Hemorrhagic risk after intravenous thrombolysis for ischemic stroke in patients with cerebral microbleeds and white matter disease.
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ABSTRACT: Objectives
Aim of this study was to evaluate the association between cerebral microbleeds (CMBs) and white matter disease (WMD) with intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) with rt-PA. We also evaluated whether CMBs characteristics and WMD burden correlate with symptomatic ICH and outcome.Methods
We included acute ischemic stroke (AIS) patients treated with IVT. The number and location of CMBs as well as severity of WMD were rated analyzing pre- or post-treatment MRI. Multivariable regression analysis was used to determine the impact of CMB and WMD on ICH subgroups and outcome measures.Results
434 patients were included. CMBs were detected in 23.3% of them. ICH occurred in 34.7% of patients with CMBs. Independent predictors of parenchymal hemorrhage were the presence of CMBs (OR 2.724, 95% CI 1.360-5.464, p = 0.005) as well as cortical-subcortical stroke (OR 3.629, 95% CI 1.841-7.151, p < 0.001) and atherothrombotic stroke subtype (OR 3.381, 95% CI 1.335-8.566, p = 0.010). Either the presence, or number, and location of CMBs, as well as WMD, was not independently associated with the development of SICH. No independent association between the presence, number, or location of CMBs or WMD and outcome measures was observed.Conclusions
The results of our study suggest that the exclusion of eligible candidates to administration of IV rt-PA only on the basis of CMBs presence is not justified. The clinical decision should be weighed with a case-by-case approach. Additional data are needed to evaluate the benefit-risk profile of rt-PA in patients carrying numerous microbleeds.
SUBMITTER: Capuana ML
PROVIDER: S-EPMC8043883 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesWe aimed to investigate effects of deep white matter hyperintensity (DWMH) and periventricular hyperintensity (PVH) on the efficacy of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS).MethodsA total of 113 AIS patients with WMH were categorized into the PVH group and the DWMH group according to the lesion location, with the division of two subgroups based on whether or not they received IVT treatment: the thrombolysis group and the control group. Kaplan-Meier analysis was used for proportional hazards of recurrent stroke. Further, multivariate Cox regression analysis was employed.ResultsOf total patients, there were 62 PVH patients and 51 DWMH patients: 27 of PVH patients and 22 of DWMH patients received IVT, and the remaining patients only received routine treatment. DWMH patients had a higher risk of END (36.4% vs. 11.1%; p = 0.034) and HT (22.7% vs. 3.7%; p = 0.038) than PVH patients in the thrombolysis group. Moreover, DWMH patients undergoing IVT also had a higher risk of END (36.4% vs. 10.3%; x2 = 5.050; p = 0.025) and HT (22.7% vs. 3.4%; x2 = 4.664; p = 0.031) than DWMH patients without IVT. Again, PVH patients had a higher rate of recurrent stroke (20.0% vs. 3.4%; p = 0.034) than DWMH patients in the control group after 90-day follow-up. Kaplan-Meier analysis showed a significant difference in cumulative probability of no major endpoint events (p = 0.039). Further, multivariate Cox regression revealed that PVH is an independent risk factor for stroke recurrence in AIS patients after adjusting confounding factors.ConclusionsThe location of WMH is closely associated with the efficacy of IVT in AIS patients.
| S-EPMC6305931 | biostudies-literature
Project description:BackgroundHemorrhagic transformation (HT) is the most serious complication of ischemic stroke patients after intravenous thrombolysis and leads to a poor clinical prognosis. This study aimed to determine the independent predictors associated with HT in stroke patients with intravenous thrombolysis and to establish and validate a nomogram that combines with predictors to predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.MethodThis study enrolled ischemic stroke patients with intravenous thrombolysis from December 2016 to June 2022. All the patients were divided into training and validation cohorts. The nomogram was composed of the significant predictors for HT in the training cohort as obtained by the multivariate logistic regression analysis. The area under the receiver operating characteristic curve was used to assess the discriminative performance of the nomogram. The calibration performance of the nomogram was assessed by the Hosmer-Lemeshow goodness-of-fit test and calibration plots. Decision curve analysis was used to test the clinical validity of the nomogram.ResultsA total of 394 patients with intravenous thrombolysis were enrolled in the study. In the training cohort (n = 257), 45 patients had HT after intravenous thrombolysis. Multivariate logistic regression analysis demonstrated early infarct signs (OR, 7.954; 95% CI, 3.553-17.803; P < 0.001), NIHSS scores (OR, 1.110; 95% CI, 1.054-1.168; P < 0.001), uric acid (OR, 0.993; 95% CI, 0.989-0.997; P = 0.001), and albumin-to-globulin ratio (OR, 0.109; 95% CI, 0.023-0.508; P = 0.005) were independent predictors for HT and constructed the nomogram. In the training and validation cohorts, the AUC of the nomogram was 0.859 and 0.839, respectively. The Hosmer-Lemeshow goodness-of-fit test and calibration plot showed good concordance between predicted and observed probability in the training and validation cohorts. Decision curve analysis indicated that the nomogram was significantly useful for predicting HT in the training and further confirmed in the validation cohort.ConclusionThis study proposes a novel and practical nomogram based on early infarct signs, NIHSS scores, uric acid, and albumin-to-globulin ratio that can well predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.
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Project description:Background Which type of recurrent stroke is associated with pulse pressure (PP) remains uncertain in ischemic stroke with cerebral microbleeds or intracerebral hemorrhage. Methods and Results The PICASSO (Prevention of Cardiovascular Events in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage) database involving 1454 subjects was analyzed. Subjects were stratified into quartiles according to the distribution of mean PP (mm Hg) during follow-up (mean, 1.9 years): <47 (first quartile), 48 to 53 (second quartile), 54 to 59 (third quartile), and ≥60 mm Hg (fourth quartile). The primary end point was hemorrhagic stroke, and the secondary end points were ischemic stroke, stroke of any type, and major adverse cardiovascular events. Adjusted time-dependent area under the receiver operating characteristic curve analysis was performed to assess the prediction accuracy of mean PP. The mean frequency of visit for blood pressure checkup was 9.4±5.5 times. The stroke incidence rate per 100 person-years was 3.14, 2.24, 5.52, and 6.22, respectively in increasing quartile of mean PP, and the rate of major adverse cardiovascular events was 3.82, 2.84, 6.37, and 7.14, respectively. In the presence of mean arterial pressure, hemorrhagic stroke risk was higher in the highest quartile (adjusted hazard ratio, 6.03; 95% CI, 1.04-34.99) versus the lowest quartile, which was evident at higher mean systolic blood pressure. Higher mean PP as a continuous variable was also a predictor of hemorrhagic stroke (1.09, 1.03-1.15). The time-dependent area under the receiver operating characteristic curve for hemorrhagic stroke was 0.79. Conclusions Long-term elevated PP with higher systolic blood pressure confers a greater risk of subsequent hemorrhagic stroke among stroke patients with cerebral microbleeds or intracerebral hemorrhage. Registration URL: https://www.clinicaltrials.gov; Unique identifier, NCT01013532.
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Project description:Background and purposeTimely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with "Stroke Code" (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis.MethodsThe study period was divided into the "pre-SC era" (January 2006 to July 2010) and "SC era" (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras.ResultsDuring the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n?=?91, 13.9%) to the SC era (n?=?216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ?60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ?2) at discharge (49.5 vs. 39.6%, P?=?0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality.ConclusionThe SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time.
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Project description:ObjectivesWe evaluated the impact of malnutrition as estimated by the controlling nutritional status (CONUT) score and prognostic nutritional index (PNI) on hemorrhagic transformation (HT) and stroke outcomes after intravenous thrombolysis (IVT).Materials and methodsUsing a multicenter registry database, we enrolled 808 patients with acute ischemic stroke who received IVT between August 2013 and May 2021. We defined malnutrition as a CONUT score ≥ 2 and low PNI. The primary outcome measure was the occurrence of symptomatic HT contributing to early neurologic deterioration (END-SHT) after IVT. Multivariable analysis was performed to analyze the association between CONUT score, PNI, and END-SHT after IVT.ResultsThe rate of END-SHT was higher with increasing CONUT scores and PNI values. In the multivariable analysis, CONUT score ≥ 5 and low PNI were significantly associated with END-SHT (odds ratio [95% confidence interval], CONUT score ≥ 5: 12.23 [2.41-62.07], p = 0.003; low PNI: 4.98 [1.76-14.09], p = 0.003). The receiver operating characteristic curve showed that both the CONUT score and PNI had good predictive ability. The cutoff values for CONUT and PNI were 5 and 42.3, respectively, for END-SHT.ConclusionMalnutrition, as denoted by a higher CONUT score and lower PNI, was associated with END-SHT. The joint application of both nutritional markers could be useful in predicting END-SHT after IVT.
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Project description:Background and objectivesCerebral microbleeds (CMBs) are common in patients with acute ischemic stroke and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown.MethodsWe performed a prespecified analysis of the prospective randomized controlled multicenter Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial including patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with IV thrombolysis with alteplase at 0.9 mg/kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by 3 raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale (mRS) score ≤1, and symptomatic ICH according to National Institutes of Neurological Disease and Stroke trial criteria 22 to 36 hours after treatment.ResultsOf 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis. Ninety-eight (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB; 37 (8.1%) had 2 to 4 CMBs; and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a nonsignificant increased risk of symptomatic ICH (11.2% vs 4.2%; adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.99-5.43, p = 0.052) but had no effect on functional outcome at 90 days (mRS score ≤1: 45.8% vs 50.7%; adjusted OR 0.99, 95% CI 0.59-1.64, p = 0.955). Patients receiving alteplase had better functional outcome (mRS score ≤1: 54.6% vs 44.6%, adjusted OR 1.61, 95% CI 1.07-2.43, p = 0.022) without evidence of heterogeneity in relation to CMB presence (p of the interactive term = 0.546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy related) or not strictly lobar CMB distribution.DiscussionIn the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in patients with acute ischemic stroke with ≥1 CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm ratio in patients with a larger number of CMBs.Trial registration informationClinicalTrials.gov identifier NCT01525290; ClinicalTrialsRegister.EU identifier 2011-005906-32.Classification of evidenceThis study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.
| S-EPMC8792812 | biostudies-literature
Project description:ObjectiveThe objective of this study was to investigate the safety and efficacy of remote ischemic conditioning (RIC) combined with intravenous thrombolysis (IVT) in the treatment of acute ischemic stroke (AIS).MethodsPatients with AIS who underwent IVT were enrolled and 1:1 randomized to the RIC group and sham-RIC group in this study. RIC (or sham-RIC) was performed twice within 6-24 h of IVT. The subjects in the two groups were followed up for 90 days. The safety outcome included the ratio of hemorrhagic transformation (HT), adverse events during the follow-up, blood pressure within the first 24 h after IVT, and laboratory tests 24 h after IVT. The efficacy outcome included the modified Rankin Scale (mRS) score, National Institute of Health Stroke Scale (NIHSS) score during the follow-up, and level of high-sensitivity C-reactive protein (hs-CRP) tested 24 h after IVT.ResultsForty-nine patients (24 in the RIC group and 25 in the sham-RIC group) were recruited. No significant difference was observed in the ratio of HT, adverse events, blood pressure, coagulation function or liver function between groups. In addition, there was no significant difference in mRS score and NIHSS score during the follow-up between groups. However, patients in the RIC group exhibited a significant lower level of hs-CRP compared with the control group (P = 0.048).InterpretationRIC combined with IVT is safe in the treatment of AIS. The neuroprotective and anti-inflammatory effects of this therapy warrant further study on a larger scale.
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Project description:BackgroundTwo markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease.Aim and/or hypothesisTo test for independent associations between two Alzheimer's disease-susceptibility gene loci--APOE ? and the TOMM40 '523' poly-T repeat--and white matter hyperintensities/cerebral microbleed burden in community-dwelling older adults.MethodsParticipants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ? and TOMM40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation?=?0·7; range?=?71-74).ResultsNo significant effects of APOE ? or TOMM40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants.ConclusionsLack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature.
| S-EPMC4950052 | biostudies-literature
Project description:Background and purposePrevious studies have shown that diffusion tensor imaging suggests a diffuse loss of white matter integrity in people with white matter hyperintensities or lacunes. The purpose of this study was to investigate whether the presence of cerebral microbleeds and their distribution are related to the integrity of white matter microstructures.Materials and methodsThe study comprised 982 participants who underwent brain MR imaging to determine microbleed status. The cross-sectional relation between microbleeds and the microstructural integrity of the white matter was assessed by 2 statistical methods: a multilinear regression model based on the average DTI parameters of normal-appearing white matter and Tract-Based Spatial Statistics analysis, a tract-based voxelwise analysis. Fiber tractography was used to spatially describe the microstructural abnormalities along WM tracts containing a cerebral microbleed.ResultsThe presence of cerebral microbleeds was associated with lower mean fractional anisotropy and higher mean diffusivity, axial diffusivity, and radial diffusivity, and the association remained when cardiovascular risk factors and cerebral small-vessel disease markers were further adjusted. Tract-Based Spatial Statistics analysis indicated strictly lobar cerebral microbleeds associated with lower fractional anisotropy, higher mean diffusivity, and higher radial diffusivity in the internal capsule and corpus callosum after adjusting other cerebral small-vessel disease markers, while only a few voxels remained associated with deep cerebral microbleeds. Diffusion abnormalities gradients along WM tracts containing a cerebral microbleed were not found in fiber tractography analysis.ConclusionsCerebral microbleeds are associated with widely distributed changes in white matter, despite their focal appearance on SWI.
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