on admission: no warfarin (NW), 129 patients; PT-INR <1.60 (poor control: PC), 29 patients; PT-INR 1.60-1.99 (low-intensity control: LC), 14 patients; and PT-INR ≥2.00 (high-intensity control: HC), 8 patients. Median (interquartile range: IQR) of infarct volume was 55 mL (IQR 14-175) in the NW, 42 mL (IQR 27-170) in the PC, 36 mL (IQR 6-130) in the LC, and 11 mL (IQR 0-39) in the HC groups. The infarct volume of the HC group was significantly smaller than in the other 3 groups, but no difference existed between the LC and PC groups or the LC and NW groups.

Conclusions: Warfarin control at PT-INR of 1.60-1.99 is not effective for reducing the severity of ischemic stroke in NVAF patients.
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http://dx.doi.org/10.1253/circj.CJ-16-0707DOI Listing
February 2017

Characteristics of cryptogenic stroke in cancer patients.

Ann Clin Transl Neurol 2016 Apr 11;3(4):280-7. Epub 2016 Feb 11.

Department of Neurology Osaka University Graduate School of Medicine Osaka Japan.

Objective: To clarify the characteristics of cryptogenic stroke in patients with active cancer.

Methods: Patients with or without cancer diagnosed with acute ischemic stroke between January 2006 and February 2015 were extracted from a prospectively collected stroke database of Osaka University Hospital. Patients were categorized according to the presence of active cancer and known stroke mechanisms.

Results: Among 1191 patients with acute ischemic stroke, 145 (12%) had active cancer. Patients with active cancer were diagnosed more often with cryptogenic stroke than were patients without cancer (47% vs. 12%, P < 0.001). Compared with cryptogenic stroke patients without cancer, cryptogenic stroke patients with active cancer had fewer atherosclerotic risk factors, lower nutrition status, higher plasma D-dimer levels, and multiple vascular lesions. In a multivariate logistic analysis, plasma D-dimer level (odds ratio [OR] per 1 standard deviation increase: 6.30; 95% confidence interval [CI]: 2.94-15.69; P < 0.001), and the presence of multiple vascular lesions (OR: 6.40; 95% CI: 2.35-18.35; P < 0.001) were independent predictors of active cancer. When comparing active cancer patients who had known stroke mechanisms with those who had cryptogenic stroke, high plasma D-dimer levels, multiple vascular lesions, and receiving chemotherapy and/or radiation therapy were associated with cryptogenic stroke etiology.

Interpretation: In cryptogenic stroke, patients with active cancer has a unique pathology characterized by high plasma D-dimer levels and multiple vascular lesions. The hypercoagulable state and malnutrition due to cancer and its treatments potentially influence the development of cryptogenic stroke in cancer patients.
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http://dx.doi.org/10.1002/acn3.291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818743PMC
April 2016

Prediction of Early Reperfusion From Repeated Arterial Spin Labeling Perfusion Magnetic Resonance Imaging During Intravenous Thrombolysis.

Stroke 2016 Jan 29;47(1):247-50. Epub 2015 Oct 29.

From the Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany (S.O., M.G., J.S.-S., M.E.W., A.G., M.G.H., K.S., R.K.); mediri GmbH, Heidelberg, Germany (J.G., M.G.); Institute for Medical Image Computing MEVIS, Fraunhofer MEVIS, Bremen, Germany (M.G.); MR-Imaging and Spectroscopy, Faculty 01 (Physics/Electrical Engineering), University of Bremen, Bremen, Germany (M.G.); and Department of Neurology, Klinikum Kempten, Kempten-Oberallgaeu, Germany (R.K.).

Background And Purpose: There are few in vivo data on the pathophysiology of reperfusion during systemic thrombolysis. We monitored the time course of cerebral perfusion changes in patients during thrombolysis with repeated arterial spin labeling perfusion magnetic resonance imaging.

Methods: Ten patients with proximal arterial occlusion within 4.5 hours after symptom onset were prospectively enrolled. All patients received intravenous thrombolysis during the magnetic resonance imaging examination. Repeated arterial spin labeling perfusion images were acquired during the 60-minute therapy and at follow-up after 24 to 72 hours. Clinical data, magnetic resonance imaging features, and cerebral perfusion changes were analyzed.

Results: Before thrombolysis, arterial spin labeling hypoperfusion and fluid-attenuation inversion recovery vascular hyperintensity in the territory of the occluded arteries were observed in all patients. In 5 patients, extensive arterial transit artifacts (ATA) developed in the hypoperfused area. The ATA corresponded with fluid-attenuation inversion recovery vascular hyperintensities. All 5 patients who developed extensive ATA in the hypoperfused area had complete reperfusion after thrombolysis, whereas the 5 without extensive ATA showed no or only partial reperfusion (P<0.01). The development of ATA preceded the normalization of tissue perfusion.

Conclusions: The development of ATA during thrombolysis is associated with early reperfusion after thrombolysis. arterial spin labeling assessment during intravenous thrombolysis has the potential to guide subsequent therapeutic strategies in patients with acute stroke.
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http://dx.doi.org/10.1161/STROKEAHA.115.011482DOI Listing
January 2016

Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors.

J Alzheimers Dis 2016 ;49(2):503-13

Department of Neurology, Tokyo Women's Medical University, Tokyo, Japan.

Background: Homocysteine has been identified as a potential risk factor for stroke, cerebral small-vessel diseases (SVD), and dementia.

Objective: The present study aimed to investigate the predictive value of homocysteine levels on incident dementia while simultaneously controlling for MRI findings and vascular risk factors.

Methods: Within a Japanese cohort of participants with vascular risk factors in an observational study, we evaluated the association between baseline total homocysteine (tHcy) levels (per 1 μmol/L and the tertile of tHcy), the prevalence of MRI-findings at baseline, and incident all-cause dementia. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities, and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tHcy and each of MRI findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between tHcy and dementia.

Results: In the 643 subjects (age: 67.2 ± 8.4 years, male: 59% ; education: 12.9 ± 2.6 years), multivariable analyses adjusted for several potential confounders, including estimated glomerular filtration rate (eGFR) and intima-media thickness, showed that highest tHcy tertile was associated with lacunas, CMBs, and strictly deep CMBs. During the mean 7.3-year follow-up (range: 2-13), 47 patients were diagnosed with dementia (Alzheimer's disease: 24; vascular dementia: 18; mixed-type: 3; other: 2). After adjusting for age, gender, APOE ɛ4, education, BMI, MMSE, hypertension, cerebrovascular events, eGFR, and MRI-findings, tHcy level (hazard ratios [HR]: 1.08, p = 0.043) and the highest tertile of tHcy (HR: 2.50, p = 0.047) for all-cause dementia remained significant.

Conclusions: Our results provide additional evidence of tHcy that contributes to increased susceptibility to dementia risk.
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http://dx.doi.org/10.3233/JAD-150458DOI Listing
September 2016

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.

PLoS One 2015 2;10(7):e0132321. Epub 2015 Jul 2.

Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

Background: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.

Methods: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.

Results: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.

Conclusion: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132321PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489855PMC
May 2016

MRI Characteristics of the Evolution of Supratentorial Recent Small Subcortical Infarcts.

Front Neurol 2015 26;6:118. Epub 2015 May 26.

Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg , Mannheim , Germany.

Objective: Morphological changes of recent small subcortical infarcts are not well defined. The purpose of the present study was to describe the MRI characteristics of the evolution for this stroke subtype.

Methods: We conducted a retrospective review of patients diagnosed with definite supratentorial recent small subcortical infarcts according to the ASCO classification with baseline and follow-up MRI (≥90 days of stroke onset). We investigated the incidence of cavity formation, the infarct volume change, and the positional relationship between infarct lesions and preexisting white matter hyperintensities (WMHs) of presumed vascular origin.

Results: We identified 62 patients with a median age of 71 years (range: 30-87). Median follow-up period was 26 months (range: 3-99). Cavity formation was observed in 38 infarct lesions (61%). Eighteen lesions (29%) were partially adjacent to WMHs and 7 (11%) were fused into WMHs. In a multiple logistic regression analysis, age [odds ratio per 5-year increase: 1.34; 95% confidence interval (CI): 1.03-1.80; p = 0.03] and baseline infarct volume (odds ratio per 1-ml increase: 4.7; 95% CI: 1.6-19.7; p = 0.003) were independent predictors of cavity formation. There was a significant volume reduction between baseline and follow-up infarct lesions (median volume reduction rate: 44%).

Conclusion: More than one-third of recent small subcortical infarcts do not lead to cavity formation and 40% of infarct lesions overlap with WMHs. Our data indicate the continuity between recent small subcortical infarcts and WMHs.
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http://dx.doi.org/10.3389/fneur.2015.00118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443727PMC
June 2015