Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy(CME)

Department of Neuroradiology, University Hospital Munich, Marchioninistrasse 15, 81377 Munich, Germany.
Neurology (Impact Factor: 8.3). 04/2010; 74(17):1346-50. DOI: 10.1212/WNL.0b013e3181dad605
Source: PubMed

ABSTRACT Cerebral amyloid angiopathy (CAA) typically presents with lobar intracerebral macrohemorrhages (ICH) or microbleeds (MBs). Several case reports also found superficial siderosis (SS) in patients with CAA. We aimed to assess the value of SS for the in vivo diagnosis of CAA, and tested whether the inclusion of SS as a criterion alters the sensitivity and specificity of the Boston criteria for CAA-related hemorrhage.
We retrospectively analyzed the T2*-weighted MRIs of 38 patients with histopathologically proven CAA and of 22 control patients with histopathologically proven non-CAA ICHs regarding the presence of ICHs, MBs, and SS. We compared the sensitivity and specificity of the classic Boston criteria to that of modified criteria, which included SS as a criterion.
ICHs were present in 71% of the patients with CAA, and in all control patients. MBs were found in 47.4% of patients with CAA and in 22.7% of controls. SS was detected in 60.5% of patients with CAA, but in none of the controls. The classic criteria had a sensitivity of 89.5% for CAA-related hemorrhage, while inclusion of SS increased their sensitivity to 94.7% (not significant). On the contrary, the specificity of the Boston criteria was 81.2% both for the classic and for the modified criteria.
Superficial siderosis (SS) occurs with high prevalence in cerebral amyloid angiopathy (CAA) and is rare in non-CAA forms of intracerebral hemorrhages. Thus, we propose that inclusion of SS in the Boston criteria might enhance their sensitivity for CAA-related hemorrhage without loss of specificity.

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Available from: Jennifer Linn, Feb 19, 2014
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    • "Within the past decade, a second type of brain siderosis restricted to the supratentorial compartment and the convexities of the cerebral hemispheres, has been identified and referred to as 'cortical' superficial siderosis (cSS) (Linn et al., 2008). cSS has a different range of potential causes and clinical presentation to classical siderosis, but in older individuals is emerging as a key feature of cerebral amyloid angiopathy (CAA), a common and important age-related cerebral small vessel disorder (Linn et al., 2010; Viswanathan and Greenberg, 2011; Charidimou et al., 2012a). cSS is associated with characteristic clinical symptoms , including transient focal neurological episodes (Greenberg et al., 1993), and might be a marker of future intracerebral haemorrhage (ICH) risk in CAA patients (Charidimou et al., 2013c; Linn et al., 2013). "
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    ABSTRACT: Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. In cerebral amyloid angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intracerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
    Brain 06/2015; DOI:10.1093/brain/awv162 · 10.23 Impact Factor
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    • "According to these criteria, the detection of multiple (2) strictly lobar hemorrhages (large or small, symptomatic or asymptomatic) without known underlying cause in individuals aged .55 years is highly specific of the disease [4]. However, validation studies of these criteria have been mostly based on patients admitted because of lobar ICH [4] [13] [14], precluding the study of the diagnostic value of lobar MBs without symptomatic ICH. At a community level, the Rotterdam and Framingham studies have shown that healthy elderly individuals with strictly lobar MBs have an increased frequency of the APOE-ε4 allele (compared with patients with MBs not strictly confined to lobar regions) [11] [15], which is in agreement with increased APOE-ε4 frequencies seen in patients with " probable CAA " [16]. "
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    ABSTRACT: The Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH. We identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathologic assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria. We included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of "probable CAA" (≥2 strictly lobar MBs) was 87.5 (95% confidence interval [CI], 60.4-97.8) and 25 (95% CI, 13.2-78) in hospital and general populations, respectively. Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; 128. DOI:10.1016/j.jalz.2015.04.009 · 17.47 Impact Factor
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    • "Curvilinear low intensities on an appropriately weighted (T2 or T2*) sequence that lie adjacent to the brain surface are referred to as superficial siderosis. Similar to mH, siderosis is attributed to deposition of iron in the form of hemosiderin and is thought to represent residua of a blood leakage from a vessel into the adjacent subarachnoid space or the periadventitial compartment (as opposed to leakage into parenchyma to form an mH) [18] "
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    ABSTRACT: Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-β burden in Alzheimer's disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer's Association Research Roundtable convened a working group to review the publicly available trial data, attempts at developing animal models, and the literature on the natural history and pathology of related conditions. The spectrum of ARIA includes signal hyperintensities on fluid attenuation inversion recoverysequences thought to represent "vasogenic edema" and/or sulcal effusion (ARIA-E), as well as signal hypointensities on GRE/T2* thought to represent hemosiderin deposits (ARIA-H), including microhemorrhage and superficial siderosis. The etiology of ARIA remains unclear but the prevailing data support vascular amyloid as a common pathophysiological mechanism leading to increased vascular permeability. The workgroup proposes recommendations for the detection and monitoring of ARIA in ongoing AD clinical trials, as well as directions for future research.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 07/2011; 7(4):367-85. DOI:10.1016/j.jalz.2011.05.2351 · 17.47 Impact Factor
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