Cortical Superficial Siderosis Burden Predicts Hemorrhage and Poor Outcomes After Stroke Thrombolysis

BACKGROUND: Cerebral amyloid angiopathy (CAA) is thought to increase the risk of postthrombolytic intracranial bleeding, yet CAA neuroimaging markers and magnetic resonance imaging criteria have not been systematically evaluated in large acute stroke trials. We, therefore, examined the association of radiological Boston CAA criteria and their constituent markers with hemorrhagic risks and functional outcomes after intravenous thrombolysis in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: Blinded raters recorded lobar cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity multispot sign, and centrum semiovale enlarged perivascular spaces, and classified possible and probable CAA according to radiological Boston criteria iterations, versions 1.0, 1.5, and 2.0. Multivariable logistic or ordinal regressions, adjusted for age, sex, baseline stroke severity, diabetes, hypertension, onset-to-needle time, thrombolytic agent, and endovascular therapy, assessed associations of these features/criteria with safety end points: symptomatic intracerebral hemorrhage (ICH), any ICH, Heidelberg hemorrhage grade, 90-day mortality, and functional outcomes (modified Rankin Scale score of 0-1 and ordinal modified Rankin Scale score shift). RESULTS: Among 1600 patients in the trial, 482 had suitable magnetic resonance imaging (mean age, 71 years; 47.1% female). Cortical superficial siderosis burden emerged as the dominant harmful marker: each increment was associated with increased risk of symptomatic ICH (adjusted odds ratio [aOR] per additional affected sulcus, 3.88 [95% CI, 2.87-5.26]), any ICH (aOR, 1.91 [95% CI, 1.22-2.98]), hemorrhage severity, 90-day mortality (aOR, 1.42 [95% CI, 1.18-1.71]), worse modified Rankin Scale scores (adjusted common odds ratio, 1.74 [95% CI, 1.58-1.91]), and lower odds of excellent functional recovery (aOR, 0.70 [95% CI, 0.64-0.77]). Fulfilling probable radiological Boston criteria, versions 1.0 and 1.5, increased odds of any ICH (aOR, 2.57 and 2.39 [95% CI, 2.05-3.23]; aOR, 2.39 [95% CI, 1.71-3.34], respectively), whereas fulfilling possible Boston criteria, version 1.5, was associated with worse modified Rankin Scale scores (adjusted common odds ratio, 2.34 [95% CI, 1.30-4.22]). Boston criteria, version 2.0, were not significantly associated with any hemorrhagic outcomes. CONCLUSIONS: In thrombolyzed patients with acute ischemic stroke, cortical superficial siderosis burden is strongly and consistently associated with higher risk of severe hemorrhage, disability, and death, making it a particularly relevant CAA marker when weighing thrombolytic risk versus benefit. Meeting radiological Boston criteria, versions 1.0 or 1.5, increases hemorrhagic risk, but meeting the latest 2.0 criteria does not.