Cerebral Microbleeds: Histopathological Correlation of Neuroimaging

Shoamanesh, Ashkan; Kwok, Chun Shing; Benavente, Oscar

doi:10.1159/000331466

Cited by 238 publications

(175 citation statements)

References 60 publications

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“…The strongest association occurred between TNF-a and CMBs. TNF-a is a key regulatory cytokine that is predominantly secreted by macrophages/ microglia (the predominant cell type found underlying CMBs in pathologic/autopsy samples) 12 and can exert diverse regulatory functions through 2 cell membrane receptors, TNFR1 and TNFR2. 13 CMBs are believed to result from a state of increased vascular fragility/permeability and represent hemosiderin-laden macrophages.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, they are often associated with a surrounding degree of tissue necrosis. 12 Accordingly, their association with TNFR2 has several plausible explanations. TNF-a has been consistently observed to increase vascular permeability and blood-brain barrier dysfunction in animal models.…”

Section: Resultsmentioning

confidence: 99%

“…Previous radiographic-pathologic concordance studies have not investigated such differences in persons with CMBs, 12 and relevant in vivo circulating biomarker data in patients with CAA are lacking. However, pathologic and experimental studies have noted activated macrophages/microglia, reactive astrocytes, and T lymphocytes adjacent to cerebral vascular amyloid deposits, with a broad inflammatory response including complement, reactive oxygen species, and proinflammatory cytokines, such as interleukin-6, CD40L, and TNF-a.…”

Section: Resultsmentioning

confidence: 99%

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Inflammatory biomarkers, cerebral microbleeds, and small vessel disease

Shoamanesh¹,

Preis²,

Beiser³

et al. 2015

Neurology

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195

155

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Objective: We investigated the association between circulating biomarkers of inflammation and MRI markers of small vessel disease.Methods: We performed a cross-sectional study relating a panel of 15 biomarkers, representing systemic inflammation (high-sensitivity C-reactive protein, interleukin-6, monocyte chemotactic protein-1, tumor necrosis factor a, tumor necrosis factor receptor 2, osteoprotegerin, and fibrinogen), vascular inflammation (intercellular adhesion molecule 1, CD40 ligand, P-selectin, lipoproteinassociated phospholipase A 2 mass and activity, total homocysteine, and vascular endothelial growth factor), and oxidative stress (myeloperoxidase) to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease (CSVD) on MRI in 1,763 stroke-free Framingham offspring (mean age 60.2 6 9.1 years, 53.7% women). Results:We observed higher levels of circulating tumor necrosis factor receptor 2 and myeloperoxidase in the presence of cerebral microbleed (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1-4.1 and OR 1.5, 95% CI 1.1-2.0, respectively), higher levels of osteoprotegerin (OR 1.1, 95% CI 1.0-1.2), intercellular adhesion molecule 1 (OR 1.7, 95% CI 1.1-2.5), and lipoproteinassociated phospholipase A 2 mass (OR 1.5, 95% CI 1.1-2.1), and lower myeloperoxidase (OR 0.8, 95% CI 0.7-1.0) in participants with greater white matter hyperintensity volumes and silent cerebral infarcts.Conclusions: Our study supports a possible role for inflammation in the pathogenesis of CSVD, but suggests that differing inflammatory pathways may underlie ischemic and hemorrhagic subtypes. If validated in other samples, these biomarkers may improve stroke risk prognostication and point to novel therapeutic targets to combat CSVD. Neurology ® 2015;84:825-832 GLOSSARY CAA 5 cerebral amyloid angiopathy; CI 5 confidence interval; CMB 5 cerebral microbleed; CSVD 5 cerebral small vessel disease; ICAM-1 5 intercellular adhesion molecule 1; ln 5 natural logarithm; Lp-PLA 2 5 lipoprotein-associated phospholipase A 2 ; OR 5 odds ratio; ROC 5 receiver operating characteristic; SCI 5 silent cerebral infarct; TNF-a 5 tumor necrosis factor a; TNFR2 5 tumor necrosis factor receptor 2; WMH 5 white matter hyperintensity.Cerebral small vessel disease (CSVD) assessed using brain MRI is characterized by 3 main findings that include cerebral microbleeds (CMBs), lacunes of presumed vascular origin (silent cerebral infarcts [SCIs]), and white matter hyperintensity (WMH). The vascular changes underlying ischemic and hemorrhagic CSVD likely include activation of the inflammatory cascade with endothelial failure and resulting neurovascular unit dysfunction.1-3 However, the specific mediators implicated in ischemic and hemorrhagic CSVD may differ.The Framingham Offspring Cohort provides a large, middle-age, community-based sample in which to investigate the association between systemic biomarkers of inflammation and MRI markers of CSVD. Given the complexity of i...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory biomarkers, cerebral microbleeds, and small vessel disease

Shoamanesh¹,

Preis²,

Beiser³

et al. 2015

Neurology

Self Cite

195

155

View full text Add to dashboard Cite

show abstract

“…A further limitation is that we did not routinely undertake MRI in all included patients, and were therefore unable to investigate additional markers of cerebral SVD underlying ICH, such as cerebral microbleeds, dilated perivascular spaces or cerebral atrophy. 23,24 The use of standardised MRI prior to IADSA would have strengthened our study as it is better able to differentiate between the type of SVD (i.e. cerebral amyloid angiopathy or hypertensive arteriopathy), and is superior for the detection of other underlying causes for ICH (e.g cavernomas or mass lesions).…”

Section: Discussionmentioning

confidence: 96%

Developing an algorithm to identify patients with intracerebral haemorrhage secondary to a macrovascular cause

Wilson

Ogungbemi

Ambler

et al. 2017

European Stroke Journal

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Introduction: Determining the cause of spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is critical to guide treatment and prognosis. We investigated whether small vessel disease (SVD) in addition to clinical and other radiological findings on acute neuroimaging predicts a low risk of a macrovascular cause (e.g. an arterio-venous malformation, aneurysm or dural arteriovenous fistula). Patients and methods:We identified patients with acute spontaneous ICH who underwent acute non-contrast CT, CT angiography (CTA) and intra-arterial digital subtraction angiography (IADSA) at our institution from January 2010 to April 2014. Logistic regression including CTA result, SVD, age, pre-ICH hypertension and ICH location was used to derive a prediction model, validated using bootstrapping. Results: 173 patients (46% female, median age 49) of whom 78 had a macrovascular cause on IADSA were included. Predictors of a macrovascular cause were: abnormal CTA (OR 67.4; p < 0.001); absence of SVD (OR 5.0; p ¼ 0.019); and absence of pre-ICH hypertension (OR 3.4; p ¼ 0.05). In our internally derived prediction model, the combination of CTA, SVD and pre-ICH hypertension predicted the likelihood of an underlying macrovascular cause (optimism-adjusted ROC area 0.919). Patients with negative CTA, SVD and pre-ICH hypertension have a low likelihood of an underlying macrovascular cause (1.8%). Discussion and conclusion: A combination of CTA, SVD and pre-ICH hypertension predict the likelihood of finding a macrovascular cause in patients with acute spontaneous ICH, allowing informed decisions regarding the likely benefit and risk of IADSA.

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“…The term Bcerebral microbleeds^refers to focal areas of signal loss in brain parenchyma measuring ≤10 mm on T2*-weighted gradient-recalled echo or susceptibility-weighted MRI due to hemosiderin deposits within microhemorrhages [109,110]. In the general population, microbleeds are associated with increasing age, hypertension, cerebral amyloid angiopathy, and worse cognitive function [111,113].…”

Section: Cerebral Microbleedsmentioning

confidence: 99%

Neurocritical Care for Patients with Kidney Dysfunction

Park¹

2017

J Neurocrit Care

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Chronic kidney disease (CKD) is an independent risk factor for the development of cerebrovascular disease, particularly small vessel disease which can manifest in a variety of phenotypes ranging from lacunes to microbleeds. Small vessel disease likely contributes to cognitive dysfunction in the CKD population. Nontraditional risk factors for vascular injury in uremia include loss of calcification inhibitors, hyperphosphatemia, increased blood pressure variability, elastinolysis, platelet dysfunction, and chronic inflammation. In this review, we discuss the putative pathways by which these mechanisms may promote cerebrovascular disease and thus increase risk of future stroke in CKD patients.

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Cerebral Microbleeds: Histopathological Correlation of Neuroimaging

Cited by 238 publications

References 60 publications

Inflammatory biomarkers, cerebral microbleeds, and small vessel disease

Inflammatory biomarkers, cerebral microbleeds, and small vessel disease

Developing an algorithm to identify patients with intracerebral haemorrhage secondary to a macrovascular cause

Neurocritical Care for Patients with Kidney Dysfunction

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