Hyperintense acute reperfusion marker associated with hemorrhagic transformation in the WAKE-UP trial.
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ABSTRACT: Introduction
Hyperintense acute reperfusion marker (HARM) is an indicator of early disruption of the blood-brain-barrier. Our aim was to investigate the incidence of HARM in patients with a diffusion weighted imaging (DWI) - fluid attenuated inversion recovery (FLAIR) mismatch and determine the association between this marker and hemorrhagic complications as well as clinical outcome.Patients and methods
We included patients from the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial who underwent baseline perfusion weighted imaging (PWI). HARM was defined as a hyperintense signal in the cerebrospinal fluid space on FLAIR imaging at 24 h after baseline imaging. We compared baseline characteristics in patients with and without HARM and investigated the association between HARM and any hemorrhagic transformation (HT) and parenchymal hematoma (PH) in a multivariate logistic regression. We also explored HARM as an independent predictor of poor outcome, defined as a modified Rankin Scale of 3-6 at 90 days.Results
HARM was present in 14 of 223 (6%) patients with a DWI-FLAIR mismatch and baseline characteristics were similar in patients with vs without HARM. HARM showed an independent relationship with any HT (OR 6.67; 95%CI 1.72-26.58) and any PH (OR 6.92; 95%CI 1.34-29.49). The rate of HARM was similar in patients with good and poor outcome (5%, p = 0.90).Conclusion
In the WAKE-UP trial, the incidence of HARM was only 6% at 24 h. An association was present between HARM and hemorrhagic complications, but no relationship with functional outcome was observed.
SUBMITTER: Wouters A
PROVIDER: S-EPMC8370087 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeIn the present study, we aimed to investigate the frequency of blood brain barrier injury in posterior circulation infarction as demonstrated by the hyperintense acute reperfusion marker (HARM) on fluid attenuated inversion recovery images (FLAIR).MethodsFrom a MRI report database we identified patients with posterior circulation infarction who underwent MRI, including perfusion-weighted images (PWI), within 12 hours after onset and follow-up MRI within 24 hours and analyzed diffusion-weighted images (DWI), PWI, FLAIR, and MR angiography (MRA). On FLAIR images, the presence of HARM was noted by using pre-specified criteria (focal enhancement in the subarachnoid space and/or the ventricles).ResultsOverall 16 patients (median age of patients 68.5 (IQR 55.5-82.75) years) with posterior circulation infarction were included. Of these, 13 (81.3%) demonstrated PCA occlusion, and 3 (18.7%) patients BA occlusion on MRA. Initial DWI demonstrated ischemic lesions in the thalamus (68.8%), splenium (18.8%), hippocampus (75%), occipital lobe (81.3%), mesencephalon (18.8%), pons (18.8%), and cerebellum (50%). On follow-up MRA recanalization was noted in 10 (62.5%) patients. On follow-up FLAIR images, HARM was observed in 8 (50%) patients. In all of these, HARM was detected remote from the acute ischemic lesion. HARM was more frequently observed in patients with vessel recanalization (p = 0.04), minor infarction growth (p = 0.01), and smaller ischemic lesions on follow-up DWI (p = 0.05).ConclusionsHARM is a frequent finding in posterior circulation infarction and associated with vessel recanalization, minor infarction growth as well as smaller infarction volumes in the course. Neuroradiologists should be cognizant of the fact that HARM may be present on short interval follow-up FLAIR images in patients with acute ischemic infarction who initially underwent MRI and received intravenous gadolinium-based contrast agents.
| S-EPMC4915711 | biostudies-literature
Project description:The hyperintense acute reperfusion marker (HARM) is a delayed enhancement of the subarachnoid or subpial space observed on post-contrast fluid-attenuated inversion recovery (FLAIR) images and is associated with permeability changes to the blood-brain barrier in acute stroke. We investigated the relationship between HARM and stroke etiology based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. In addition, we evaluated the relationship between HARM and stroke locations with respect to vascular territories and anatomic compartments.We recruited 264 consecutive patients (109 women; mean age 68.63?years) who were diagnosed with acute ischemic stroke and underwent brain magnetic resonance imaging (MRI) including post-contrast FLAIR and DWI within 7?days of symptom onset from May 2015 to March 2016 for this retrospective study. Post-contrast FLAIR images were obtained 5?min after gadolinium administration. The mean time interval between the onset of stroke symptoms and MRI acquisition in total included patients was 18?h and 7?min (median 12?h and 57?min, range 2-127?h). We analyzed the overall incidence and distribution patterns of HARM in acute ischemic stroke cases and compared the relative incidence and distribution patterns of HARM between the subgroups of stroke etiology based on conventional TOAST classification. We obtained odds ratio (OR) of HARM in different stroke locations based on vascular territories and anatomical compartments. This study was approved by our institutional review board.Among the 264 patients, 67 (25.38%) patients were HARM positive and 197 (74.62%) patients were HARM negative. There was significant difference in HARM incidence among the stroke subgroups (p?<?0.001). Small vessel occlusion (SVO) was associated with the HARM-negative group (p?<?0.001), while large artery atherosclerosis (LAA) and cardioembolism (CE) were associated with the HARM-positive group (p?=?0.001). Also, regional pattern of HARM on the same vascular territory as the acute infarction was dominantly demonstrated regardless of stroke etiology. The OR for HARM from middle cerebral artery (MCA) infarction was 1.868 [95% confidence interval (CI): 1.025-3.401]. The OR for HARM from cortical infarction was 9.475 (95% CI: 4.754-18.883) compared to other anatomic compartments.The presence of the HARM was significantly associated with embolic infarctions including LAA and CE. Conversely, SVO was exclusively associated with the absence of the HARM. Second, MCA and cortical infarction showed a more pronounced HARM compared to infarctions at other vascular territories and anatomic compartments. According to the results in the current study, we speculate that the presence of HARM on post-contrast FLAIR images was associated with specific stroke causes especially in embolic causes.
| S-EPMC5727375 | biostudies-literature
Project description:It aimed to investigate the incidence and final diagnosis of hyperintense acute reperfusion marker (HARM) signs in patients initially suspected of having a transient ischemic attack (TIA).In retrospective manner, a series of consecutive series of patients who arrived at the emergency department and was initially assessed as TIA within 12 hours of symptom onset between July 2015 and December 2016 were enrolled. Conventional magnetic resonance imaging protocol including diffusion-weighted imaging (DWI) and pre- and post-contrast fluid attenuation inversion recovery imaging (FLAIR) was conducted to evaluate the ischemic lesion and prognosis. Through the review of medical records and imaging studies, their final diagnosis and its association with HARM signs on post-contrast FLAIR were investigated.A total of 174 subjects were enrolled (mean age, 64.0 ± 12.9 years old; male, 54.6%; DWI lesion, 17.8%). HARM signs were observed in 18 (10%) patients, and their final diagnoses were classified as true TIA (n = 11, 61%), seizure (2, 11%), posterior reversible encephalopathy (2, 11%), reversible cerebral vascular constriction (1, 6%) and unclassified encephalopathy (2, 11%). The co-occurrence of HARM and DWI lesions were observed in 7 subjects which were 6 subjects of true TIA (ischemic stroke) and 1 subject with RCVS related ischemic stroke.The observation of HARM sign would be helpful to confirm the ischemic insult and distinguish the other disease.
| S-EPMC6531152 | biostudies-literature
Project description:Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. Methods: We performed a post-hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Results: Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Conclusion: Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.
| S-EPMC7483750 | biostudies-literature
Project description:Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT.From the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment.Inclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5-3.1). In patients treated with IV-rtPA (n?=?203), the OR was 1.3 (95%CI 0.4-4.0), and in patients not treated with IV-rtPA (n?=?96), the OR was 0.8 (95%CI 0.1-4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference -1 to 14 %).Our results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status.
| S-EPMC4648971 | biostudies-literature
Project description:Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Results: Here, 85% of all patients (n = 140) and 95% of middle cerebral artery (MCA) occlusion patients (n = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth (p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) <2 at 90 days poststroke; p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), p-value for interaction was 0.11. Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012.
| S-EPMC7890254 | biostudies-literature
Project description:Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. We explored the association between low triiodothyronine (T3) syndrome and HT in AIS patients. A total of 208 consecutive participants with HT and 208 age- and sex-matched stroke patients without HT were enrolled in this study. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction (HI) type 1 or 2 or parenchymal hematoma (PH) type 1 or 2. HT was also classified into asymptomatic or symptomatic. The incidence of low T3 syndrome was significantly higher among patients who developed HT than among those without HT. Moreover, the more severe the HT, the lower the detected T3 levels. Multivariate-adjusted binary logistic regression showed that low T3 syndrome was an independent risk factor for HT and symptomatic HT in AIS patients. Low T3 syndrome was also significantly associated with a higher risk of PH, but not with the risk of HI. Thus, low T3 syndrome was independently associated with the risk of HT, symptomatic HT, and severe HT (PH) in AIS patients, which suggests monitoring T3 could be a useful means of preventing HT in patients with ischemic stroke.
| S-EPMC6738409 | biostudies-literature
Project description:IntroductionHemorrhagic transformation (HT) is a complex and multifactorial complication among patients with acute ischemic stroke (AIS), and the inflammatory response has been considered as a risk factor for HT. We aimed to evaluate the stratification of FAR (fibrinogen-to-albumin ratio), an inflammatory biomarker, in HT patients.MethodsA total of 256 consecutive stroke patients with HT and 256 age- and gender-matched stroke patients without HT were included in this study. HT during hospitalization was diagnosed by follow-up imaging assessment and was classified into hemorrhagic infarction (HI) and parenchymal hematoma (PH) according to the recommendations of European Cooperative Acute Stroke Study II classification. Blood samples were obtained at admission.ResultsHigher levels of FAR were observed in patients with HT compared with the non-HT group [10.29 (8.39-12.95) vs. 8.60 (7.25-10.8), p < .001], but no significant difference was found between the PH and HI [10.88 (8.72-13.40) vs. 10.13 (8.14-12.60), p > .05]. Patients were assigned to groups of high FAR (≥9.51) and low FAR (<9.51) based on the optimal cut-off value. After adjustment for potential confounders, the high FAR remained independently associated with the increased risk of HT (OR = 5.027, 95% CI = 5.027 (2.309-10.942), p < .001).ConclusionsHigh FAR was independently associated with the increased risk of HT after AIS.
| S-EPMC7821560 | biostudies-literature
Project description:Background: In patients with acute ischemic stroke, hemorrhagic transformation is a major complication after intravenous thrombolysis. This study aimed to investigate the relationship between serum magnesium levels and hemorrhagic transformation (HT) after thrombolytic therapy. Methods: We retrospectively analyzed data from 242 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China. Baseline serum magnesium levels were measured before intravenous thrombolysis, and the occurrence of HT was evaluated using computed tomography images reviewed within 24-36 h after therapy. The relationship between serum magnesium levels and HT was examined using multivariate logistic regression, subgroup analysis, and restricted cubic spline models. Results: Of the 242 included patients, 43 (17.8%) developed HT. Patients with HT had significant lower serum magnesium levels than those without HT (0.81 ± 0.08 vs. 0.85 ± 0.08 mmol/L, p = 0.007). Multivariable logistic regression analysis indicated that patients with higher serum magnesium levels had lower risk of HT (OR per 0.1-mmol/L increase 0.43, 95% CI 0.27-0.73, p = 0.002). However, this association did not persist when baseline levels of serum magnesium were higher than the median value (0.85 mmol/L) in subgroup analysis (OR per 0.1-mmol/L increase 0.58, 95% CI 0.14-2.51, p = 0.47). This threshold effect was also observed in the restricted cubic spline model when serum magnesium levels were above 0.88 mmol/L. No association between symptomatic HT and serum magnesium levels was observed in our study (OR per 0.1-mmol/L increase 0.52, 95% CI 0.25-1.11, p = 0.092). Conclusions: Lower serum magnesium levels in patients with ischemic stroke are associated with an increased risk of HT after intravenous thrombolysis, but perhaps only when serum magnesium is below a certain minimal concentration.
| S-EPMC7492199 | biostudies-literature
Project description:BackgroundsThere have been neither appropriate guidelines nor clinical studies about the use of antithrombotics after hemorrhagic transformation (HT). We sought to find whether the use of antithrombotics after hemorrhagic infarction might be associated with aggravation of HT and neurological deterioration.MethodsThis retrospective study included prospectively registered consecutive patients with acute ischemic stroke and HT in our tertiary stroke center. We focused on the hemorrhagic infarction. Aggravation of HT was defined as either enlargement of the original HT or newly developed HT within the infarcted area by visual analysis. We analyzed relationships between antithrombotics and HT, and neurological deterioration after HT in patients with hemorrhagic infarction. In addition, we assessed composite outcomes including neurological deterioration, vascular events, and death at 1 month after HT. We analyzed relationships between antithrombotics after discharge and composite outcomes within 1 month after HT.Results222 patients were finally analyzed. Of the 150 patients with hemorrhagic infarction, 75 (50.0%) were type 1. The use of warfarin after detection of hemorrhagic infarction more frequently increased aggravation of HT than did the use of antiplatelets (4 of 24 vs 3 of 69; p = 0.094), but neither warfarin nor antiplatelets caused more HT than no medication. In addition, the use of antithrombotics after hemorrhagic infarction was not significantly associated with neurological deterioration after HT. The frequency of composite events at 1 months was significantly lower in patients treated with antithrombotics than those treated without (p = 0.041).ConclusionIn conclusion, the results of this study suggest that antithrombotics can safely be used after hemorrhagic infarction and may not be associated with neurological deterioration and aggravation of HT. Further studies are needed to confirm our results.
| S-EPMC3938534 | biostudies-literature