Corticosteroid Treatment and Hemorrhage Risk in Cerebral Amyloid Angiopathy with Cortical Superficial Siderosis: A Matched Cohort Analysis

Cortical superficial siderosis (cSS) is the strongest marker of future intracranial hemorrhage (ICH) in cerebral amyloid angiopathy (CAA), a condition without disease-modifying therapy. Emerging evidence suggests that cSS may reflect meningovascular inflammation potentially amenable to immunosuppression. We conducted a single-center matched cohort study comparing high-dose corticosteroid therapy versus no immunosuppression in patients with probable CAA and cSS. Treated patients were matched 1:2 to untreated patients by demographics, cSS multifocality, and baseline intracerebral hemorrhage. The primary outcome was incident ICH; secondary outcomes were any cerebrovascular event and mortality. Kaplan-Meier analysis assessed event-free survival. cSS progression was evaluated in patients with [≥]6 months MRI follow-up, and inflammation in a subgroup with post-contrast vessel-wall-imaging (VWI). Thirty-six patients were included (12 treated, 24 untreated; mean age 77.4 years; 91% disseminated cSS). Over a median follow-up of 2.23 years, 11 patients had cerebrovascular events (15 ICHs, 3 ischemic strokes), all in the untreated group (p=0.041 for ICH; p=0.037 for any event). Mortality did not differ (p=0.634). cSS progressed in 2/6 (33%) treated versus 4/7 (57%) untreated patients. Baseline VWI detected inflammation in 7/9 patients (78%), which regressed after corticosteroids. Corticosteroid therapy was associated with fewer cerebrovascular events in high-risk CAA, supporting prospective controlled validation.