Cortical superficial siderosis and recurrent intracerebral hemorrhage risk in cerebral amyloid angiopathy: Large prospective cohort and preliminary meta-analysis

Abstract

Background We aimed to investigate cortical superficial siderosis as an MRI predictor of lobar intracerebral hemorrhage (ICH) recurrence risk in cerebral amyloid angiopathy (CAA), in a large prospective MRI cohort and a systematic review. Methods We analyzed a single-center MRI prospective cohort of consecutive CAA-related ICH survivors. Using Kaplan–Meier and Cox regression analyses, we investigated cortical superficial siderosis and ICH risk, adjusting for known confounders. We pooled data with eligible published cohorts in a two-stage meta-analysis using random effects models. Covariate-adjusted hazard rations (adj-HR) from pre-specified multivariable Cox proportional hazard models were used. Results The cohort included 240 CAA-ICH survivors (cortical superficial siderosis prevalence: 36%). During a median follow-up of 2.6 years (IQR: 0.9–5.1 years) recurrent ICH occurred in 58 patients (24%). In prespecified multivariable Cox regression models, cortical superficial siderosis presence and disseminated cortical superficial siderosis were independent predictors of increased symptomatic ICH risk at follow-up (HR: 2.26; 95% CI: 1.31–3.87, p = 0.003 and HR: 3.59; 95% CI: 1.96–6.57, p < 0.0001, respectively). Three cohorts including 443 CAA-ICH patients in total were eligible for meta-analysis. During a mean follow-up of 2.5 years (range: 2–3 years) 92 patients experienced recurrent ICH (pooled risk ratio: 6.9% per year, 95% CI: 4.2%–9.7% per year). In adjusted pooled analysis, any cortical superficial siderosis and disseminated cortical superficial siderosis were the only independent predictors associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95% CI: 1.5–3.7; p < 0.0001, and adj-HR: 4.4; 95% CI: 2–9.9; p < 0.0001, respectively). Conclusions In CAA-ICH patients, cortical superficial siderosis presence and extent are the most important MRI prognostic risk factors for lobar ICH recurrence. These results can help guide clinical decision making in patients with CAA.

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

“…9,34 Further more, we did not find strong evidence of differ ences within exploratory subgroup analyses to suggest that superficial siderosis or diagnostic criteria for cerebral amyloid angiopathy might modify the risk of intracerebral haemorrhage with antiplatelet therapy. 5,35 Although these brain imaging features are associated with higher absolute risks of intracerebral haemorrhage recurrence in observa tional studies, 6,7 we did not find strong evidence that there was heterogeneity in the effects of antiplatelet therapy in these subgroups.…”

“…5,9,10,34 More over, there was no strong evidence of heterogeneity between subgroups, and the effect estimates in almost all sub groups were consistent with the trial's overall finding that antiplatelet therapy might reduce the risk of recurrent intracerebral haemorrhage. Furthermore, despite the association between superficial siderosis and recurrent intracerebral haemorrhage, 6 the effect of antiplatelet therapy on recurrent intracere bral haemorrhage in people with superficial siderosis (HR 0•70, 95% CI 0•17-2•93) might affect clinical equipoise and increase recruitment of people with this imaging feature in future randomised trials of antithrombotic therapies.…”

“…[1][2][3] Some brain imaging features of intracerebral haem orrhage and cerebral small vessel diseases are associ ated with a higher risk of intracerebral haemorrhage recurrence in general, and in people taking antiplatelet therapy. [4][5][6][7][8] For example, the proportional increase in the risk of intracerebral haemorrhage recurrence is up to five times higher after lobar versus nonlobar haemorrhage, 8 up to sixtimes higher with presence versus absence of cerebral microbleeds on MRI, 7 and roughly fourtimes higher with presence versus absence of superficial siderosis on MRI. 6 Consequently, guidelines and opin ions suggest that location of intracerebral haemorrhage and some features of cerebral small vessel diseases can guide therapeutic decisions.…”

Neurofilament light chain predicts risk of recurrence in cerebral amyloid angiopathy-related intracerebral hemorrhage

“…Patients with CAA show substantially higher risks of recurrent ICH at a rate of 6.9 -10% per year [1][2][3] compared with deep ICH of about 3% per year [4], leading to subsequent disability and mortality. So far, the prediction of ICH recurrence and disease severity for CAA mostly depends on brain imaging features, including the number of previous ICH and cerebral microbleeds (CMBs), posterior white matter hyperintensities (WMH) [1,5] and cortical superficial siderosis (cSS), among which cSS is most clinically relevant [2,3]. However CAA-related MRI features represent vascular endpoints of CAA rather than neurodegenerative processes that might influence disease progression and recurrence risk [6].…”

Current approaches to diagnosing in intracerebral hemorrhage

“…Риск рецидива после ЦАА-ассоциированного ВМК составляет 9-26% в год и особенно высок при диссеминированном КПС [28]. Наличие и распространенность КПС -единственные независимые предикторы рецидива долевого ВМК [29]. Визуализация двух и более ЦМК повышает риск рецидива ЦАА-ассоциированного ВМК в 3-4 раза, тогда как вероятность повторного гипертензионного ВМК возрастает лишь при наличии более 10 ЦМК (в 5,6 раза) [27].…”