Cortical superficial siderosis progression in cerebral amyloid angiopathy

ObjectiveTo investigate the prevalence, predictors, and clinical relevance of cortical superficial siderosis (cSS) progression in cerebral amyloid angiopathy (CAA).MethodsConsecutive patients with symptomatic CAA meeting Boston criteria in a prospective cohort underwent baseline and follow-up MRI within 1 year. cSS progression was evaluated on an ordinal scale and categorized into mild (score 1–2 = cSS extension within an already present cSS focus or appearance of 1 new cSS focus) and severe progression (score 3–4 = appearance of ≥2 new cSS foci). Binominal and ordinal multivariable logistic regression were used to determine cSS progression predictors. We investigated future lobar intracerebral hemorrhage (ICH) risk in survival analysis models.ResultsWe included 79 patients with CAA (mean age, 69.2 years), 56 (71%) with lobar ICH at baseline. cSS progression was detected in 23 (29%) patients: 15 (19%) patients had mild and 8 (10%) severe progression. In binominal multivariable logistic regression, ICH presence (odds ratio [OR], 7.54; 95% confidence interval [CI], 1.75–53.52; p = 0.016) and baseline cSS (OR, 10.41; 95% CI, 2.84–52.83; p = 0.001) were independent predictors of cSS progression. In similar models, presence of disseminated (but not focal) cSS at baseline (OR, 5.58; 95% CI, 1.81–19.41; p = 0.004) was an independent predictor of cSS progression. Results were similar in ordinal multivariable logistic regression models. In multivariable Cox regression analysis, severe cSS progression was independently associated with increased future ICH risk (HR, 5.90; 95% CI, 1.30–26.68; p = 0.021).ConclusionscSS evolution on MRI is common in patients with symptomatic CAA and might be a potential biomarker for assessing disease severity and future ICH risk. External validation of these findings is warranted.

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Acute convexity subarachnoid haemorrhage and cortical superficial siderosis in probable cerebral amyloid angiopathy without lobar haemorrhage

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-316368 ◽

2017 ◽

Vol 89 (4) ◽

pp. 397-403 ◽

Cited By ~ 5

Author(s):

Andreas Charidimou ◽

Grégoire Boulouis ◽

Panagiotis Fotiadis ◽

Li Xiong ◽

Alison M Ayres ◽

...

Keyword(s):

Logistic Regression ◽

Subarachnoid Haemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Clinical Symptoms ◽

Small Vessel Disease ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Multivariable Logistic Regression ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

IntroductionAcute non-traumatic convexity subarachnoid haemorrhage (cSAH) is increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated: (a) the overlap between acute cSAH and cortical superficial siderosis—a new CAA haemorrhagic imaging signature and (b) whether acute cSAH presents with particular clinical symptoms in patients with probable CAA without lobar intracerebral haemorrhage.MethodsMRI scans of 130 consecutive patients meeting modified Boston criteria for probable CAA were analysed for cortical superficial siderosis (focal, ≤3 sulci; disseminated, ≥4 sulci), and key small vessel disease markers. We compared clinical, imaging and cortical superficial siderosis topographical mapping data between subjects with versus without acute cSAH, using multivariable logistic regression.ResultsWe included 33 patients with probable CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with acute cSAH were more commonly presenting with transient focal neurological episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH. Patients with acute cSAH were also more often clinically presenting with transient focal neurological episodes compared with cortical superficial siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001). Cortical superficial siderosis prevalence (but no other CAA severity markers) was higher among patients with cSAH versus those without, especially disseminated cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8, p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to 50.6, p=0.001) were independently associated with acute cSAH.ConclusionsThis probable CAA cohort provides additional evidence for distinct disease phenotypes, determined by the presence of cSAH and cortical superficial siderosis.

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MRI-visible perivascular spaces in cerebral amyloid angiopathy and hypertensive arteriopathy

Neurology ◽

10.1212/wnl.0000000000003746 ◽

2017 ◽

Vol 88 (12) ◽

pp. 1157-1164 ◽

Cited By ~ 74

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Marco Pasi ◽

Eitan Auriel ◽

Ellis S. van Etten ◽

...

Keyword(s):

Logistic Regression ◽

Cerebral Amyloid Angiopathy ◽

Rating Scale ◽

Multinomial Logistic Regression ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Multivariable Logistic Regression ◽

Cerebral Amyloid ◽

High Degree

Objective:To assess MRI-visible enlarged perivascular spaces (EPVS) burden and different topographical patterns (in the centrum semiovale [CSO] and basal ganglia [BG]) in 2 common microangiopathies: cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA).Methods:Consecutive patients with spontaneous intracerebral hemorrhage (ICH) from a prospective MRI cohort were included. Small vessel disease MRI markers, including cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), and white matter hyperintensities (WMH), were rated. CSO-EPVS/BG-EPVS were assessed on a validated 4-point visual rating scale (0 = no EPVS, 1 = <10, 2 = 11–20, 3 = 21–40, and 4 = >40 EPVS). We tested associations of predefined high-degree (score >2) CSO-EPVS and BG-EPVS with other MRI markers in multivariable logistic regression. We subsequently evaluated associations with CSO-EPVS predominance (i.e., CSO-EPVS > BG-EPVS) and BG-EPVS predominance pattern (i.e., BG-EPVS > CSO-EPVS) in adjusted multinomial logistic regression (reference group, BG-EPVS = CSO-EPVS).Results:We included 315 patients with CAA-ICH and 137 with HA-ICH. High-degree CSO-EPVS prevalence was greater in CAA-related ICH vs HA-related ICH (43.8% vs 17.5%, p < 0.001). In multivariable logistic regression, high-degree CSO-EPVS was associated with lobar CMB (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.10–1.61, p = 0.003) and cSS (OR 2.08, 95% CI 1.30–3.32, p = 0.002). Deep CMBs (OR 2.85, 95% CI 1.75–4.64, p < 0.0001) and higher WMH volume (OR 1.02, 95% CI 1.01–1.04, p = 0.010) were predictors of high-degree BG-EPVS. A CSO-EPVS–predominant pattern was more common in CAA-ICH than in HA-ICH (75.9% vs 39.4%, respectively, p < 0.0001). CSO-PVS predominance was associated with lobar CMB burden and cSS, while BG-EPVS predominance was associated with HA-ICH and WMH volumes.Conclusions:Different patterns of MRI-visible EPVS provide insights into the dominant underlying microangiopathy type in patients with spontaneous ICH.

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P4-196: Clinical Impacts of Cortical Superficial Siderosis in Patients With Clinically Diagnosed Cerebral Amyloid Angiopathy

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.2288 ◽

2016 ◽

Vol 12 ◽

pp. P1099-P1099

Author(s):

Young Kyoung Jang ◽

Hee Jin Kim ◽

Yeo Jin Kim ◽

Jin San Lee ◽

Juyoun Lee ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

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Abstract TP330: Proportion of Intracerebral Haemorrhage Due to Cerebral Amyloid Angiopathy in the East and West

Stroke ◽

10.1161/str.51.suppl_1.tp330 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Yusuke Yakushiji ◽

Jun Tanaka ◽

Duncan Wilson ◽

Andreas Charidimou ◽

Tomoyuki Noguchi ◽

...

Keyword(s):

Logistic Regression ◽

Cerebral Amyloid Angiopathy ◽

Intracerebral Haemorrhage ◽

East Asian ◽

Sensitivity Analyses ◽

Amyloid Angiopathy ◽

Asian Populations ◽

Multivariable Logistic Regression ◽

Cerebral Amyloid ◽

Centre Origin

Objectives: We investigated whether the proportion of intracerebral haemorrhage (ICH) due to cerebral amyloid angiopathy (CAA) differs between patients of Eastern and Western origin. Methods: This is a retrospective international cross-sectional study of consecutive first-ever spontaneous ICH patients (including patients with surgical intervention) admitted to one stroke centre in the United Kingdom (Western centre origin) and one in Japan (Eastern centre origin) during the same period. We classified spontaneous ICH into “CAA-related ICH” defined by the Edinburgh CT diagnostic criteria, and “other ICH”. We used multivariable logistic regression analyses to assess the relationship between CAA-ICH and geographical location (Western or Eastern centre origin) or ethnicity (Western [reference], East Asian, or other) with adjustment for confounders. Results: Of 334 patients (median age, 71 years; male, 54%; Western centre origin, 58%), 15% were classified as CAA-ICH, and 85% were defined as other ICH. In multivariable logistic regression analysis, Eastern centre and ethnicity had a lower proportion of CAA-ICH (odds ratio [OR] vs Western centre origin 0.47, 95%CI 0.23-0.98; OR [vs. white] 0.41, 95%CI 0.20-0.97, respectively).The estimated incidence of CAA-related ICH in East Asian was similar to that in White populations, but the rate of other ICH was 2.5-fold higher in East Asian populations. Sensitivity analyses using the modified Boston criteria for diagnosis of CAA-related ICH showed similar results. Conclusions: The proportion CAA-ICH is lower in an Eastern compared to a Western population; this appears to be explained by a higher incidence of ICH due to hypertensive (deep perforator) arteriopathy in East Asian populations.

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Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000008590 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2192-e2202 ◽

Cited By ~ 5

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Steven M. Greenberg ◽

Anand Viswanathan

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Meta Analysis ◽

Bleeding Risk ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Class Iii ◽

Cerebral Amyloid ◽

T2 Mri ◽

Cortical Superficial Siderosis

ObjectiveTo assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA).MethodsThis was a meta-analysis of clinical cohorts of symptomatic patients with CAA who had T2*-MRI at baseline and clinical follow-up for future intracerebral hemorrhage (ICH). We pooled data in a 2-stage meta-analysis using random effects models. Covariate-adjusted hazard ratios (adjHR) from multivariable Cox proportional hazard models were used.ResultsWe included data from 6 eligible studies (n = 1,239). cSS pooled prevalence was 34% (95% confidence interval [CI] 26%–41%; I2 87.94%; p < 0.001): focal cSS prevalence was 14% (95% CI 12%–16%; I2 6.75%; p = 0.37), and disseminated cSS prevalence was 20% (95% CI 13%–26%; I2 90.39%; p < 0.001). During a mean follow-up of 3.1 years (range 1–4 years), 162/1,239 patients experienced a symptomatic ICH-pooled incidence rate 6.9% per year (95% CI 3.9%–9.8% per year; I2 83%; p < 0.001). ICH incidence rates per year according to cSS status were 3.9% (95% CI 1.7%–6.1%; I2 70%; p = 0.018) for patients without cSS, 11.1% (95% CI 7%–15.2%; I2 56.8%; p = 0.074) for cSS presence, 9.1% (95% CI 5.5%–12.8%; I2 0%; p = 0.994) for focal cSS, and 12.5% (95% CI 5.3%–19.7%; I2 73.2%; p = 0.011) for disseminated cSS. In adjusted pooled analysis, any cSS presence was independently associated with increased future ICH risk (adjHR 2.14; 95% CI 1.19–3.85; p < 0.0001). Focal cSS was linked with ICH risk (adjHR 2.11; 95% CI 1.31–2.41; p = 0.002), while disseminated cSS conferred the strongest bleeding risk (adjHR 4.28; 95% CI 2.91–6.30; p < 0.0001).ConclusionIn patients with CAA, cSS presence and extent are the most important MRI prognostic risk factors for future ICH, likely useful in treatment planning.Classification of evidenceThis study provides Class III evidence that in symptomatic CAA survivors with baseline T2*-MRI, cSS (particularly if disseminated, i.e., affecting >3 sulci) increases the risk of future ICH.

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Clinical and radiological differences between patients with probable cerebral amyloid angiopathy and mixed cerebral microbleeds

Journal of Neurology ◽

10.1007/s00415-020-10038-8 ◽

2020 ◽

Vol 267 (12) ◽

pp. 3602-3608 ◽

Cited By ~ 1

Author(s):

Ulf R. Jensen-Kondering ◽

Caroline Weiler ◽

Patrick Langguth ◽

Naomi Larsen ◽

Charlotte Flüh ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Cerebral Microbleeds ◽

Superficial Siderosis ◽

Periventricular White Matter ◽

Amyloid Angiopathy ◽

Imaging Features ◽

Significant Difference ◽

Comprehensive Comparison ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

Abstract Background The key imaging features of cerebral amyloid angiopathy (CAA) are lobar, cortical, or cortico-subcortical microbleeds, macrohaemorrhages and cortical superficial siderosis (cSS). In contrast, hypertensive angiopathy is characterized by (micro) haemorrhages in the basal ganglia, thalami, periventricular white matter or the brain stem. Another distinct form of haemorrhagic microangiopathy is mixed cerebral microbleeds (mixed CMB) with features of both CAA and hypertensive angiopathy. The distinction between the two entities (CAA and mixed CMB) is clinically relevant because the risk of haemorrhage and stroke should be well balanced if oral anticoagulation is indicated in CAA patients. We aimed to comprehensively compare these two entities. Methods Patients with probable CAA according to the modified Boston criteria and mixed CMB without macrohaemorrhage were retrospectively identified from our database. Comprehensive comparison regarding clinical and radiological parameters was performed between the two cohorts. Results Patients with CAA were older (78 ± 8 vs. 74 ± 9 years, p = 0.036) and had a higher prevalence of cSS (19% vs. 4%, p = 0.027) but a lower prevalence of lacunes (73% vs. 50%, p = 0.018) and deep lacunes (23% vs. 51%, p = 0.0003) compared to patients with mixed CMB. Logistic regression revealed an association between the presence of deep lacunes and mixed CMB. The other collected parameters did not reveal a significant difference between the two groups. Conclusions CAA and mixed CMB demonstrate radiological differences in the absence of macrohaemorrhages. However, more clinically available biomarkers are needed to elucidate the contribution of CAA and hypertensive angiopathy in mixed CMB patients.

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Cortical superficial siderosis multifocality in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000004665 ◽

2017 ◽

Vol 89 (21) ◽

pp. 2128-2135 ◽

Cited By ~ 40

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Duangnapa Roongpiboonsopit ◽

Eitan Auriel ◽

Marco Pasi ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Interrater Reliability ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Recurrence Rates ◽

Rating Method ◽

Cerebral Amyloid ◽

Annual Risk ◽

Cortical Superficial Siderosis

Objective: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.Methods: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.Results: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).Conclusions: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.

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