Added Prognostic Value of Hemorrhagic Transformation Quantification in Patients With Acute Ischemic Stroke

 

What are the protocols needed to prevent this from happening and then GET TO 100% RECOVERY?

 

Added Prognostic Value of Hemorrhagic Transformation Quantification in Patients With Acute Ischemic Stroke

Katinka R. van Kranendonk^1*, Kilian M. Treurniet^1,2, Anna M. M. Boers³, Olvert A. Berkhemer^1,4,5, Jonathan M. Coutinho⁶, Hester F. Lingsma⁷, Wim H. van Zwam⁸, Aad van der Lugt⁵, Robert J. van Oostenbrugge⁹, Diederik W. J. Dippel⁴, Yvo B. W. E. M. Roos⁶, Henk A. Marquering^1,10, Charles B. L. M. Majoie¹ and the MR CLEAN investigators

• ¹Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, Netherlands
• ²Department of Radiology, Haaglanden Medical Center (HMC), Den Haag, Netherlands
• ³Nico.lab, Amsterdam, Netherlands
• ⁴Department of Neurology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, Netherlands
• ⁵Department of Radiology & Nuclear Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, Netherlands
• ⁶Department of Neurology, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, Netherlands
• ⁷Department of Public Health, Center for Medical Decision Making, Erasmus MC-University Medical Center Rotterdam, Rotterdam, Netherlands
• ⁸Department of Radiology and Nuclear Medicine, Cardiovascular Research Institute Maastricht (CARIM), University Medical Center, Maastricht, Netherlands
• ⁹Department of Neurology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, Netherlands
• ¹⁰Department of Biomedical Engineering and Physics, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, Netherlands

Introduction and Aim: Hemorrhagic transformation (HT) frequently occurs after acute ischemic stroke and negatively influences the functional outcome. Usually, HT is classified by its radiological appearance. Discriminating between the subtypes can be complicated, and interobserver variation is considerable. Therefore, we aim to quantify rather than classify hemorrhage volumes and determine the association of hemorrhage volume with functional outcome in comparison with the European Cooperative Acute Stroke Study II classification.

Patients and Methods: We included patients from the MR CLEAN trial with follow-up imaging. Hemorrhage volume was estimated by manual delineation of the lesion, and HT was classified according to the European Cooperative Acute Stroke Study II classification [petechial hemorrhagic infarction types 1 (HI1) and 2 (HI2) and parenchymal hematoma types 1 (PH1) and 2 (PH2)] on follow-up CT 24 h to 2 weeks after treatment. We assessed functional outcome using the modified Rankin Scale 90 days after stroke onset. Ordinal logistic regression with and without adjustment for potential confounders was used to describe the association of hemorrhage volume with functional outcome. We created regression models including and excluding total lesion volume as a confounder.

Results: We included 478 patients. Of these patients, 222 had HT. Median hemorrhage volume was 3.37 ml (0.80–12.6) and per HT subgroup; HI1: 0.2 (0.0–1.7), HI2: 3.2 (1.7–6.1), PH1: 6.3 (4.2–13), and PH2: 47 (19–101). Hemorrhage volume was associated with functional outcome [adjusted common odds ratio (acOR): 0.83, 95% CI: 0.73–0.95] but not anymore after adjustment for total lesion volume (acOR: 0.99, 95% CI: 0.86–1.15, per 10 ml). Hemorrhage volume in patients with PH2 was significantly associated with functional outcome after adjusting total lesion volume (acOR: 0.70, 95% CI: 0.50–0.98).

Conclusion: HT volume is associated with functional outcomes in patients with acute ischemic stroke but not independent of total lesion volume. The extent of a PH2 was associated with outcome, suggesting that measuring hemorrhage volume only provides an additional benefit in the prediction of the outcome when a PH2 is present.

Introduction

Hemorrhagic transformation (HT) commonly occurs as a natural progression or as a complication of reperfusion therapy for acute ischemic stroke (1, 2). Large, but also small HT subtypes were found to be associated with poor functional outcome (3). Incidence varies and differences in definition of HT between studies complicate comparisons between studies. Usually, HT is classified according to the European Cooperative Acute Stroke Study II (ECASS II) classification based on radiological appearance (4). This classification divides HT in four groups: hemorrhagic infarction type 1 (HI1), which is defined as small petechiae along the margins of the infarct; hemorrhagic infarction type 2 (HI2), defined as confluent petechiae within the infarcted area but no space-occupying effect; parenchymal hematoma type 1 (PH1) as blood clots in 30% or less of the infarcted area with some slight space-occupying effect; and parenchymal hematoma type 2 (PH2) as blood clots in more than 30% of the infarcted area with substantial space-occupying effect (4).

The ECASS classification only takes hemorrhage volume relative to the infarct volume into account when a PH is present, and therefore, small hemorrhages could be classified as PH2 when the infarct is small. The opposite is true when large hematomas develop within massive infarcts. These hematomas are not classified as PH2 when their relative size is <30% of the infarct while their objective size could be more than 40 ml. These hemorrhages might lead to symptomatic intracranial hemorrhage (sICH). However, according to the Heidelberg Bleeding classification, ICH other than PH2 might be symptomatic, but it is advised not to classify those hemorrhages as sICH (5).

Further, an agreement between observers for HT is only fair, as discriminating between HT subtypes can be challenging (6, 7). This limited agreement might contribute to a variation in the reported incidence of HT between studies.

As an alternative to the current rather crude classification of HT, we aim to quantify the hemorrhage volume of patients with HT and to assess its prognostic value by determining the association of hemorrhage volume with functional outcome in comparison with the ECASS II classification. Additionally, we determine whether hemorrhage volumes smaller than 30% of lesion volume might have been symptomatic.