Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011932
Author(s):  
Juan Pablo Castello ◽  
Marco Pasi ◽  
Jessica R Abramson ◽  
Axana Rodriguez-Torres ◽  
Sandro Marini ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Ethnic Differences ◽  
Small Vessel Disease ◽  
Ethnic Disparities ◽  
Recurrence Risk ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Racial Ethnic

Objective:Black and Hispanic survivors of Intracerebral Hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic Cerebral Small Vessel Disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk.Methods:We analyzed data from the Massachusetts General Hospital ICH study (MGH-ICH, n=593) and the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study (n= 329). Using CSVD markers derived from MRIs obtained within 90 days of index ICH, we classified ICH cases as cerebral amyloid angiopathy (CAA)-related, hypertensive arteriopathy (HTNA)-related, and mixed etiology. We quantified CSVD burden using validated global, CAA-specific, and HTNA-specific scores. We compared CSVD subtype and severity among White, Black, and Hispanic ICH survivors and investigated its association with ICH recurrence risk.Results:We analyzed data for 922 ICH survivors (655 White, 130 Black, 137 Hispanic). Minority ICH survivors had greater global CSVD (p=0.011) and HTNA burden (p=0.021) on MRI. Furthermore, minority survivors of HTNA-related and mixed etiology ICH demonstrated higher HTNA burden, resulting in increased ICH recurrence risk (all p < 0.05).Conclusions:We uncovered significant differences in CSVD subtypes and severity among White and minority survivors of primary ICH, with direct implication for known disparities in ICH recurrence risk. Future studies of racial / ethnic disparities in ICH outcomes will benefit from including detailed MRI-based assessment of CSVD subtypes and severity, and investigating social determinants of health.

Prevention of Cerebral Small Vessel Disease

2017 ◽  
Vol 37 (03) ◽  
pp. 316-325 ◽  
Author(s):  
Eric Smith
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Unmet Need ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Cerebral Amyloid

AbstractCerebral small vessel disease can cause either ischemic stroke or intracerebral hemorrhage. Accounting for up to 25% of all strokes, it is also the second biggest contributor to the risk of dementia, and is the most common incidentally discovered finding on brain imaging. There are two main causes of cerebral small vessel disease: arteriolosclerotic small vessel disease (with hypertension as the main modifiable risk factor) and cerebral amyloid angiopathy (predominantly caused by β-amyloid deposits limited to the cerebral small arteries, arterioles, and capillaries). Prevention should include the treatment of hypertension and diabetes, if present, and the modification of lifestyle factors such as obesity and poor nutrition. Patients with small subcortical ischemic strokes should be treated with antithrombotics; dual antiplatelet therapy may be more effective than aspirin for the first 3 weeks following acute stroke, but is not more effective than aspirin for long-term prevention. Unresolved questions include the effectiveness of nonaspirin prevention strategies to prevent early recurrence or stroke extension in small subcortical ischemic stroke, and whether symptomatic or silent small vessel disease should influence decisions regarding selection for carotid revascularization or anticoagulation for atrial fibrillation. There is an unmet need for disease-modifying preventive therapies for cerebral amyloid angiopathy, the second most-common cause of spontaneous intracerebral hemorrhage.

Abstract 3208: Sensitivity and Reliability of SWI Compared to T2* GRE MRI for Detection of Microbleeds in Cerebral Amyloid Angiopathy

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Ah-Ling Cheng ◽  
Cheryl R McCreary ◽  
M. L Lauzon ◽  
Richard Frayne ◽  
Mayank Goyal ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Intraclass Correlation ◽  
Case Series ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Healthy Controls ◽  
Vessel Disease ◽  
Cerebral Amyloid

Introduction: Case examples and small case series suggest that MRI susceptibility weighted imaging (SWI) may be more sensitive for cerebral microbleed (CMB) detection compared to MRI T2* gradient-recalled echo (GRE). However, there are few data on CMB counts measured by SWI vs. GRE, or inter-rater reliability, in groups of patients with cerebral small vessel disease. We used data from a prospective cohort study of cerebral amyloid angiopathy (CAA), a cerebral small-vessel disease marked by high numbers of CMBs, to quantify the sensitivity and reliability of SWI vs. GRE for CMB detection. Methods: Nine patients with symptomatic CAA (mean age 71±8.3; 7 males and 2 females) and 21 healthy non-CAA controls (mean age 68±6.3; 10 M/11 F) underwent T2* GRE and SWI on a 3.0T MR scanner. Probable CAA was diagnosed according to the Boston criteria prior to study entry using information from clinical MRI with GRE sequences. Two raters (labeled 1 and 2) independently interpreted the GRE and SWI scans blinded to clinical information. The phase-filtered magnitude image was used for SWI interpretation. Agreement reliability was assessed using the kappa coefficient (where a kappa of ≥0.60 indicates good agreement) or the intraclass correlation coefficient (ICC). Results: Overall, the raters identified 1,432 CMBs in the 9 CAA cases (range 1-434 per patient) and 8 CMBs in the healthy controls (range 0-3). Rater 1 identified CMBs in 5/21 healthy controls on SWI and 5/21 on GRE, while rater 2 identified CMBs in 4/21 on SWI and 3/21 on GRE (kappa 0.70 for GRE and 0.57 for SWI). In CAA cases more CMBs were seen on SWI compared to the GRE sequence but the difference was significant only for rater 1 (rater 1: on average 85% more per patient on SWI than on GRE, p=0.008; rater 2: 19% more, p=0.25). Among CAA cases the reliability between raters was poor for GRE (ICC 0.36) but excellent for SWI (0.94, p<0.05 for comparison with GRE). Review suggested that the differing reliability was because rater 1 was less likely than rater 2 to identify faint lesions on GRE as CMB, whereas these lesions were more conspicuous on SWI. If SWI rather than GRE were used to determine CAA status according to the Boston criteria, all 9 CAA cases would remain classified as probable CAA but 2/21 controls would be reclassified as either possible (n=1) or probable (n=1) asymptomatic CAA based on the detection of one or more lobar microbleeds on SWI. Conclusions: SWI confers greater reliability as well as greater sensitivity for CMB detection compared to GRE, and should be the preferred sequence for quantifying CMBs. SWI may more frequently identify lobar microbleeds that could represent asymptomatic CAA. Further research is needed to determine whether the Boston criteria require revision to take into account the greater sensitivity of SWI for CMB detection.

scholarly journals Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds

Neurology ◽  
2017 ◽  
Vol 89 (8) ◽  
pp. 820-829 ◽  
Author(s):  
Andreas Charidimou ◽  
Toshio Imaizumi ◽  
Solene Moulin ◽  
Alexandro Biffi ◽  
Neshika Samarasekera ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Meta Analysis ◽  
Brain Mri ◽  
Recurrence Risk ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Random Effects Models ◽  
Pooled Data ◽  
Vessel Disease

Objective:We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity).Methods:This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2–4, 5–10, and >10 CMBs), using random effects models.Results:We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2–12.6 vs 1.1%, 95% CI 0.5–1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1–3 years): OR 3.1 (95% CI 1.4–6.8; p = 0.006), 4.3 (95% CI 1.8–10.3; p = 0.001), and 3.4 (95% CI 1.4–8.3; p = 0.007) for 2–4, 5–10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1–15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts.Conclusions:CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials.

scholarly journals Cerebral Small Vessel Disease and Functional Outcome Prediction After Intracerebral Hemorrhage

Neurology ◽  
2021 ◽  
Vol 96 (15) ◽  
pp. e1954-e1965
Author(s):  
Isabel C. Hostettler ◽  
Ghil Schwarz ◽  
Gareth Ambler ◽  
Duncan Wilson ◽  
Gargi Banerjee ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Small Vessel Disease ◽  
Characteristic Curve ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cortical Atrophy ◽  
Vessel Disease ◽  
Lemeshow Test ◽  
Ich Score

ObjectiveTo determine whether CT-based cerebral small vessel disease (SVD) biomarkers are associated with 6-month functional outcome after intracerebral hemorrhage (ICH) and whether these biomarkers improve the performance of the preexisting ICH prediction score.MethodsWe included 864 patients with acute ICH from a multicenter, hospital-based prospective cohort study. We evaluated CT-based SVD biomarkers (white matter hypodensities [WMH], lacunes, brain atrophy, and a composite SVD burden score) and their associations with poor 6-month functional outcome (modified Rankin Scale score >2). The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test were used to assess discrimination and calibration of the ICH score with and without SVD biomarkers.ResultsIn multivariable models (adjusted for ICH score components), WMH presence (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12–2.06), cortical atrophy presence (OR 1.80, 95% CI 1.19–2.73), deep atrophy presence (OR 1.66, 95% CI 1.17–2.34), and severe atrophy (either deep or cortical) (OR 1.94, 95% CI 1.36–2.74) were independently associated with poor functional outcome. For the revised ICH score, the AUROC was 0.71 (95% CI 0.68–0.74). Adding SVD markers did not significantly improve ICH score discrimination; for the best model (adding severe atrophy), the AUROC was 0.73 (95% CI 0.69–0.76). These results were confirmed when lobar and nonlobar ICH were considered separately.ConclusionsThe ICH score has acceptable discrimination for predicting 6-month functional outcome after ICH. CT biomarkers of SVD are associated with functional outcome, but adding them does not significantly improve ICH score discrimination.Trial Registration InformationClinicalTrials.gov Identifier: NCT02513316.

scholarly journals Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

2020 ◽  
Vol 21 (11) ◽  
pp. 3862 ◽  
Author(s):  
Jayant Patwa ◽  
Swaran Jeet Singh Flora
Keyword(s):  
Heavy Metals ◽  
Heavy Metal ◽  
Blood Vessels ◽  
Small Vessel Disease ◽  
Vascular Dysfunction ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Amyloid Angiopathy ◽  
Vessel Disease ◽  
Antioxidant Defense Enzymes

Heavy metals are considered a continuous threat to humanity, as they cannot be eradicated. Prolonged exposure to heavy metals/metalloids in humans has been associated with several health risks, including neurodegeneration, vascular dysfunction, metabolic disorders, cancer, etc. Small blood vessels are highly vulnerable to heavy metals as they are directly exposed to the blood circulatory system, which has comparatively higher concentration of heavy metals than other organs. Cerebral small vessel disease (CSVD) is an umbrella term used to describe various pathological processes that affect the cerebral small blood vessels and is accepted as a primary contributor in associated disorders, such as dementia, cognitive disabilities, mood disorder, and ischemic, as well as a hemorrhagic stroke. In this review, we discuss the possible implication of heavy metals/metalloid exposure in CSVD and its associated disorders based on in-vitro, preclinical, and clinical evidences. We briefly discuss the CSVD, prevalence, epidemiology, and risk factors for development such as genetic, traditional, and environmental factors. Toxic effects of specific heavy metal/metalloid intoxication (As, Cd, Pb, Hg, and Cu) in the small vessel associated endothelium and vascular dysfunction too have been reviewed. An attempt has been made to highlight the possible molecular mechanism involved in the pathophysiology, such as oxidative stress, inflammatory pathway, matrix metalloproteinases (MMPs) expression, and amyloid angiopathy in the CSVD and related disorders. Finally, we discussed the role of cellular antioxidant defense enzymes to neutralize the toxic effect, and also highlighted the potential reversal strategies to combat heavy metal-induced vascular changes. In conclusion, heavy metals in small vessels are strongly associated with the development as well as the progression of CSVD. Chelation therapy may be an effective strategy to reduce the toxic metal load and the associated complications.

scholarly journals Association of cerebral small vessel disease and cognitive decline after intracerebral hemorrhage

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011050
Author(s):  
Marco Pasi ◽  
Lansing Sugita ◽  
Li Xiong ◽  
Andreas Charidimou ◽  
Gregoire Boulouis ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Dementia Diagnosis ◽  
Vessel Disease ◽  
Ct Data ◽  
New Onset

Objective:We sought to determine whether MRI-based Cerebral Small Vessel Disease (CSVD) burden assessment, in addition to clinical and CT data, improved prediction of cognitive impairment after spontaneous Intracerebral Hemorrhage (ICH).Methods:We analyzed data from ICH survivors enrolled in a single-center prospective study. We employed three validated CSVD burden scores: global, cerebral amyloid angiopathy (CAA)-specific, hypertensive arteriopathy (HTNA)-specific. We quantified cognitive performance by administering the modified Telephone Interview for Cognitive Status (TICS-m) test. We utilized linear mixed models to model cognitive decline rates, and survival models for new-onset dementia. We calculated CSVD scores’ cut-offs to maximize predictive performance for dementia diagnosis.Results:We enrolled 612 ICH survivors, and followed them for a median of 46.3 months (Inter-Quartile Range: 35.5-58.7). A total of 214/612 (35%) participants developed dementia. Higher global CSVD scores at baseline were associated with faster cognitive decline (Coeff -0.25, Standard Error [SE] 0.02) and dementia risk (Sub-Hazard Ratio 1.35, 95% CI 1.10-1.65). The global score outperformed the CAA and HTNA scores in predicting post-ICH dementia (all p<0.05). Compared to a model including readily available clinical and CT data, inclusion of the global CSVD score resulted in improved prediction of post-ICH dementia (Area Under the Curve [AUC] 0.89, SE 0.02 vs. AUC 0.81, SE 0.03, p = 0.008 for comparison). Global CSVD scores ≥ 2 had highest sensitivity (83%) and specificity (91%) for dementia diagnosis.Conclusions:A validated MRI-based CSVD score is associated with cognitive performance after ICH, and improved diagnostic accuracy for predicting new onset of dementia.

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