scholarly journals Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease

2020 ◽  
Vol 78 (3) ◽  
pp. 1229-1236
Author(s):  
Mana Shams ◽  
Juha Martola ◽  
Andreas Charidimou ◽  
Tobias Granberg ◽  
Daniel Ferreira ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Serum Albumin ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Vessel Disease ◽  
Significant Difference ◽  
Metal Levels ◽  
T Tau

Background: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. Objective: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. Methods: This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. Results: No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOE ɛ4 carriers. Conclusion: CSF iron levels are elevated with cerebral microbleeds in APOE ɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.

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 is associated with the severity of diabetic retinopathy in type 1 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002274
Author(s):  
Marika I Eriksson ◽  
Paula Summanen ◽  
Daniel Gordin ◽  
Carol Forsblom ◽  
Sara Shams ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Vessel Disease

IntroductionCerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain’s vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes.Research design and methodsFor this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33–45) years; 53% female; diabetes duration 21.6 (18.2–30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score).ResultsIn type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20–61) vs 20 (20–35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20–65) vs 20 (20–35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts.ConclusionsPresence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.

scholarly journals Associations between blood and cerebrospinal fluid flow impairments assessed with phase-contrast MRI and brain damage in patients with age-related cerebral small vessel disease

2019 ◽  
pp. 16-23
Author(s):  
E.I. Kremneva ◽  
B.M. Akhmetzyanov ◽  
L.A. Dobrynina ◽  
M.V. Krotenkova
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Damage ◽  
Phase Contrast ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Csf Flow ◽  
Phase Contrast Mri ◽  
Vessel Disease ◽  
Age Related

Hemodynamic parameters of blood and cerebrospinal fluid (CSF) flow can be measured in vivo using phase-contrast MRI (PC-MRI). This opens new horizons for studying the mechanisms implicated in the development and progression of age-related cerebral small vessel disease (SVD). In this paper, we analyze associations between cerebral arterial, venous and CSF flow impairments and SVD features visible on MRI. The study was carried out in 96 patients with SVD (aged 60.91 ± 6.57 years) and 23 healthy volunteers (59.13 ± 6.56 years). The protocol of the MRI examination included routine MRI sequences (T2, FLAIR, T1, SWI, and DWI) applied to assess the severity of brain damage according to STRIVE advisory standards and PC-MRI used to quantify blood flow in the major arteries and veins of the neck, the straight and upper sagittal sinuses, and CSF flow at the aqueduct level. We analyzed the associations between linear and volumetric parameters of blood/CSF flow and the degree of brain matter damage using the Fazekas scale. We observed a reduction in tABF, stVBF, sssVBF, aqLF, Saq, and ICC values and a rise in Pi associated with WMH progression, as well as a gradual decline in tABF and an increase in Pi, Saq and ICC associated with a growing number of lacunes (р < 0.05). Patients with early (< 5) MB had lower sssVBF and stVBF rates in comparison with patients without MB; aqLF, Saq, and ICC values were elevated in patients with 5 to 10 MB, as compared to patients without MB or early (< 5) MB. The established associations between MRI findings in patients with SVD and blood/CSF flow impairments suggest the important role of mechanisms implicated in the disruption of Monro–Kellie intracranial homeostasis in promoting SVD.

Cerebral small vessel disease: cerebrospinal fluid aspects

2014 ◽  
pp. 200-216
Author(s):  
Anders Wallin ◽  
Maria Bjerke ◽  
Leonardo Pantoni ◽  
Philip B. Gorelick
Keyword(s):  
Cerebrospinal Fluid ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease

Brain MRI in Monogenic Cerebral Small Vessel Diseases: A Practical Handbook

2021 ◽  
Vol 21 ◽  
Author(s):  
Leonardo Ulivi ◽  
Mirco Cosottini ◽  
Gianmichele Migaleddu ◽  
Giovanni Orlandi ◽  
Nicola Giannini ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Next Generation ◽  
Vessel Disease ◽  
Generation Sequencing ◽  
Cerebral Small Vessel Diseases

: Monogenic cerebral small vessel diseases are a topic of growing interest, as several genes responsible have been recently described and new sequencing techniques such as Next generation sequencing are available. Brain imaging is a key exam in these diseases. First, since it is often the first exam performed, an MRI is key in selecting patients for genetic testing and for interpreting Next generation sequencing reports. In addition, neuroimaging can be helpful in describing the underlying pathological mechanisms involved in cerebral small vessel disease. With this review, we aim to provide Neurologists and Stroke physicians with an up-to date overview of the current neuroimaging knowledge on monogenic small vessel diseases.

P2806A novel sirolimus drug eluting stent for Small-Vessel Disease: results from en-ABL e-registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Testa ◽  
S Dani ◽  
D Desai ◽  
R Pandya ◽  
P Parekh ◽  
...  
Keyword(s):  
Stent Thrombosis ◽  
Small Vessel Disease ◽  
Large Vessel ◽  
Small Vessel ◽  
Drug Eluting Stent ◽  
Vessel Disease ◽  
Significant Difference ◽  
Myocardial Infraction ◽  
Drug Eluting

Abstract Objective The aim of the study was to assess the clinical outcome of Abluminus DES in patients with small vessels. Background Percutaneous coronary intervention (PCI) of small coronary vessel (≤2.75 mm) associated with more chances of restenosis and repeat revascularization even when drug eluting stent employed. Methods A total of 2,500 patients enrolled in en-ABL e-registry which is a prospective, multicentre observational post market registry. Out of 2,500 patients, 1,253 patients had small vessel (SV, ≤2.75 mm) while 1,247 had large vessel (LV, >3mm) disease. The primary endpoint was major adverse cardiac events (MACE) which is composite of cardiac death, target vessel myocardial infraction (TV-MI) and target lesion/vessel revascularization (TLR) at 1 year follow up. The secondary endpoint were stent thrombosis and MACE up to 2 years. Results Baseline characteristics were well matched in both groups. In the SV group had higher prevalence of diabetes as compared to large vessel 43.0% vs 25.7%. Total 1,400 lesions treated with 1,612 Abluminus DES and 1,569 lesions treated with 1,675 Abluminus DES in SV and LV groups respectively. The mean diameter of stent was 2.61±0.23 and 3.3±0.3 mm in SV and LV groups respectively. There was a significant difference in MACE in treatment groups (3.7% vs. 1.4%, p=0.004 respectively) at 1 year. No significant differences were observed between SV and LV groups in terms of death/myocardial infarction or stent thrombosis. There were increment of only one TLR and no stent thrombosis reported at 2-year follow-up. Conclusion This result suggests the efficacy and safety of novel Abluminus DES in small vessel disease.

scholarly journals Relationship Between Step Counts and Cerebral Small Vessel Disease in Japanese Men

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3584-3591
Author(s):  
Mohammad Moniruzzaman ◽  
Aya Kadota ◽  
Hiroyoshi Segawa ◽  
Keiko Kondo ◽  
Sayuki Torii ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Odds Ratios ◽  
Japanese Men ◽  
Lacunar Infarcts ◽  
Step Counts ◽  
Vessel Disease ◽  
Steps Per Day

Background and Purpose: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. Methods: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006–2008) using a pedometer. CSVD was assessed at follow-ups (2012–2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. Results: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175–10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30–0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29–0.86]), and lacunar infarcts (0.52 [95% CI, 0.30–0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. Conclusions: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

scholarly journals Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease

Stroke ◽  
2020 ◽  
Vol 51 (5) ◽  
pp. 1404-1410 ◽  
Author(s):  
Michelle P. Lin ◽  
Thomas G. Brott ◽  
David S. Liebeskind ◽  
James F. Meschia ◽  
Kevin Sam ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Large Vessel ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Poor Recruitment

Background and Purpose— Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke. Methods— Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders. Results— Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend P <0.001; adjusted P =0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 ( P trend=0.015). No patient with an SVD score of 4 had good collaterals. Conclusions— Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.

Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment

2013 ◽  
Vol 73 (5) ◽  
pp. 584-593 ◽  
Author(s):  
Jae-Hyun Park ◽  
Sang Won Seo ◽  
Changsoo Kim ◽  
Geon Ha Kim ◽  
Hyun Jin Noh ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
In Vivo Imaging ◽  
Small Vessel Disease ◽  
Cerebral Microbleeds ◽  
Small Vessel ◽  
Vessel Disease

scholarly journals Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment

2015 ◽  
Vol 36 (3) ◽  
pp. 621-628 ◽  
Author(s):  
Sara Shams ◽  
Tobias Granberg ◽  
Juha Martola ◽  
Xiaozhen Li ◽  
Mana Shams ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Serum Albumin ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Csf Biomarkers ◽  
Barrier Dysfunction ◽  
T Tau

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer’s disease and mild cognitive impairment ( p < 0.05). CSF/serum albumin ratios were high with multiple CMBs ( p < 0.001), reflecting accompanying blood–brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer’s patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer’s disease ( p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

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