Abstract Body: Introduction
Cerebrovascular white matter disease (WMD) severity is linked to vascular risk factors like hypertension, hyperlipidemia, and diabetes. In stroke, it has been associated with infarct growth, hemorrhagic transformation, and poor outcomes. WMD severity may also indicate poor collateral circulation, compromise of the blood brain barrier, and microvascular dysfunction, predicting higher infarct burden and stroke severity. We hypothesized that severe WMD in large vessel occlusion (LVO) stroke patients would correlate with worse 90-day functional outcomes, measured by the modified Rankin Scale (mRS).

Methods
We analyzed the DEFUSE 3 trial dataset, which studied extended window endovascular therapy for LVO patients with a target perfusion mismatch. WMD burden was assessed using Fazekas scoring on post-stroke T2 FLAIR sequences by three raters. Data were categorized into low (Fazekas 0-1) and high (Fazekas 2-3) WMD burden. Analysis was performed using the independent samples Mann-Whitney U and Chi-square tests. Adjusted analysis was done with binary and ordinal logistic regression analysis.

Results
Of 155 patients with post-stroke FLAIR sequences, 117 (75.5%) had high WMD burden. Patients with high WMD burden were older, more often non-Hispanic, and had more hypertension (Table 1). Initially, high WMD burden was associated with a worse median 90-day mRS (4 vs 3, p=0.010) and fewer patients with good 90-day mRS (27% vs 47%, p=0.022). However, after adjusting for covariates, WMD burden was not independently associated with good 90-day mRS (OR 0.52, 95% CI 0.22-1.26) or 90d mRS shift (cOR 1.50, 95%CI 0.74-3.04, p=0.266) for each point increase in mRS. There was a strong trend to worse 90-day NIH Stroke Scale score in high WMD burden (median 8 vs 4, p=0.059), but no association with presence of post-stroke hemorrhagic transformation, defined as Parenchymal Hematoma type 1 or 2 (13% vs 10%, p=0.566).

Conclusions
WMD burden did not have an independent association with 90-day functional outcomes or hemorrhagic transformation in the DEFUSE 3 cohort. This analysis is limited by the fact that DEFUSE 3 was not designed to look at the hypothesis in question, included a relatively small sample size, and had very few patients with hemorrhagic transformation. This study confirms the association between age and the presence of hypertension with an increased risk of more severe WMD, but this finding does not necessarily translate to worse outcomes in acute stroke.