Clinical features of high-degree centrum semiovale-perivascular spaces in cerebral amyloid angiopathy

Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.

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Abstract P442: The Association of Amyloid and Tau Burden With Centrum Semiovale Perivascular Spaces in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.52.suppl_1.p442 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Elif Gokcal ◽

Alex A Becker ◽

Mitchell J Horn ◽

Alvin S Das ◽

Kristin Schwab ◽

...

Keyword(s):

Regression Model ◽

Cerebral Amyloid Angiopathy ◽

Structural Mri ◽

Ordinal Regression ◽

White Matter Hyperintensity ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Centrum Semiovale ◽

Ordinal Regression Model ◽

Cerebral Amyloid

Background: The mechanisms linking cerebral amyloid angiopathy (CAA) to enlarged perivascular spaces in centrum semiovale (CSO-EPVS) and whether other Alzheimer’s Disease (AD) pathologies might affect CSO-EPVS are unclear. We hypothesized that amyloid but not tau load would independently correlate with CSO-EPVS in CAA. Methods: Fifty prospectively enrolled nondemented probable CAA patients underwent high-resolution structural MRI, Pittsburgh compound B (PiB, for amyloid), and 18 F-flortaucipir (FTP, for tau) PET imaging. Microbleeds (all lobar, LMB) were counted and white matter hyperintensity volume (WMH) was quantified. CSO-EPVS were counted on T 2 -MRI sequence and graded using a previously validated scale (range 0-4). A multivariate ordinal regression model was used to assess the independent associations between CSO-EPVS and mean cortical amyloid as well as tau deposition, after adjusting for relevant covariates. Results: Patients had a mean age of 69.3±7.2. Age, sex, presence of hypertension, intracerebral hemorrhage (ICH), LMB counts, and WMH were not associated with CSO-EPVS grades (p>0.2 for all comparisons). Higher PiB uptake significantly correlated with increased CSO-EPVS (rho=0.45, p=0.001). Higher FTP showed a trend for correlation with CSO-EPVS (rho=0.26, p=0.069). In an ordinal regression model with CSO-EPVS grade as the dependent variable and both amyloid and tau levels included as predictors along with covariates presented above, the association of CSO-EPVS remained significant with higher PiB uptake (β=3.97, 95%CI 1.1-6.8, p=0.007) but not with FTP uptake (p=0.167). Conclusion: Results of this study suggest that CSO-EPVS is independently associated with amyloid but not with tau deposition in CAA. CSO-EPVS was not associated with age or classical vascular risk factors or presence of ICH. Our results support the view that vascular amyloid but not other AD pathologies such as tau might contribute to EPVS in patients with CAA.

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Abstract WP226: Topography of Dilated Perivascular Spaces in Patients with Markers of Cerebral Amyloid Angiopathy and Hypertensive Vasculopathy

Stroke ◽

10.1161/str.44.suppl_1.awp226 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Sergi Martinez-Ramirez ◽

Octavio Pontes-Neto ◽

Andrew P Dumas ◽

Eitan Auriel ◽

Mahmut Edip Gurol ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Independent Predictor ◽

Small Vessel ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Quantitative Score ◽

Independent Risk Factors ◽

Cerebral Amyloid ◽

High Degree ◽

Prospective Longitudinal

Objectives: To investigate whether the topography of dilated perivascular spaces (DPVS) corresponds with markers of particular small vessel diseases such as cerebral amyloid angiopathy (CAA) and hypertensive vasculopathy. Methods: Patients were recruited from an ongoing single-center prospective longitudinal cohort study of patients evaluated in a memory clinic. All patients underwent structural, high-resolution MRI, and had a clinical assessment performed within 1 year of scan. DPVS were rated in basal ganglia (BG-DPVS) and white matter (WM-DPVS) on T1 sequences, using an established 4-point semi-quantitative score. DPVS degree was classified as high (score >2) or low (score ≤ 2). Independent risk factors for high degree of BG-DPVS and WM-DPVS were investigated. Results: Eighty-nine patients were included (mean age 72.7 ± 9.9 years, 57% female). High degree of WM-DPVS was more frequent than low degree in patients with presence of strictly lobar MB (45.5% versus 28.4% of subjects). High BG-DPVS degree was associated with older age, hypertension, and higher WMH volumes. In multivariate analysis increased lobar MB count was an independent predictor of high degree of WM-DPVS [OR 1.53 (95% CI 1.06-2.21), p=0.02]. By contrast, hypertension was an independent predictor of high degree of BG-DPVS [OR 9.4 (95% (CI 1-85.2), p=0.04]. Conclusions: The associations of WM-DPVS with lobar MB and BG-DPVS with hypertension raise the possibility that the distribution of DPVS may indicate the presence of underlying small vessel diseases such as CAA and HV, in patients with cognitive impairment.

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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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Cerebral Amyloid Angiopathy in Amyloid-Positive Patients from a Memory Clinic Cohort

Journal of Alzheimer s Disease ◽

10.3233/jad-201218 ◽

2021 ◽

Vol 79 (4) ◽

pp. 1661-1672

Author(s):

Ana Sofia Costa ◽

João Pinho ◽

Domantė Kučikienė ◽

Arno Reich ◽

Jörg B. Schulz ◽

...

Keyword(s):

Cognitive Impairment ◽

Cognitive Decline ◽

Cerebral Amyloid Angiopathy ◽

Clinical Severity ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Memory Clinic ◽

Centrum Semiovale ◽

Cerebral Amyloid

Background: The overlap between cerebral amyloid angiopathy (CAA) and Alzheimer’s disease (AD) is frequent and relevant for patients with cognitive impairment. Objective: To assess the role of the diagnosis of CAA on the phenotype of amyloid-β (Aβ) positive patients from a university-hospital memory clinic. Methods: Consecutive patients referred for suspected cognitive impairment, screened for Aβ pathological changes in cerebrospinal fluid (CSF), with available MRI and neuropsychological results were included. We determined the association between probable CAA and clinical, neuropsychological (at presentation and after a mean follow-up of 17 months in a sub-sample) and MRI (atrophy, white matter hyperintensities, perivascular spaces) characteristics. Results: Of 218 amyloid-positive patients, 8.3% fulfilled criteria for probable CAA. A multivariable logistic regression showed an independent association of probable CAA with lower Aβ1–42 (adjusted odds ratio [aOR] = 0.94, 95% confidence interval [95% CI] = 0.90–0.98, p = 0.003), and Aβ1–40 (aOR = 0.98, 95% CI=0.97–0.99 p = 0.017) levels in CSF, and presence of severe burden of enlarged perivascular spaces (EPVS) in the centrum semiovale (aOR = 3.67, 95% CI = 1.21–11.15, p = 0.022). Linear mixed-model analysis showed that both groups significantly deteriorated in global clinical severity, executive function and memory. Nevertheless, the presence of probable CAA did not differently affect the rate of cognitive decline. Conclusion: The presence of probable CAA in Aβ positive patients was associated with lower Aβ1–42 and Aβ1–40 CSF levels and increased centrum semiovale EPVS burden, but did not independently influence clinical phenotype nor the rate of cognitive decline within our follow-up time window.

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Intracerebral Hemorrhage Recurrence in Patients with and without Cerebral Amyloid Angiopathy

Cerebrovascular Diseases Extra ◽

10.1159/000513503 ◽

2021 ◽

pp. 15-21

Author(s):

João Pinho ◽

José Manuel Araújo ◽

Ana Sofia Costa ◽

Fátima Silva ◽

Alexandra Francisco ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Cerebral Amyloid Angiopathy ◽

Cox Regression ◽

Recurrence Risk ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Centrum Semiovale ◽

Cerebral Amyloid ◽

Clinical Records

Background: Intracerebral hemorrhage (ICH) recurrence risk is known to be higher in patients with cerebral amyloid angiopathy (CAA) as compared to other causes of ICH. Risk factors for ICH recurrence are not completely understood, and our goal was to study specific imaging microangiopathy markers. Methods: Retrospective case-control study of patients with non-traumatic ICH admitted to a single center between 2014 and 2017 who underwent magnetic resonance imaging (MRI). Clinical characteristics of the index event and occurrence of death and ICH recurrence were collected from clinical records. MRI images were independently reviewed by 2 neuroradiologists. Groups of patients with CAA-related and CAA-unrelated ICH defined were compared. Presence of CAA was defined according to the Boston modified criteria. Survival analysis with Kaplan-Meier curves and Cox-regression analyses was performed to analyze ICH recurrence-free survival. Results: Among 448 consecutive patients with non-traumatic ICH admitted during the study period, 104 were included in the study, mean age 64 years (±13.5), median follow-up of 27 months (interquartile range, IQR 16–43), corresponding to 272 person-years of total follow-up. CAA-related ICH patients presented higher burden of lobar microbleeds (p < 0.001), higher burden of enlarged perivascular spaces (EPVS) in centrum semiovale (p < 0.001) and more frequently presented cortical superficial siderosis (cSS; p < 0.001). ICH recurrence in patients with CAA was 12.7 per 100 person-years, and no recurrence was observed in patients without CAA. Variables associated with ICH recurrence in the whole population were age (hazard ratio [HR] per 1-year increment = 1.05, 95% CI 1.00–1.11, p = 0.046), presence of disseminated cSS (HR 3.32, 95% CI 1.09–10.15, p = 0.035) and burden of EPVS in the centrum semiovale (HR per 1-point increment = 1.80, 95% CI 1.04–3.12, p = 0.035). Conclusions: This study confirms a higher ICH recurrence risk in patients with CAA-related ICH and suggests that age, disseminated cSS, and burden of EPVS in the centrum semiovale are associated with ICH recurrence.

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Abstract 36: The Boston Criteria V2.0 for Cerebral Amyloid Angiopathy: Updated Criteria and Multicenter MRI-Neuropathology Validation

Stroke ◽

10.1161/str.52.suppl_1.36 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Matthew Frosch ◽

Jean-Claude Baron ◽

Marco Pasi ◽

...

Keyword(s):

White Matter ◽

Intracerebral Hemorrhage ◽

Diagnostic Accuracy ◽

Cerebral Amyloid Angiopathy ◽

Brain Mri ◽

Amyloid Angiopathy ◽

Perivascular Spaces ◽

Validation Sample ◽

Temporal Validation ◽

Cerebral Amyloid

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.

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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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