Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: A prospective study

In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci.

Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0-4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH.

The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9-5.1 years), the annual ICH recurrence rates per cSS scores (0-4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77-5.75; p < 0.0001).

The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.