Association of plasma GFAP with elevated brain amyloid is dependent on severity of white matter lesions in an Asian cognitively impaired cohort.

INTRODUCTION: While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. METHODS: Using a Singapore-based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aß+). RESULTS: When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH- group (ß = 0.383; P < 0.001). The diagnostic performance of plasma GFAP in identifying Aß+ was significantly higher in the WMH- group (area under the curve [AUC] = 0.896) than in the WMH+ group (AUC = 0.712, P = 0.008). DISCUSSION: The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Highlight: Glial fibrillary acidic protein (GFAP)'s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD).Plasma GFAP was measured in a cohort with CSVD and brain amyloid.Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD.Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD.

Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic Patients.

Introduction: White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating cognitive health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. We propose that lesion network mapping (LNM), enables to infer if brain networks are connected to lesions, and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed this approach to test the following hypotheses: (1) LNM-informed markers surpass WMH volumes in predicting cognitive performance, and (2) WMH contributing to cognitive impairment map to specific brain networks. Methods & results: We analyzed cross-sectional data of 3,485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in 4 cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity across 480 atlas-based gray and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. The capacity of total and regional WMH volumes and LNM scores in predicting cognitive function was compared using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention and executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater disruptive effects of WMH on regional connectivity, in gray and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Conclusion: Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network effects, particularly in attentionrelated brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

Stroke in Asia.

Background There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well-developed and less developed countries with large disparities in stroke care resources. In addition, Asian countries are in varying phases of epidemiological transition. Summary In this review, we examined recent epidemiological features of ischaemic stroke and intracerebral haemorrhage in Asia with recent developments in hyperacute stroke reperfusion therapy and technical improvements in intracerebral haemorrhage. The article also discussed the spectrum of cerebrovascular diseases in Asia which include intracranial atherosclerosis, intracerebral haemorrhage, infective aetiologies of stroke, moyamoya disease, vascular dissection, radiation vasculopathy and cerebral venous thrombosis. Key Messages The review of selected literature and recent updates, call for attention to the different requirements for resources within Asia and highlights the breadth of cerebrovascular diseases still requiring further research and more effective therapies.

The AHA/ASA & DSM-V diagnostic criteria for vascular cognitive impairment identify cases with predominant vascular pathology.

BACKGROUND: There are major challenges in determining the aetiology of vascular cognitive impairment (VCI) clinically, especially in the presence of mixed pathologies, such as vascular and amyloid. Most recently, two criteria (American Heart Association/American Stroke Association [AHA/ASA] and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-V]) have been proposed for the clinical diagnosis of VCI but have not as yet been validated using neuroimaging. AIMS: This study aims to determine whether the AHA/ASA and DSM-V criteria for VCI can distinguish between cases with predominantly vascular pathology and cases with mixed pathology. METHODS: 186 subjects were recruited from a cross-sectional memory clinic-based study at the National University Hospital, Singapore. All subjects underwent clinical and neuropsychological assessment, MRI and [11C] PiB PET scans. Diagnosis of the etiological subtypes of VCI [probable vascular mild cognitive impairment (VaMCI), possible VaMCI, non-VaMCI, probable vascular dementia (VaD), possible VaD, non-VaD] were performed following AHA/ASA and DSM-V criteria. Brain amyloid burden was determined for each subject with standardised uptake value ratio (SUVR) values ≥ 1.5 classified as amyloid positive. RESULTS: Using κ statistics, both criteria had excellent agreement for probable VaMCI, probable VaD, and possible VaD (κ=1.00), and good for possible VaMCI (κ=0.71). Using the AHA/ASA criteria, the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) was significantly lower compared to possible VaMCI (26.7%), non-VaMCI (33.3%), possible VaD (73.3%) and non-VaD (76.2%) )(p<0.001). Similarly, using the DSM-V criteria the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) were significantly lower compared to possible VaMCI (26.3%), non-VaMCI (32.1%), possible VaD (73.3%) and non-VaD (76.2%)(p<0.001). In both criteria, there was good agreement in differentiating individuals with non-VaD and possible VaD, with significantly higher (p<0.001) global [11C]-PiB SUVR, from individuals with probable VaMCI and probable VaD, who had predominant vascular pathology. CONCLUSIONS: The AHA/ASA and DSM-V criteria for VCI can identify VCI cases with little to no concomitant amyloid pathology, hence supporting the utility of AHA/ASA and DSM-V criteria in diagnosing patients with predominant vascular pathology.

Sonothrombolysis for Ischemic Stroke.

Stroke is a major cause of death and disability globally, with ischemic stroke being the predominant mechanism. While spontaneous recanalization may occur, significant neuronal injury would have occurred in the interim. Intravenous thrombolysis administered within the first 4.5 h after stroke onset and endovascular thrombectomy within 24 h in patients with a salvageable penumbra improves functional independence. Ultrasound has been shown in both in vivo and in vitro models to enhance clot lysis, even more-so in the presence of thrombolytic agents. The use of transcranial Doppler and transcranial color-coded Doppler ultrasound in acute IS has been reported in case series, case-controlled studies, and clinical trials. While ultrasound at a frequency of 300 kHz increases the risk of intracranial hemorrhage, the 2 MHz range ultrasound aids thrombolysis and improves recanalization without significantly increasing the risk of symptomatic intracranial hemorrhage. Despite this, functional independence was not increased in clinical trials, nor was a benefit shown with the adjunctive use of microbubbles or microspheres. Nonetheless, newer technologies such as endovascular ultrasound, endovascular delivery of microbubbles, and thrombolytic-filled microbubbles await clinical trials. More evidence is needed before sonothrombolysis can be routinely used in the hyperacute management of ischemic stroke.

Prehospital stroke care in Singapore.

ABSTRACT: Due to the narrow window of opportunity for stroke therapeutics to be employed, effectiveness of stroke care systems is predicated on the efficiency of prehospital stroke systems. A robust prehospital stroke system of care that provides a rapid and well-coordinated response maximises favourable poststroke outcomes, but achieving this presents a unique set of challenges dependent on demographic and geographical circumstances. Set in the context of a highly urbanised first-world nation with a rising burden of stroke, Singapore's prehospital stroke system has evolved to reflect the environment in which it operates. This review aims to characterise the current state of prehospital stroke care in Singapore, covering prehospital aspects of the stroke survival chain from symptom onset till arrival at the emergency department. We identify areas for improvement and innovation, as well as provide insights into the possible future of prehospital stroke care in Singapore.

Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients.

INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-ß1-42 (Aß42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. HIGHLIGHTS: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aß42 status in 11 memory clinic cohorts. Aß42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.

Dual Antiplatelet Therapy for the Acute Management and Long-term Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack, An Updated Review.

To improve the efficacy over antiplatelet monotherapy, dual antiplatelet therapy (DAPT) has been increasingly adopted in the management of non-cardioembolic stroke. For minor ischemic stroke and high-risk transient ischemic attack, the aspirin-clopidogrel combination is now recommended for acute short-term treatment, whereas aspirin-ticagrelor combination may be considered in selected patients, especially those with resistance to clopidogrel. For long-term stroke prevention, aspirin-dipyridamole combination has been used as an alternative to antiplatelet monotherapy, and aspirin or clopidogrel combined with cilostazole may be prescribed for added protection in high-risk patients. In this paper, we review the development of DAPT from a historical perspective and describe the findings from major clinical trials published up until the end of 2023. Using the 2021 American Heart Association guideline for secondary stroke prevention as a basis for our recommendations, we further discuss areas of controversy and more recent developments to provide an updated review for clinicians to consider in their daily practice.

A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke.

Background: Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities. Methods: We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. "The best available studies" based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus. Results: Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as "the best studies" across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects. Conclusion: Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.

Validation of general pain scores from multidomain assessment tools in stroke.

Purpose: We describe how well general pain reported in multidomain assessment tools correlated with pain-specific assessment tools; associations between general pain, activities of daily living and independence after stroke. Materials and methods: Analyses of individual participant data (IPD) from the Virtual International Stroke Trials Archive (VISTA) described correlation coefficients examining (i) direct comparisons of assessments from pain-specific and multidomain assessment tools that included pain, (ii) indirect comparisons of pain assessments with the Barthel Index (BI) and modified Rankin Scale (mRS), and (iii) whether pain identification could be enhanced by accounting for reported usual activities, self-care, mobility and anxiety/depression; factors associated with pain. Results: European Quality of Life 3- and 5-Level (EQ-5D-3L and EQ-5D-5L), RAND 36 Item Health Survey 1.0 (SF-36) or the 0-10 Numeric Pain Rating Scale (NPRS) were available from 10/94 studies (IPD = 10,002). The 0-10 NPRS was the only available pain-specific assessment tool and was a reference for comparison with other tools. Pearson correlation coefficients between the 0-10 NPRS and (A) the EQ-5D-3L and (B) EQ5D-5 L were r = 0.572 (n = 436) and r = 0.305 (n = 1,134), respectively. mRS was better aligned with pain by EQ-5D-3L (n = 8,966; r = 0.340) than by SF-36 (n = 623; r = 0.318). BI aligned better with pain by SF-36 (n = 623; r = -0.320). Creating a composite score using the EQ-5D 3 L and 5 L comprising pain, mobility, usual-activities, self-care and anxiety/depression did not improve correlation with the 0-10 NPRS. Discussion: The EQ-5D-3L pain domain aligned better than the EQ-5D-5L with the 0-10 NPRS and may inform general pain description where resources and assessment burden hinder use of additional, pain-specific assessments.

A Comparative Study of Three Dementia Screening Instruments (CSI-D, CMMSE, and ECAQ) in a Multi-Ethnic Asian Population.

Background-There is no validated dementia screening tool for multi-ethnic Asian populations comprising Chinese, Malays, and Indians. This study aimed to establish the psychometric properties of the Community Screening Instrument for Dementia (CSI-D), Chinese Mini Mental State Examination (CMMSE), and Elderly Cognitive Assessment Questionnaire (ECAQ) in multi-ethnic Singapore. Methods-Participants were randomly drawn from a community-based neurological diseases study of older adults conducted in Singapore, with oversampling to allow similar subject numbers from the three major ethnicities: Chinese, Malay, and Indian. The CSI-D, CMMSE, and ECAQ were administered by trained research nurses using a standardised translated questionnaire in a language the participant was most conversant in. Participants were independently diagnosed as a case/non-case of dementia using the DSM-IV. Results-There were 259 participants (85 Chinese, 85 Malays, and 89 Indians, mean age 70.15 years, 65.4% female, 58.8% had no/minimal formal education); 22.8% (n = 59) had dementia. Correlations between the measures were substantial. All the measures had acceptable overall discriminative abilities. Diagnostic accuracies of the instruments did not differ across the ethnic groups. Effects of education were present in the cognitive screening measures. Conclusions-The CSI-D, CMMSE, and ECAQ are valid dementia instruments in this multi-ethnic Asian setting.

Use of MLC901 in cerebral venous sinus thrombosis: Three case reports.

BACKGROUND: Cerebral venous sinus thrombosis (CVT) is rare cause of cerebrovascular disease. The incidence is 0.5% of all stroke. The majority of affected patients are young adults (mean age: 35-40 years) with mild to moderate disabilities. Poor outcome with severe disability is seen in 13% of cases. Early diagnosis and treatment are important for good outcomes and preventing complications. Treatment options are limited and mostly based on consensus. NeuroAiD II™ (MLC901; Moleac Pte, Ltd, Singapore) has a potential beneficial role in post-stroke recovery, by aiding the natural brain recovery process. CASE SUMMARY: MLC901 consists of nine natural herbal ingredients. Studies have shown its safety profile and aid in post stroke recovery. The aim of this case series was to demonstrate the potential role of MLC901 in stroke recovery of patients with cerebral venous sinus thrombosis (CVST) who received MLC901 in addition to standard of care. The prescribed dose of MLC901 is 400 mg/cap two capsules, three times a day. Data from these patients were prospectively collected at baseline and at monthly visits, for a duration of 3 mo. Outcome measures included adherence to therapy, side effects, National Institutes of Health Stroke Scale, Glasgow Coma Scale, modified Rankin Scale, and the Short Orientation-Memory-Concentration Test. MLC901 was well tolerated and no side effects were reported. All patients were stable with improved condition. CONCLUSION: This case series highlights the potential therapeutic effects of MLC901 on CVST and provides support for further studies.

Emerging Stroke Risk Factors: A Focus on Infectious and Environmental Determinants.

This review focuses on emerging risk factors for stroke, including air pollution and climate change, gut microbiota, high altitude, and systemic infection. Up to 14% of all stroke-associated mortality is attributed to air pollution and is more pronounced in developing countries. Fine particulate matter and other air pollutants contribute to an increased stroke risk, and this risk appears to increase with higher levels and duration of exposure. Short term air pollution exposure has also been reported to increase the stroke risk. The gut microbiota is a complex ecosystem of bacteria and other microorganisms that reside in the digestive system and affect multiple body systems. Disruptions in the gut microbiota may contribute to stroke development, possibly by promoting inflammation and atherosclerosis. High altitudes have been associated with erythrocytosis and cerebrovascular sinus thrombosis, but several studies have reported an increased risk of thrombosis and ischemic stroke at high altitudes, typically above 3000 m. Systemic infection, particularly infections caused by viruses and bacteria, can also increase the risk of stroke. The risk seems to be greatest in the days to weeks following the infection, and the pathophysiology is complex. All these emerging risk factors are modifiable, and interventions to address them could potentially reduce stroke incidence.

Serum Placental Growth Factor as a Marker of Cerebrovascular Disease Burden in Alzheimer's Disease.

BACKGROUND: Concomitant cerebrovascular diseases (CeVD) have been identified as an important determinant of Alzheimer's disease (AD) progression. Development of robust blood-based biomarkers will provide critical tools to evaluate prognosis and potential interventional strategies for AD with CeVD. OBJECTIVE: This study investigated circulating placental growth factor (PlGF), a potent pro-angiogenic factor related to endothelial dysfunction and vascular inflammation, in an Asian memory clinic cohort of non-demented individuals as well as AD, including its associations with neuroimaging markers of CeVD. METHODS: 109 patients with AD, 76 cognitively impaired with no dementia (CIND), and 56 non-cognitively impaired (NCI) were included in this cross-sectional study. All subjects underwent 3T brain magnetic resonance imaging to assess white matter hyperintensities (WMH), lacunes, cortical infarcts, and cerebral microbleeds (CMBs). Serum PlGF concentrations were measured by electrochemiluminescence immunoassays. RESULTS: Serum PlGF was elevated in AD, but not CIND, compared to the NCI controls. Adjusted concentrations of PlGF were associated with AD only in the presence of significant CeVD. Elevated PlGF was significantly associated with higher burden of WMH and with CMBs in AD patients. CONCLUSIONS: Serum PlGF has potential utility as a biomarker for the presence of CeVD, specifically WMH and CMBs, in AD. Further studies are needed to elucidate the underlying pathophysiological mechanisms linking PlGF to CeVD, as well as to further assess PlGF's clinical utility.

Serum Brevican as a Biomarker of Cerebrovascular Disease in an Elderly Cognitively Impaired Cohort.

In the brain, the extracellular matrix (ECM) composition shapes the neuronal microenvironment and can undergo substantial changes with cerebral pathology. Brevican is integral to the formation of the ECM's neuroprotective perineuronal nets (PNNs). Decreased brevican levels were reported in vascular dementia (VaD) but not in Alzheimer's disease (AD). However, the status of brevican in clinical cohorts with high concomitance of AD pathological burden and cerebrovascular disease (CeVD) is unclear. In this study, 32 non-cognitively impaired (NCI), 97 cognitively impaired no dementia (CIND), 46 AD, and 23 VaD participants recruited from memory clinics based in Singapore underwent neuropsychological and neuroimaging assessments, together with measurements of serum brevican. Association analyses were performed between serum brevican and neuroimaging measures of CeVDs, including white matter hyperintensities (WMHs), lacunes, cortical infarcts, and cerebral microbleeds. Using an aggregated score for CeVD burden, only CIND participants showed lower brevican levels with higher CeVD compared to those with lower CeVD burden (p = 0.006). Among the CeVD subtypes assessed, only elevated WMH burden was associated with lower brevican levels (OR = 2.7; 95% CI = 1.3-5.5). Our findings suggest that brevican deficits may play a role in early cerebrovascular damage in participants at risk of developing dementia.

Lipidomics profiling reveals distinct patterns of plasma sphingolipid alterations in Alzheimer's disease and vascular dementia.

BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are two of the commonest causes of dementia in the elderly. Of the myriad biomolecules implicated in dementia pathogenesis, sphingolipids have attracted relatively scant research attention despite their known involvement in multiple pathophysiological processes. The potential utility of peripheral sphingolipids as biomarkers in dementia cohorts with high concomitance of cerebrovascular diseases is also unclear. METHODS: Using a lipidomics platform, we performed a case-control study of plasma sphingolipids in a prospectively assessed cohort of 526 participants (non-cognitively impaired, NCI = 93, cognitively impaired = 217, AD = 166, VaD = 50) using a lipidomics platform. RESULTS: Distinct patterns of sphingolipid alterations were found in AD and VaD, namely an upregulation of d18:1 species in AD compared to downregulation of d16:1 species in VaD. In particular, GM3 d18:1/16:0 and GM3 d18:1/24:1 showed the strongest positive associations with AD. Furthermore, evaluation of sphingolipids panels showed specific combinations with higher sensitivity and specificity for classification of AD (Cer d16:1/24:0. Cer d18:1/16:0, GM3 d16:1/22:0, GM3 d18:1/16:0, SM d16:1/22:0, HexCer d18:1/18:0) and VAD (Cer d16:1/24:0, Cer d18:1/16:0, Hex2Cer d16:1/16:0, HexCer d18:1/18:0, SM d16:1/16:0, SM d16:1/20:0, SM d18:2/22:0) compared to NCI. CONCLUSIONS: AD and VaD are associated with distinct changes of plasma sphingolipids, warranting further studies into underlying pathophysiological mechanisms and assessments of their potential utility as dementia biomarkers and therapeutic targets.

Association of brain arterial diameters with demographic and anatomical factors in a multi-national pooled analysis of cohort studies.

BACKGROUND AND PURPOSE: Brain arterial diameters are markers of cerebrovascular disease. Demographic and anatomical factors may influence arterial diameters. We hypothesize that age, sex, height, total cranial volume (TCV), and persistent fetal posterior cerebral artery (fPCA) correlate with brain arterial diameters across populations. METHODS: Participants had a time-of-flight MRA from nine international cohorts. Arterial diameters of the cavernous internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery (BA) were measured using LAVA software. Regression models assessed the association between exposures and brain arterial diameters. RESULTS: We included 6,518 participants (mean age: 70 ± 9 years; 41% men). Unilateral fPCA was present in 13.2% and bilateral in 3.2%. Larger ICA, MCA, and BA diameters correlated with older age (Weighted average [WA] per 10 years: 0.18 mm, 0.11 mm, and 0.12 mm), male sex (WA: 0.24 mm, 0.13 mm, and 0.21 mm), and TCV (WA: for one TCV standard deviation: 0.24 mm, 0.29 mm, and 0.18 mm). Unilateral and bilateral fPCAs showed a positive correlation with ICA diameters (WA: 0.39 mm and 0.73 mm) and negative correlation with BA diameters (WA: -0.88 mm and -1.73 mm). Regression models including age, sex, TCV, and fPCA explained on average 15%, 13%, and 25% of the ICA, MCA, and BA diameter interindividual variation, respectively. Using height instead of TCV as a surrogate of head size decreased the R-squared by 3% on average. CONCLUSION: Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations.

Ischemic Stroke: New Insights from Risk Factors, Mechanisms and Outcomes.

Ischemic stroke (IS) is the most common form of stroke globally [...].

Revolutionizing the Management of Large-Core Ischaemic Strokes: Decoding the Success of Endovascular Therapy in the Recent Stroke Trials.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last two years, four randomised controlled trials have been published on this topic-RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review aims to summarise the recent evidence presented by these four trials and highlight some of the limitations in our current understanding of this topic.