Deep Microbleeds Research Articles

Predictors of cerebral microbleeds in patients with autosomal dominant polycystic kidney disease

ObjectivesIndividuals with autosomal dominant polycystic kidney disease (ADPKD) can present with vascular abnormalities, including intracranial aneurysms. However, whether ADPKD is associated with cerebral small-vessel disease, such as cerebral microbleeds (CM), remains unclear. The study analyzes the prevalence of CM and the associated clinical and radiological factors in patients with ADPKD. MethodsThe retrospective study enrolled 140 consecutive patients with ADPKD from July 2014 to May 2023. Brain MRIs were analyzed for the presence of CM with susceptibility-weighted imaging (SWI), which were categorized based on lesion location (lobar, deep, or infratentorial). ResultIn this study, the prevalence of CM is 26.4%. Chronic kidney disease (CKD) stage (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.04–1.88, p = 0.027) and leukoaraiosis grade (OR: 3.29, 95% CI: 1.43–7.56, p = 0.005) were strongly associated with CM. Additionally, both CKD stage (OR: 1.48, 95% CI: 1.06–2.07, p = 0.023) and leukoaraiosis grade (OR: 2.81, 95% CI: 1.30–6.05, p = 0.008) were associated with lobar microbleeds, whereas only leukoaraiosis grade was also related to deep (OR: 9.00, 95% CI: 3.06–26.44, p < 0.001) and infratentorial (OR: 2.48, 95% CI: 1.10–5.61, p = 0.029) microbleeds. The prediction model based on age, CKD stage and leukoaraiosis grade had diagnostic performance with area under curve: 0.804, 0.688, 0.697, respectively. ConclusionWe recommend that patients with ADPKD who are aged 58 or older, and who have CKD of at least stage 3, undergo brain MRI for detection of CM.

Associations of Cerebral Small Vessel Disease and Chronic Kidney Disease in Patients With Acute Intracerebral Hemorrhage: A Cross-Sectional Study.

Chronic kidney disease (CKD) may be associated with the pathogenesis and phenotype of cerebral small vessel disease (SVD), which is the commonest cause of intracerebral hemorrhage (ICH). The purpose of this study was to investigate the associations of CKD with ICH neuroimaging phenotype, volume, and location, total burden of small vessel disease, and its individual components. In 2 cohorts of consecutive patients with ICH evaluated with MRI, we investigated the frequency and severity of CKD based on established Kidney Disease Improving Global Outcomes criteria, requiring estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.732 ≥ 3 months apart to define CKD. MRI scans were rated for ICH neuroimaging phenotype (arteriolosclerosis, cerebral amyloid angiopathy, mixed location SVD, or cryptogenic ICH) and the presence of markers of SVD (white matter hyperintensities [WMHs], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces, defined according to the STandards for ReportIng Vascular changes on nEuroimaging criteria). We used multinomial, binomial logistic, and ordinal logistic regression models adjusted for age, sex, hypertension, and diabetes to account for possible confounding caused by shared risk factors of CKD and SVD. Of 875 patients (mean age 66 years, 42% female), 146 (16.7%) had CKD. After adjusting for age, sex, and comorbidities, patients with CKD had higher rates of mixed SVD than those with eGFR >60 (relative risk ratio 2.39, 95% CI 1.16-4.94, p = 0.019). Severe WMHs, deep microbleeds, and lacunes were more frequent in patients with CKD, as was a higher overall SVD burden score (odds ratio 1.83 for each point on the ordinal scale, 95% CI 1.31-2.56, p < 0.001). Patients with eGFR ≤30 had more CMBs (median 7 [interquartile range 1-23] vs 2 [0-8] for those with eGFR >30, p = 0.007). In patients with ICH, CKD was associated with SVD burden, a mixed SVD phenotype, and markers of arteriolosclerosis. Our findings indicate that CKD might independently contribute to the pathogenesis of arteriolosclerosis and mixed SVD, although we could not definitively account for the severity of shared risk factors. Longitudinal and experimental studies are, therefore, needed to investigate causal associations. Nevertheless, stroke clinicians should be aware of CKD as a potentially independent and modifiable risk factor of SVD.

Association of brain microbleeds with risk factors, cognition, and MRI markers in MESA.

Little is known about the epidemiology of brain microbleeds in racially/ethnically diverse populations. In the Multi-Ethnic Study of Atherosclerosis, brain microbleeds were identified from 3T magnetic resonance imaging susceptibility-weighted imaging sequences using deep learning models followed by radiologist review. Among 1016 participants without prior stroke (25% Black, 15% Chinese, 19% Hispanic, 41% White, mean age 72), microbleed prevalence was 20% at age 60 to 64.9 and 45% at ≥85 years. Deep microbleeds were associated with older age, hypertension, higher body mass index, and atrial fibrillation, and lobar microbleeds with male sex and atrial fibrillation. Overall, microbleeds were associated with greater white matter hyperintensity volume and lower total white matter fractional anisotropy. Results suggest differing associations for lobar versus deep locations. Sensitive microbleed quantification will facilitate future longitudinal studies of their potential role as an early indicator of vascular pathology.

Phenotype and imaging features associated with APP duplications

BackgroundAPP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers.MethodsClinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls.ResultsMajor neurocognitive disorders were found in 90.2% symptomatic APP duplication carriers, with prominent behavioral impairment in 9.7%. Symptomatic intracerebral hemorrhages were reported in 29.2% and seizures in 51.2%. CSF Aβ42 levels were abnormal in 18/19 patients and 14/19 patients fulfilled MRI radiological criteria for CAA, while only 5 displayed no hemorrhagic features. We found no correlation between CAA radiological signs and duplication size. Compared to CAA controls, APP duplication carriers showed less disseminated cortical superficial siderosis (0% vs 37.5%, p = 0.004 adjusted for the delay between symptoms onset and MRI). Deep microbleeds were found in two APP duplication carriers. In addition to neurofibrillary tangles and senile plaques, CAA was diffuse and severe with thickening of leptomeningeal vessels in all 9 autopsies. Lewy bodies were found in substantia nigra, locus coeruleus, and cortical structures of 2/9 patients, and one presented vascular amyloid deposits in basal ganglia.DiscussionPhenotypes associated with APP duplications were heterogeneous with different clinical presentations including dementia, hemorrhage, and seizure and different radiological presentations, even within families. No apparent correlation with duplication size was found. Amyloid burden was severe and widely extended to cerebral vessels as suggested by hemorrhagic features on MRI and neuropathological data, making APP duplication an interesting model of CAA.

Abstract 160: Etiologies Of Intracerebral Hemorrhage In Patients With Atrial Fibrillation On Or Off Oral Anticoagulants: The Neuro-Afib Study

Background: Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulants (OAC) used to prevent ischemic strokes (IS) in patients with atrial fibrillation (AF). As different ICH etiologic factors correspond to different ICH risks, we aimed to present the causes of ICH in AF patients who were or were not using OAC, based on data from a multicenter contemporary cohort. Methods: The Neuro-AFib study is a multicenter effort to elucidate the current causes and consequences of IS and ICH in AF patients. Detailed clinical, laboratory and multimodal imaging data were collected from consecutive patients with AF admitted to 15 US stroke centers with an IS or ICH between 1/2018-12/2019. Etiologic factors of AF patients who were admitted with ICH on OAC (OAC-ICH) and off OAC (nonOAC-ICH) will be compared. Results: A total of 868 patients presented with ICH and had a diagnosis of AF, either previously known (88%) or diagnosed during admission (12%). 571 patients (66%) were on OAC at the time of their ICH of whom 58% were on direct OAC (DOAC), 40% on warfarin and 2% on heparin. OAC-ICH patients were older than nonOAC-ICH (76.6±10 vs 74.4±13, p=0.006) while sex distribution was the same in both groups (43% female). CHA 2 DS 2 -VASC was higher in OAC-ICH (4.3±1.6 vs 3.9±1.9, p=0.001) but HAS-BLED score was the same in both groups (2.7±1.1). Cerebral amyloid angiopathy (CAA) was diagnosed in 42.5% of the ICH patients based on modified Boston criteria while hypertensive cerebral small vessel disease (HTN-cSVD) in 57.5%. HTN-cSVD was the more common ICH etiology among OAC-ICH (65%) compared to nonOAC-ICH (49%). Among OAC-ICHs, DOAC-related ICHs tended to be more commonly of hypertensive etiology when compared to warfarin-ICH (p=0.09). Conclusions: Our study is the first to report the etiologic mechanisms of ICH in AF patients on or off OAC. CAA is known to be a major cause of OAC-ICH with exceedingly high recurrence rates. Despite this fact, HTN-cSVD was more common among OAC-ICH (especially DOAC-ICH) patients, supporting the view that the presence/absence of HTN-cSVD risk markers such as deep microbleeds are as important as CAA-markers in determining the optimal stroke prevention method in AF patients (left atrial appendage closure vs lifelong OAC).

Enlarged perivascular spaces are associated with decreased brain tau deposition.

The aim of this study was to investigate the associations of enlarged perivascular spaces (EPVS) in the basal ganglia (BG) and centrum semiovale (CSO) with beta-amyloid (Aβ) and tau deposition in older adults with a diverse cognitive spectrum. A total of 163 (68 cognitively normal and 95 cognitively impaired) older participants underwent [11 C] Pittsburgh compound B and [18 F] AV-1451 PET, and MRI. EPVS in the BG and CSO and other small vessel disease markers, such as white matter hyperintensities, lacunes, and deep and lobar microbleeds, were assessed. Increased EPVS in the BG showed a significant association with lower cerebral tau deposition, even after controlling for other small vessel disease markers. Further exploratory analyses showed that this association was significant in cognitively impaired, Aβ-positive, or APOE4-positive individuals, but not significant in the cognitively normal, Aβ-negative, or APOE4-negative participants. In contrast to EPVS in the BG, EPVS in the CSO did not have any relationship with cerebral tau deposition. In addition, none of the two types of EPVS were associated with cerebral Aβ deposition. Brain tau deposition appears to be reduced with increased EPVS in the BG, especially in individuals with cognitive impairment, pathological amyloid burden, or genetic Alzheimer's disease risk.

Subclinical hypothyroidism is associated with basal ganglia enlarged perivascular spaces and overall cerebral small vessel disease load.

The association between subclinical hypothyroidism (SCH) and cerebral small vessel disease (CSVD) in the stroke-free population is currently unclear. A total of 354 individuals without a history of stroke were enrolled in this study. Demographic data, medical history, vascular risk factors, carotid arteriosclerosis, and the results of laboratory tests were collated. SCH is defined as an elevation in thyroid-stimulating hormone levels, but with normal free thyroxine levels. Magnetic resonance imaging (MRI) was used to assess 4 markers of CSVD, including white matter hyperintensities (WMHs), lacunes, deep microbleeds, and enlarged perivascular spaces (EPVSs). The overall CSVD load was then ranked using an ordinal scale ranging from 0 to 4. Brain atrophy was measured semi-quantitatively on MRI. A binary logistic regression model was used to explore the association of SCH with each CSVD marker after adjusting for confounding factors. The ordinal regression model was used to explore the association of SCH with CSVD burden and brain atrophy after adjusting for confounding factors. The mean age of the participants (66.9% males) was 69.4±12.8 years. SCH was observed in 44 (12.4%) participants. MRI findings revealed 13% of cases with lacunes, 6.2% with microbleeds, 50.3% with confluent WMH, and 49.2% with extensive basal ganglia EPVS. Assessment of total CSVD burden showed that 29.1% scored 1, 30.5% scored 2, 6.5% scored 3, and 2.3% scored ≥3. SCH was associated with extensive basal ganglia EPVS [odds ratio (OR) =2.175; 95% confidence interval (CI): 1.075 to 4.401] and total CSVD load (OR =1.879; 95% CI: 1.028 to 3.438). SCH was not associated with advanced brain atrophy. SCH is associated with the advanced total burden of CSVD and basal ganglia EPVS in the stroke-free population.

Editors' Note: Detection of Cerebral Microbleeds With Venous Connection at 7-Tesla MRI

The etiology of cerebral microhemorrhages was further explored in the recently published observational cohort of 51 people who underwent 7T magnetic resonance imaging (MRI), as reported by Dr. Rotta et al . Using Quantitative Susceptibility Mapping of healthy elderly adults and adults with cerebral amyloid angiopathy (CAA) and hypertensive vasculopathy, the investigators observed a disproportionate burden of microbleeds with venous connections among patients with CAA vs control groups. This observation might suggest that some of these microbleeds have a venous origin. Although microbleeds in association with a venous connection represented a minority of microbleeds (only 14%), they were strongly tied to CAA over other conditions. Drs. Chen and Wang commented that cortical vessels may be mistaken for lobar microbleeds, leading to a misclassification bias. Furthermore, Drs. Chen and Wang observed a higher prevalence of deep microbleeds in association with a venous connection in their previous autopsy study. The investigators affirm that these results warrant validation using histopathology. Furthermore, one reason for their unique observations may be the higher sensitivity for detecting microbleeds when using an MRI with a greater magnet strength. The etiology of cerebral microhemorrhages was further explored in the recently published observational cohort of 51 people who underwent 7T magnetic resonance imaging (MRI), as reported by Dr. Rotta et al . Using Quantitative Susceptibility Mapping of healthy elderly adults and adults with cerebral amyloid angiopathy (CAA) and hypertensive vasculopathy, the investigators observed a disproportionate burden of microbleeds with venous connections among patients with CAA vs control groups. This observation might suggest that some of these microbleeds have a venous origin. Although microbleeds in association with a venous connection represented a minority of microbleeds (only 14%), they were strongly tied to CAA over other conditions. Drs. Chen and Wang commented that cortical vessels may be mistaken for lobar microbleeds, leading to a misclassification bias. Furthermore, Drs. Chen and Wang observed a higher prevalence of deep microbleeds in association with a venous connection in their previous autopsy study. The investigators affirm that these results warrant validation using histopathology. Furthermore, one reason for their unique observations may be the higher sensitivity for detecting microbleeds when using an MRI with a greater magnet strength.

Implication of Small Vessel Disease MRI Markers in Alzheimer's Disease and Lewy Body Disease.

Small vessel disease (SVD) magnetic resonance imaging (MRI) markers including deep and periventricular white matter hyperintensities (PWMH), lacunes, and microbleeds are frequently observed in Alzheimer's disease (AD) and Lewy body disease (LBD), but their implication has not been clearly elucidated. To investigate the implication of SVD MRI markers in cognitively impaired patients with AD and/or LBD. We consecutively recruited 57 patients with pure AD-related cognitive impairment (ADCI), 49 with pure LBD-related cognitive impairment (LBCI), 45 with mixed ADCI/LBCI, and 34 controls. All participants underwent neuropsychological tests, brain MRI, and amyloid positron emission tomography. SVD MRI markers including the severity of deep and PWMH and the number of lacunes and microbleeds were visually rated. The relationships among vascular risk factors, SVD MRI markers, ADCI, LBCI, and cognitive scores were investigated after controlling for appropriate covariates. LBCI was associated with more severe PWMH, which was conversely associated with an increased risk of LBCI independently of vascular risk factors and ADCI. PWMH was associated with attention and visuospatial dysfunction independently of vascular risk factors, ADCI, and LBCI. Both ADCI and LBCI were associated with more lobar microbleeds, but not with deep microbleeds. Our findings suggest that PWMH could reflect degenerative process related with LBD, and both AD and LBD independently increase lobar microbleeds.

Severity of Small Vessel Disease Biomarkers Reduces the Magnitude of Cognitive Recovery after Ischemic Stroke

Objective: The objective of this study was to evaluate the impact of radiological biomarkers suggestive of cerebral small vessel disease (SVD) on the evolution of cognitive performances after an ischemic stroke (IS). Methods: We studied patients with a supratentorial IS recruited consecutively to a prospective monocentric longitudinal study. A cognitive assessment was performed at baseline, 3 months, and 1 year and was based on a Montreal Cognitive Assessment, an Isaacs set test of verbal fluency (IST), and a Zazzo’s cancellation task (ZCT) for the evaluation of attentional functions and processing speed. The following cerebral SVD biomarkers were detected on a 3-T brain MRI performed at baseline: white matter hyperintensities (WMHs), deep and lobar microbleeds, enlarged perivascular spaces in basal ganglia and centrum semiovale, previous small deep infarcts, and cortical superficial siderosis (cSS). Generalized linear mixed models were used to evaluate the relationship between these biomarkers and changes in cognitive performances. Results: A total of 199 patients (65 ± 13 years, 68% male) were analyzed. Overall, the cognitive performances improved, more significantly in the first 3 months. Severe WMH was identified in 34% of the patients, and focal cSS in 3.5%. Patients with severe WMH and focal cSS had overall worse cognitive performances. Those with severe WMH had less improvement over time for IST (β = −0.16, p = 0.02) and the number of errors to ZCT (β = 0.19, p = 0.02), while those with focal cSS had less improvement over time for ZCT completion time (β = 0.14, p = 0.01) and number of errors (β = 0.17, p = 0.008), regardless of IS volume and location, gray matter volume, demographic confounders, and clinical and cardiovascular risk factors. Conclusion: The severity of SVD biomarkers, encompassing WMH and cSS, seems to reduce the magnitude of cognitive recovery after an IS. The detection of such SVD biomarkers early after stroke might help to identify patients with a cognitive vulnerability and a higher risk of poststroke cognitive impairment.

White matter abnormalities are key components of cerebrovascular disease impacting cognitive decline.

While cerebrovascular disease can be observed in vivo using MRI, the multiplicity and heterogeneity in the mechanisms of cerebrovascular damage impede accounting for these measures in ageing and dementia studies. Our primary goal was to investigate the key sources of variability across MRI markers of cerebrovascular disease and evaluate their impact in comparison to amyloidosis on cognitive decline in a population-based sample. Our secondary goal was to evaluate the prognostic utility of a cerebrovascular summary measure from all markers. We included both visible lesions seen on MRI (white matter hyperintensities, cortical and subcortical infarctions, lobar and deep microbleeds) and early white matter damage due to systemic vascular health using diffusion changes in the genu of the corpus callosum. We identified 1089 individuals aged ≥60 years with concurrent amyloid-PET and MRI scans from the population-based Mayo Clinic Study of Aging. We divided these into discovery and validation datasets. Using the discovery dataset, we conducted principal component analyses and ascertained the main sources of variability in cerebrovascular disease markers. Using linear regression and mixed effect models, we evaluated the utility of these principal components and combinations of these components for the prediction of cognitive performance along with amyloidosis. Our main findings were (i) there were three primary sources of variability among the CVD measures—white matter changes are driven by white matter hyperintensities and diffusion changes; number of microbleeds (lobar and deep); and number of infarctions (cortical and subcortical); (ii) Components of white matter changes and microbleeds but not infarctions significantly predicted cognition trajectories in all domains with greater contributions from white matter; and (iii) The summary vascular score explained 3–5% of variability in baseline global cognition in comparison to 3–6% variability explained by amyloidosis. Across all cognitive domains, the vascular summary score had the least impact on memory performance (∼1%). Though there is mechanistic heterogeneity in the cerebrovascular disease markers measured on MRI, these changes can be grouped into three components and together explain variability in cognitive performance equivalent to the impact of amyloidosis on cognition. White matter changes represent dynamic ongoing damage, predicts future cognitive decline across all domains and diffusion measurements help capture white matter damage due to systemic vascular changes. Therefore, measuring and accounting for white matter changes using diffusion MRI and white matter hyperintensities along with microbleeds will allow us to capture vascular contributions to cognitive impairment and dementia.

Detection of Cerebral Microbleeds With Venous Connection at 7-Tesla MRI.

Cerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein. 7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein. A total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%). Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.

Abstract 39: Acute Blood Pressure Dysregulation Increases the Risk of Border Zone Ischemic Lesions in Hypertensive Intracerebral Hemorrhage

Background: Intensive blood pressure (BP) reduction is regarded as the gold standard therapy for acute intracerebral hemorrhage (ICH), but its associations to cerebral hypoperfusion and ischemic lesions have been suspected. This study aims to investigate the impact of acute BP reduction on the development of acute ischemic lesions (AILs) at border zone (BZ) areas in patients with hypertensive ICH. Methods: We enrolled patients with acute hypertensive ICH (hemorrhagic lesions restricted to deep region [Strictly deep-ICH] or located in mixed lobar and deep areas [Mixed-ICH]) who received brain MRI within 7 days after ICH onset. BZ AILs were defined as lesions locating at BZ areas that were hyperintense on DWI sequence and hypointense on ADC series (figure). Acute SBP change was the difference between the initial SBP and the SBP recorded at 24 hours after ICH onset. Results: Of the 274 enrolled patients (62.5 ± 12.7 years old, 65% male), 11 subjects had BZ AILs. Compared to patients without BZ AILs, patients with lesions had wider amount of acute SBP reduction (71.7 ± 33.6 vs. 43.0 ± 32.2 mmHg, P = 0.023), more lobar and deep microbleeds (MB) and larger white matter hyperintensity volume (all p &lt; 0.05). Using ROC curve analysis, acute SBP drop at more than 54mmHg was linked to the occurrence of AILs (sensitivity 82%, specificity 64%, P = 0.002). In multiple logistic regression model, acute SBP decline at above 54mmHg (OR 11.45, 95%CI 2.06 - 63.49, P = 0.005) and higher deep MB burden ( P = 0.032) raised the risk of AILs after adjustment for age, sex, and image markers of cerebral small vessel disease. In subgroup analysis, larger acute SBP drop remained to be an independent risk factor for development of AILs in patients with Mixed-ICH ( P = 0.008), but not in patients with strictly deep-ICH ( P = 0.715). Conclusion: Acute SBP change in hypertensive ICH, especially in Mixed-ICH, increases the risk of AILs at BZ areas, showing widespread microangiopathy that is vulnerable to rapid BP dysregulation to ischemia.

Relationship of Four Blood Pressure Indexes to Subclinical Cerebrovascular Diseases Assessed by Brain MRI in General Japanese Men.

Aim: The relationship of blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) to subclinical cerebrovascular diseases (SCVDs) remains unclear. This study aimed to elucidate the relationship of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men. Methods: In general Japanese men aged 40–79 years ( N =616), office BP indexes were measured at two visits (Visits 1 [2006–2008] and 2 [2010–2014]). MRI images obtained on the third visit (2012–2015) were examined for prevalent SCVDs: lacunar infarction, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), microbleeds, and intracranial artery stenosis (ICAS). Using a multivariable logistic regression analysis, we computed and estimated the odds ratio of each prevalent SCVD for one standard deviation higher BP indexes. The same analyses were performed using home BP. Results: All four office BP indexes at both visits associated with lacunar infarction. Visit 1 and 2 DBP and Visit 1 MAP associated with PVH and DSWMH, and Visit 1 SBP associated with DSWMH. All Visit 2 BP indexes appear to show stronger association with microbleeds than Visit 1 indexes, and Visit 1 and 2 SBP, PP, and MAP showed similar associations with ICAS. Additional analyses using home BP indexes revealed similar relationships; however, the significance of some relationships decreased. Conclusion: In general Japanese men, BP indexes were associated with most of SCVDs, and BP indexes measured at different periods associated with different SCVDs assessed by MRI.

Insights in the pathophysiology of haemorrhagic strokes in a sub-Sahara African country, an epidemiological and MRI study.

Intra-cerebral Haemorrhage (ICH) seems more prevalent in sub-Saharan Africa (SSA) than in High-Income Countries (HIC) with poorer clinical outcome. Higher impact of hypertension and/or amyloid angiopathy could account for this disproportion. Here, we sought to (i) retrospectively compare ICH clinical and imaging patterns in Belgium and Guinea and in a subsequent cohort (ii) prospectively compare brain MRI characteristics to seek evidence for a different proportion of amyloid angiopathy patterns. Ninety one consecutive patients admitted for spontaneous ICH at Brussels Erasme-ULB Hospital and at Conakry Ignace Deen-UGANC were retrospectively compared in terms of ICH volume estimated with the ABC/2 method, clinical characteristics and modified ranking (mRS) score at 30days. mRS was dichotomised as good outcomes (≤3) and poor outcomes (>3). A prospective cohort of 30 consecutive patients with ICH admitted at CHU Conakry Ignace Deen-UGANC was prospectively included to undergo brain MRI. Results of the Guinean MRI were compared to 30 patients randomly selected from Brussels' initial cohort. Paired Student's t-test and Mann-Whitney u-test were used for group comparisons. Age of ICH onset was higher in Belgium (68±17years vs. 56±14years, P<0.01) while ICH volume and 30-day mortality rate were higher in Guinea (20ml vs. 11ml, P<0.01 and mortality 33% vs. 10 %, P<0.01). ICH burden in survivors in Conakry and Brussels showed respectively good outcomes in 56.7% and 60.4% (P=0.09) and poor outcomes in 10.3% vs. 29.6% (P<0.001). MRI analysis of the prospective cohort failed to disclose significant differences regarding brain MRI characteristics. Intra-cerebral Haemorrhage affected patients 15years younger in Guinea with larger haematoma volumes and higher mortality than in Belgium. MRI findings did not show more prevalent amyloid angiopathy pathology suggesting that better primary prevention of hypertension could positively impact ICH epidemiology in Guinea.

Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments.

We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P=0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P=0.041) than the dentate group. Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

In vivo neuroinflammation and cerebral small vessel disease in mild cognitive impairment and Alzheimer’s disease

IntroductionAssociations between cerebral small vessel disease (SVD) and inflammation have been largely examined using peripheral blood markers of inflammation, with few studies measuring inflammation within the brain. We investigated the...

Association of Ultrasonography and MRI Findings with Stroke Recurrence: Differences Between Patients with Past Histories of Atherothrombotic Versus Lacunar Infarctions

Objective: This study investigated the association of MRI and ultrasonography findings with stroke recurrence in patients with past histories of atherothrombotic infarctions (ATIs) or lacunar infarctions (LIs). Methods: We prospectively analyzed the incidence of stroke recurrence. Deep and lobar cerebral microbleeds (MBs), asymptomatic lacunae, asymptomatic intracerebral hemorrhages (ICHs), severe white matter lesions (WML), and intima-media thickness (IMT) were investigated on enrollment. Stroke recurrence rates were compared by using the log-rank test. The odds ratios for recurrent strokes were derived using multivariate logistic regression models, adjusted for risk factors. Results: We evaluated the stroke recurrence rate in 362 ATI patients and 309 LI patients. The log-rank test and multivariate analyses revealed that the incidence of recurrent stroke was significantly higher in ATI patients with mean IMT greater than or equal to 1.1 mm, asymptomatic ICHs, or lobar MBs than in those without. The incidence was significantly higher in LI patients with asymptomatic ICHs, asymptomatic LIs, and severe WMLs than in those without. In ATI patients, those with strictly lobar MBs or mixed MBs (deep and lobar MBs) had significantly higher recurrence rates than those without MB. In LI patients, those with strictly deep MBs or mixed MBs had higher recurrence rates than those without MB, and the incidences of those with mixed MBs was larger than those with strictly deep MBs. Conclusions: There were differences between ATI and LI patients in terms of the association of MRI and ultrasonography findings, in particularly strictly lobar or deep MBs, with the incidence of stroke recurrence.

Neuroimaging consequences of cerebral small vessel disease in patients with obstructive sleep apnea–hypopnea syndrome

ObjectiveThis study aimed to investigate the association between severity of obstructive sleep apnea–hypopnea syndrome (OSAHS) and the neuroimaging consequences of cerebral small vessel disease (SVD).MethodsPatients with OSAHS and age‐ and gender‐matched healthy control subjects completed the mini‐mental state examination and underwent an evoked‐related potential study and overnight polysomnographic monitoring. Magnetic resonance imaging (MRI) was performed to detect markers of silent cerebral SVD, including Virchow–Robin spaces (VRS) rated on a five‐point scale, white matter lesions, lacunar infarcts, and deep microbleeds. Multinomial logistic regression models were used to examine the associations of the apnea–hypopnea index (AHI) and arousal index (AI) values, mean oxyhemoglobin saturation, the duration of snoring history, and MRI markers of small vessel disease with the incidence of enlarged VRS.ResultsThe study included 72 patients with severe OSAHS and 53 volunteers without OSAHS. The duration of snoring history ranged from 5 to 22 years in the OSAHS group. Smaller P3 amplitudes at Cz were found in OSAHS patients than control subjects (p < .05), which is associated with neurocognitive impairment. Enlarged VRS were more prevalent in the basal ganglia and centrum semiovale of patients with OSAHS than in the control group. No significant between‐group differences were observed in the number of white matter lesions, lacunar infarcts, and deep microbleeds. Enlarged VRS were positively correlated with AHI and AI values in the OSAHS group (r = .63, p < .001; r = .55, p < .001, respectively).ConclusionsSilent cerebral SVD was more prevalent in patients with OSAHS than in the controls. Enlarged VRS observed in the basal ganglia and centrum semiovale were positively correlated with severity of OSAHS, which may contribute to cognitive impairment.

Microbleeds after Carotid Artery Stenting: Small Embolism May Induce Cerebral Microbleeds

Background: Since the advent of magnetic resonance imaging technology, cerebral microbleeds can be diagnosed in vivo. However, the underlying mechanism of cerebral microbleed formation is not fully understood. Objectives: This study aimed to identify the factors associated with cerebral microbleeds after carotid artery stenting (CAS). Method: We retrospectively examined 125 patients who underwent CAS for carotid stenosis. Cerebral microbleeds were investigated using T2*-weighted gradient-echo (GRE) imaging before and after CAS. We analyzed the possible association of new microbleeds with the following risk factors: the number of baseline microbleeds and ischemic cerebral lesions, the occurrence of cerebral hyperperfusion syndrome, and new ischemic cerebral lesions after CAS. Results: Baseline cerebral microbleeds were detected in 53 patients (42.4%). New cerebral microbleeds after CAS were observed in 13 of 125 patients (10.4%) and were exclusively associated with new ischemic lesions but not with other risk factors. No patient showed a merged image of a new cerebral microbleed on GRE imaging or a new ischemic lesion on diffusion-weighted imaging. Lobar and deep microbleeds were noted in 12/13 (92.3%) and 1 patient (7.7%), respectively. Of 12 patients with new microbleeds, 10 (76.9%) and 2 (15.4%) had a new microbleed in the ipsilateral and contralateral hemispheres, respectively. Conclusions: We found that new cerebral microbleeds developed after CAS and that these might be associated with new ischemic lesions, mostly in the territory of the treated carotid artery. We speculate that these microbleeds result from the deoxygenation of hemoglobin in the embolus or, alternatively, small hemorrhagic transformation of ischemic lesions.