Multiple Silent Lacunes Are Associated with Recurrent Ischemic Stroke

Background: Silent lacunes are a common finding on brain imaging in ischemic stroke patients, but the prognostic significance of these lesions is uncertain. We aimed at investigating the association of silent lacunes and the risk of ischemic stroke recurrence, death, and cardiovascular events in a cohort of patients with incident ischemic stroke and no atrial fibrillation (AF). Methods: We included 786 patients (mean age 59.5 (SD 14.0); 42.9% females) in a registry-based, observational cohort study on patients with first-ever ischemic stroke. On brain MRI we assessed the number of silent lacunes as none, single, or multiple and we calculated stratified incidence rates of the outcomes. Cox proportional hazard ratios (HRs) adjusted for age, gender, congestive heart failure, hypertension, diabetes, and vascular disease were calculated with no silent lacunes as reference. In additional analyses, we further adjusted for white matter hyperintensities. Patients were followed up until death or recurrence of ischemic stroke. Results: In 81 (10.3%) patients, a single silent lacune was present, and in 87 (11.1%) patients, multiple silent lacunes were present. Patients with at least one silent lacune were older (mean age 66.1 vs. 57.7, p < 0.001) and were more often hypertensive (60.1 vs. 43.4%, p < 0.001) compared to patients with no silent lacunes. During a median follow-up time of 2.9 (interquartile range 3.1) years, we observed 53 recurrent ischemic strokes, 76 deaths, and 96 cardiovascular events. Incidence rates per 100 person-years of ischemic stroke recurrence were 1.6, 2.5, and 5.0 for none, single, and multiple silent lacunes respectively. Corresponding incidence rates were 2.6, 2.4, and 4.4 for death, and 3.4, 4.0, and 6.6 for cardiovascular events respectively. Adjusted HRs of ischemic stroke recurrence were 1.53 (0.67-3.49) and 2.52 (1.25-5.09) for a single and multiple silent lacunes, respectively. Further adjustment for white matter hyperintensities maintained positive association although not significant. Corresponding adjusted HRs were 0.56 (0.25-1.25) and 0.65 (0.33-1.25) for death and 1.16 (0.61-2.22) and 1.51 (0.86-2.66) for cardiovascular events. Conclusions: In this large cohort of patients with incident ischemic stroke and no AF, an increasing number of silent lacunes was associated with increasing incidence rates of ischemic stroke recurrence. In the adjusted Cox proportional hazard analyses, the presence of multiple silent lacunes was significantly associated with an increased risk of ischemic stroke recurrence. The risk of death or cardiovascular events was not significantly influenced by the presence of silent lacunes.

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Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke

Brain Sciences ◽

10.3390/brainsci9010016 ◽

2019 ◽

Vol 9 (1) ◽

pp. 16 ◽

Cited By ~ 2

Author(s):

Imama Naqvi ◽

Emi Hitomi ◽

Richard Leigh

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Stroke ◽

Blood Brain Barrier ◽

White Matter Hyperintensities ◽

Brain Barrier ◽

Common Finding ◽

Blood Brain ◽

History Of ◽

Iv Tpa

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.

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White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction

Cerebrovascular Diseases ◽

10.1159/000450962 ◽

2016 ◽

Vol 43 (1-2) ◽

pp. 17-24 ◽

Cited By ~ 3

Author(s):

Søren Due Andersen ◽

Torben Bjerregaard Larsen ◽

Anders Gorst-Rasmussen ◽

Yousef Yavarian ◽

Gregory Y.H. Lip ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Risk Score ◽

White Matter Hyperintensities ◽

Stroke Risk ◽

Risk Scores ◽

Stroke Recurrence ◽

Cerebral White Matter ◽

Clinical Scores ◽

Recurrence Prediction

Background: Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA2DS2VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. Methods: In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA2DS2VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. Results: White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA2DS2VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed improved C-statistics: the recalibrated CHA2DS2VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). Conclusions: An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA2DS2VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence.

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Association of Dementia-Related Psychosis With Long-term Care Use and Death

Neurology ◽

10.1212/wnl.0000000000011632 ◽

2021 ◽

Vol 96 (12) ◽

pp. e1620-e1631

Author(s):

James B. Wetmore ◽

Yi Peng ◽

Heng Yan ◽

Suying Li ◽

Muna Irfan ◽

...

Keyword(s):

Long Term Care ◽

Fold Increase ◽

Proportional Hazard ◽

Comorbid Conditions ◽

Term Care ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Increased Risk ◽

Cox Proportional Hazard Regression

ObjectiveTo determine the association of dementia-related psychosis (DRP) with death and use of long-term care (LTC); we hypothesized that DRP would be associated with increased risk of death and use of LTC in patients with dementia.MethodsA retrospective cohort study was performed. Medicare claims from 2008 to 2016 were used to define cohorts of patients with dementia and DRP. Outcomes were LTC, defined as nursing home stays of >100 consecutive days, and death. Patients with DRP were directly matched to patients with dementia without psychosis by age, sex, race, number of comorbid conditions, and dementia index year. Association of DRP with outcomes was evaluated using a Cox proportional hazard regression model.ResultsWe identified 256,408 patients with dementia. Within 2 years after the dementia index date, 13.9% of patients developed DRP and 31.9% had died. Corresponding estimates at 5 years were 25.5% and 64.0%. Mean age differed little between those who developed DRP (83.8 ± 7.9 years) and those who did not (83.1 ± 8.7 years). Patients with DRP were slightly more likely to be female (71.0% vs 68.3%) and white (85.7% vs 82.0%). Within 2 years of developing DRP, 16.1% entered LTC and 52.0% died; corresponding percentages for patients without DRP were 8.4% and 30.0%, respectively. In the matched cohort, DRP was associated with greater risk of LTC (hazard ratio [HR] 2.36, 2.29–2.44) and death (HR 2.06, 2.02–2.10).ConclusionsDRP was associated with a more than doubling in the risk of death and a nearly 2.5-fold increase in risk of the need for LTC.

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Significance of Platelet and AFP Levels and Liver Function Parameters for HCC Size and Survival

The International Journal of Biological Markers ◽

10.5301/jbm.5000064 ◽

2014 ◽

Vol 29 (3) ◽

pp. 215-223 ◽

Cited By ~ 14

Author(s):

Brian I. Carr ◽

Vito Guerra ◽

Edoardo G. Giannini ◽

Fabio Farinati ◽

Francesca Ciccarese ◽

...

Keyword(s):

Tumor Size ◽

Blood Platelet ◽

Tumor Diameter ◽

Proportional Hazard ◽

Gamma Glutamyl Transpeptidase ◽

Vein Thrombosis ◽

Risk Of Death ◽

Cox Proportional Hazard ◽

Maximum Tumor Diameter ◽

Glutamyl Transpeptidase

Background Hepatocellular carcinoma (HCC) is a heterogeneous disease with both tumor and liver factors being involved. Aims To investigate HCC clinical phenotypes and factors related to HCC size. Methods Prospectively-collected HCC patients' data from a large Italian database were arranged according to the maximum tumor diameter (MTD) and divided into tumor size terciles, which were then compared in terms of several common clinical parameters and patients' survival. Results An higer MTD tercile was significantly associated with increased blood alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase (GGTP), and platelet levels. Patients with higher platelet levels had larger tumors and higher GGTP levels, with lower bilirubin levels. However, patients with the highest AFP levels had larger tumors and higher bilirubin levels, reflecting an aggressive biology. AFP correlation analysis revealed the existence of 2 different groups of patients: those with higher and with lower AFP levels, each with different patient and tumor characteristics. The Cox proportional-hazard model showed that a higher risk of death was correlated with GGTP and bilirubin levels, tumor size and number, and portal vein thrombosis (PVT), but not with AFP or platelet levels. Conclusions An increased tumor size was associated with increased blood platelet counts, AFP and GGTP levels. Platelet and AFP levels were important indicators of tumor size, but not of survival.

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Risks of Stroke Recurrence and Mortality After First and Recurrent Strokes in Denmark: A Nationwide Registry Study

Neurology ◽

10.1212/wnl.0000000000013118 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013118

Author(s):

Nils Skajaa ◽

Kasper Adelborg ◽

Erzsébet Horváth-Puhó ◽

Kenneth J Rothman ◽

Victor W. Henderson ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Risk Score ◽

Recurrent Stroke ◽

Recurrent Event ◽

Risk Scores ◽

Stroke Recurrence ◽

Stroke Severity ◽

Risk Of Death ◽

First Time

Background and Objectives:To examine risks of stroke recurrence and mortality after first and recurrent stroke.Methods:Using Danish nationwide health registries, we included patients (age ≥18 years) with first-time ischemic stroke (N = 105,397) or intracerebral hemorrhage (N = 13,350) during 2004–2018. Accounting for the competing risk of death, absolute risks of stroke recurrence were computed separately for each stroke subtype and within strata of age groups, sex, stroke severity, body mass index, smoking, alcohol, the Essen stroke risk score, and atrial fibrillation. Mortality risks were computed after first and recurrent stroke.Results:After adjusting for competing risks, the overall 1-year and 10-year risks of recurrence were 4% and 13% following first-time ischemic stroke and 3% and 12% following first-time intracerebral hemorrhage. For ischemic stroke, the risk of recurrence increased with age, was higher for men and following mild than more severe stroke. The most marked differences were across Essen risk scores, for which recurrence risks increased with increasing scores. For intracerebral hemorrhage, risks were similar for both sexes and did not increase with Essen risk score. For ischemic stroke, the 1-year and 10-year risks of all-cause mortality were 17% and 56% after a first-time stroke and 25% and 70% after a recurrent stroke; corresponding estimates for intracerebral hemorrhage were 37% and 70% after a first-time event and 31% and 75% after a recurrent event.Conclusion:The risk of stroke recurrence was substantial following both subtypes, but risks differed markedly among patient subgroups. The risk of mortality was higher after a recurrent than first-time stroke.

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Abstract WP359: Microembolic Signals Are Associated With Stroke Readmission in Patients With Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.wp359 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Nasir Fakhri ◽

Simin Mahinrad ◽

Arth Srivastava ◽

Eric Liotta ◽

Richard Bernstein ◽

...

Keyword(s):

Ischemic Stroke ◽

Recurrent Stroke ◽

Incidence Rates ◽

High Risk Population ◽

Stroke Patients ◽

Entire Cohort ◽

Cox Proportional Hazard ◽

Stroke Population ◽

Cox Proportional Hazard Models ◽

Ischemic Attack

Background: Microembolic signals (MES) identified by transcranial Doppler (TCD) are strong predictors of recurrent stroke in patients with carotid disease. In this study, we investigated the association of MES with transient ischemic attack (TIA) or stroke readmission among ischemic stroke patients. Methods: We included a total of 789 patients (mean age 62±17 years, 55% male) who were consecutively admitted to Northwestern Memorial hospital with a diagnosis of stroke. All patients who underwent TCD studies within the first 48 hours of admission were included. Using an electronic database warehouse, patients were followed during 12 months for any hospital readmission due to ischemic stroke or TIA. Risk of stroke readmission was estimated using multivariate Cox proportional hazard models. Results: MES were detected in 95 patients on admission. During 12 months of follow-up, incidence rates for stroke and TIA readmission, and stroke readmission alone were 23.0 and 7.0 per 100 person-years across the entire cohort, respectively. In multivariate adjusted models, patients with MES, as compared to patients without MES, had 1.80-fold (95% CI=1.07, 2.53; p =0.008) higher risk of stroke and TIA readmission, and 2.30-fold (95% CI=1.13, 4.67, p =0.021) higher risk of readmission due to stroke alone. Conclusion: We showed that the presence of MES early after stroke admission is associated with higher risk of stroke and TIA readmission in stroke patients. This not only highlights the importance of identifying MES in the stroke population upon first admission, but also the need to further identify and implement therapeutic strategies to reduce stroke burden and prevent readmission in this high-risk population.

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Clinical effects and economical impact of dutasteride and finasteride therapy in Italian men with LUTS

Archivio Italiano di Urologia e Andrologia ◽

10.4081/aiua.2013.4.200 ◽

2013 ◽

Vol 85 (4) ◽

pp. 200 ◽

Cited By ~ 4

Author(s):

Luca Cindolo ◽

Francesco Berardinelli ◽

Caterina Fanizza ◽

Marilena Romero ◽

Luisella Pirozzi ◽

...

Keyword(s):

Impact Analysis ◽

Budget Impact ◽

Treated Patient ◽

Incidence Rates ◽

Administrative Databases ◽

Clinical Effects ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Initial Cohort ◽

Using Data

Objectives: To investigate differences in the risk of benign prostatic hyperplasia (BPH)- related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients under dutasteride or finasteride treatment. Material and methods: A retrospective cohort study was conducted using data from record-linkage of administrative databases. Men aged ≥ 40 years old who had received a prescription for at least 10 boxes/year (index years: 2004-06) were included. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity scorematched analysis and a 5-to-1, greedy 1:1 matching algorithm were performed. The budget impact analysis of dutasteride vs finasteride in BPH-treated patient was performed. Results: From an initial cohort of about 1.5 million of Italian men, 19620 were selected. The overall hospitalization for BPH-non surgical reasons, for BPH-related surgery and for new detection of PCa incidence rates (IRs) were 8.20 (95% CI, 7.62-8.23), 18.0 (95% CI, 17.12-18.93) and 8.62 (95% CI, 8.03-9.26) per 1000 person-years, respectively. The multivariate analysis after the propensity score-matching showed that dutasteride was associated with an independent reduced likelihood of hospitalization for BPH-related surgery (HR 0.82; 95% CI 0.73-0.93; p = 0.0025) and of newly detected PCa (HR: 0.76,95% CI, 0.65-0.85; p = 0.0116). The IR for BPH-non surgical reasons was 8.07 (95% CI, 7.10-9.17) and 9.25 (95% CI, 8.19-10.44) per 1000 person-years, respectively. The IR for BPH-related surgery was 18.28 (95% CI, 17.17-20.32) and 21.28 (95% CI, 19.24-23.06) per 1000 person-years among patients under dutasteride compared with those under finasteride, respectively. For new-onset PCa, the IR was 8.01 (95% CI, 7.07-9.08) and 9.38 (95% CI, 8.32-10.58) per 1000 person-years The pharmacoeconomical evaluation showed that the net budget impact of the use of dutasteride vs. finasteride in 1000 BPH-treated patient for 1 year induces a saving of 3933 €. Conclusions: The clinical effects of dutasteride and finasteride are slightly different. The likelihood of hospitalization for BPH-related surgery and of newly detected PCa seems to be in favor of dutasteride. The budget impact analyses showed a slightly benefit for dutasteride. Comparative prospective studies are necessary to confirm these results.

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The Evolution of White Matter Hyperintensities

US Neurology ◽

10.17925/usn.2010.05.02.10 ◽

2010 ◽

Vol 05 (02) ◽

pp. 10 ◽

Cited By ~ 1

Author(s):

Vanessa G Young ◽

Jillian J Kril ◽

◽

Keyword(s):

White Matter ◽

Blood Brain Barrier ◽

White Matter Hyperintensities ◽

Brain Barrier ◽

Common Finding ◽

Elderly Subjects ◽

Vascular Integrity ◽

Blood Brain ◽

Mri Scans ◽

Mri Changes

White matter hyperintensities (WMHs) are a common finding on magnetic resonance imaging (MRI) scans of elderly subjects. Despite their frequency, the clinical correlates and etiology of WMH remain controversial, with many conflicting results published. This is due, in part, to the varied populations studied. Nevertheless, the prevailing opinion is that these lesions are of vascular origin due to the strong associations with vascular risk factors and stroke. Neuropathological studies have also yielded varied results. Interestingly, while a number of associations with variables such as demyelination and gliosis have been reported, no single pathological variable has been found to account for the MRI changes. The most consistent associations are with reduced vascular integrity and increased bloodbrain barrier permeability. Further studies investigating the bloodbrain barrier may assist in elucidating the origin of these common abnormalities.

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