Hyperintense acute reperfusion marker associated with hemorrhagic transformation in the WAKE-UP trial

 

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Hyperintense acute reperfusion marker associated with hemorrhagic transformation in the WAKE-UP trial

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Anke Wouters*, Lauranne Scheldeman*, Patrick Dupont, ...

First Published June 12, 2021 Research Article 

https://doi.org/10.1177/23969873211007686

Article information

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.

Keywords Ischemic stroke, DWI-FLAIR mismatch, HARM, hemorrhage, magnetic resonance imaging

Introduction

A paradigm shift towards tissue-based treatment strategies instead of relying on rigid time-windows has reshaped the current landscape of acute stroke care. The interest in imaging markers to guide treatment decisions and to predict tissue fate is increasing. Magnetic resonance imaging (MRI) can visualize both parenchymal and hemodynamic changes in ischemic brain tissue. Evaluating a mismatch between the DWI lesion vs the penumbral tissue, as visualized by perfusion weighted imaging (PWI-DWI mismatch),^1–3 or in relation to the presence of vasogenic edema on FLAIR (the DWI-FLAIR mismatch)⁴ are selection strategies to increase the amount of acutely treated stroke patients.

Another less frequently reported imaging characteristic is the hyperintense acute reperfusion marker (HARM) defined as a delayed sign of early blood-brain-barrier (BBB) disruption. Leakage of gadolinium contrast results in enhancement of the cerebrospinal fluid (CSF) compartment on postgadolinium FLAIR images; an altered function of the BBB is thought to be responsible for this phenomenon.^5–8 The reported incidence of HARM in ischemic stroke patients is highly variable and ranges from 5.5% to 40.4%.^5,6,9–12 No consensus exists on the association of HARM with hemorrhagic transformation (HT) and clinical outcome.^5,6,10,11

We investigated the presence of HARM in patients with a DWI-FLAIR mismatch from the randomized Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial.⁴ Furthermore, we explored the association of HARM with hemorrhagic transformation and functional outcome at 90 days.

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