Presence Of Microbleeds Research Articles

Disease progression, transient ischemic attack, and de novo parenchymal lesions in asymptomatic moyamoya disease: results of a 5-year interim analysis of the AMORE study

OBJECTIVE Recently, the authors have reported the 5-year risk of stroke in patients with asymptomatic moyamoya disease (MMD). In this report, the aim was to clarify patients’ 5-year risk of disease progression, transient ischemic attack (TIA), and de novo parenchymal lesions and to identify their predictors. METHODS This multicenter, prospective cohort study (Asymptomatic Moyamoya Registry [AMORE]) in Japan is still ongoing. Participants were enrolled if they were 20–70 years of age, had bilateral or unilateral MMD, experienced no episodes suggestive of TIA and stroke, were functionally independent (modified Rankin Scale score of 0 or 1), and had been followed up for 10 years. Clinical and radiological data were obtained at enrollment and annually thereafter for 5 years. In this 5-year interim analysis, the authors defined disease progression, TIA, and de novo parenchymal lesions as the secondary endpoints. The predictors for these events were identified, using a stratification analysis method. RESULTS A total of 103 patients were enrolled and prospectively followed up for 5 years. On annual MRA examinations, disease progression occurred in 39 hemispheres in 26 patients. The incidence of disease progression was 5.9% per patient-year, and the predictors included younger age (OR 5.72, 95% CI 1.28–25.56; p = 0.0223) and hypercholesterolemia (OR 5.41, 95% CI 1.37–21.28; p = 0.0158). TIA occurred in 12 hemispheres in 10 patients, for an incidence of 2.3% per patient-year. The disease progression prior to TIA was a significant predictor for TIA (OR 5.00, 95% CI 1.31–19.0; p = 0.0184). De novo microbleeds were found in 11 hemispheres in 10 patients (2.3% per patient-year). The presence of microbleeds at enrollment was a significant predictor for de novo microbleeds (OR 5.53, 95% CI 1.17–26.13; p = 0.0309). CONCLUSIONS Patients with asymptomatic MMD may carry a significant risk of disease progression, TIA, and de novo microbleeds during the first 5 years after initial diagnosis. Practitioners should very carefully follow up with them to improve their outcome, using MRI and MRA at regular intervals. Clinical trial registration no.: UMIN000006640 (https://www.umin.ac.jp).

Hemorrhagic Moyamoya Angiopathy in European Patients.

Moyamoya angiopathy (MMA) is an important cause of juvenile stroke but an overall rare disease among European populations compared with East Asian cohorts. Consecutively, hemorrhagic MMA is described well in East Asian cohorts, but knowledge in non-Asian patients is limited. Literature suggests that disease presentation may vary between those cohorts, also including hemorrhage frequencies. Hence, this article aims to analyze hemorrhagic MMA in European patients. We screened for patients of European origin with MMA from a single-center consecutive database of a German hospital specialized on MMA. Those who had a record of intracranial hemorrhage were analyzed individually regarding the type of hemorrhage and use of antiplatelet therapy before and after bleeding onset. To identify associated factors of intracranial hemorrhage, an age- and sex-matched control group was identified from the pool of patients without a history of hemorrhage. Both groups had a comparable follow-up time and were compared in terms of disease presentation, therapeutic interventions, and imaging characteristics, using both univariate tests and multivariate logistic regression analysis. From a pool of 332 patients with MMA we identified 288 of European ancestry. From those, 36 had a record of intracranial hemorrhage (12.5%). Thirty-three patients presenting with 37 events were included for further analysis and case-control-comparison. Most events were intracerebral hemorrhage (n=20; 54%) and subarachnoid hemorrhage (n=11; 30%). 78% developed hemorrhage although no antiplatelet therapy was in use (n=29). Seven patients developed intracranial hemorrhage ipsilateral to prior bypass surgery (21%), while 29 of the control patients had a bypass surgery (88%; P=0.0001). There was no significant difference in terms of unilateral or bilateral disease type, history of hypertension, as well as imaging characteristics (high Suzuki stage and the presence of collateral pathways in conventional angiography, as well as ischemic defects and the presence of microbleeds on cerebral magnetic resonance imaging; P>0.05 in multivariate analysis, respectively). Bypass surgery was negatively associated with the development of intracranial hemorrhage in MMA in European patients. There was no difference in terms of a history of hypertension between groups, indicating that blood pressure is not the major contributor for rupture of fragile collateral vessels. The investigated imaging characteristics were not associated to hemorrhage onset and, therefore, are not suitable as a tool of screening for patients at risk.

Small vessel disease and cognitive reserve oppositely modulate global network redundancy and cognitive function: A study in middle-to-old aged community participants.

Cerebral small vessel disease (SVD) can disrupt the global brain network and lead to cognitive impairment. Conversely, cognitive reserve (CR) can improve one's cognitive ability to handle damaging effects like SVD, partly by optimizing the brain network's organization. Understanding how SVD and CR collectively influence brain networks could be instrumental in preventing cognitive impairment. Recently, brain redundancy has emerged as a critical network protective metric, providing a nuanced perspective of changes in network organization. However, it remains unclear how SVD and CR affect global redundancy and subsequently cognitive function. Here, we included 121 community-dwelling participants who underwent neuropsychological assessments and a multimodal MRI examination. We visually examined common SVD imaging markers and assessed lifespan CR using the Cognitive Reserve Index Questionnaire. We quantified the global redundancy index (RI) based on the dynamic functional connectome. We then conducted multiple linear regressions to explore the specific cognitive domains related to RI and the associations of RI with SVD and CR. We also conducted mediation analyses to explore whether RI mediated the relationships between SVD, CR, and cognition. We found negative correlations of RI with the presence of microbleeds (MBs) and the SVD total score, and a positive correlation of RI with leisure activity-related CR (CRI-leisure). RI was positively correlated with memory and fully mediated the relationships between the MBs, CRI-leisure, and memory. Our study highlights the potential benefits of promoting leisure activities and keeping brain redundancy for memory preservation in older adults, especially those with SVD.

Abstract TP166: White Matter Hyperintensity Burden Associated With Stroke Severity, Aphasia, and Motor Deficits During Intracerebral Hemorrhage Hospitalization

Introduction: Cerebral Small Vessel Disease (CSVD) is associated with cognitive disruptions after intracerebral hemorrhage (ICH), however evidence connecting CSVD to specific neurological deficits after ICH is limited. Methods: Electronic medical record data were retrieved for adult patients (>18 years) with admission for primary non-traumatic ICH, available admission NIHSS scores, and CSVD assessment. CSVD burden was graded from 0-4, with 1 point assessed for: 1) deep Fazekas white matter hyperintensity (WMH) score of 2-3 or periventricular (PV) Fazekas score of 3; 2) cerebral microbleed presence; 3) lacune presence; 4) > 20 basal ganglia perivascular spaces. Severe CSVD was assessed scores ≥ 3, and individual marker severity was assessed using the same criteria. The primary outcome was moderate-severe stroke (total NIHSS score ≥5). Secondary outcomes were severe motor deficit (motor score >12), complete aphasia (language score = 3), and cortical deficit (any impairment in language, extinction, and gaze). Associations between CSVD and NIHSS were determined using multivariable logistic regression, adjusting for major clinical and demographic factors. Adjusted odds ratios (aOR) and 95% confidence interval (CI) are reported. Results: The cohort included 1024 patients (median age [interquartile range]: 71 [61-79], 53% male). Patients were 22% Hispanic and had a racial distribution of 61% White, 24% Black, 8% Asian, 7% other. The median NIHSS score was 4 [1-11]; 477 (47%) showed moderate-severe NIHSS scores and 262 (26%) showed severe CSVD. Severe PV WMH burden was independently associated with moderate-severe NIHSS score (vs non-severe; aOR, 95% CI: 1.55, [1.02-2.36]). Severe deep WMH burden (vs non-severe) was independently associated with aphasia (1.97, [1.02-3.81]), and motor deficit (3.95, [1.22-12.73]) (Figure 1). Conclusion: Severe WMH burdens increase odds of neurological deficit among patients with primary ICH.

Patients with normal pressure hydrocephalus have fewer enlarged perivascular spaces in the centrum semiovale compared to cognitively unimpaired individuals

IntroductionEnlarged perivascular spaces (ePVS) may be an indicator of glymphatic dysfunction. Limited studies have evaluated the role of ePVS in idiopathic normal pressure hydrocephalus (iNPH). We aimed to characterize the distribution and number of ePVS in iNPH compared to controls. MethodsThirty-eight patients with iNPH and a pre-shunt MRI were identified through clinical practice. Age- and sex-matched controls who had negative MRIs screening for intracranial metastases were identified through a medical record linkage system. The number of ePVS were counted in the basal nuclei (BN) and centrum semiovale (CS) using the Wardlaw method blinded to clinical diagnosis. Imaging features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), callosal angle, Fazekas white matter hyperintensity (WMH) grade, and the presence of microbleeds and lacunes were also evaluated. ResultsBoth iNPH patients and controls had a mean age of 74 ± 7 years and were 34% female with equal distributions of hypertension, dyslipidemia, diabetes, stroke, and history of smoking. There were fewer ePVS in the CS of patients with iNPH compared to controls (12.66 vs. 20.39, p < 0.001) but the same in the BN (8.95 vs. 11.11, p = 0.08). This remained significant in models accounting for vascular risk factors (p = 0.002) and MRI features of DESH and WMH grade (p = 0.03). ConclusionsFewer centrum semiovale ePVS may be a biomarker for iNPH. This pattern may be caused by mechanical obstruction due to upward displacement of the brain leading to reduced glymphatic clearance.

Cerebral microbleeds and asundexian in non-cardioembolic ischemic stroke: Secondary analyses of the PACIFIC-STROKE randomized trial.

Cerebral microbleeds are magnetic imaging resonance (MRI) markers of hemorrhage-prone cerebral small vessel disease that predict future risk of ischemic stroke and intracranial hemorrhage (ICrH). There exist concerns about the net benefit of antithrombotic therapy in patients with microbleeds. We aimed to investigate the effects of an oral factor-XIa inhibitor (asundexian), that is hypothesized to inhibit thrombosis without compromising hemostasis, on the development of new microbleeds over time and interactions between microbleeds and asundexian treatment on clinical outcomes. We additionally assessed associations between baseline microbleeds and the risks of clinical and neuroimaging outcomes in patients with non-cardioembolic ischemic stroke. This is a secondary analysis of the PACIFIC-STROKE, international, multi-center Phase 2b double-blind, randomized clinical trial. PACIFIC-STROKE enrolled patients aged ⩾ 45 years with mild-to-moderate non-cardioembolic ischemic stroke who presented within 48 h of symptom onset for whom antiplatelet therapy was intended. Microbleeds were centrally adjudicated, and participants with an interpretable T2*-weighted sequence at their baseline MRI were included in this analysis. Patients were randomized to asundexian (10/20/50 mg daily) versus placebo plus standard antiplatelet treatment. Regression models were used to estimate the effects of (1) all pooled asundexian doses and (2) asundexian 50 mg daily on new microbleed formation on 26-week MRIs. Cox proportional hazards or regression models were additionally used to estimate interactions between treatment assignment and microbleeds for ischemic stroke/transient ischemic attack (TIA) (primary outcome), and ICrH, all-cause mortality, hemorrhagic transformation (HT), and new microbleeds (secondary outcomes). Of 1746 participants (mean age, 67.0 ± 10.0; 34% female) with baseline MRIs, 604 (35%) had microbleeds. During a median follow-up of 10.6 months, 7.0% (n = 122) had ischemic stroke/TIA, 0.5% (n = 8) ICrH, and 2.1% (n = 37) died. New microbleeds developed in 10.3% (n = 155) of participants with adequate follow-up MRIs and HT in 31.4% (n = 345). In the total sample of patients with adequate baseline and 26-week follow-up MRIs (n = 1507), new microbleeds occurred in 10.2% of patients assigned to any asundexian dose and 10.5% of patients assigned to placebo (OR, 0.96; 95% CI, 0.66-1.41). There were no interactions between microbleeds and treatment assignment for any of the outcomes (p for interaction > 0.05). The rates of new microbleeds, HT, and ICrH were numerically less in patients with microbleeds assigned to asundexian relative to placebo. The presence of microbleeds was associated with a higher risk of HT (aOR, 1.6; 95% CI, 1.2-2.1) and new microbleeds (aOR, 4.4; 95% CI, 3.0-6.3). Factor XIa inhibition with asundexian appears safe in patients with non-cardioembolic ischemic stroke and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI. These preliminary findings will be confirmed in the ongoing OCEANIC-STROKE randomized trial. ClinicalTrials.gov Identifier: NCT04304508.

The role of cerebrovascular pathology in the association between amyloid‐β and tau in cognitively unimpaired and impaired individuals

AbstractBackgroundAlthough cerebrovascular pathology often co‐exists with Alzheimer’s disease pathology, it remains incompletely understood to what extent it can contribute to the progression of Alzheimer’s disease pathology. We investigated whether cerebrovascular pathology (white matter lesions [WML] and microbleeds) modified the association between amyloid‐ß (Aß) and both cross‐sectional and longitudinal tau in cognitively unimpaired (CU) and cognitively impaired (CI) individuals.MethodWe included 1240 participants from the Swedish BioFINDER‐2 cohort including 402 Aß‐negative CU, 147 Aß‐positive CU, 257 Aß‐negative CI (MCI and non‐AD dementia) and 434 Aß‐positive CI participants (MCI and AD dementia) (Table 1). All underwent baseline [18F]RO948 (tau)‐PET, and a subset (n = 678) underwent longitudinal tau‐PET (2.6±1.0‐years). We extracted tau‐PET SUVr in a temporal meta‐region‐of‐interest. For Aß, we used global [18F]flutemetamol‐PET SUVr for CU and Aß‐status (+/‐) for CI participants. Global WML volume was calculated using the SPM lesion segmentation tool, corrected for intra‐cranial volume and log‐transformed. Presence of microbleeds was dichotomized into absent or present ( = 1) by visual read. Primary analyses included age‐, sex‐ and APOE e4‐corrected linear mixed models between tau‐PET (outcome) and interactions between time, Aß and WML volume/microbleeds (predictors).ResultUpon correcting for age, sex and e4‐carriership, Aß‐positive CU and CI participants showed significantly more microbleeds compared to Aß‐negative participants of the same cognitive stage (both p&lt;0.05), but no differences in WML volume was observed (both p&gt;0.05). In CU, we observed a significant interaction effect between = 1 microbleed and higher Aß‐load with both greater cross‐sectional tau (ß = 0.67 [CI: 0.45‐0.89], p&lt;0.001) and longitudinal tau (ß = 0.11 [CI: 0.07‐0.16], p&lt;0.001) (Fig‐1, Table‐2). In CU, we also observed a significant interaction effect between larger WML volumes and higher Aß‐load with greater cross‐sectional tau (ß = 0.14 [CI: 0.06‐0.22], p = 0.001). When including both microbleeds and WML volume in the same model, only effects of microbleeds remained significant (Table‐2). No significant effects were observed in CI participants.ConclusionIn CU (but not CI) individuals, cerebrovascular pathology may modify the association between Aß and tau by accelerating tau accumulation in the presence of Aß. These results might suggest an early effect of cerebrovascular pathology on the interplay between Aß and tau.

Proteomic‐based Biological Aging Clock and MRI Markers of Cerebrovascular Disease: Atherosclerosis Risk in Community Study

AbstractBackgroundBiological aging state can be quantified by composite metrics called aging clocks using proteomics. Proteomic aging clocks (PACs) are accurate, easily measured, and are associated with age‐related diseases including Alzheimer’s Disease and Related Dementias. We aim to investigate whether an accelerated biological aging (a discrepancy between chronological age and PAC) is associated with subclinical cerebrovascular structural changes.Method1494 participants from the Atherosclerosis Risk in Communities (ARIC) Study with proteomics and 3T brain MRI data at ARIC visit 5 in 2011‐13 (mean age 76, 59% female, 25% Black) were included. Nearly 5000 plasma proteins were measured using the SomaScan assay. PAC was developed using elastic net regression model and was internally validated. Age acceleration was calculated as residuals after regressing PAC on chronological age (positive value indicates biological age is higher than the person’s chronological age). Linear and logistic regression models were used to assess the associations of age acceleration with white matter hyperintensity volume (in cm3, log2 transformed, median [IQR]: 11[6‐20]) and the presence of: subcortical (n = 281), lacunar (n = 263), and cortical infarcts (n = 150), and microbleeds (n = 355).ResultAccelerated age (median [IQR]:‐0.04[‐1.4,1.3]; correlation with chronological age = 0) was associated with MRI markers of cerebrovascular disease after adjusting for demographic, cardiovascular risk factors, education, and kidney function. Every five years higher age acceleration was associated with larger white matter hyperintensity volume (Difference:0.34[95%CI 0.19,0.49]), higher odds of lacunar (OR:1.61[1.13,2.30]), subcortical (OR:1.63[1.15, 2.32]), and cortical infarcts (OR:1.72[1.11,2.67]). There was no association with presence of microbleeds (OR:1.25[0.91,1.73]) (Figure). Findings were consistent after excluding participants with clinical stroke and there was no difference between APOEe4+ and APOEe4‐ participants.ConclusionHigher accelerated age is cross‐sectionally associated with a greater prevalence of MRI markers of cerebrovascular disease. Understanding this relation has potential to help with risk stratification and personalized prevention and treatment strategies to promote brain health.

Prevalence, incidence, and prognostic indicators of Dementia in patients with TIA and Stroke: the Population‐based Rotterdam Study

AbstractBackgroundRisk of dementia is high after major stroke, but reliable estimates of dementia by stroke severity, accounting for competing risk of mortality, in a population‐based setting are scarce. In this study, we aimed to determine risk and prognostic indicators of dementia before and after TIA and stroke.MethodWe included all individuals with first‐ever TIA or stroke from the population‐based Rotterdam Study, between 2002‐2018, and matched those on age (+/‐3 years) and sex, using an incidence density sampling approach. We determined prevalence of pre‐event dementia by event severity (TIA vs. minor stroke [NIHSS≤3] vs. major stroke [NIHSS&gt;3]). Similarly, we determined risk of dementia at 1‐,5‐ and 10‐year post‐event using the subdistribution hazards (SDH) cumulative incidence function (CIF), and explored prognostic indicators of dementia.ResultAmong 1352 participants with first‐ever TIA or stroke (mean age: 79.4 (9.5) years, 59.7% women), 466 had TIA, 392 minor stroke, 494 major stroke. Prevalence of pre‐event dementia was higher among patients with major stroke (90/494; 18.2%) than among those with minor stroke (29/392; 7.3%), TIA (37/466; 7.9%). During 10‐year follow‐up, dementia occurred in 784 of 4703 participants without pre‐event dementia or reference participants. Compared to TIA patients, dementia risk was higher after major stroke (HR 2.17; 95% CI 1.53–3.07) and minor stroke (HR 1.63; 95% CI 1.17–2.26). Dementia risk was associated with male sex (SDH‐ratio 1.23; 95% CI 1.04–1.45), age (per 1‐year increase: 1.07; 1.06–1.08), higher education (0.61; 0.44–0.86), diabetes mellitus (1.29; 1.06–1.56), atrial fibrillation (1.40; 1.14–.71), and premorbid cognition (MMSE≤24, 2.39; 1.87–3.05). Among 417 patients with available pre‐event brain MRI, white matter hyperintensity burden (per 1‐% increase of proportion of total brain volume: 1.24; 95% CI 1.07–1.45) and presence of microbleeds (2.14; 1.18–3.86) were indicators of post‐stroke dementia.ConclusionDementia incidence after TIA and stroke is increased in patients with major stroke and to a lesser extent minor stroke, but not TIA. Event severity in combination with clinical and imaging indicators may hold potential for the prediction of cognitive decline after stroke.

The role of cerebrovascular pathology in the association between amyloid‐β and tau in cognitively unimpaired and impaired individuals

AbstractBackgroundAlthough cerebrovascular pathology often co‐exists with Alzheimer’s disease pathology, it remains incompletely understood to what extent it can contribute to the progression of Alzheimer’s disease pathology. We investigated whether cerebrovascular pathology (white matter lesions [WML] and microbleeds) modified the association between amyloid‐β (Aβ) and both cross‐sectional and longitudinal tau in cognitively unimpaired (CU) and cognitively impaired (CI) individuals.MethodWe included 1240 participants from the Swedish BioFINDER‐2 cohort including 402 Aβ‐negative CU, 147 Aβ‐positive CU, 257 Aβ‐negative CI (MCI and non‐AD dementia) and 434 Aβ‐positive CI participants (MCI and AD dementia) (Table 1). All underwent baseline [18F]RO948 (tau)‐PET, and a subset (n = 678) underwent longitudinal tau‐PET (2.6±1.0‐years). We extracted tau‐PET SUVr in a temporal meta‐region‐of‐interest. For Aβ, we used global [18F]flutemetamol‐PET SUVr for CU and Aβ‐status (+/‐) for CI participants. Global WML volume was calculated using the SPM lesion segmentation tool, corrected for intra‐cranial volume and log‐transformed. Presence of microbleeds was dichotomized into absent or present (≥1) by visual read. Primary analyses included age‐, sex‐ and APOE ε4‐corrected linear mixed models between tau‐PET (outcome) and interactions between time, Aβ and WML volume/microbleeds (predictors).ResultUpon correcting for age, sex and ε4‐carriership, Aβ‐positive CU and CI participants showed significantly more microbleeds compared to Aβ‐negative participants of the same cognitive stage (both p&lt;0.05), but no differences in WML volume was observed (both p&gt;0.05). In CU, we observed a significant interaction effect between ≥1 microbleed and higher Aβ‐load with both greater cross‐sectional tau (β = 0.67 [CI: 0.45‐0.89], p&lt;0.001) and longitudinal tau (β = 0.11 [CI: 0.07‐0.16], p&lt;0.001) (Fig‐1, Table‐2). In CU, we also observed a significant interaction effect between larger WML volumes and higher Aβ‐load with greater cross‐sectional tau (β = 0.14 [CI: 0.06‐0.22], p = 0.001). When including both microbleeds and WML volume in the same model, only effects of microbleeds remained significant (Table‐2). No significant effects were observed in CI participants.ConclusionIn CU (but not CI) individuals, cerebrovascular pathology may modify the association between Aβ and tau by accelerating tau accumulation in the presence of Aβ. These results might suggest an early effect of cerebrovascular pathology on the interplay between Aβ and tau.

June 2023 Stroke Highlights.

June 2023 Stroke Highlights.

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Vascular hyperintensities on baseline FLAIR images are associated with functional outcome in stroke patients with successful recanalization after mechanical thrombectomy

PurposeThe purpose of this study was to assess the prognostic value of vascular hyperintensities on FLAIR images (VHF) at admission MRI in patients with acute ischemic stroke (AIS) achieving successful recanalization after mechanical thrombectomy. Materials and methodsPatients with AIS treated by mechanical thrombectomy following admission MRI from the single-center HIBISCUS-STROKE cohort were assessed for eligibility. VHF were categorized using a four-scale classification and were considered poor when grade < 3 (i.e., absence of distal VHF). Recanalization was considered successful when modified thrombolysis in cerebral infarction score was ≥ 2B Functional outcome was considered poor if modified Rankin scale (mRS) at three months was > 2. Univariable and multiple variable logistic regressions were performed to identify factors associated with poor functional outcome despite successful recanalization. ResultsA total of 108 patients were included. There were 65 men and 43 women with a median age of 70.5 years (interquartile range: 55.0, 81.0; age range: 22.0–93.0 years). Among them, 39 subjects (36.1%) had poor functional outcome at three months. Univariable logistic regressions indicated that poorly extended VHF (VHF grade < 3) were associated with a poor functional outcome (P = 0.008) as well as age, hypertension and diabetes, baseline National Institute of Health Stroke Scale (NIHSS) score, pre-stroke mRS, lack of intravenous thrombolysis, cerebral microangiopathy and the presence of microbleeds. Multivariable analysis confirmed that poor VHF status was independently associated with a poor functional outcome (odds ratio [OR], 4.26; 95% confidence interval [CI]: 1.55–12.99; P = 0.007) in combination with hypertension (OR, 1.25; 95% CI: 0.87–1.85; P = 0.02), baseline NIHSS score (OR, 1.09; 95% CI: 1.04–1.20; P = 0.03), pre-stroke mRS (OR, 2.05; 95% CI: 1.07–4.61; P = 0.05) and lack of intravenous thrombolysis (OR, 0.23; 95% CI: 0.08–0.61; P = 0.004). ConclusionPoorly extended VHF (grade <3) at admission MRI are associated with a poor functional outcome at three months despite successful recanalization by mechanical thrombectomy.

SWI by 7T MR Imaging for the Microscopic Imaging Diagnosis of Astrocytic and Oligodendroglial Tumors.

Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible. 7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored. Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, P < .01). Scoring for malignancy was significantly different among the World Health Organization grade II (n = 10), grade III (n = 4), and grade IV (n = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas (P < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas (P < .01) with a sensitivity of 85.7% and specificity of 100%. Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.

Predictors of post-stroke cognitive impairment using acute structural MRI neuroimaging: A systematic review and meta-analysis.

Stroke survivors are at an increased risk of developing post-stroke cognitive impairment and post-stroke dementia; those at risk could be identified by brain imaging routinely performed at stroke onset. This systematic review aimed to identify features which are associated with post-stroke cognitive impairment (including dementia) on magnetic resonance imaging (MRI) performed at stroke diagnosis. We searched the literature from inception to January 2022 and identified 10,284 records. We included studies that performed MRI at the time of stroke (0-30 days after a stroke) and assessed cognitive outcome at least 3 months after stroke. We synthesized findings from 26 papers, comprising 27 stroke-populations (N = 13,114, average age range = 40-80 years, 19-62% female). When data were available, we pooled unadjusted (ORu) and adjusted (ORa) odds ratios.We found associations between cognitive outcomes and presence of cerebral atrophy (three studies, N = 453, ORu = 2.48, 95% CI = 1.15-4.62), presence of microbleeds (two studies, N = 9151, ORa = 1.36, 95% CI = 1.08-1.70), and increasing severity of white matter hyperintensities (three studies, N = 704, ORa = 1.26, 95% CI = 1.06-1.49). Increasing cerebral small vessel disease score was associated with cognitive outcome following unadjusted analysis only (two studies, N = 499, ORu = 1.34, 95%CI = 1.12-1.61; three studies, N = 950, ORa = 1.23, 95% CI = 0.96-1.57). Associations remained after controlling for pre-stroke cognitive impairment. We did not find associations between other stroke features and cognitive outcome, or there were insufficient data. Acute stroke MRI features may enable healthcare professionals to identify patients at risk of post-stroke cognitive problems. However, there is still substantial uncertainty about the prognostic utility of acute MRI for this.

Isolated Central Nervous System Vasculitides in COVID-19: A Systematic Review of Case Reports and Series

Cerebral vasculitides, both isolated or in systemic disorders, could be triggered by infections, and few cases have been associated to coronavirus disease 2019 (COVID-19). This study searched for publications in Pubmed, EMBASE, and Cochrane library databases for case reports and series of isolated central nervous system (CNS) vasculitides triggered by severe acute respiratory syndrome coronavirus-2. We included 12 studies (published from June 2020 to July 2022) and collected 39 adult patients (5/39 pathologically or radiologically proven, 34/39 suggestive for primary CNS vasculitis or PCNSV). All cases had a positive real-time polymerase chain reaction on a nasopharyngeal swab or a respiratory tract specimen. About the 85% of the included cases were males, and disease onset occurred later than 50 years old in all but three subjects. In total, 33/39 patients presented severe COVID-19 pneumonia, frequently requiring intensive care unit care. The most common neurological features were headache, obnubilation, and coma. PCNSV was suspected mainly on radiological findings, whereas the cerebrospinal fluid analysis was minimally altered. Magnetic resonance imaging showed vessel wall enhancement in 32/39 cases, generally with the concomitant presence of microbleeds, subarachnoid haemorrhages, and/or multiple ischemic lesions. Despite the severe respiratory and neurological disease course, most cases (93%) improved spontaneously or after a course of high-dose intravenous steroids with no need for immunosuppression. In conclusion, PCNSV could rarely relate to COVID-19 and independently from pulmonary disease severity. Adults with COVID-19-related PCNSV could have a favourable prognosis.

Atrial cardiopathy is associated with cerebral microbleeds in ischemic stroke patients

ObjectiveCerebral microbleeds (CMB) are small accumulations of hemosiderin associated with cerebrovascular risk factors, but whether they are associated with atrial cardiopathy is not known. The goal of this study is to determine, among ischemic stroke patients, the association between study-defined atrial cardiopathy and CMB presence, location, and number.MethodsIschemic stroke patients admitted to Johns Hopkins (2015–2019) with transthoracic echocardiography and electrocardiography were included. Cerebral microbleeds were defined as small, round hypo-intensities on T2* susceptibility weighted imaging or gradient recalled echo magnetic resonance imaging sequences. Atrial cardiopathy was defined as the presence of ≥1: left atrium diameter >4.0 cm (males) or >3.8 cm (females), PR interval >200 ms, or N-terminal pro-B-type natriuretic peptide >250 pg/ml. Binary/Ordinal logistic regression models were used to determine the association between atrial cardiopathy, and cerebral microbleed presence, location (lobar/deep), or number, each, adjusted for potential confounders.ResultsPatients (N = 120) were mean age 60 years (range 22–98), 46% female, 62% black, and 39% were on anti-thrombotic medication at time of admission. 39 (32%) participants had ≥1 cerebral microbleeds. Forty-six (38%) patients had atrial cardiopathy. Atrial cardiopathy was associated with higher odds of having cerebral microbleeds (OR 2.50, 95% CI 1.02–6.15). Atrial cardiopathy was associated with lobar cerebral microbleeds (OR 2.33, 95% CI 1.01–5.37) in univariate analysis but not with deep cerebral microbleeds (OR 0.45, 95% CI 0.13–1.54), with neither association significant after adjustment. There was no difference in risk of having 1 vs. no cerebral microbleeds (RRR 2.51, 95% CI 0.75–8.37) and >1 cerebral microbleed vs none (RRR 2.57, 95% CI 0.87–7.60) among those with atrial cardiopathy.ConclusionsAtrial cardiopathy is associated with the presence, but not burden, of cerebral microbleeds in ischemic stroke patients. We cautiously suggest that atrial cardiopathy, either directly or through shared vascular risk, may contribute to the presence of CMB.

High Prevalence of Cerebral Microbleeds in Young Ischemic Stroke Patients.

Most studies of cerebral microbleeds place more emphasis on the elderly, which made it difficult to obtain data on youth, particularly young ischemic stroke patients. Our study sought to investigate the incidence and related risk factors of cerebral microbleeds in young ischemic stroke patients. Young ischemic stroke patients who sought medical advice at Beijing Chaoyang Hospital between June 2016 and September 2020 were included in our study. The clinical and imaging data of these patients were collected and assessed. These patients were grouped by cerebral microbleed presence, count, and location. Univariate and multivariate logistic regression analyses were performed to investigate the association between these groups and screen the influencing factors of cerebral microbleeds in young patients with ischemic stroke. Among the 187 young ischemic stroke patients, the prevalence of microbleeds was 16%. The presence of cerebral microbleeds was associated with hypertension (odds ratio [OR] 8.787, 95% confidence interval [CI] 1.016-76.006, P=0.048), lower estimated glomerular filtration rate (OR 0.976, 95%CI 0.957-0.995, P=0.014) and moderate/severe white matter hyperintensity (OR 10.681, 95%CI 3.611-31.595, P<0.001) in young ischemic stroke patients. Cerebral microbleeds were common in young ischemic stroke patients and were associated with hypertension, lower estimated glomerular filtration rate, and moderate/severe white matter hyperintensity.

Ischaemic Stroke Complicating Infective Endocarditis: Microbleeds Are the Diagnostic Clue

Introduction: Ischemic strokes represent a classic complication of infective endocarditis (IE) and are most often related to the fragmentation of valvular vegetation. In most cases, they occur in the Sylvian territory and are related to Staphylococcus aureus. MRI can demonstrate, in addition to the AVCI image, cerebral microbleeds (CMBs) that are very suggestive of the diagnosis. We present the case of a patient who presented an ischemic stroke occurring in the context of infective endocarditis. Observation: A 32-year-old woman with no previous medical history initially presented with acute febrile headache, two weeks later she developed right hemiplegia with aphasia in the context of fever. Her general examination revealed lesions on the soles of her feet, in the form of nodules, infected in places, suggestive of Janeway nodules (characteristic of IE). The brain MRI showed an ischemic stroke in the Sylvian territory, with the presence of multiple microbleeds on the magnetic susceptibility sequences. The biological examination showed a severe inflammatory syndrome; the transthoracic echocardiography (TTE) confirmed the presence of vegetation on the aortic valve; and the blood cultures showed a Staphylococcus aureus. Antibiotic therapy was started, and the patient was transferred to the cardiology department. Discussion: Our observation has a double interest. The first is clinical due to the presence of plantar nodules (Janeway’s nodules) that are characteristic of IE which should orientate the diagnosis before the installation of the stroke, and the second is radiological and linked to the discovery of microbleeds. Their presence is increasingly reported in the literature, but their pathophysiology is not yet very clear. Conclusion: Stroke is the most frequent extracardiac complication during IE. The presence of microbleeds contributes to early diagnosis, especially in asymptomatic forms.

Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials.

To study the relationship between the presence of cerebral microbleeds (CMBs) and acute hematoma characteristics among patients with primary intracerebral hemorrhage (ICH). We pooled individual patient data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 (MISTIE III) trial. We included individuals with a brain MRI scan. Exposure was the presence of a CMB. The coprimary outcomes were admission ICH volume and hematoma expansion. Mixed-effects linear and logistic regression models were used, with demographics and comorbid conditions considered fixed effects and the study cohort treated as a random effect. Additional analyses assessed the relationship between CMB topography and number and hematoma characteristics. Of the 1,499 patients with ICH enrolled in the parent trials, 466 (31.1%) were included in this analysis, and 231 (49.6%) patients had CMBs. In adjusted models, presence of CMBs was associated with smaller ICH volume (β = -0.26, 95% confidence interval [CI] -0.44 to -0.08) and lower odds of hematoma expansion (odds ratio 0.65, 95% CI 0.40-0.95; p = 0.04). The strength of association between CMBs and hematoma characteristics increased with increasing number of CMBs. The location of the CMBs and the severity of leukoaraiosis did not modify these results. In a pooled cohort of patients with ICH, our results are consistent with the hypothesis that more severe underlying small vessel disease, as represented by CMBs, leads to smaller baseline hematoma volumes and reduced hematoma expansion. Underlying cerebral small vessel disease may be of prognostic significance after ICH. ClinicalTrials.gov Identifier: NCT01176565 and NCT01827046. This study provides Class II evidence that the presence of microbleeds on MRI is associated with a smaller ICH volume at presentation and a lower rate of hematoma expansion on follow-up imaging.