Neuropathology and long-term outcome in cerebral amyloid angiopathy patients with intracerebral hemorrhage

Background 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). Methods 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 binary logistic regression. Cox proportional hazard regression models assessed mortality or recurrent ICH risk associations. Results Among 93 ICH patients, 63 (67.7%) had CAA. Pathological grading showed Grade 1: 8 (12.7%), Grade 2: 12 (19.0%), Grade 3 or 4: 43 (68.3%). Among 32 CAA patients with cortical specimens, 23 (71.9%) had dense-core plaques and 26 (81.3%) diffuse plaques. Dense-core plaques occurred exclusively in moderate-to-severe CAA. After adjusting for age, sex, antiplatelet medication and alcohol abuse, CAA severity predicted 1-year mortality (adjusted OR = 18.49; 95% CI 1.78–193.03; P = 0.015). CAA severity and age predicted mortality or recurrent ICH risk (adjusted 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). Conclusions Most CAA-ICH patients had moderate-to-severe CAA in cortico-leptomeningeal regions. Cortical biopsies revealed frequent Aβ deposition as dense-core and diffuse plaques, with dense-core plaques exclusive to moderate-to-severe CAA. CAA severity correlated with long-term outcomes in CAA-ICH.