[Show abstract][Hide abstract] ABSTRACT: Objective:
To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH.
In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors.
We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037).
In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH.
[Show abstract][Hide abstract] ABSTRACT: Dementia is a global growing concern, affecting over 35 million people with a global economic impact of over $604 billion US. With an aging population the number of people affected is expected double over the next two decades. Vascular cognitive impairment (VCI) describes cognitive impairment caused by various types of cerebrovascular disease including cortical and subcortical infarcts, and more diffuse white matter injury from cerebral small vessel disease. Although VaD is traditionally considered to be the second most common form of dementia after Alzheimer's disease (AD), there is increasing recognition of the vascular contribution to neurodegeneration and dementia. In the vast majority of sporadic late onset cognitive impairment, Alzheimer's pathology coexists with vascular pathology. Moreover, cerebrovascular lesions increase the clinical expression of AD pathology, and white-matter changes may be an early feature of AD. The VaD and VCI concepts are of clinical and research importance because vascular factors may be treatable, to reduce disease progression. Indeed, recent data suggest that the "dementia epidemic" has not occurred as predicted, which may be due to improved treatment of modifiable vascular risk factors, for example hypertension or dyslipidaemia. The aim of this review is to highlight the recent advances in the understanding of VCI, with a focus on small vessel diseases of the brain as detected by recent neuroimaging techniques. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia.
Full-text · Article · Dec 2015 · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
[Show abstract][Hide abstract] ABSTRACT: Importance
Prion diseases represent the archetype of brain diseases caused by protein misfolding, with the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion-weighted imaging (DWI) has emerged as the most sensitive magnetic resonance imaging (MRI) sequence for the diagnosis of sCJD, but few studies have assessed the evolution of MRI signal as the disease progresses.Objectives
To assess the natural history of the MRI signal abnormalities on DWI in sCJD to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation.Design, Setting, and Participants
Gray matter involvement on DWI was assessed among 37 patients with sCJD in 26 cortical and 5 subcortical subdivisions per hemisphere using a semiquantitative scoring system of 0 to 2 at baseline and follow-up. A total brain score was calculated as the summed scores in the individual regions. In 7 patients, serial mean diffusivity measurements were obtained. Age at baseline MRI, disease duration, atrophy, codon 129 methionine valine polymorphism, Medical Research Council Rating Scale score, and histopathological findings were documented. The study setting was the National Prion Clinic, London, England. All participants had a probable or definite diagnosis of sCJD and had at least 2 MRI studies performed during the course of their illness. The study dates were October 1, 2008 to April 1, 2012. The dates of our analysis were January 19 to April 20, 2012.Main Outcomes and Measures
Correlation of regional and total brain scores with disease duration.Results
Among the 37 patients with sCJD in this study there was a significant increase in the number of regions demonstrating signal abnormality during the study period, with 59 of 62 regions showing increased signal intensity (SI) at follow-up, most substantially in the caudate and putamen (P < .001 for both). The increase in the mean (SD) total brain score from 30.2 (17.3) at baseline to 40.5 (20.6) at follow-up (P = .001) correlated with disease duration (r = 0.47, P = .003 at baseline and r = 0.35, P = .03 at follow-up), and the left frontal SI correlated with the degree of spongiosis (r = 0.64, P = .047). Decreased mean diffusivity in the left caudate at follow-up was seen (P < .001). Eight patients demonstrated decreased SI in cortical regions, including the left inferior temporal gyrus and the right lingual gyrus.Conclusions and Relevance
Magnetic resonance images in sCJD show increased extent and degree of SI on DWI that correlates with disease duration and the degree of spongiosis. Although cortical SI may fluctuate, increased basal ganglia SI is a consistent finding and is due to restricted diffusion. Diffusion-weighted imaging in the basal ganglia may provide a noninvasive biomarker in future therapeutic trials.
[Show abstract][Hide abstract] ABSTRACT: The International Carotid Stenting Study (ICSS, ISRCTN25337470) randomized patients with recently symptomatic carotid artery stenosis > 50% to carotid artery stenting (CAS) or endarterectomy. CAS increased the risk of new brain lesions visible on diffusion-weighted magnetic resonance imaging (DWI-MRI) more than endarterectomy in the ICSS-MRI Substudy. The predictors of new post-stenting DWI lesions were assessed in these patients.
Preview · Article · Oct 2015 · European Journal of Vascular and Endovascular Surgery
[Show abstract][Hide abstract] ABSTRACT: Intracranial haemorrhage (ICH) is the most feared and devastating complication of oral anticoagulation, with high mortality and disability in survivors. Oral anticoagulant-related ICH is increasing in incidence, most likely in part due to the increased use of anticoagulation for atrial fibrillation in the elderly populations with a high prevalence of bleeding-prone cerebral small vessel diseases. Risk scores have been developed to predict bleeding, including ICH, as well as the risk of ischaemic stroke. Recently, attention has turned to brain imaging, in particular, MRI detection of potential prognostic biomarkers, which may help better predict outcomes and individualize anticoagulant decisions. Cerebral microbleeds (CMBs)-small, round areas of signal loss on blood-sensitive MR sequences-have been hypothesized to be a marker for bleeding-prone small vessel pathology, and thus, future symptomatic ICH risk. In this review, we outline the prevalence and prognostic value of CMBs in populations affected by AF for whom anticoagulation decisions are relevant, including healthy older individuals and survivors of ischaemic stroke or ICH. We consider the limitations of currently available evidence, and discuss future research directions in relation to both prognostic markers and treatment options for atrial fibrillation.
Full-text · Article · Aug 2015 · Current Atherosclerosis Reports
[Show abstract][Hide abstract] ABSTRACT: Background
Cerebrovascular disease and neurodegeneration cause cognitive impairment and frequently coexist.AimsOur objectives were to investigate the prevalence and cognitive impact of medial temporal lobe atrophy – a radiological marker often associated with Alzheimer's disease – in a hospital stroke service.Methods
Retrospective cohort study of patients from a hospital stroke service. Patients assessed for suspected ischemic stroke or transient ischemic attack, irrespective of final diagnosis, underwent neuropsychological testing and magnetic resonance imaging. medial temporal lobe atrophy, white matter hyperintensities, lacunes, and cerebral microbleeds were rated using established criteria and validated scales. The associations between medial temporal lobe atrophy and cognition were tested using multivariable logistic regression analyses, adjusted for age and imaging markers of cerebrovascular disease.ResultsThree hundred and ninety-three patients were included, of whom 169 (43%; 95% confidence interval: 38·1–48·1%) had medial temporal lobe atrophy; in 38 patients (9·7%), medial temporal lobe atrophy was severe (mean score ≥2). In unadjusted logistic regression analyses in the whole cohort, mean medial temporal lobe atrophy score was associated with verbal memory, nominal and perceptual skills, executive function, and speed and attention. After adjustment for age, white matter hyperintensities, number of lacunes, presence of cerebral microbleeds, previous ischemic stroke or transient ischemic attack, and premorbid intelligence quotient, mean medial temporal lobe atrophy score remained associated with impairment in verbal memory (odds ratio: 1·64; 95% confidence interval 1·04–2·58) and nominal skills (odds ratio: 1·61; 95% confidence interval 1·04–2·48).Conclusions
Medial temporal lobe atrophy is common and has an independent impact on cognitive function in a stroke service population, independent of confounding factors including age and magnetic resonance imaging markers of cerebrovascular disease. Medial temporal lobe atrophy is independently related to verbal memory and nominal skills, while small vessel pathology also contributes to speed and attention, and executive and perceptual functions.
Full-text · Article · Jul 2015 · International Journal of Stroke
[Show abstract][Hide abstract] ABSTRACT: Susceptibility-weighted imaging (SWI) is a recently developed magnetic resonance imaging (MRI) technique where image contrast represents 'magnetic susceptibility effects'-a natural property of tissues. The applications of SWI are rapidly increasing, with much work being carried out to determine the usefulness of the technique in multiple disease states. Current clinical applications of the technique include detection of microbleeds, subarachnoid hemorrhage (SAH), ferromagnetic deposition in neurodegenerative disease, and characterization of cerebral tumors.
[Show abstract][Hide abstract] ABSTRACT: Abstract White matter (WM) abnormalities are frequently seen on brain MRI of HIV positive (HIV+) patients. We aimed to determine the prevalence of unexplained WM abnormalities and their associations with HIV disease and cardiovascular risk factors. We conducted a retrospective, cross-sectional study of brain MRI of HIV+ patients conducted between 2004 and 2009 at our center. Clinical and laboratory data were compiled, and images were independently reviewed for WM lesions. Images were obtained from 254 patients: 70% male, 53% white, 40% black, mean age 42 years, median current CD4 count 240 cells/mm(3), and 41% not taking antiretroviral therapy (ART). Hyperintense WM lesions were present in 161 patients (63.4%): 89 scans (35.0%) showed diffuse WM signal abnormality (DWMSA), 61 (24.0%) were consistent with small vessel disease (SVD, graded by Fazekas' scale), and 37 (14.6%) showed large asymmetrical focal WM lesions. SVD changes were associated with age and cardiovascular risk factors, and while cerebral SVD may be related to HIV infection, the MRI findings were not associated with HIV-related factors. The only risk factor for DWMSA was black race, and no correlation with cardiovascular risk factors, CD4 count, or clinical presentation was identified. DWMSA are therefore of uncertain neurological significance in HIV+ patients and could represent more than one clinicopathological entity.
Full-text · Article · May 2014 · AIDS patient care and STDs
[Show abstract][Hide abstract] ABSTRACT: Imaging plays an important role in the diagnosis and management of dementia. This review covers the imaging features of the most common dementing illnesses: Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD). It describes typical findings on structural neuroimaging and discusses functional and molecular imaging techniques such as FDG PET, amyloid PET, magnetic resonance (MR) perfusion imaging, diffusion tensor imaging (DTI) and functional MR imaging (fMRI).
Full-text · Article · Oct 2013 · European Radiology
[Show abstract][Hide abstract] ABSTRACT: We report a case of frontotemporal dementia caused by a novel MAPT mutation (Q351R) with a remarkably long amnestic presentation mimicking familial Alzheimer's disease. Longitudinal clinical, neuropsychological and imaging data provide convergent evidence for predominantly bilateral anterior medial temporal lobe involvement consistent with previously established neuroanatomical signatures of MAPT mutations. This case supports the notion that the neural network affected in MAPT mutations is determined to a large extent by the underlying molecular pathology. We discuss the diagnostic significance of anomia in the context of atypical amnesia and the impact of impaired episodic and semantic memory systems on autobiographical memory.
[Show abstract][Hide abstract] ABSTRACT: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy.
Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470.
1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7.
The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions.
Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.
No preview · Article · Jul 2013 · The Lancet Neurology
[Show abstract][Hide abstract] ABSTRACT: Cerebral microbleeds have emerged as an important new imaging marker of cerebral small vessel disease. With the development of MRI techniques that are exquisitely sensitive to paramagnetic blood products, such as T2*-weighted gradient-recalled echo and susceptibility-weighted sequences, microbleeds have been detected in ever-increasing numbers of patients in stroke and cognitive clinics, as well as in healthy older people and in a variety of other rarer diseases and syndromes. Detection of cerebral microbleeds has clinical implications with respect to the diagnosis of the underlying small vessel disease, the safety of antithrombotic use, and the risk of symptomatic intracerebral haemorrhage, cognitive impairment and dementia. This article provides a guide to the detection and clinical relevance of cerebral microbleeds in different conditions based on a comprehensive review of the literature and own findings in research and clinical practice.