White Matter Hyperintensity, Immediate Antihypertensive Treatment, and Functional Outcome After Acute Ischemic Stroke

Background and Purpose— It remains unknown that whether white matter hyperintensity (WMH) severity influences the effect of antihypertensive treatment in acute ischemic stroke. We aimed to investigate the effects of early antihypertensive treatment on death and disability among patients with acute ischemic stroke according to WMH severities. Methods— This study was a secondary analysis of the data from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Severity of WMH was evaluated using Fazekas rating scale score among 303 participants with available magnetic resonance imaging data and was categorized into none-mild WMH (Fazekas score 0–2) and moderate-severe WMH (Fazekas score 3–6). Functional outcome was death or major disability (modified Rankin Scale score of ≥3) at 14 days or hospital discharge and within 3 months. Results— WMH severity was significantly associated with an increased risk of death or major disability. Each 1 score increase in Fazekas score was associated with an adjusted odds ratio (95% CI) of 1.25 (1.03–1.51) for 14 days or hospital discharge and 1.39 (1.12–1.72) for 3-month functional outcome. There were no significant interactions between antihypertensive treatment and WMH severity (both P >0.1) on functional outcome at 14 days or hospital discharge and within 3 months. The neutral effects of immediate antihypertensive treatment were observed both in patients with moderate-severe WMH and none-mild WMH. Conclusions— Participants with higher WMH burden had increased risk of death or major disability after acute ischemic stroke. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with a variety of WMH severities. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01840072.

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Effects of White Matter Hyperintensities on 90-Day Functional Outcome after Large Vessel and Non-Large Vessel Stroke

Cerebrovascular Diseases ◽

10.1159/000509071 ◽

2020 ◽

Vol 49 (4) ◽

pp. 419-426

Author(s):

Christoph Johannes Griessenauer ◽

David McPherson ◽

Andrea Berger ◽

Ping Cuiper ◽

Nelson Sofoluke ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Brain Mri ◽

Large Vessel ◽

Favorable Outcome ◽

White Matter Hyperintensity ◽

Vessel Occlusion ◽

Brain Extraction

Introduction: White matter hyperintensity (WMH) burden is a critically important cerebrovascular phenotype related to the diagnosis and prognosis of acute ischemic stroke. The effect of WMH burden on functional outcome in large vessel occlusion (LVO) stroke has only been sparsely assessed, and direct LVO and non-LVO comparisons are currently lacking. Material and Methods: We reviewed acute ischemic stroke patients admitted between 2009 and 2017 at a large healthcare system in the USA. Patients with LVO were identified and clinical characteristics, including 90-day functional outcomes, were assessed. Clinical brain MRIs obtained at the time of the stroke underwent quantification of WMH using a fully automated algorithm. The pipeline incorporated automated brain extraction, intensity normalization, and WMH segmentation. Results: A total of 1,601 acute ischemic strokes with documented 90-day mRS were identified, including 353 (22%) with LVO. Among those strokes, WMH volume was available in 1,285 (80.3%) who had a brain MRI suitable for WMH quantification. Increasing WMH volume from 0 to 4 mL, age, female gender, a number of stroke risk factors, presence of LVO, and higher NIHSS at presentation all decreased the odds for a favorable outcome. Increasing WMH above 4 mL, however, was not associated with decreasing odds of favorable outcome. While WMH volume was associated with functional outcome in non-LVO stroke (p = 0.0009), this association between WMH and functional status was not statistically significant in the complete case multivariable model of LVO stroke (p = 0.0637). Conclusion: The burden of WMH has effects on 90-day functional outcome after LVO and non-LVO strokes. Particularly, increases from no measurable WMH to 4 mL of WMH correlate strongly with the outcome. Whether this relationship of increasing WMH to worse outcome is more pronounced in non-LVO than LVO strokes deserves additional investigation.

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Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke

Neurology ◽

10.1212/wnl.0000000000004257 ◽

2017 ◽

Vol 89 (8) ◽

pp. 805-812 ◽

Cited By ~ 27

Author(s):

Chongke Zhong ◽

Jingyuan Yang ◽

Tan Xu ◽

Tian Xu ◽

Yanbo Peng ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Scale Score ◽

Outcome Data ◽

Antihypertensive Medications ◽

Risk Of Death ◽

Cell Counts ◽

Increased Risk ◽

White Blood Cell Counts ◽

Matrix Metalloproteinases 9

Objective:To examine the association between serum matrix metalloproteinases-9 (MMP-9) levels and prognosis of acute ischemic stroke.Methods:We measured serum MMP-9 levels in 3,186 participants (2,008 men and 1,178 women) from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Study outcome data on death, major disability (modified Rankin Scale score ≥3), and vascular disease were collected at 3 months after stroke onset.Results:During 3 months of follow-up, 767 participants (24.6%) experienced major disability or died. Serum MMP-9 was significantly associated with an increased risk of death and major disability after adjustment for age, sex, time from onset to randomization, current smoking, alcohol drinking, admission NIH Stroke Scale score, diastolic blood pressure, plasma glucose, white blood cell counts, use of antihypertensive medications, and history of hypertension, coronary heart disease, and diabetes mellitus. For example, 1-SD (0.32 ng/mL) higher log–MMP-9 was associated with an odds ratio (95% confidence interval) of 1.16 (1.06–1.28) for the combined outcome of death and major disability, 1.12 (1.01–1.23) for major disability, and 1.29 (1.01–1.66) for death. The addition of serum MMP-9 to conventional risk factors improved risk prediction of the combined outcome of death or major disability (net reclassification index 9.1%, p = 0.033; integrated discrimination improvement 0.4%, p = 0.004).Conclusions:Higher serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of mortality and major disability, suggesting that serum MMP-9 could be an important prognostic factor for ischemic stroke.

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Abstract P317: White Matter Hyperintensity Lesion Burden Modulates Functional Outcome After Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.p317 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Anna K Bonkhoff ◽

Sungmin Hong ◽

Markus Schirmer ◽

Martin Bretzner ◽

Anne-Katrin Giese ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

White Matter Hyperintensity ◽

Study Cohort ◽

Stroke Severity ◽

Ischemic Lesion ◽

Long Term Outcome ◽

Index Stroke

Introduction: As a radiographic signature of end-stage small vessel disease, white matter hyperintensity (WMH) burden impacts recovery and outcomes after acute ischemic stroke (AIS). In this study, we sought to investigate the effect of WMH volume (WMHv) on stroke severity and functional outcomes independent of the infarct size and topography. Methods: We analyzed 503 AIS patients with MRI data obtained on admission for index stroke enrolled in the multi-center MRI-GENIE study (cohort 1), followed by validation of the findings in an independent single-site study of 555 AIS patients (cohort 2). Stroke severity (NIHSS score) at index stroke and the long-term outcome (3-6 months mRS score) were modeled via Bayesian linear regression. Models included WMHv, age, sex, a 10-dimensional spatial ischemic lesion representation, acute infarct (DWI) volume, and common vascular risk factors (hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease). Results: Cohorts did not differ significantly in major clinical characteristics [cohort 1: age: 65.0±14.6, 41% female, NIHSS: 5.5±5.4, mRS: 1(iqr 2); cohort 2: age: 65.0±14.8, 38% female, NIHSS: 5.0±6.0, mRS: 1(iqr 3), p >0.05 for all comparisons]. WMHv did not substantially affect AIS severity ( Fig A ); in contrast, it emerged as an independent predictor of functional outcome in both datasets ( Fig B ). Conclusions: When accounted for AIS lesion topography and stroke volume, total WMH lesion burden did not appear to modulate initial stroke severity but was associated with worse functional post-stroke outcomes. Future studies are needed to explore potential origins of these detrimental effects of pre-existing WMH burden on recovery after AIS.

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Abstract P212: Blood pressure lowering and clinical outcomes in patients with acute ischemic stroke: China Antihypertensive Trial in Acute Ischemic Stroke (CATIS)

Circulation ◽

10.1161/circ.129.suppl_1.p212 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Jiang He ◽

Yonghong Zhang ◽

Tan Xu ◽

Qi Zhao ◽

Chung-Shiuan Chen ◽

...

Keyword(s):

Blood Pressure ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Outcomes ◽

Hospital Discharge ◽

Antihypertensive Treatment ◽

Stroke Onset ◽

Odds Ratios ◽

Risk Of Death

Introduction: Observational studies have reported that a decrease in blood pressure (BP) within the first several days after stroke onset was associated with poorer, better, or no difference in adverse clinical outcomes among patients with acute ischemic stroke. Hypothesis: We investigated the association of immediate BP lowering in acute ischemic stroke patients with major clinical outcomes at 14 days or hospital discharge and at a 3 month follow-up visit. Methods: CATIS is a randomized clinical trial conducted in 4,071 Chinese patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP). Patients were randomly assigned to receive antihypertensive treatment or control. The primary outcome was a combination of death and major disability (a modified Rankin score ≥3) at 14 days or hospital discharge or at the 3 month follow-up visit. Multiple logistic regression analysis was used to adjust for baseline age, gender, SBP, NIHSS score, time of stroke onset, history of antihypertensive treatment, and intervention assignment. Results: Compared to patients with a >0-10% reduction in systolic BP within the first 24 hours after admission, the multivariable-adjusted odds ratios (95% confidence interval [CI]) for patients with ≤0%, 11-20%, and ≥21% reduction in SBP were 1.40 (1.08, 1.82), 1.00 (0.81, 1.23), and 0.98 (0.73, 1.30) at 14 days or hospital discharge; and 1.31 (1.00, 1.71), 0.82 (0.66, 1.02), and 0.78 (0.58, 1.05) at 3 months follow-up. Compared to patients with a BP 130-139/85-89 mmHg at 7 days after admission, the multivariable-adjusted odds ratios (95% CI) for patents with BP <130/85, 140-159/90-99, and ≥160/100 mmHg were 1.07 (0.82, 1.38), 1.09 (0.89, 1.34), and 1.58 (1.18, 2.11) at 14 days or hospital discharge, and 0.89 (0.67, 1.17), 1.10 (0.89, 1.36), and 1.50 (1.11, 2.03) at 3 months follow-up, respectively. Conclusions: These data indicate that a lack of BP reduction in the first 24 hours of hospitalization and higher BP levels at 7 days after admission predict increased risk of death and major disability at 14 days or hospital discharge and at 3 months follow-up.

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Abstract TP476: White Matter Hyperintensity Burden is Associated With Poor Collateral Flow and Worse Outcomes in an Acute Ischemic Stroke Cohort

Stroke ◽

10.1161/str.51.suppl_1.tp476 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Rami-James Assadi ◽

Hongyu An ◽

Yasheng Chen ◽

Andria Ford ◽

Jin-Moo Lee

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Pearson Correlation ◽

Stroke Onset ◽

White Matter Hyperintensity ◽

Flow Index ◽

Acute Ischemia ◽

Collateral Flow ◽

Core Volume

Introduction: White matter hyperintensity volume (WMHv), a quantitative neuroimaging biomarker of cerebral small vessel disease (CSVD), is associated worse outcomes after ischemic stroke. In this study, we hypothesized that worse outcomes in CSVD patients were due to poor collateral flow during acute ischemia. Methods: 47 patients with acute ischemic stroke (AIS) were prospectively enrolled in this study. Serial MRIs were performed at 3 hours and 30 days after stroke onset. 3-hour FLAIR images were used to determine WMHv, after manually delineating lesions with MIPAV. An index of collateral flow (delayed perfusion to the penumbra) was determined by subtracting core volume (volume of tissue with ADC<600) from the volume of brain tissue with Tmax>2. Patient’s NIHSS was scored at 3 hours and 30 days after stroke onset and the difference was calculated (ΔNIHSS). Log-transformed WMHv was correlated to ΔNIHSS and the collateral flow index, using Pearson correlation. Results: Mean age = 63.9 years (SD 13.5); 37% female; median 3-hour NIHSS = 13 (IQR 6.5-20); median change in NIHSS between 3h and 30d = 4 (IQR: 0-7); median core volume = 13cm3 (IQR 4.3-35.6); median WMHv = 1.257cm3 (IQR 641-3595). WMHv was associated with reduced improvement in ΔNIHSS (R=-0.42, ρ=0.005). Furthermore, WMHv demonstrated a trend for association with poor collateral flow (R=-0.28, ρ=0.062). In this dataset, we will explore the relationship between WMHv and other tissue-based metrics of collateral flow, including the hypoperfusion intensity ratio (HIR) and the cerebral blood volume ratio (rCBV). Conclusions: Our study confirms that patients with CSVD have worse outcomes after AIS. The data also raise the possibility that these worse outcomes in CSVD patients may be mediated by compromised collateral flow in the setting of acute ischemia.

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Abstract MP16: Excessive White Matter Hyperintensity Burden and Functional Outcomes After Acute Ischemic Stroke

Stroke ◽

10.1161/str.52.suppl_1.mp16 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Sungmin Hong ◽

Anne-katrin Giese ◽

Markus D Schirmer ◽

Adrian V Dalca ◽

Anna Bonkhoff ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Functional Outcomes ◽

Life Time ◽

Stroke Recovery ◽

White Matter Hyperintensity ◽

Brain Health ◽

Stroke Outcomes ◽

The Brain

Objective: Ability of the brain to recover after an acute ischemic stroke (AIS) is linked to the pre-stroke burden of white matter hyperintensity (WMH), a radiographic marker of brain health. We sought to determine the excessive WMH burden in an AIS population and investigate its association with 3-month stroke outcomes. Data: We used 2,435 subjects from the MRI-GENIE study. Three-month functional outcomes of 872 subjects among those subjects were measured by 90-day modified Ranking Scale (mRS). Methods: We automatically quantified WMH volume (WMHv) on FLAIR images and adjusted for a brain volume. We modeled a trend using the factor analysis (FA) log-linear regression using age, sex, atrial fibrillation, diabetes, hypertension, coronary artery disease and smoking as input variables. We categorized three WMH burden groups based on the conditional probability given by the model (LOW: lower 33%, MED: middle 34%, and HIGH: upper 33%). The subgroups were compared with respect to mRS (median and dichotomized odds ratio (OR) (good/poor: mRS 0-2/3-6)). Results: Five FA components out of seven with significant relationship to WMHv (p<0.001) were used for the regression modeling (R 2 =0.359). The HIGH group showed higher median (median=2, IQR=2) mRS score than LOW (median=1, IQR=1) and MED (median=1, IQR=1). The odds (OR) of good AIS outcome for LOW and MED were 1.8 (p=0.0001) and 1.6 (p=0.006) times higher than HIGH, respectively. Conclusion: Once accounted for clinical covariates, the excessive WMHv was associated with worse 3-month stroke outcomes. These data suggest that a life-time of injury to the white matter reflected in WMH is an important factor for stroke recovery and an indicator of the brain health.

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Homocysteine Level Is Associated with White Matter Hyperintensity Locations in Patients with Acute Ischemic Stroke

PLoS ONE ◽

10.1371/journal.pone.0144431 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0144431 ◽

Cited By ~ 8

Author(s):

Yuan Gao ◽

Sen Wei ◽

Bo Song ◽

Jie Qin ◽

Hui Fang ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Homocysteine Level ◽

White Matter Hyperintensity

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Abstract WP205: Pipeline for Automated White Matter Hyperintensity Segmentation in Patients With Acute Ischemic Stroke: The MRI-GENIE Study

Stroke ◽

10.1161/str.48.suppl_1.wp205 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Markus D Schirmer ◽

Adrian V Dalca ◽

Ramesh Sridharan ◽

Anne-Katrin Giese ◽

Joseph P Broderick ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Large Scale ◽

Current Knowledge ◽

Principal Component ◽

White Matter Hyperintensity ◽

Brain Extraction ◽

Fluid Attenuated Inversion Recovery ◽

Good Agreement

Introduction: White matter hyperintensity volume (WMHv) is an important and highly heritable cerebrovascular phenotype; however, manual or semi-automated approaches to clinically acquired MRI analysis hinder large-scale studies in acute ischemic stroke (AIS). In this work, we develop a high-throughput, fully automated WMHv analysis pipeline for clinical fluid-attenuated inversion recovery (FLAIR) images to facilitate rapid genetic discovery in AIS. Methods: Automated WMHv extraction from multiple subjects relies on significant pre-processing of medical scans, including co-registration of the images. To reduce the effects of anisotropic voxel sizes, each FLAIR image is upsampled using bi-cubic interpolation. Brain extraction is performed using RObust Brain EXtraction (ROBEX). Images are then registered to an in-house FLAIR template using Advanced Normalization Tools (ANTs). The spatial covariation of WMH is learned through principal component analysis (PCA) of manual outlines from 100 subjects. Areas of leukoaraiosis are identified and separated from other lesions using the PCA modes. Volumes are then computed using non-interpolated slices for each subject. Standard deviation (SD) in WMHv (9 subjects; 6 raters each) is calculated as a measure of variability. Good agreement between automated and manual outlines is assessed in 358 subjects (automated WMHv within 3SD of manual WMHv). Results: As part of the MRI - Gen etics I nterface E xploration (MRI-GENIE) study, WMHv were calculated on a set of 2703 FLAIR images of patients from 12 independent AIS cohorts (sites). Results are shown in Figure 1. Comparing manual and automated WMHv shows that 88% of the automated WMHv fall within 3 SD from the manual WMHv, suggesting good agreement. Conclusion: WMHv segmentation using a fully-automated pipeline for analysis of clinical MRIs is both feasible and accurate. Ongoing analysis of the extracted WMHv is expected to advance current knowledge of risks and outcomes in AIS.

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Dabigatran Reversal Before Intravenous Tenecteplase in Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.119.028327 ◽

2020 ◽

Vol 51 (5) ◽

pp. 1616-1619 ◽

Cited By ~ 2

Author(s):

James Beharry ◽

Michael J. Waters ◽

Roy Drew ◽

John N. Fink ◽

Duncan Wilson ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Scale Score ◽

Clinical Laboratory ◽

Intravenous Thrombolysis ◽

Interquartile Range ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion

Background and Purpose— Reversal of dabigatran before intravenous thrombolysis in patients with acute ischemic stroke has been well described using alteplase but experience with intravenous tenecteplase is limited. Tenecteplase seems at least noninferior to alteplase in patients with intracranial large vessel occlusion. We report on the experience of dabigatran reversal before tenecteplase thrombolysis for acute ischemic stroke. Methods— We included consecutive patients with ischemic stroke receiving dabigatran prestroke treated with intravenous tenecteplase after receiving idarucizumab. Patients were from 2 centers in New Zealand and Australia. We reported the clinical, laboratory, and radiological characteristics and their functional outcome. Results— We identified 13 patients receiving intravenous tenecteplase after dabigatran reversal. Nine (69%) were male, median age was 79 (interquartile range, 69–85) and median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 4–21). Atrial fibrillation was the indication for dabigatran therapy in all patients. All patients had a prolonged thrombin clotting time (median, 80 seconds [interquartile range, 57–113]). Seven patients with large vessel occlusion were referred for endovascular thrombectomy, 2 of these patients (29%) had early recanalization with tenecteplase abrogating thrombectomy. No patients had parenchymal hemorrhage or symptomatic hemorrhagic transformation. Favorable functional outcome (modified Rankin Scale score, 0–2) occurred in 8 (62%) patients. Two deaths occurred from large territory infarction. Conclusions— Our experience suggests intravenous thrombolysis with tenecteplase following dabigatran reversal using idarucizumab may be safe in selected patients with acute ischemic stroke. Further studies are required to more precisely estimate the efficacy and risk of clinically significant hemorrhage.

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Signs of Pulmonary Infection on Admission Chest Computed Tomography Are Associated With Pneumonia or Death in Patients With Acute Stroke

Stroke ◽

10.1161/strokeaha.120.028972 ◽

2020 ◽

Vol 51 (6) ◽

pp. 1690-1695

Author(s):

Jeroen C. de Jonge ◽

Richard A.P. Takx ◽

Frans Kauw ◽

Pim A. de Jong ◽

Jan W. Dankbaar ◽

...

Keyword(s):

Computed Tomography ◽

Ischemic Stroke ◽

Acute Stroke ◽

Acute Ischemic Stroke ◽

Pulmonary Infection ◽

Stroke Onset ◽

Odds Ratios ◽

Chest Computed Tomography ◽

Risk Of Death ◽

Increased Risk

Background and Purpose— In patients with acute stroke, the occurrence of pneumonia has been associated with poor functional outcomes and an increased risk of death. We assessed the presence and consequences of signs of pulmonary infection on chest computed tomography (CT) before the development of clinically overt pneumonia. Methods— In 200 consecutive patients with acute ischemic stroke who had CT angiography from skull to diaphragm (including CT of the chest) within 24 hours of symptom onset, we assessed the presence of consolidation, ground-glass-opacity and the tree-in-bud sign as CT signs of pulmonary infection and assessed the association with the development of clinically overt pneumonia and death in the first 7 days and functional outcome after 90 days with logistic regression. Results— The median time from stroke onset to CT was 151 minutes (interquartile range, 84–372). Thirty patients (15%) had radiological signs of infection on admission, and 22 (11.0%) had a clinical diagnosis of pneumonia in the first 7 days. Patients with radiological signs of infection had a higher risk of developing clinically overt pneumonia (30% versus 7.6%; adjusted odds ratios, 4.2 [95% CI, 1.5–11.7]; P =0.006) and had a higher risk of death at 7 days (adjusted odds ratios, 3.7 [95% CI, 1.2–11.6]; P =0.02), but not at 90 days. Conclusions— About 1 in 7 patients with acute ischemic stroke had radiological signs of pulmonary infection within hours of stroke onset. These patients had a higher risk of clinically overt pneumonia or death. Early administration of antibiotics in these patients may lead to better outcomes.

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