Acute ischaemic lesions are associated with cortical superficial siderosis in spontaneous intracerebral hemorrhage

ObjectiveTo investigate whether acute convexity subarachnoid hemorrhage (cSAH) associated with acute lobar intracerebral hemorrhage (ICH) increases the risk of ICH recurrence in patients with cerebral amyloid angiopathy (CAA).MethodsWe analyzed data from a prospective cohort of consecutive survivors of acute spontaneous lobar ICH fulfilling the Boston criteria for possible or probable CAA (CAA-ICH). We analyzed baseline clinical and MRI data, including cSAH (categorized as adjacent or remote from ICH on a standardized scale), cortical superficial siderosis (cSS), and other CAA MRI markers. Multivariable Cox regression models were used to assess the association between cSAH and recurrent symptomatic ICH during follow-up.ResultsWe included 261 CAA-ICH survivors (mean age 76.2 ± 8.7 years). Of them, 166 (63.6%, 95% confidence interval [CI] 57.7%–69.5%) had cSAH on baseline MRI. During a median follow-up of 28.3 (interquartile range 7.2–57.0) months, 54 (20.7%) patients experienced a recurrent lobar ICH. In Cox regression, any cSAH, adjacent cSAH, and remote cSAH were independent predictors of recurrent ICH after adjustment for other confounders, including cSS. Incidence rate of recurrent ICH in patients with cSAH was 9.9 per 100 person-years (95% CI 7.3–13.0) compared with 1.2 per 100 person-years (95% CI 0.3–3.2) in those without cSAH (adjusted hazard ratio 7.5, 95% CI 2.6–21.1).ConclusionIn patients with CAA-related acute ICH, cSAH (adjacent or remote from lobar ICH) is commonly observed and heralds an increased risk of recurrent ICH. cSAH may help stratify bleeding risk and should be assessed along with cSS for prognosis and clinical management.

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Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of 18F-THK5351 Positron Emission Tomography: A Case Report

Frontiers in Neurology ◽

10.3389/fneur.2021.645625 ◽

2021 ◽

Vol 12 ◽

Author(s):

Masaki Ikeda ◽

Koichi Okamoto ◽

Keiji Suzuki ◽

Eriko Takai ◽

Hiroo Kasahara ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Intracerebral Hemorrhage ◽

Pyramidal Tract ◽

Emission Tomography ◽

Superficial Siderosis ◽

Mao B ◽

Positron Emission ◽

The Right ◽

Cortical Superficial Siderosis

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid β. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

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Abstract WP369: Case-Fatality of Cortical Superficial Siderosis in Intracerebral Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.wp369 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Jason Mackey ◽

Kelsey Gagesch ◽

Ashley D Blatsioris ◽

Elizabeth A Moser ◽

Chandan Saha ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Case Fatality ◽

Clinical Trial Design ◽

Index Admission ◽

Superficial Siderosis ◽

Risk Of Death ◽

Kaplan Meier ◽

Hemosiderin Deposition ◽

Cortical Superficial Siderosis

Introduction: Cortical superficial siderosis (CSS) is a neuroimaging biomarker of interest in intracerebral hemorrhage (ICH) and represents hemosiderin deposition in the supratentorial sulci. CSS increases risk for recurrent ICH and is associated with cognitive impairment, but the long-term outcomes of ICH patients with CSS are unknown. We sought to characterize the long-term case-fatality of ICH patients with CSS. Methods: We performed a retrospective convenience study of primary ICH patients who underwent MRI during the index admission. We evaluated each hemisphere for presence of CSS, as well as other SVD markers, and performed Kaplan-Meier analysis to compare the survival curves of those with and without CSS. Vital status was ascertained via chart review and a National Death Index query when necessary. Results: Of 121 patients who underwent an MRI in our cohort, 95 had usable GRE or SWI sequences. Overall CSS prevalence was 11.6% (11/95): 18.2% (10/55) in lobar ICH and 2.5% (1/40) in deep ICH. Univariate predictors of CSS presence included older age (75.6 vs. 63.8, p=.01), larger hematoma volume (10.5mL vs. 4.6, p=.02), and prior ICH (54.5% vs. 10.7%, p=.002). There were no differences between the groups in MBs, EPVS, WMD scores, or DWI lesions. Patients with CSS had a significantly different survival history than those without CSS (log-rank p=.034). Twenty-five percent of the patients with CSS died by 4.4 months after index admission, compared with 45.1 months for those without CSS. The risk of death for the patients with CSS was 2.6 times (95% CI: 1.06-6.41) higher than those without. Four of 11 (36.4%) CSS patients lived at least 4 years after index ICH. Conclusions: Characterization of CSS in ICH patients may improve disease subtyping and clinical trial design. Future studies with larger and more generalizable cohorts are needed to assess how CSS focality vs. dissemination affects case-fatality and whether CSS is an independent predictor of case-fatality.

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Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy

Neurology ◽

10.1212/01.wnl.0000435298.80023.7a ◽

2013 ◽

Vol 81 (19) ◽

pp. 1666-1673 ◽

Cited By ~ 87

Author(s):

A. Charidimou ◽

A. P. Peeters ◽

R. Jager ◽

Z. Fox ◽

Y. Vandermeeren ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Hemorrhage Risk ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

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

International Journal of Stroke ◽

10.1177/1747493019830065 ◽

2019 ◽

Vol 14 (7) ◽

pp. 723-733 ◽

Cited By ~ 7

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Duangnapa Roongpiboonsopit ◽

Li Xiong ◽

Marco Pasi ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Prospective Cohort ◽

Cox Regression ◽

Meta Analysis ◽

Recurrence Risk ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

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.

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Combining Imaging and Genetics to Predict Recurrence of Anticoagulation-Associated Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.120.028310 ◽

2020 ◽

Vol 51 (7) ◽

pp. 2153-2160 ◽

Cited By ~ 2

Author(s):

Alessandro Biffi ◽

Sebastian Urday ◽

Patryk Kubiszewski ◽

Lee Gilkerson ◽

Padmini Sekar ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Classification Scheme ◽

Low Risk ◽

Joint Analysis ◽

Superficial Siderosis ◽

Validation Data ◽

Data Set ◽

Cerebral Microbleed ◽

Increased Risk ◽

Cortical Superficial Siderosis

Background and Purpose: For survivors of oral anticoagulation therapy (OAT)–associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E ( APOE ) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. Results: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P <0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. Conclusions: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

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Cortical superficial siderosis in the general population: The Framingham Heart and Rotterdam studies

International Journal of Stroke ◽

10.1177/1747493020984559 ◽

2021 ◽

pp. 174749302098455

Author(s):

Ashkan Shoamanesh ◽

Saloua Akoudad ◽

Jayandra J. Himali ◽

Alexa S. Beiser ◽

Charles DeCarli ◽

...

Keyword(s):

General Population ◽

Intracerebral Hemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Brain Mri ◽

Community Dwelling ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Supporting Evidence ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

Objective We aimed to characterize cortical superficial siderosis, its determinants and sequel, in community-dwelling older adults. Methods The sample consisted of Framingham ( n = 1724; 2000–2009) and Rotterdam ( n = 4325; 2005–2013) study participants who underwent brain MRI. In pooled individual-level analysis, we compared baseline characteristics in patients with cortical superficial siderosis to two reference groups: (i) persons without hemorrhagic MRI markers of cerebral amyloid angiopathy (no cortical superficial siderosis and no microbleeds) and (ii) those with presumed cerebral amyloid angiopathy based on the presence of strictly lobar microbleeds but without cortical superficial siderosis. Results Among a total of 6049 participants, 4846 did not have any microbleeds or cortical superficial siderosis (80%), 401 had deep/mixed microbleeds (6.6%), 776 had strictly lobar microbleeds without cortical superficial siderosis (12.8%) and 26 had cortical superficial siderosis with/without microbleeds (0.43%). In comparison to participants without microbleeds or cortical superficial siderosis and to those with strictly lobar microbleeds but without cortical superficial siderosis, participants with cortical superficial siderosis were older (OR 1.09 per year, 95% CI 1.05, 1.14; p < 0.001 and 1.04, 95% CI 1.00, 1.09; p = 0.058, respectively), had overrepresentation of the APOE ɛ4 allele (5.19, 2.04, 13.25; p = 0.001 and 3.47, 1.35, 8.92; p = 0.01), and greater prevalence of intracerebral hemorrhage (72.57, 9.12, 577.49; p < 0.001 and 81.49, 3.40, >999.99; p = 0.006). During a mean follow-up of 5.6 years, 42.4% participants with cortical superficial siderosis had a stroke (five intracerebral hemorrhage, two ischemic strokes and four undetermined strokes), 19.2% had transient neurological deficits and 3.8% developed incident dementia. Conclusion Our study adds supporting evidence to the association between cortical superficial siderosis and cerebral amyloid angiopathy within the general population. Community-dwelling persons with cortical superficial siderosis may be at high risk for intracerebral hemorrhage and future neurological events.

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