Pathological findings from surgical specimens and long-term outcome in cerebral amyloid angiopathy patients with intracerebral hemorrhage

Abstract

Sporadic cerebral amyloid angiopathy (CAA) is a small-vessel disease. We sought to assess pathological findings and outcomes in CAA patients with non-traumatic intracerebral lobe hemorrhage (ICH). Sixty-three CAA-ICH patients underwent Hematoxylin-eosin, amyloid-β, smooth muscle actin, and CD34 staining. Arterioles were graded using a CAA-severity scale. Prospective ≥ 12-month follow-up identified prognostic factors via Spearman correlation analysis and binary logistic regression. Cox proportional hazard regression models assessed mortality or recurrent ICH risk associations. Among 93 Chinese ICH patients, 63 (67.7%) were diagnosed with CAA. Pathological grading showed Grade 1: 8 (12.7%), Grade 2: 12 (19.0%), Grade 3–4: 43 (68.3%). The median preoperative hematoma volumes in patients with Grade 1, Grade 2, and Grades 3–4 CAA were 42 mL (30–53), 50 mL (41–60), and 55 mL (48–89), respectively (p = 0.016). Among 32 CAA patients with available cortical specimens, 23 (71.9%) exhibited dense-core plaques and 26 (81.3%) showed diffuse plaques. Dense-core plaques were observed predominantly in moderate-to-severe (Grades 2–4) CAA. Cortical superficial siderosis (cSS) moderately correlated with CAA severity (R = 0.528, p = 0.006). After adjusting for age, sex, antiplatelet therapy, and alcohol abuse, CAA severity predicted 1-year mortality (adjusted odds ratio [OR] = 18.49; 95% confidence interval [CI], 1.78–193.03; p = 0.015). Both CAA severity and age predicted mortality or recurrent ICH risk (adjusted hazard ratio [HR] = 4.16; 95% CI, 1.54–11.24; p = 0.005; and adjusted HR = 1.08; 95% CI, 1.02–1.14; p = 0.008, respectively). CAA severity also independently predicted the risk of recurrent ICH (adjusted HR = 5.65; 95% CI, 1.25–25.62; p = 0.025). Most CAA-ICH patients had moderate-to-severe CAA in cortico-leptomeningeal regions. Cortical biopsies revealed frequent amyloid-β (Aβ) deposition in dense-core and diffuse plaques, with dense-core plaques predominating in moderate-to-severe CAA. CAA severity correlated with long-term outcomes in CAA-ICH.