Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy

Objective: We investigated the prevalence and clinical-radiologic associations of cortical superficial siderosis (cSS) in patients with probable cerebral amyloid angiopathy (CAA) compared to those with intracerebral hemorrhage (ICH) not attributed to CAA. Methods: We conducted a retrospective multicenter cohort study of 120 patients with probable CAA and 2 comparison groups: 67 patients with either single lobar ICH or mixed (deep and lobar) hemorrhages; and 22 patients with strictly deep hemorrhages. We rated cSS, ICH, white matter changes, and cerebral microbleeds. Results: cSS was detected in 48 of 120 (40%; 95% confidence interval [CI]: 31.2%–49.3%) patients with probable CAA, 10 of 67 (14.9%; 95% CI: 7.4%–25.7%) with single lobar ICH or mixed hemorrhages, and 1 of 22 (4.6%; 95% CI: 0.1%–22.8%) patients with strictly deep hemorrhages (p < 0.001 for trend). Disseminated cSS was present in 29 of 120 (24%; 95% CI: 16.8%–32.8%) patients with probable CAA, but none of the other patients with ICH (p < 0.001). In probable CAA, age (odds ratio [OR]: 1.09; 95% CI: 1.03–1.15; p = 0.002), chronic lobar ICH (OR: 3.94; 95% CI: 1.54–10.08; p = 0.004), and a history of transient focal neurologic episodes (OR: 11.08; 95% CI: 3.49–35.19; p < 0.001) were independently associated with cSS. However, cSS occurred in 17 of 48 patients with probable CAA (35.4%; 95% CI: 22.2%–50.5%) without chronic lobar ICH. Conclusions: cSS (particularly if disseminated) is a common and characteristic feature of CAA. Chronic lobar ICH is an independent risk factor for cSS, but the causal direction and mechanism of association are uncertain. Hemorrhage into the subarachnoid space, independent of previous (chronic) lobar ICH, must also contribute to cSS in CAA. Transient focal neurologic episodes are the strongest clinical marker of cSS.