Temporal Net Water Uptake Evolution and Its Association with Functional Outcome in Acute Ischemic Stroke

Subacute lesion growth after acute ischemic stroke (AIS) is associated with worse functional outcomes. The ischemic lesion severity can be assessed with net water uptake (NWU), a CT-based marker of edema. Pretreatment NWU has been associated with worse functional outcomes; however, it remains unclear how the temporal changes in NWU influence functional outcomes. In this study, we aimed to determine how associations between NWU and functional outcome vary across imaging times up to 1 week after stroke.

We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MRCLEAN-NO IV) trial with anterior circulation large vessel occlusion who were treated with endovascular treatment and had baseline, 24-hour, and 1-week follow-up noncontrast CT scans. Functional outcome at 90 days was evaluated using the mRS, analyzed both as functional independence (mRS 0-2) and across the full ordinal distribution (mRS 0-6). In the primary analysis, associations between NWU measured at different imaging time points and functional independence were examined using univariable and multivariable logistic regression models. To evaluate temporal changes in NWU, ΔNWU was calculated at different time intervals (baseline to 24 hours, 24 hours to 1 week, and baseline to 1 week), and its association with outcomes was analyzed using analogous regression models.

Of 539 MRCLEAN-NO IV patients, 115 were included in this study. The median time from stroke onset to randomization was 92 (IQR, 70-140) minutes. The median NWU evolved from 4.3% (interquartile range [IQR], 2.1%-6.8%) at baseline to 9.0% (IQR, 3.0%-13%) at 24 hours and 15% (IQR, 11%-19%) at 1 week. The median patient-level change (ΔNWU) from baseline to 1 week was 10% (IQR, 5.3%-16%). NWU measured at 1 week, but not at baseline or 24 hours, was significantly associated with functional dependence, with an adjusted OR (aOR) of 0.66 (95% CI, 0.47-0.90) per 5-percentage-point increase in NWU. Furthermore, a higher increase in NWU from baseline to 1-week imaging was significantly associated with functional dependence, with an aOR of 0.66 (95% CI, 0.47-0.86) per 5-percentage-point increase in ΔNWU_1wk-BL.

In our population, NWU measured at 1 week is associated with 90-day clinical outcomes, suggesting that lesion evolution continues in the first week after stroke onset and may therefore represent a target for secondary treatments to improve clinical outcomes.