Publications by authors named "Fergus Doubal"

Purpose: Cerebral small vessel disease (cSVD) is a highly prevalent disorder leading to physical, cognitive and functional decline. We report key barriers in the management of individuals with cSVD, the potential benefit of cSVD-dedicated health services, and evidence from existing models of care for adults with cSVD.

Methods: We examined information from a scientific seminar developed between seven experts in cSVD during the eighth European Stroke Organisation Conference that discussed the optimal health care for adults with cSVD and what health services dedicated to cSVD should include.

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Background: White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.

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Article Synopsis
  • The study aimed to evaluate relationships between three key cerebrovascular functions (blood-brain barrier permeability, vascular pulsatility, and cerebrovascular reactivity) in patients with cerebral small vessel diseases (SVD), including both sporadic cases and a genetic condition known as CADASIL.
  • Researchers used advanced brain imaging techniques to analyze these functions in a group of 77 patients, assessing how they relate to SVD severity, subtype, and specific brain changes.
  • Findings revealed that worse white matter hyperintensity (WMH) was linked to lower cerebrovascular reactivity and blood plasma volume fraction, with the type of SVD having little impact on these vascular functions after accounting for WMH severity.
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Background And Objectives: In patients with cerebral small vessel disease (SVD), impaired cerebrovascular reactivity (CVR) is related to worse concurrent SVD burden, but less is known about cerebrovascular reactivity and long-term SVD lesion progression and clinical outcomes. We investigated associations between cerebrovascular reactivity and 1-year progression of SVD features and clinical outcomes.

Methods: Between 2018 and 2021, we recruited patients from the Edinburgh/Lothian stroke services presenting with minor ischemic stroke and SVD features as part of the Mild Stroke Study 3, a prospective observational cohort study (ISRCTN 12113543).

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Optical coherence tomography angiography (OCT-A) retinal imaging enables visualization of the retinal microvasculature that is developmentally related to the brain and can offer insight on cerebrovascular health. We investigated retinal phenotypes and neuroimaging markers of small vessel disease (SVD) in individuals with obstructive sleep apnoea (OSA). We enrolled 44 participants (mean age 50.

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Article Synopsis
  • A significant portion of ischemic strokes are classified as lacunar subtypes, often characterized by recent small subcortical infarcts (RSSIs), but the long-term effects of these conditions are not well understood.
  • In a study involving 108 participants, hemosiderin deposits (HDs) were found in over half of them within 3 months, and in about 77% within 12 months, with a notable "rim" pattern suggesting they could resemble primary hemorrhage.
  • The study highlighted that the volume of the infarct and a higher total small vessel disease (SVD) score are predictive of the presence of HDs, emphasizing the importance of not misinterpreting these deposits as signs of bleeding in chronic
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Background: White matter hyperintensity (WMH) progression is well documented; WMH regression is more contentious, which might reflect differences in defining WMH change. We compared four existing WMH change definitions in one population to determine the effect of definition on WMH regression.

Methods: We recruited patients with minor non-disabling ischaemic stroke who underwent MRI 1-3 months after stroke and 1 year later.

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Article Synopsis
  • - The study aimed to investigate how often new brain infarcts occur within a year after a minor stroke and their connections to existing cerebral small vessel disease (SVD), vascular risk factors, and cognitive decline.
  • - Researchers followed 229 stroke patients over a year, using MRI scans to find 117 new infarcts in 24.8% of participants, primarily in small subcortical areas rather than cortical areas.
  • - The baseline SVD score was found to be the strongest predictor of new infarcts, while cognitive tests at one year showed lower scores correlated with previous cognitive performance and intelligence, indicating a potential decline in cognitive function related to these infarcts.
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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.

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White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, are related to worse clinical outcomes after stroke. We assessed the impact of white matter hyperintensity changes over 1 year after minor stroke on change in mobility and dexterity, including differences between the dominant and non-dominant hands and objective in-person assessment versus patient-reported experience. We recruited participants with lacunar or minor cortical ischaemic stroke, performed medical and cognitive assessments and brain MRI at presentation and at 1 year.

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Article Synopsis
  • Cerebral small vessel disease (cSVD) can lead to strokes, dementia, and other health issues but there isn't a specific treatment for it yet.
  • *Recent studies suggest that sorting out which patients to include and what results to measure has made it harder to run effective trials for cSVD.
  • *Future trials should include many types of patients and focus on tracking mental health, using techniques to reduce lost data to improve our understanding of cSVD.
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A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.

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Background: Cerebral small vessel disease (SVD) is a common neurological disorder contributing to stroke, dementia, and disability. No treatment options exist although clinical trials are ongoing. We aimed to understand what matters to people and families affected by SVD to inform future research.

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Background: White matter hyperintensities (WMHs) might regress and progress contemporaneously, but we know little about underlying mechanisms. We examined WMH change and underlying quantitative magnetic resonance imaging tissue measures over 1 year in patients with minor ischemic stroke with sporadic cerebral small vessel disease.

Methods And Results: We defined areas of stable normal-appearing white matter, stable WMHs, progressing and regressing WMHs based on baseline and 1-year brain magnetic resonance imaging.

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Introduction: The prevalence of cerebral smallvessel disease (SVD) and vascular dementia according to workplace or domestic exposure to hazardous substances is unclear.

Methods: We included studies assessing occupational and domestic hazards/at-risk occupations and SVD features. We pooled prevalence estimates using random-effects models where possible, or presented a narrative synthesis.

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  • There’s growing interest in using perivascular spaces (PVS) as a biomarker for brain dysfunction due to their link to cerebrovascular diseases, prompting the development of new neuroimaging techniques.
  • A study evaluates improvements to a common PVS segmentation method using vesselness filters on MRI scans from patients with small vessel disease, emphasizing the need for tailored threshold selections based on different brain regions.
  • Findings suggest T2-weighted MRI images are preferable for assessing PVS, as the Frangi filter outperforms others in accurately segmenting PVS, particularly against noise and threshold variability.
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Background: Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease.

Methods: We did a multicentre, open-label, randomised crossover trial with blinded endpoint assessment at five specialist centres in Europe.

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Background: Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We aimed to investigate these cross-sectional relationships.

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Infection is a rare cause of panhypopituitarism and has not been reported in the context of Lemierre's syndrome. We present the case of a previously well 19-year-old man, who presented acutely unwell with meningitis and sepsis. was isolated from peripheral blood cultures and identified on cerebrospinal fluid with 16S rDNA Polymerase Chain Reaction (PCR).

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Background: The paranasal sinus mucosal thickening, visible in magnetic resonance imaging (MRI), maybe a source of inflammation in microvessels, but its relationship with small vessel disease (SVD) is unclear. We reviewed the literature and analysed a sample of patients with sporadic SVD to identify any association between paranasal sinus opacification severity and SVD neuroimaging markers.

Methods: We systematically reviewed MEDLINE and EMBASE databases up to April 2020 for studies on paranasal sinus mucosal changes in patients with SVD, cerebrovascular disease (CVD), and age-related neurodegenerative diseases.

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Article Synopsis
  • - The study reviews existing controversies about brain fluid dynamics and tests if conventional MRI can visualize brain fluid outflow pathways and their connection to small vessel disease (SVD).
  • - Researchers conducted a pilot study on 19 subjects and found significant increases in signal intensity along various fluid outflow routes after administering Gadolinium contrast, indicating that interstitial fluid drainage can be assessed using MRI.
  • - The results showed a link between fluid drainage and increased perivascular spaces in the brain, suggesting further research is needed to explore this relationship in humans.
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Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI.

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Article Synopsis
  • Cerebral small vessel disease (cSVD) can cause strokes and affect thinking and mood, but there are no specific treatments for it.
  • Researchers wanted to see if two medications, isosorbide mononitrate (ISMN) and cilostazol, were safe and effective for people who had a type of stroke called lacunar stroke.
  • In a study involving 400 people, almost 91% were successfully included, and most stayed in the study for the whole year to see how the medications worked.
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Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter.

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Background: Neuropsychiatric symptoms could form part of an early cerebral small vessel disease prodrome that is detectable before stroke or dementia onset. We aimed to identify whether apathy, depression, anxiety, and subjective memory complaints associate with longitudinal white matter hyperintensity (WMH) progression.

Methods: Community-dwelling older adults from the observational Lothian Birth Cohort 1936 attended three visits at mean ages 73, 76, and 79 years, repeating MRI, Mini-Mental State Examination, neuropsychiatric (Dimensional Apathy Scale, Hospital Anxiety and Depression Scale), and subjective memory symptoms.

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