Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke

Abstract

Background-and-Purpose We performed a meta-analysis to assess whether leukoaraiosis on brain CT scans of acute ischemic stroke patients treated with intravenous (IV) thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) and/or poor functional outcome at 3–6 months post-stroke. Methods We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3–6 month modified Rankin Score (mRS) >2. Results Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR: 1.55; 95%CI: 1.17–2.06, p=0.002) and severe leukoaraiosis (OR: 2.53; 95%CI: 1.92–3.34, p<0.0001), compared to patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in six included studies (n=4976, adjusted-OR: 1.75, 95%CI: 1.35–2.27; p<0.0001). OR for leukoaraiosis and poor 3–6 month outcome was 2.02 (95%CI: 1.54–2.65, p<0.0001), with significant statistical heterogeneity (I2:75.7%, p=0.002). In adjusted analysed, leukoaraiosis was an independent predictor of poor outcome (n=3688, adjusted-OR: 1.61, 95%CI: 1.44–1.79; p<0.0001). In post-hoc analyses, including only leukoaraiosis patients in RCTs (IST-3, NINDS, ECASS-1-2; n=2234), tPA vs. control was associated with higher sICH risk (OR: 5.50; 95%CI: 2.49–12.13), but lower poor outcome risk (OR: 0.75; 95%CI: 0.60–0.95). Conclusions Leukoaraiosis might increase post-IV thrombolysis sICH risk and poor outcome post-stroke. Despite increased sICH risk, IV tPA treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding IV thrombolysis.

Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

“…62,63 An additional growing body of research suggests that subclinical cerebrovascular disease such as amyloid angiopathy or white matter hyperintensities, which may be associated with endothelial injury, is also associated with a higher risk of sICH. 64,65 Ischemic injury to cerebral endothelial cells and the associated underlying components of the neurovascular unit leads to a series of biological processes resulting in breakdown of the blood-brain barrier. Animal models of ischemia and reperfusion demonstrate an association between hemorrhage and degradation of the basal lamina.…”

Rapid Automated Quantification of Cerebral Leukoaraiosis on CT Images: A Multicenter Validation Study

“…CT analytic software was recently developed that aims to delineate territorial infarcts (30) and acute ischemia (31), or to predict hemorrhagic transformation after ischemic stroke (19). One promising application for WML quantification is treatment selection for acute ischemic stroke because cerebral WML load predicts poor functional outcome (4,5) and intracranial hemorrhagic transformation (7,8). At present, this CT-imaging predictor of poor functional outcome and other predictors (eg, acute ischemia) have not been found to interact with revascularization therapy in their association with intracranial hemorrhage, and therefore are not recommended for treatment stratification (4,32).…”

Successful intravenous Alteplase for a centenarian woman with acute ischaemic stroke

“…In this patient, the baseline brain CT image showed leukoaraiosis, which is defined as a diffuse white matter abnormality (with a low density on brain CT images). Leukoaraiosis is common in the elderly and a neuroimaging marker of small cerebral vessel disease related to ageing and hypertension . The presence of eukoaraiosis is independently associated with the risk of spontaneous sICH .…”

“…Leukoaraiosis is common in the elderly and a neuroimaging marker of small cerebral vessel disease related to ageing and hypertension. 16 The presence of eukoaraiosis is independently associated with the risk of spontaneous sICH. 17 Moreover, pre-existing leukoaraiosis on brain CT scans might be associated with a higher risk of thrombolysis-related sICH.…”