Hyperintense acute reperfusion marker on FLAIR is not associated with early haemorrhagic transformation in the elderly

Różański, Michał; Ebinger, Martin; Schmidt, W. U.; Hotter, Benjamin; Pittl, Sandra; Heuschmann, Peter U.; Jungehuelsing, Jan G.; Fiebach, Jochen B.

doi:10.1007/s00330-010-1881-9

Cited by 29 publications

(45 citation statements)

References 35 publications

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“…Our results help explain prior studies that reported conflicting findings about the relationship between BBB disruption and hemorrhagic transformation. 6 Specifically, our findings support the hypothesis that diffuse mild BBB disruption is potentially reversible while focal severe BBB dysfunction signals the risk of BBB rupture.…”

Section: Discussionsupporting

confidence: 79%

Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia

Simpkins

Dias

Leigh

et al. 2016

Stroke

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Background & Purpose Animal models of acute cerebral ischemia have demonstrated that diffuse blood-brain barrier (BBB) disruption can be reversible following early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use an MRI biomarker of BBB permeability to differentiate these two forms of BBB disruption. Methods Acute stroke patients imaged with MRI prior to, 2 hours after, and 24 hours after treatment with IV tPA were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pre-treatment MRI were compared to the occurrence of parenchymal hematoma (PH) formation on the 24-hour MRI scan using logistic regression. Results Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (p=0.006), indicating that early reperfusion is associated with decreased BBB permeability while sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (p=0.013). Conclusions This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with IV tPA.

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Section: Discussionsupporting

confidence: 79%

Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia

Simpkins

Dias

Leigh

et al. 2016

Stroke

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“…8,9,[23][24][25] Such findings, which are believed to result from some degree of BBB disruption or a change in vascular permeability, can mimic SAH, intraventricular hemorrhage, or socalled hyperintense acute reperfusion marker on fluid-attenuated inversion recovery MR imaging [25][26][27] and may cause unnecessary delay in anticoagulant/antiaggregant treatment. After apparently uneventful endovascular coiling of intracranial aneurysms, a sig- True-positive 7 7 2 2 6 6 8 10 True-negative 51 53 58 64 61 57 53 50 False-positive 10 8 8 2 4 8 8 11 False-negative 5 5 5 5 2 2 4 2 Note:-BBBD indicates blood-brain barrier disruption.…”

Section: Discussionmentioning

confidence: 99%

Flat Detector Angio-CT following Intra-Arterial Therapy of Acute Ischemic Stroke: Identification of Hemorrhage and Distinction from Contrast Accumulation due to Blood-Brain Barrier Disruption

Kau

Hauser

Obmann

et al. 2014

American Journal of Neuroradiology

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BACKGROUND AND PURPOSE:Flat panel detector CT in the angiography suite may be valuable for the detection of intracranial hematomas; however, abnormal contrast enhancement frequently mimics hemorrhage. We aimed to assess the accuracy of flat panel detector CT in detecting/excluding intracranial bleeding after endovascular stroke therapy and whether it was able to reliably differentiate hemorrhage from early blood-brain barrier disruption.

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“…In previous studies on HARM, commonly used gadolinium-containing contrast agents were Magnevist [5,6] or Gadovist [8]. Differences between those complexes in transfer rate via the BBB have not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…The bright appearance of the CSF-filled space on fluid attenuated inversion recovery (FLAIR) images due to leakage of gadolinium was termed ‘hyperintense acute reperfusion marker' (HARM) [5,6]. Some studies showed its association with a higher rate of hemorrhagic transformation [5,6], others found no such relationship [7,8]. No detailed longitudinal examinations of changes in the BBB in stroke patients exist.…”

Section: Introductionmentioning

confidence: 99%

Early Time Course of FLAIR Signal Intensity Differs between Acute Ischemic Stroke Patients with and without Hyperintense Acute Reperfusion Marker

Ostwaldt¹,

Różański²,

Schmidt³

et al. 2014

Cerebrovasc Dis

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Background: In animal models of stroke, the time course of blood-brain barrier (BBB) disruptions has been elaborately studied. In human patients, leakage of gadolinium into cerebrospinal fluid (CSF) space, visualized on MRI fluid attenuated inversion recovery (FLAIR) images, is considered a sign of BBB disruptions. It was termed ‘hyperintense acute reperfusion marker' (HARM) and was associated with hemorrhages. However, the time course of the leakage is unknown and difficult to study in human patients. Also, the association of HARM with signal intensities and enhancement in the parenchyma on FLAIR images has not been thoroughly researched. Methods: We analyzed imaging data of acute ischemic stroke patients who underwent repetitive MRI examinations within the first 36 h after the time of symptom onset. HARM was evaluated on FLAIR images. Regions of interest (ROI) of the hyperintensities on diffusion-weighted imaging (DWI) were determined for each time point and mirrored to the contralateral side. The ROI were furthermore corrected for CSF-filled space, using apparent diffusion coefficient (ADC) images. The corrected ROI were used to determine mean signal intensities of the lesions relative to the contralateral side on FLAIR, ADC and B₀ images for each time point. Results: The 18 included patients (5 females; median age: 69 years; median NIHSS score: 5) received 3-5 MRI examinations on the first day and 1-2 examinations on day 2 after stroke. Eight of the patients (44.4%) showed HARM on at least 1 examination. In 6 of these patients, HARM was already seen at the second examination, at the earliest 3.5 h after symptom onset. The HARM-positive patients had higher relative signal intensities (rSI) on FLAIR images in the parenchyma corresponding to the DWI-positive tissue compared with the HARM-negative patients. This difference between groups was statistically significant for the 2nd and 3rd examination (medians of 4.31 and 6.37 h from symptom onset, p < 0.001 and p = 0.005, respectively). No significant difference in rSI between groups was seen for ADC or B₀ images. Conclusion: HARM does not only represent a contrast medium leakage from the pial system into the CSF space. It is accompanied by a markedly increased rSI in the early ischemic lesion on FLAIR images, which is likely due to parenchymal enhancement. The lack of differences on B₀ images excludes a pure T2 effect.

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Hyperintense acute reperfusion marker on FLAIR is not associated with early haemorrhagic transformation in the elderly

Abstract: HARM was not associated with HT in the elderly after ischaemic stroke, independent of treatment. While it may indicate dysfunction of the blood-brain barrier (BBB), it does not necessarily amount to HT.

Cited by 29 publications

References 35 publications

Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia

Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia

Flat Detector Angio-CT following Intra-Arterial Therapy of Acute Ischemic Stroke: Identification of Hemorrhage and Distinction from Contrast Accumulation due to Blood-Brain Barrier Disruption

Early Time Course of FLAIR Signal Intensity Differs between Acute Ischemic Stroke Patients with and without Hyperintense Acute Reperfusion Marker

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