Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy

Abstract

Objective: To investigate whether cortical superficial siderosis (cSS) on MRI, especially if disseminated (involving more than 3 sulci), increases the risk of future symptomatic lobar intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA).Methods: European multicenter cohort study of 118 patients with CAA (104 with baseline symptomatic lobar ICH) diagnosed according to the Boston criteria. We obtained baseline clinical, MRI, and follow-up data on symptomatic lobar ICH. Using Kaplan-Meier and Cox regression analyses, we investigated cSS and ICH risk, adjusting for known confounders.Results: During a median follow-up time of 24 months (interquartile range 9-44 months), 23 of 118 patients (19.5%, 95% confidence interval [CI]: 12.8%-27.8%) experienced symptomatic lobar ICH. Any cSS and disseminated cSS were predictors of time until first or recurrent ICH (logrank test: p 5 0.0045 and p 5 0.0009, respectively). ICH risk at 4 years was 25% (95% CI: 7.6%-28.3%) for patients without siderosis; 28.9% (95% CI: 7.7%-76.7%) for patients with focal siderosis; and 74% (95% CI: 44.1%-95.7%) for patients with disseminated cSS (log-rank test: p 5 0.0031). In Cox regression models, any cSS and disseminated cSS were both independently associated with increased lobar ICH risk, after adjusting for $2 microbleeds and age (hazard ratio: 2.53; 95% CI: 1.05-6.15; p 5 0.040 and hazard ratio: 3.16; 95% CI: 1.35-7.43; p 5 0.008, respectively). These results remained consistent in sensitivity analyses including only patients with symptomatic lobar ICH at baseline. Conclusions:Our findings indicate that cSS, particularly if disseminated, is associated with an increased risk of symptomatic lobar ICH in CAA. cSS may help stratify future bleeding risk in CAA, with implications for prognosis and treatment. Neurology ® 2013;81:1666-1673 GLOSSARY CAA 5 cerebral amyloid angiopathy; CI 5 confidence interval; CMB 5 cerebral microbleed; cSS 5 cortical superficial siderosis; FLAIR 5 fluid-attenuated inversion recovery; GRE 5 gradient-recalled echo; HR 5 hazard ratio; ICH 5 intracerebral hemorrhage.Sporadic cerebral amyloid angiopathy (CAA) is a highly prevalent, age-related small-vessel disease 1 caused by amyloid-b deposition in cortical and leptomeningeal vessel walls. 2 CAA is a major cause of lobar intracerebral hemorrhage (ICH), particularly in elderly patients.2-5 Spontaneous ICH is one of the most catastrophic forms of stroke, with a high risk of recurrence [6][7][8] ; CAA-related lobar ICH may carry a greater risk than deep ICH presumed to be due to hypertensive arteriopathy, 8,9 but this is currently difficult to predict. Predisposing factors for lobar ICH and lobar ICH recurrence in CAA include APOE e4 and e2 alleles, 10 hemorrhagic neuroimaging markers of CAA such as lobar cerebral microbleeds (CMBs), 11 and anticoagulant or antiplatelet use. 12 Little is known about cortical superficial siderosis (cSS), a recently identified neuroimaging marker of CAA, 13 and the risk of subsequent

Pathogenetical Subtypes of Recurrent Intracerebral Hemorrhage

“…7 In addition, patients with CAA have demonstrated increased susceptibility to ICH caused by drugs including anticoagulants and antithrombotic or thrombolytic agents. 9 This condition would be categorized as medication-related ICH by the SMASH-U classification system because of the sequence of the diagnostic flow chart, 5 which could lead to an underestimation in the percentage of CAA. No proven strategy exists to prevent the recurrence of CAA-related ICH; nonetheless, the avoidance of anticoagulants or thrombolytic agents may be beneficial.…”

“…8 CAA-related ICH is predominantly superficial or lobar in location, resulting from the rupture of small or medium sized arteries in the cortical and leptomeningeal regions. 9 It has been proposed that the Boston criteria be used for the clinical diagnosis of CAA based on the tendency of CAA-related ICH to result in multiple hemorrhages, to locate in the lobar, cortical, or subcortical regions, and to occur among older patients. 10 However, multiple simultaneous hemorrhages or recurrent ICH can also be caused by HA.…”

White Matter Perivascular Spaces Are Related to Cortical Superficial Siderosis in Cerebral Amyloid Angiopathy

“…To test this hypothesis and to gain insights into potential mechanisms, we investigated the relationship between MRI-visible CSO-PVS and cSS in patients with possible or probable CAA according to the Boston criteria. cohort study at 4 stroke centers over defined time periods as previously described 10,11 were evaluated. 10,11 and this analysis were (1) CAA, defined according to the Boston criteria, 9 including lobar CMBs, but not cSS and (2) available MRI sequences of adequate quality including T2-weighted, T2*-weighted gradient-recalled echo (T2*-GRE), and fluid attenuation inversion recovery sequences.…”

“…cohort study at 4 stroke centers over defined time periods as previously described 10,11 were evaluated. 10,11 and this analysis were (1) CAA, defined according to the Boston criteria, 9 including lobar CMBs, but not cSS and (2) available MRI sequences of adequate quality including T2-weighted, T2*-weighted gradient-recalled echo (T2*-GRE), and fluid attenuation inversion recovery sequences. The selection process of this multicenter cohort has been described previously: 10,11 in brief, from a total of 358 patients with suspected CAA/spontaneous ICH screened, 144 were initially excluded because of MRI was not performed or was not available/interpretable.…”

“…10,11 and this analysis were (1) CAA, defined according to the Boston criteria, 9 including lobar CMBs, but not cSS and (2) available MRI sequences of adequate quality including T2-weighted, T2*-weighted gradient-recalled echo (T2*-GRE), and fluid attenuation inversion recovery sequences. The selection process of this multicenter cohort has been described previously: 10,11 in brief, from a total of 358 patients with suspected CAA/spontaneous ICH screened, 144 were initially excluded because of MRI was not performed or was not available/interpretable. After reviewing available MRI and clinical data, 56 patients not fulfilling the Boston criteria for CAA were further excluded, leaving a total of 158 CAA patients potentially eligible for the current analysis:…”