Publications by authors named "Hugh Markus"
Article Synopsis
- Cerebral small vessel disease (cSVD) is linked to serious conditions like lacunar stroke and vascular dementia, but there's limited research on how managing traditional cardiovascular risk factors can specifically reduce stroke risk in cSVD.
- This study used Mendelian randomization to explore genetic factors associated with various cardiovascular risk factors and how they relate to cSVD and lacunar stroke, examining data from large genetic studies.
- Findings indicated that higher blood pressure and factors like diabetes, obesity, and smoking are linked to increased cSVD risk, while higher HDL levels and regular vigorous activity showed protective effects; blood pressure-lowering medications like calcium channel blockers were also found potentially beneficial.
Background: The association between SARS-CoV-2 spike protein and cerebrovascular diseases raised a concern of cerebrovascular safety of COVID-19 vaccines. We aimed to determine the risk of radiological cerebral small vessel disease (cSVD) progression with BNT162b2 and CoronaVac.
Methods: In this community-based prospective cohort study, community-dwelling subjects underwent brain MRI before and 4 months after vaccination with BNT162b2 or CoronaVac.
Article Synopsis
- NOTCH3cys variants are common and linked to various small vessel diseases, including early-onset stroke and dementia, but there is no comprehensive staging system to assess their severity.
- A cohort study created and validated a simple staging system for NOTCH3-SVD by analyzing data from several international cohorts and the UK Biobank, focusing on the impact of these variants on CVD outcomes and cognition.
- The new system includes 9 disease stages, aiding in understanding the relationship between stages and clinical outcomes like ischemic strokes, cognitive function, and brain damage.
Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals.
J Neurol Neurosurg Psychiatry
November 2024
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype is becoming milder with better risk factor treatments and other care improvements is unknown. In a large longitudinal CADASIL cohort, we determined whether the prognosis has changed over 23 years.
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- Enlarged perivascular spaces are linked to cerebral small vessel disease and may indicate issues with glymphatic drainage, though the exact mechanisms are still unclear.
- A study involving 54 patients analyzed the relationship between these spaces, inflammation in both the central nervous system and the body, and blood-brain barrier permeability using advanced imaging techniques.
- Findings revealed that greater perivascular spaces in white matter were associated with increased microglial activation (measured by 11C-PK11195 binding), while no correlation was found for the basal ganglia or with blood biomarkers for systemic inflammation.
Article Synopsis
- Approximately 50 million people live with dementia worldwide, a number expected to triple by 2050, with vascular contributions affecting around 20 million people currently.
- Vascular Cognitive Impairment (VCI) includes a range of cognitive decline due to cerebrovascular issues, often co-occurring with Alzheimer's disease, yet remains a neglected area in research with limited treatment options.
- Management focuses on preventing strokes and controlling vascular risk factors, while ongoing research aims to introduce new treatment strategies and emphasizes the need for cognitive assessments in cardiovascular studies.
Background: Genetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure.
Methods: Vascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH.
Background: NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. NOTCH3 variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense variants in NOTCH3 are well-studied in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), patients with biallelic variants in NOTCH3 are extremely rare and not well characterised.
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- Cerebral small vessel disease is a leading cause of vascular dementia, and diffusion tensor imaging (DTI) is more effective at detecting white matter damage than traditional MRI methods, though it's less accessible.
- Researchers created a deep learning model to generate synthetic maps of fractional anisotropy (FA) and mean diffusivity (MD) from standard T1 MRI scans, using data from nearly 5,000 participants and additional validation datasets.
- The generated synthetic FA/MD maps closely matched actual brain scans and were nearly as accurate in predicting dementia risk, providing a faster alternative for clinical settings where DTI isn’t available.
Background: Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischemic strokes. In acute lacunar ischemic stroke, despite often mild initial symptoms, early neurological deterioration (END) occurs in approximately 15-20% of patients and is associated with poor functional outcome, yet its mechanisms are not well understood.
Aims: In this review, we systematically evaluated data on: (1) definitions and incidence of END, (2) mechanisms of small vessel occlusion, (3) predictors and mechanisms of END, and (4) prospects for the prevention or treatment of patients with END.
Article Synopsis
- - The study investigated cerebral small-vessel disease (cSVD), a genetic cause of stroke, by analyzing a cohort of suspected familial cases using whole-genome sequencing to identify known and novel genetic variants associated with the disease.
- - Among 257 suspected cSVD cases, 8.9% had variants in known cSVD genes, and 23.6% of those without known causes carried potentially harmful variants; however, none were statistically linked to the disease.
- - The research suggests that rare variants in noncoding and matrisomal genes may contribute to cSVD, impacting tissue development and brain endothelial cell function, but more research is needed to verify these findings.
Background: Cerebrospinal fluid (CSF) circulation is essential in removing metabolic wastes from the brain and is an integral component of the glymphatic system. Abnormal CSF circulation is implicated in neurodegenerative diseases. Low b-value magnetic resonance imaging quantifies the variance of CSF motion, or pseudodiffusivity.
View Article and Find Full Text PDFTenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial.
Lancet Neurol
August 2024
Article Synopsis
- The study compared the effectiveness of intravenous tenecteplase and alteplase in treating ischaemic stroke patients identified as having salvageable brain tissue using perfusion imaging, focusing on whether tenecteplase is at least as effective (non-inferior) to alteplase in terms of patient outcomes after 3 months.
- Conducted across 35 hospitals in eight countries, the trial enrolled 680 patients aged 18 and older, who were randomly assigned to receive either tenecteplase or alteplase, with the primary outcome being the rate of patients without disability measured through the modified Rankin Scale.
- The trial was halted early due to positive results
Background: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection.
Methods: The systematic review was registered in PROSPERO (CRD42023468063).
Importance: Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients.
Objective: To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection.
Introduction: Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood-brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability.
View Article and Find Full Text PDFInternal carotid artery atherosclerosis is a major risk factor for stroke, accounting for 15-20% of ischaemic strokes. Revascularisation procedures-either carotid endarterectomy or carotid artery stenting-can reduce the risk of stroke for those with significant (>50%) luminal stenosis but particularly for those with more severe (70-99%) stenosis. However, advances in medical pharmacotherapy have implications for the relative benefit from surgery for symptomatic carotid atherosclerosis, as well as our approach to asymptomatic disease.
View Article and Find Full Text PDFBackground: Fatigue is a common symptom in cerebral small vessel disease (SVD), but its pathogenesis is poorly understood. It has been suggested that inflammation may play a role. We determined whether central (neuro) inflammation and peripheral inflammation were associated with fatigue in SVD.
View Article and Find Full Text PDFBackground: The importance of thromboembolism in the pathogenesis of lacunar stroke (LS), resulting from cerebral small vessel disease (cSVD), is debated, and although antiplatelets are widely used in secondary prevention after LS, there is limited trial evidence from well-subtyped patients to support this approach. We sought to evaluate whether altered anticoagulation plays a causal role in LS and cSVD using 2-sample Mendelian randomization.
Methods: From a recent genome-wide association study (n=81 190), we used 119 genetic variants associated with venous thrombosis at genome-wide significance (<5*10) and with a linkage disequilibrium r<0.
Background: Recent studies, using diffusion tensor image analysis along the perivascular space (DTI-ALPS), suggest impaired perivascular space (PVS) function in cerebral small vessel disease, but they were cross-sectional, making inferences on causality difficult. We determined associations between impaired PVS, measured using DTI-ALPS and PVS volume, and cognition and incident dementia.
Methods: In patients with lacunar stroke and confluent white matter hyperintensities, without dementia at baseline, recruited prospectively in a single center, magnetic resonance imaging was performed annually for 3 years, and cognitive assessments, including global, memory, executive function, and processing speed, were performed annually for 5 years.