Background.Increased white matter hyperintensity(WMH) burden may be associated with chronic endothelial injury, impaired cerebrovascular reactivity, blood-brain barrier(BBB) disruption, and chronic hypoperfusion.Objectives.To evaluate whether in patients with acute ischemic stroke (AIS) treated with IV thrombolysis moderate to severe WMH predicts development of cerebral oedema(CE) with consequent implications for infarct growth(IG) and functional outcome.Methods. We analyzed data of patients treated with IV rt-PA at the Sapienza University of Rome and included in the SITS-ISTR. WMH was measured by modified Fazekas scale on baseline FLAIR MRI mainly on the contralateral hemisphere. CE was measured by a visual score on baseline MRI FLAIR performed within 24 hrs of symptom onset. Outcome measures were IG and modified Rankin Scale(mRS) score(3-6 as poor outcome) at 90 days.Results.Overall, 440 patients were included (mean age[SD] 69.3[13.6]; 41.4% women; median[IQR] NIHSS 8[4-15]);84 (22.6%) patients had moderate/severe WMH. CE was observed in 121(36.8%) patients. In univariate analyses, moderate/severe WMH was significantly associated with the development of CE (p=0.005).Patients with CE at baseline were more likely to have early neurological deterioration, symptomatic intracerebral hemorrhage, and IG(p<0.05 each). Both WMH and CE resulted significantly associated with 90-day poor functional outcome(p<0.01). In multivariate analysis, after adjusting for confounding variables, moderate/severe WMH independently predicts development of CE(OR 5.52, 95%CI 2.08-14.62,p=0.001).Discussion.In AIS patients treated with IV thrombolysis, WMH severity, as potential sign of chronic microvascular dysfunction and increase of BBB permeability, predicts the development of CE. Individuation of specific quantitative WMH volume cutoffs may have implication for improving infarct growth and functional outcome prediction.
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