Hemorrhage recurrence risk factors in cerebral amyloid angiopathy: Comparative analysis of the overall small vessel disease severity score versus individual neuroimaging markers

Introduction An MRI-based score of total small vessel disease burden (CAA-SVD-Score) in cerebral amyloid angiopathy (CAA) has been demonstrated to correlate with severity of pathologic changes. Evidence suggests that CAA-related intracerebral hemorrhage (ICH) recurrence risk is associated with specific disease imaging manifestations rather than overall severity. We compared the correlation between the CAA-SVD-Score with the risk of recurrent CAA-related lobar ICH versus the predictive role of each of its components. Methods Consecutive patients with CAA-related ICH from a single-center prospective cohort were analyzed. Radiological markers of CAA related SVD damage were quantified and categorized according to the CAA-SVD-Score (0–6 points). Subjects were followed prospectively for recurrent symptomatic ICH. Adjusted Cox proportional hazards models were used to investigate associations between the CAA-SVD-Score as well as each of the individual MRI signatures of CAA and the risk of recurrent ICH. Results In 229 CAA patients with ICH, a total of 56 recurrent ICH events occurred during a median follow-up of 2.8 years [IQR 0.9–5.4 years, 781 person-years). Higher CAA-SVD-Score (HR = 1.26 per additional point, 95%CI [1.04–1.52], p = 0.015) and older age were independently associated with higher ICH recurrence risk. Analysis of individual markers of CAA showed that CAA-SVD-Score findings were due to the independent effect of disseminated superficial siderosis (HR for disseminated cSS vs none: 2.89, 95%CI [1.47–5.5], p = 0.002) and high degree of perivascular spaces enlargement (RR = 3.50–95%CI [1.04–21], p = 0.042). Conclusion In lobar CAA-ICH patients, higher CAA-SVD-Score does predict recurrent ICH. Amongst individual elements of the score, superficial siderosis and dilated perivascular spaces are the only markers independently associated with ICH recurrence, contributing to the evidence for distinct CAA phenotypes singled out by neuro-imaging manifestations.