Lobar Microbleeds Research Articles

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 < 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.

Cerebral amyloid angiopathy-related inflammation: current status and future implications.

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid β (Aβ)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aβ and anti-Aβ antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

Brain Glucose Metabolism in Cerebral Amyloid Angiopathy: An FDG-PET Study.

The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is currently based on the Boston criteria, which largely rely on hemorrhagic features on brain magnetic resonance imaging. Adding to these criteria 18F-fluoro-deoxy-D-glucose (FDG) positron emission tomography, a widely available imaging modality, might improve their accuracy. Here we tested the hypothesis that FDG uptake is reduced in posterior cortical areas, particularly the primary occipital cortex, which pathologically bear the brunt of vascular Aβ deposition. From a large memory clinic database, we retrospectively included all patients in whom both brain magnetic resonance imaging and FDG positron emission tomography had been obtained as part of routine clinical care and who fulfilled the Boston criteria for probable CAA. None had a history of symptomatic intracerebral hemorrhage. FDG data processing involved (1) spatial normalization to the Montreal Neurology Institute/International Consortium for Brain Mapping 152 space and (2) generation of standardized FDG uptake (relative standardized uptake value; relative to the pons). The relative standardized uptake value data obtained in 13 regions of interest sampling key cortical areas and the cerebellum were compared between the CAA and age-matched control groups using 2 separate healthy subject databases and image-processing pipelines. The presence of significant hypometabolism (2-tailed P<0.05) was assessed for the bilaterally averaged regions-of-interest relative standardized uptake values. Fourteen patients fulfilling the Boston criteria for probable CAA (≥2 exclusively lobar microbleeds) were identified. Significant hypometabolism (P range, 0.047 to <0.0001) consistently affected the posterior cortical areas, including the superior and inferior parietal, primary visual, lateral occipital, lateral temporal, precuneus, and posterior cingulate regions of interest. The anterior cortical areas were marginally or not significantly hypometabolic, and the cerebellum was spared. Supporting our hypothesis, significant glucose hypometabolism predominantly affected posterior cortical regions, including the visual cortex. These findings from a small sample may have diagnostic implications but require replication in larger prospective studies. In addition, whether they generalize to CAA-related symptomatic intracerebral hemorrhage warrants specific studies.

Striped occipital cortex and intragyral hemorrhage: Novel magnetic resonance imaging markers for cerebral amyloid angiopathy

Background and aimTo investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH).MethodsWe performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features.ResultsWe included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging.ConclusionWhereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA.

Intracerebral Hemorrhage Recurrence in Patients with and without Cerebral Amyloid Angiopathy

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.

Cortical superficial siderosis in the general population: The Framingham Heart and Rotterdam studies.

We aimed to characterize cortical superficial siderosis, its determinants and sequel, in community-dwelling older adults. The sample consisted of Framingham (n = 1724; 2000-2009) and Rotterdam (n = 4325; 2005-2013) study participants who underwent brain MRI. In pooled individual-level analysis, we compared baseline characteristics in patients with cortical superficial siderosis to two reference groups: (i) persons without hemorrhagic MRI markers of cerebral amyloid angiopathy (no cortical superficial siderosis and no microbleeds) and (ii) those with presumed cerebral amyloid angiopathy based on the presence of strictly lobar microbleeds but without cortical superficial siderosis. Among a total of 6049 participants, 4846 did not have any microbleeds or cortical superficial siderosis (80%), 401 had deep/mixed microbleeds (6.6%), 776 had strictly lobar microbleeds without cortical superficial siderosis (12.8%) and 26 had cortical superficial siderosis with/without microbleeds (0.43%). In comparison to participants without microbleeds or cortical superficial siderosis and to those with strictly lobar microbleeds but without cortical superficial siderosis, participants with cortical superficial siderosis were older (OR 1.09 per year, 95% CI 1.05, 1.14; p < 0.001 and 1.04, 95% CI 1.00, 1.09; p = 0.058, respectively), had overrepresentation of the APOE ɛ4 allele (5.19, 2.04, 13.25; p = 0.001 and 3.47, 1.35, 8.92; p = 0.01), and greater prevalence of intracerebral hemorrhage (72.57, 9.12, 577.49; p < 0.001 and 81.49, 3.40, >999.99; p = 0.006). During a mean follow-up of 5.6 years, 42.4% participants with cortical superficial siderosis had a stroke (five intracerebral hemorrhage, two ischemic strokes and four undetermined strokes), 19.2% had transient neurological deficits and 3.8% developed incident dementia. Our study adds supporting evidence to the association between cortical superficial siderosis and cerebral amyloid angiopathy within the general population. Community-dwelling persons with cortical superficial siderosis may be at high risk for intracerebral hemorrhage and future neurological events.

A case of inflammatory cerebral amyloid angiopathy with white matter lesions appearing after brain biopsy

A 76-year-old woman with a 7-year history of dementia presented to our hospital with generalized convulsive seizure for the first time. Contrast-enhanced brain magnetic resonance imaging revealed leptomeningeal enhancement mainly in the right occipital lobe and multiple lobar microbleeds in the bilateral cerebral and cerebellar subcortex. No white matter lesions were observed. A brain biopsy of the right parieto-occipital lobe revealed cerebral amyloid angiopathy (CAA). White matter lesions appeared in the right parieto-occipital lobe three days after the biopsy, and we considered inflammatory CAA. Three courses of methylprednisolone pulse followed by oral prednisolone therapy gradually reduced leptomeningeal and white matter lesions. An apolipoprotein E genotype investigation identified the ε2/ε3 genotype. In patients with inflammatory CAA, a risk of exacerbation should be considered after brain biopsy, in which the ε2 allele might play a role.

Vascular Risk Factors, Imaging, and Outcomes in Transient Ischemic Attack/Ischemic Stroke Patients with Neuroimaging Evidence of Probable/Possible Cerebral Amyloid Angiopathy.

Background In TIA/ischemic stroke patients, the clinical significance of lobar microbleeds potentially indicating cerebral amyloid angiopathy (CAA) is unknown. We assessed vascular risk factors and outcomes, including cognition, in TIA/ischemic stroke patients with neuroimaging evidence of probable/possible CAA. Methods This prospective cohort was conducted from August 2015 and January 2018 at 40 centers. 2625 participants were collected. Eligible participants were aged at least 55 years. Montreal Cognitive Assessment (MoCA) score is less than or equal to 26. A total of 1620 patients were included. 1604 (99.0%) and 1582 (97.7%) participants are followed up at 3 and 12 months. The primary outcomes were death or disability (mRS score, 3-6) and Montreal Cognitive Assessment (MoCA) at 3 months and 12 months. Demographic and vascular risk factors were measured at baseline (smoking, alcohol, diabetes, atrial fibrillation, hypertension, hypercholesterolemia, coronary artery disease, ischemic stroke, and transient ischemic attack). Blood samples were collected within 24 hours of admission. MRI was recommended for all patients. MoCA score was evaluated at baseline and follow-up. Results In total, 291/1620 patients with ischemic stroke/TIA (32.7% female and mean age, 67.8 years) had neuroimaging evidence of probable/possible CAA. Higher age, history of hypertension, atrial fibrillation, ischemic stroke, alcohol, and high glucose at the admission were more common in the patients. Mean MoCA changed from 21.4 at 3 months (SD 5.2) to 22.3 at 12 months (SD 4.7), difference 0.3 (SD 3.8). At the 3-month and 12-month follow-up, there were significant differences in age, education level, and sex among different cognitive groups. Higher age, lower education (less than high school), and female sex were the predictors of changing in MoCA score from 3 months to 12 months. Moreover, age (more than 66 years) and education (less than high school) are strongly associated with MoCA at 3- and 12-month follow-up. 30 of 286 (10.5%) and 37 of 281 (13.2%) patients had poor outcome of death or disability (modified Rankin Scale score, 3-6) at follow-up 3 and 12 months. Cortical superficial siderosis (cSS) was associated with higher mRS at follow-up. cSS status, cSS count 1-2, cSS strictly lobar, and strictly deep might be the risks of outcomes in adjusted analyses. Conclusion This study suggested that an increasing number of vascular risk factors and imaging markers were significantly associated with outcomes of TIA/ischemic stroke patients with CAA pattern. Male, young patients with high education should get better cognitive recovery.

Amyloid angiopathy may contribute to white‐matter hyperintensities in Alzheimer’s disease

AbstractBackgroundCerebral amyloid angiopathy (CAA) is characterised by the accumulation of amyloid‐b (Aβ) in cerebral vessels and is often coexistent with Alzheimer’s disease (AD). However, the overlap between CAA and AD and the contribution of CAA pathology to cerebrovascular lesions are not well understood. We hypothesize that in subjects with high Aβ load, the presence of imaging markers of CAA would be associated with greater white matter hyperintensities (WMH) burden.MethodData used in the preparation of this article was obtained from the Australian Imaging Biomarkers and Lifestyle flagship study of ageing (AIBL). See www.aibl.csiro.au. We analysed MRI (SWI and FLAIR) and 11C‐PiB‐PET data from 98 cognitively normal (CN), 34 mild‐cognitive impairment (MCI) and 38 AD participants. Subjects were classified as being Aβ+ if their Aβ load was above 20 centiloid.SWI images were manually read for lobar microbleeds (LMB) and superficial siderosis. Subjects were classified as probable‐CAA (PCAA, 2 or more LMB or siderosis), possible‐CAA (SCAA, single LMB or siderosis) or non‐CAA (NCAA) based on the modified Boston criteria. Subjects classified as SCAA (n = 24) were excluded from further analysis since literature shows this group to be heterogenous and having low incidence of CAA pathology. WMH were automatically quantified on FLAIR. Group comparisons of WMH load were made using Kruskal Wallis rank test. A GLM was performed comparing WMH (log10 transformed) and CAA/ Aβ+ classification with age, intracranial volume, gender, APOE‐ε4 genotype and use of anti‐platelet or anticoagulant medication modelled as covariates.ResultSignificantly higher WMH volume was observed in PCAA (n = 17) than NCAA (n = 129) (p‐value = 0.021, d = 0.36). When amyloid status was considered, PCAA/Aβ+ (n = 15) subjects had a significantly higher WMH load than NCAA/Aβ+ (n = 57) subjects (p‐value = 0.012, d = 0.57) and NCAA/Aβ‐ (n = 72) subjects (p‐value = 0.0006, d = 0.76) (Figure 1). PCAA/Aβ‐ (n = 2) were removed from further analysis. GLM results showed a significant association of WMH with PCAA/Aβ+ as compared to NCAA/Aβ+ (p‐value = 0.02, beta = 0.322 [0.056,0.588]).ConclusionOur findings suggest that CAA may contribute to WMH burden in subjects with high Aβ load. Further studies are required to validate our observations and characterise the contributions of CAA compared to small vessel disease associated with traditional risk factors towards the phenotype of AD.

Association between cortical microinfarcts and total small vessel disease burden in cerebral amyloid angiopathy on 3-Tesla magnetic resonance imaging.

Cortical microinfarcts (CMIs) are frequently found in the brains of patients with advanced cerebral amyloid angiopathy (CAA) at autopsy. The small vessel disease (SVD) score for CAA (i.e., the CAA-SVD score) has been proposed to evaluate the severity of CAA-associated vasculopathic changes by a combination of magnetic resonance imaging (MRI) markers. The aim of this study was to examine the association between total CAA-SVD score and features of CMIs on in vivo 3-Tesla MRI. Eighty patients with probable CAA were retrospectively analyzed. Lobar cerebral microbleeds, cortical superficial siderosis, enlargement of perivascular space in the centrum semiovale and white matter hyperintensity were collectively assessed, and the total CAA-SVD score was calculated. The presence of CMI was also examined. Of the 80 patients, 13 (16.25%) had CMIs. CMIs were detected more frequently in the parietal and occipital lobes. A positive correlation was found between total CAA-SVD score and prevalence of CMI (ρ=0.943; p=0.005). Total CAA-SVD score was significantly higher in patients with CMIs than in those without (p=0.009). In a multivariable logistic regression analysis, the presence of CMIs was significantly associated with total CAA-SVD score (odds ratio 2.318 [95% confidence interval 1.228-4.376]; p=0.01, per each additional point). The presence of CMIs with a high CAA-SVD score could be an indicator of more severe amyloid-associated vasculopathic changes in patients with probable CAA.

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.

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source

The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging. To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy. Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial. Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. The primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality. Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI, 1.54-3.15), multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P = .97). Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes. ClinicalTrials.gov Identifier: NCT02313909.

Lobar microbleeds are associated with cognitive impairment in patients with lacunar infarction

Associations between cognitive decline and cerebral microbleeds (CMBs) have received increasing attention. An association between CMB distribution (deep or lobar) and cognitive decline has been reported, but these findings are controversial. We investigated the association between magnetic resonance imaging (MRI) findings, including CMBs, and cognitive function in patients with first-ever lacunar infarction. We retrospectively included consecutive patients admitted with first-ever lacunar infarction identified by MRI from July 1, 2011, to December 31, 2018. We excluded patients diagnosed with dementia, including strategic single-infarct dementia, before or after the onset of stroke. The Mini-Mental State Examination (MMSE) was performed within 3 days of admission. We searched the records of 273 patients (age 72.0 ± 11.2 years, 95 females). The median MMSE score was 27 (interquartile range 25.5–29). In a univariate analysis, the MMSE score was associated with age, body mass index (BMI), education, dyslipidemia, chronic kidney disease (CKD), periventricular hyperintensity, medial temporal atrophy, lobar CMBs, and mixed CMBs (p < 0.20). The lacunar infarction location was not associated with the MMSE score. In a multivariate analysis of these factors, lobar CMBs (p < 0.001) and mixed CMBs (p = 0.008) were independently associated with the MMSE score. Lobar CMBs were associated with cognitive impairment.

Efficacy and Safety of Direct Oral Anticoagulant for Treatment of Atrial Fibrillation in Cerebral Amyloid Angiopathy

A 75-year-old man with a history of atrial fibrillation (AF) and anticoagulant therapy presented with a headache. Cerebral amyloid angiopathy (CAA) was diagnosed after MRI of the brain revealed cortical superficial siderosis, lobar intracerebral hemorrhage, and lobar microbleeds. Anticoagulant therapy was carefully discontinued. Several years later, he was admitted with sudden onset left upper-extremity weakness. In addition to CAA bleeding lesions, a diffusion-weighted brain MRI showed multiple infarct lesions of high signal intensity. The administration of edoxaban 7.5 mg/day (later increased up to 30 mg/day) prevented ischemic stroke recurrence without exacerbation of cerebral bleeding. This could indicate that CAA patients with AF who had previous adverse effects from warfarin can safely use newer direct oral anticoagulants, such as edoxaban, to prevent ischemic stroke without danger of cerebral hemorrhage. The superiority of edoxaban as compared with warfarin might be due to its antioxidant effect because vascular oxidative stress plays a causal role in CAA-induced cerebrovascular dysfunction, CAA-induced cerebral hemorrhage, and CAA formation itself. We explained the beneficial effect of edoxaban for CAA by the mechanism of oxidative stress in the paper.

Asymptomatic Striatocapsular slit-like Hemorrhage as a Severity Marker in Patients with Hypertensive Angiopathy

BackgroundConcomitant asymptomatic striatocapsular slit-like hemorrhage (SSH) is occasionally found in patients of spontaneous intracerebral hemorrhage (ICH), but was seldomly described in the literature. In this study, we described the clinico-radiological features of asymptomatic SSH in ICH patients with hypertensive microangiopathy. Methods and Results246 patients with strictly deep or mixed deep and lobar ICH/microbleeds were included. SSH was defined as hypointense lesions involving the lateral aspect of lentiform nucleus or external capsule in slit shape (>1.5 cm) on susceptibility-weighted imaging without history of associated symptoms. Demographics and neuroimaging markers were compared between patients with SSH and those without. Patients with SSH (n=24, 10%) and without SSH had comparable age (62.0 ± 12.6 vs. 62.3 ± 13.5, p = 0.912) and vascular risk factor profiles including the diagnosis of chronic hypertension, diabetes, and dyslipidemia (all p>0.05). SSH was associated with more common lobar microbleeds (79.2% vs 48.2%, p = 0.005), lacunes (75% vs. 41.4%, p = 0.002) and higher white matter hyperintensity (WMH) volumes (24.1 [10.4–46.3] vs. 13.9 [7.0–24.8] mL, p = 0.012) on MRI, as well as more frequent left ventricular hypertrophy (LVH) (50.0% vs. 20.5%, p = 0.004) and albuminuria (41.7% vs. 19.4%, p = 0.018). In multivariable analyses, SSH remains independently associated with LVH (p = 0.017) and albuminuria (p = 0.032) after adjustment for age, sex, microbleed, lacune and WMH volume. ConclusionsAsymptomatic SSH is associated with more severe cerebral small vessel disease-related change on brain MRI, and hypertensive cardiac and renal injury, suggesting a more advanced stage of chronic hypertension.

Clinical and radiological differences between patients with probable cerebral amyloid angiopathy and mixed cerebral microbleeds

BackgroundThe key imaging features of cerebral amyloid angiopathy (CAA) are lobar, cortical, or cortico-subcortical microbleeds, macrohaemorrhages and cortical superficial siderosis (cSS). In contrast, hypertensive angiopathy is characterized by (micro) haemorrhages in the basal ganglia, thalami, periventricular white matter or the brain stem. Another distinct form of haemorrhagic microangiopathy is mixed cerebral microbleeds (mixed CMB) with features of both CAA and hypertensive angiopathy. The distinction between the two entities (CAA and mixed CMB) is clinically relevant because the risk of haemorrhage and stroke should be well balanced if oral anticoagulation is indicated in CAA patients. We aimed to comprehensively compare these two entities.MethodsPatients with probable CAA according to the modified Boston criteria and mixed CMB without macrohaemorrhage were retrospectively identified from our database. Comprehensive comparison regarding clinical and radiological parameters was performed between the two cohorts.ResultsPatients with CAA were older (78 ± 8 vs. 74 ± 9 years, p = 0.036) and had a higher prevalence of cSS (19% vs. 4%, p = 0.027) but a lower prevalence of lacunes (73% vs. 50%, p = 0.018) and deep lacunes (23% vs. 51%, p = 0.0003) compared to patients with mixed CMB. Logistic regression revealed an association between the presence of deep lacunes and mixed CMB. The other collected parameters did not reveal a significant difference between the two groups.ConclusionsCAA and mixed CMB demonstrate radiological differences in the absence of macrohaemorrhages. However, more clinically available biomarkers are needed to elucidate the contribution of CAA and hypertensive angiopathy in mixed CMB patients.

White matter atrophy in cerebral amyloid angiopathy.

We postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA. White matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function. Patients with CAA (n = 72) had significantly lower pWMV (27.97% ± 2.63) when compared to age-matched HC (n = 72; mean difference [MD], 2.38%; p < 0.0001) and patients with AD (n = 72; MD, 1.57%; p < 0.0001). Differences were most pronounced in the posterior occipital regions in both comparisons. When comparisons were restricted to groups of patients with CAA but no intracerebral hemorrhage (n = 32) or hypertension (n = 32), and age-matched HC and AD, the significant differences were unaltered. Within the CAA cohort, higher age, lobar microbleed counts, and presence of hypertension were associated with lower pWMV (p = 0.0007, p = 0.031, and p = 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function. Patients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.

Highlights of Selected Articles July 2020.

Highlights of Selected Articles July 2020.

Interactions Between Acute Infarcts and Cerebrovascular Pathology Predict Poststroke Dementia.

Chronic cerebrovascular pathology accelerates the incidence of poststroke dementia (PSD). Whether the risk of PSD varies according to different types of chronic cerebrovascular pathology remains unclear. We investigated whether PSD is associated with a unique pattern of interactions between chronic cerebrovascular pathologies and acute stroke lesions. In this case-control study of acute mild stroke patients (n=185), cases included patients who developed PSD at a 6-month poststroke follow-up, and controls included patients who remained nondemented at 6 months, matched on prestroke cognitive status. Magnetic resonance imaging was performed at initial stroke presentation; neuropsychological assessments were performed 6 months after the stroke. White matter hyperintensities (WMH), chronic lacunes, microbleeds, and acute infarcts were not associated with PSD after controlling for demographics, cardiovascular risk, and global cortical atrophy. The risk of PSD was largest for patients with acute large subcortical infarcts (>15 mm) and concomitant periventricular WMH compared with patients with large subcortical infarcts and punctate/absent periventricular WMH [odds ratio (OR)=5.85, 95% confidence interval (CI)=1.85-40.04]. A moderate risk of PSD was observed for patients with acute multiple small infarcts (3 to 15 mm) and concomitant lacunes (OR=2.48, 95% CI=0.94-6.51) or concomitant lobar microbleeds (OR=2.20, 95% CI=0.89-5.41), compared with patients with acute multiple small infarcts and absent lacunes or microbleeds. Single small infarcts did not interact with cerebrovascular pathology to affect PSD. The risk of PSD varies depending on the presence of chronic cerebrovascular pathologies and type of acute infarcts. Clinical implications support a precision medicine approach for stratifying those at highest risk of PSD.

Impaired cerebral autoregulation is associated with poststroke cognitive impairment.

ObjectiveTo investigate whether dynamic cerebral autoregulation (CA) and neuroimaging characteristics are determinants of poststroke cognitive impairment (PSCI).MethodsEighty patients within 7 days of acute ischemic stroke and 35 age‐ and sex‐matched controls were enrolled. In the patients with stroke, brain magnetic resonance imaging and dynamic CA were obtained at baseline, and dynamic CA was followed up at 3 months and 1 year. Montreal Cognitive Assessment (MoCA) was performed at 3 months and 1 year. Patients with a MoCA score <23 at 1 year were defined as having PSCI, and those with a MoCA score that decreased by 2 points or more between the 3‐month and 1‐year assessments were defined as having progressive cognitive decline.ResultsIn total, 65 patients completed the study and 16 developed PSCI. The patients with PSCI exhibited poorer results for all cognitive domains than did those without PSCI. The patients with PSCI also had poorer CA (lower phase shift between cerebral blood flow and blood pressure waveforms in the very low frequency band) compared with that of the patients without PSCI and controls at baseline and 1 year. CA was not different between the patients without PSCI and controls. In the multivariate analysis, low education level, lobar microbleeds, and impaired CA (very low frequency phase shift [≤46°] within 7 days of stroke), were independently associated with PSCI. In addition, impaired CA was associated with progressive cognitive decline.InterpretationLow education level, lobar microbleeds, and impaired CA are involved in the pathogenesis of PSCI.