Abstract
Background: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar intracerebral hemorrhage (ICH) in the elderly. CAA-related ICH survivors are at substantial risk for recurrent ICH, accounting for the significant morbidity of the disease. Identifying predictors of recurrence is therefore crucial. Recent data have implicated cortical superficial siderosis (cSS) as a key hemorrhagic MRI signature of CAA, and a possible marker of increased risk for CAA-ICH recurrence. However, data remain limited. We obtained precise estimates on cSS as an independent predictor of ICH recurrence risk in CAA cohorts from a systematic review of published studies pooled with data from our centre. Methods: We included cohort studies of consecutive CAA-related ICH patients based on the original Boston criteria, with available blood-sensitive MRI sequences at baseline for cSS assessment, and adequate follow-up for recurrent symptomatic ICH. The strength of the association between cSS and recurrent ICH was quantified using random effects models. Covariate-adjusted hazard rations (adj-HR) as provided from pre-specified Cox proportional hazard models were used for a two-stage meta-analysis. Results: Three cohorts including 443 CAA-ICH patients were eligible for analysis. The pooled prevalence of cSS presence and disseminated cSS (>3 affected sulci) was 32% (95%CI: 32%-41%) and 21% (95%CI: 18%-25%) respectively. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH, a pooled risk ratio of 6.9% per year (I 2 : 63%, p=0.07). In adjusted pooled analysis, any cSS and disseminated cSS were both independently associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95%CI: 1.5-3.8; p<0.0001, I 2 : 0% and adj-HR: 4.1; 95%CI: 2.6-6.6; p<0.0001, I 2 : 47%), after adjusting for multiple strictly lobar microbleeds presence and increasing age. Conclusions: Our findings in a large population of CAA patients with ICH and a large number of recurrence events, indicate that cSS, particularly if disseminated, is the single most important prognostic risk factor on MRI for future recurrent lobar ICH. The provided estimates may help stratify future bleeding risk in CAA, with clinical implications for prognosis and treatment.
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