Background: Cerebral amyloid angiopathy (CAA) is thought to increase the risk of post thrombolytic intracranial bleeding, yet CAA neuroimaging markers and MRI 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 Alteplase compared to Tenecteplase (AcT) trial. Methods: Blinded-raters recorded lobar cerebral microbleeds (CMBs), cortical superficial siderosis(CSS), white matter hyperintensity (WMH) multispot-sign, and centrum semiovale enlarged perivascular spaces, and classified "possible" and "probable" CAA according to radiological Boston criteria iterations 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 endpoints: symptomatic intracerebral hemorrhage(sICH), any ICH, Heidelberg hemorrhage grade, and 90-day mortality; and functional outcomes (modified Rankin Scale mRS 0-1 and ordinal mRS shift). Results: Among 1,600 patients in the trial, 482 had suitable MRIs (mean age 71, 47.1% female). CSS burden emerged as the dominant harmful marker: each increment was associated with increased risk of sICH (adjusted odds ratio aOR per additional affected sulcus:3.88;95%CI:2.87–5.26), any ICH (aOR:1.91;1.22–2.98), hemorrhage severity, 90-day mortality (aOR:1.42;1.18–1.71), worse mRS scores(adjusted common OR acOR:1.74;1.58–1.91), and lower odds of excellent functional recovery (aOR:0.70;0.64–0.77). Fulfilling "probable" radiological Boston criteria v1.0 and v1.5 increased odds of any ICH (aOR:2.57 and 2.39;2.05-3.23; aOR 2.39,1.71-3.34 respectively), whereas fulfilling "possible" Boston criteria v1.5 was associated with worse mRS scores(acOR:2.34;1.30–4.22). Boston criteria v2.0 was not significantly associated with any hemorrhagic outcomes. Conclusions: In thrombolyzed patients with acute ischemic stroke, CSS 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 vs benefit. Meeting radiological Boston criteria versions 1.0 or 1.5 increases hemorrhagic risk but meeting the latest 2.0 criteria does not.
Marzoughi et al. (Thu,) studied this question.