Introduction: Mechanisms of cortical superficial siderosis (cSS) in cerebral amyloid angiopathy (CAA) are unknown, but might include in situ bleeding from amyloid laden superficial vessels or blood products redistribution from acute lobar intracerebral hemorrhage (ICH).
Hypothesis: We aimed to identify factors related to the extent and multifocality of cSS.
Methods: We analyzed consecutive CAA-related ICH patients diagnosed with Boston criteria from a prospective cohort. cSS multifocality, was rated for spatially distinct foci involvement and bi-hemispheric distribution on a 0-4 scale (1 point: 1 sulcus or focal immediately adjacent sulci, 2 points: 2 or more non-adjacent sulci OR more than 3 adjacent sulci, in each hemisphere) with excellent interrater reliability (k=0.87). Radiological markers of CAA and ICH characteristics were assessed using quantitative methods or validated visual scales, and their association with cSS multifocality was investigated in multivariable regression.
Results: The cohort included 312 CAA patients (53% male; mean age 71.7). cSS was found in 34.6%: unifocal in 42 patients (13.5%), multifocal in 66 (23.1%). Presence and multifocality of cSS were not related with characteristics of the acute ICH such as ICH volume, ICH side or areas of acute subarachnoid blood on initial CT. ICH side did not predict cSS side or multifocality at that side. cSS multifocality was related to the presence of IVH in patients who had a single ICH without microbleeds (MB), but not in patients with multiple hemorrhagic lesions (ICH and/or MBs). In ordinal logistic regression, cSS multifocality was related to lobar microbleeds burden (OR: 1.57; 95%CI: 1.27-1.94; p<0.0001) and MRI centrum semiovale perivascular spaces (PVS, OR: 2.05; 95%CI: 1.26-3.33; p=0.004) but not basal ganglia PVS or leukoaraiosis volume. A secondary analysis using Cox regression showed that cSS multifocality was an independent risk factor for recurrent ICH (HR: 2.21; 95%CI: 1.09-4.52 and 3.91; 95%CI: 1.40-10.9 for multifocality presence and severity) after adjusting for other confounders.
Conclusion: Extent and multifocality of cSS appear to be markers of CAA severity and independent predictors of ICH recurrence, and can provide insights potential into pathomechanisms.