The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

Abstract

Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake.Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test.Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups.Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.

Large mismatch profile predicts rapidly progressing brain edema in acute anterior circulation large vessel occlusion patients undergoing endovascular thrombectomy

“…This study provides a new way to assess the RPBE (an increase of more than two points in cerebral edema mass effect within 24 h). The occurrence of RPBE observed in this study (26.2%) is comparable with the 24 h net water uptake observed in previous research (20.6-22.0%) (25,26). Although RPBE is a semi-quantitative assessment, it shows the predictive value for poor early clinical outcomes (Table 2), which is consistent with previous studies (7,8,27).…”

“…Animal experiments have shown that rapidly progressing cerebral edema may occur after LVO, and increased BBB permeability was observed 20–155 min after MCA occlusion ( 29 ). A recent study reported that a larger edema volume within 24 h was associated with more edema and lesion progression ( 25 ). The mismatch ratio is the ratio of the penumbra volume to the infarct core volume, combining the infarct core with the mismatched volume.…”

Infarct Evolution in Patients with Anterior Circulation Large-Vessel Occlusion Randomized to IV Alteplase and Endovascular Treatment versus Endovascular Treatment Alone

“…This practice could have affected the accuracy of our FIV assessments because it is known that edema affects the FIV on NCCT after stroke, and it can be challenging to distinguish edema from infarcted tissue on NCCT. 39 However, the FIVs were not different for patients who received a median 24-hour followup DWI versus patients with 24-hour follow-up NCCT. In addition, it has been demonstrated that FIV assessed on 24-hour NCCT is equally strongly associated with functional outcome as the FIV measured on 1-week NCCT, regardless of the fact that infarct growth between 24-hour and 1-week imaging is common.…”

Association of Blood Biomarkers of Inflammation With Penumbra Consumption After Mechanical Thrombectomy in Patients With Acute Ischemic Stroke

“…13 In addition, in these studies, true lesion growth was not distinguished from edema, although the latter may account for up to one-third of the lesion volume. 3,4,23 The use of a nonlinear coregistered MRI approach may limit this bias.…”