Abstract
Introduction: In malignant infarction, brain edema leads to secondary neurological deterioration and poor outcome. We investigated whether swelling is associated with outcome in a broader range of stroke severity. Methods: Two research cohorts (NBO and EPITHET) comprising 98 acute stroke subjects with prospective serial brain magnetic resonance imaging (MRI) were analyzed. The categorical presence of swelling and/or infarct growth (IG) was assessed on diffusion weighted MRI (DWI) by comparing baseline and 3-5 day follow-up scans. IG was defined using the ASPECTS system (small IG = decrease in ASPECTS ≥ 1; large IG = decrease in ASPECTS ≥ 2). The increase in lesion volume (ΔDWI) was then subdivided into swelling and IG volumes using region-of-interest analysis. The relationship of these imaging markers with outcome was evaluated using univariate and multivariate regression, with poor outcome defined as a 90 day modified Rankin Scale score of 3-6. Receiver operating characteristic (ROC) curve analysis was undertaken to define a threshold for prediction of poor outcome. Results: The presence of swelling independently predicted poor outcome after adjustment for age, admission NIH stroke scale score, admission glucose, and baseline DWI volume (OR4.55, 95%CI 1.21-18.9, p<0.02). Volumetric analysis confirmed ΔDWI was associated with outcome (OR4.29, 95%CI 2.00-11.5, p<0.001). After separating ΔDWI into swelling and IG volumes, swelling remained an independent predictor of poor outcome (OR1.15, 95%CI 1.02-1.43, p<0.02). While large IG was associated with poor outcome (OR7.05, 95%CI 1.04-143, p=0.045), small IG was not. ROC curve analysis identified a swelling volume of ≥11mL as the threshold with greatest sensitivity (77%) and specificity (75%) for predicting poor outcome (AUC=0.798). Conclusions: Both swelling and IG contribute to total lesion growth in the days following stroke. Swelling is an independent predictor of poor outcome in moderate to severe stroke.
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