Amyloid Spells and High Blood Pressure: Imminent Danger

We present the case of a 71-year-old male, admitted after a generalized tonic-clonic seizure, with a history of recurrent left arm and face paresthesias, associated with sulcal cortical subarachnoid hemorrhages. During the next 48 h, he remained agitated with a high blood pressure profile; he also suffered a cardiac arrest in relation to a severe left fronto-parietal and a smaller right parietal parenchymal hemorrhage that developed over the subarachnoid hemorrhage locations. There were no intracranial vascular abnormalities. Three months later, an MRI revealed disseminated superficial siderosis. He was discharged with a modified Rankin scale of 4. He died 1 month later of unknown cause. A diagnosis of probable cerebral amyloid angiopathy was assumed. Patients with pathologically proven cerebral amyloid angiopathy that present with transient focal neurological symptoms in relation to cortical bleeds, the so-called ‘myloid spells' seem to be at an increased risk of future parenchymal hemorrhages. Avoiding antiplatelet agents in these cases has been proposed. Our case suggests that these patients should be monitored closely in the hyperacute phase , and tight blood pressure control should be considered as the immediate risk of bleeding may be high, even without a definitive diagnosis of cerebral amyloid angiopathy.

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Abstract 212: Cortical Superficial Siderosis and Risk of Recurrent Intracerebral Haemorrhage in Cerebral Amyloid Angiopathy: A Meta-analysis

Stroke ◽

10.1161/str.48.suppl_1.212 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Solene Moulin ◽

Duangnapa Roongpiboonsopit ◽

Nicolas Raposo ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Meta Analysis ◽

Large Population ◽

Recurrence Risk ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Increased Risk ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

Background: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar intracerebral hemorrhage (ICH) in the elderly. CAA-related ICH survivors are at substantial risk for recurrent ICH, accounting for the significant morbidity of the disease. Identifying predictors of recurrence is therefore crucial. Recent data have implicated cortical superficial siderosis (cSS) as a key hemorrhagic MRI signature of CAA, and a possible marker of increased risk for CAA-ICH recurrence. However, data remain limited. We obtained precise estimates on cSS as an independent predictor of ICH recurrence risk in CAA cohorts from a systematic review of published studies pooled with data from our centre. Methods: We included cohort studies of consecutive CAA-related ICH patients based on the original Boston criteria, with available blood-sensitive MRI sequences at baseline for cSS assessment, and adequate follow-up for recurrent symptomatic ICH. The strength of the association between cSS and recurrent ICH was quantified using random effects models. Covariate-adjusted hazard rations (adj-HR) as provided from pre-specified Cox proportional hazard models were used for a two-stage meta-analysis. Results: Three cohorts including 443 CAA-ICH patients were eligible for analysis. The pooled prevalence of cSS presence and disseminated cSS (>3 affected sulci) was 32% (95%CI: 32%-41%) and 21% (95%CI: 18%-25%) respectively. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH, a pooled risk ratio of 6.9% per year (I 2 : 63%, p=0.07). In adjusted pooled analysis, any cSS and disseminated cSS were both independently associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95%CI: 1.5-3.8; p<0.0001, I 2 : 0% and adj-HR: 4.1; 95%CI: 2.6-6.6; p<0.0001, I 2 : 47%), after adjusting for multiple strictly lobar microbleeds presence and increasing age. Conclusions: Our findings in a large population of CAA patients with ICH and a large number of recurrence events, indicate that cSS, particularly if disseminated, is the single most important prognostic risk factor on MRI for future recurrent lobar ICH. The provided estimates may help stratify future bleeding risk in CAA, with clinical implications for prognosis and treatment.

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Abstract WP371: Cortical Superficial Siderosis and Mortality in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.48.suppl_1.wp371 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Duangnapa Roongpiboonsopit ◽

Andreas Charidimou ◽

Gregoire Boulouis ◽

Li Xiong ◽

Arne Lauer ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Mortality Risk ◽

Older Age ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Increased Risk ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis ◽

Overall Mortality

Objective: To investigate whether magnetic resonance imaging (MRI) markers of cerebral small vessel disease predict overall mortality in cerebral amyloid angiopathy (CAA) patients. Methods: Subjects were consecutive survivors (age≥55) of spontaneous symptomatic CAA-related-lobar ICH and CAA presenting without lobar ICH, diagnosed according to the Boston criteria drawn from an ongoing longitudinal cohort study and Memory Disorder Unit. All subjects had brain MRI at presentation. Baseline clinical, imaging, laboratory data and mortality information were collected. Neuroimaging markers including focal (≤3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), cortical subarachnoid hemorrhage (cSAH), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS) and white matter hyperintensities (WMH) were evaluated. Overall mortality risk was assessed using Cox proportional hazards models adjusting for potential confounders. Results: A total of 335 patients with probable CAA were enrolled, 196 presenting with lobar ICH and 139 without lobar ICH. During a median follow-up time of 3.44 years (interquartile range 1.61- 5.52 years), 181 of 335 patients (54.0%) died, 37.3% were patients with lobar ICH and 16.7% were those without. In univariable analysis, disseminated cSS, moderate to severe WMH, higher age and CAA related-lobar ICH group were predictors of overall mortality (p<0.05 for all comparisons). After adjusting for moderate to severe WMH and multiple CMBs (CMBs ≥5 foci), disseminated cSS remained as an independent neuroimaging predictor of overall mortality (HR 1.66; 95% CI 1.05-2.64, p = 0.030). Other predictors of mortality were older age (HR 1.08; 95% CI 1.06-1.11, p < 0.001) and presence of lobar ICH (HR 1.87; 95% CI 1.34-2.61, p < 0.001). The mortality risk was even greater in patients with both disseminated cSS and lobar ICH (HR 2.28; 95% CI 1.41-3.69, p = 0.001) and as well as in older patients (age>75 years) with disseminated cSS (HR 1.86; 95% CI 1.08-3.23, p = 0.026). Conclusion: Disseminated cSS is an independent neuroimaging biomarker of increased risk of overall mortality in probable CAA, particular in those patients with lobar ICH and older age. These findings may serve identify important markers of CAA severity.

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Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000003866 ◽

2017 ◽

Vol 88 (17) ◽

pp. 1607-1614 ◽

Cited By ~ 34

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Li Xiong ◽

Michel J. Jessel ◽

Duangnapa Roongpiboonsopit ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Cox Regression ◽

Small Vessel Disease ◽

Rank Test ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Increased Risk ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

Objective:To investigate whether cortical superficial siderosis (cSS) is associated with increased risk of future first-ever symptomatic lobar intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA) presenting with neurologic symptoms and without ICH.Methods:Consecutive patients meeting modified Boston criteria for probable CAA in the absence of ICH from a single-center cohort were analyzed. cSS and other small vessel disease MRI markers were assessed according to recent consensus recommendations. Patients were followed prospectively for future incident symptomatic lobar ICH. Prespecified Cox proportional hazard models were used to investigate cSS and first-ever lobar ICH risk adjusting for potential confounders.Results:The cohort included 236 patients with probable CAA without lobar ICH at baseline. cSS prevalence was 34%. During a median follow-up of 3.26 years (interquartile range 1.42–5.50 years), 27 of 236 patients (11.4%) experienced a first-ever symptomatic lobar ICH. cSS was a predictor of time until first ICH (p = 0.0007, log-rank test). The risk of symptomatic ICH at 5 years of follow-up was 19% (95% confidence interval [CI] 11%–32%) for patients with cSS at baseline vs 6% (95% CI 3%–12%) for patients without cSS. In multivariable Cox regression models, cSS presence was the only independent predictor of increased symptomatic ICH risk during follow-up (HR 4.04; 95% CI 1.73–9.44, p = 0.001), after adjusting for age, lobar cerebral microbleeds burden, and white matter hyperintensities.Conclusions:cSS is consistently associated with an increased risk of future lobar ICH in CAA with potentially important clinical implications for patient care decisions such as antithrombotic use.

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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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Late-Life Vascular Risk Score in Association With Postmortem Cerebrovascular Disease Brain Pathologies

Stroke ◽

10.1161/strokeaha.120.030226 ◽

2021 ◽

Author(s):

Shahram Oveisgharan ◽

Lei Yu ◽

Ana Capuano ◽

Zoe Arvanitakis ◽

Lisa L. Barnes ◽

...

Keyword(s):

Cerebrovascular Disease ◽

Cerebral Amyloid Angiopathy ◽

Risk Score ◽

Odds Ratio ◽

Amyloid Angiopathy ◽

Individual Level ◽

Framingham Risk ◽

Increased Risk ◽

Cerebral Amyloid ◽

The Individual

Background and Purpose: The general cardiovascular Framingham risk score (FRS) identifies adults at increased risk for stroke. We tested the hypothesis that baseline FRS is associated with the presence of postmortem cerebrovascular disease (CVD) pathologies. Methods: We studied the brains of 1672 older decedents with baseline FRS and measured CVD pathologies including macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. We employed a series of logistic regressions to examine the association of baseline FRS with each of the 5 CVD pathologies. Results: Average age at baseline was 80.5±7.0 years and average age at death was 89.2±6.7 years. A higher baseline FRS was associated with higher odds of macroinfarcts (odds ratio, 1.10 [95% CI, 1.07–1.13], P <0.001), microinfarcts (odds ratio, 1.04 [95% CI, 1.01–1.07], P =0.009), atherosclerosis (odds ratio, 1.07 [95% CI, 1.04–1.11], P <0.001), and arteriolosclerosis (odds ratio, 1.04 [95% CI, 1.01–1.07], P =0.005). C statistics for these models ranged from 0.537 to 0.595 indicating low accuracy for predicting CVD pathologies. FRS was not associated with the presence of cerebral amyloid angiopathy. Conclusions: A higher FRS score in older adults is associated with higher odds of some, but not all, CVD pathologies, with low discrimination at the individual level. Further work is needed to develop a more robust risk score to identify adults at risk for accumulating CVD pathologies.

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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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Advances in cerebral amyloid angiopathy imaging

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419844113 ◽

2019 ◽

Vol 12 ◽

pp. 175628641984411 ◽

Cited By ~ 2

Author(s):

Szu-Ju Chen ◽

Hsin-Hsi Tsai ◽

Li-Kai Tsai ◽

Sung-Chun Tang ◽

Bo-Chin Lee ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Imaging Techniques ◽

White Matter Hyperintensity ◽

Superficial Siderosis ◽

Clinical Aspects ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Imaging Studies ◽

Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease caused by β -amyloid (Aβ) deposition at the leptomeningeal vessel walls. It is a common cause of spontaneous intracerebral hemorrhage and a frequent comorbidity in Alzheimer’s disease. The high recurrent hemorrhage rate in CAA makes it very important to recognize this disease to avoid potential harmful medication. Imaging studies play an important role in diagnosis and research of CAA. Conventional computed tomography and magnetic resonance imaging (MRI) methods reveal anatomical alterations, and remains as the most reliable tool in identifying CAA according to modified Boston criteria. The vascular injuries of CAA result in both hemorrhagic and ischemic manifestations and related structural changes on MRI, including cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity, MRI-visible perivascular spaces, and cortical microinfarcts. As imaging techniques advance, not only does the resolution of conventional imaging improve, but novel skills in functional and molecular imaging studies also enable in vivo analysis of vessel physiological changes and underlying pathology. These modern tools help in early detection of CAA and may potentially serve as sensitive outcome markers in future clinical trials. In this article, we reviewed past studies of CAA focusing on utilization of various conventional and novel imaging techniques in both research and clinical aspects.

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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 progression in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000009321 ◽

2020 ◽

Vol 94 (17) ◽

pp. e1853-e1865 ◽

Cited By ~ 3

Author(s):

Thanakit Pongpitakmetha ◽

Panagiotis Fotiadis ◽

Marco Pasi ◽

Gregoire Boulouis ◽

Li Xiong ◽

...

Keyword(s):

Logistic Regression ◽

Cerebral Amyloid Angiopathy ◽

Ordinal Scale ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Cox Regression Analysis ◽

Multivariable Logistic Regression ◽

Potential Biomarker ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

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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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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