[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.
Current Atherosclerosis Reports 08/2015; 17(8):524. DOI:10.1007/s11883-015-0524-7 · 3.06 Impact Factor
[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.
International Journal of Stroke 07/2015; DOI:10.1111/ijs.12544 · 4.03 Impact Factor
[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.
The Lancet Neurology 07/2013; DOI:10.1016/S1474-4422(13)70135-2 · 21.82 Impact Factor
[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.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP. METHODS: Measurements of the midbrain and pontine base on midsagittal T1-weighted MRI were performed in confirmed PSP (n = 12), Parkinson disease (n = 2), and multiple system atrophy (MSA) (n = 7), and in controls (n = 8). Using receiver operating characteristic curve analysis, cutoff values were applied to a clinically diagnosed cohort of 62 subjects that included PSP (n = 21), Parkinson disease (n = 10), MSA (n = 10), and controls (n = 21). RESULTS: The mean midbrain measurement of 8.1 mm was reduced in PSP (p < 0.001) with reduction in the midbrain to pons ratio (PSP smaller than MSA; p < 0.001). In controls, the mean midbrain ratio was approximately two-thirds of the pontine base, in PSP it was <52%, and in MSA the ratio was greater than two-thirds. A midbrain measurement of <9.35 mm and ratio of 0.52 had 100% specificity for PSP. In the clinically defined group, 19 of 21 PSP cases (90.5%) had a midbrain measurement of <9.35 mm. CONCLUSIONS: We have developed a simple and reliable measurement in pathologically confirmed disease based on the topography of atrophy in PSP with high sensitivity and specificity that may be a useful tool in the clinic.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND PURPOSE:Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD.MATERIALS AND METHODS:VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed.RESULTS:On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia.CONCLUSIONS:Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology.
American Journal of Neuroradiology 03/2013; 34(9). DOI:10.3174/ajnr.A3504 · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose—Cerebral microbleeds (CMBs) are a marker of small vessel diseases, including hypertensive arteriopathy and cerebral amyloid angiopathy, and may be associated with cognitive impairment. The relationship between CMBs and cognitive function in ischemic cerebrovascular disease remains uncertain. We, therefore, investigated the cognitive impact of CMBs in a cohort of patients with ischemic stroke or transient ischemic attack.
Methods—All patients underwent detailed and comprehensive neuropsychological testing and standardized MRI, including fluid attenuation inversion recovery, T1, T2, and gradient-recalled echo T2*-weighted sequences. CMBs, white matter changes, lacunes, and territorial cortical infarcts (defined by standardized criteria) were identified, and associations with cognition assessed.
Results—Three hundred twenty patients with a diagnosis of ischemic stroke or transient ischemic attack were included. Of these, 72 (22.5%) had at least 1 CMB. Of all the cognitive domains tested, only executive impairment was more prevalent in patients with CMBs than without (38% versus 25%; P=0.039). In univariate analysis, the presence of strictly lobar (but not deep) CMBs was associated with executive impairment (odds ratio, 2.49; 95% confidence interval, 1.16–5.36; P=0.019). In adjusted multivariate analyses, the presence (OR, 2.34; 95% confidence interval, 1.08–5.09; P=0.031) and number (OR, 1.33; 95% confidence interval, 1.04–1.69; P=0.022) of strictly lobar CMBs were significantly associated with executive impairment. CMBs were not associated with impairment in other cognitive domains.
Conclusions—Strictly lobar CMBs are independently associated with executive dysfunction in patients with ischemic stroke or transient ischemic attack. Our findings suggest that a microangiopathy related to strictly lobar CMBs (eg, cerebral amyloid angiopathy) contributes to cognitive impairment in this population.
[Show abstract][Hide abstract] ABSTRACT: Transient focal neurological episodes (TFNE) are recognized in cerebral amyloid angiopathy (CAA) and may herald a high risk of intracerebral hemorrhage (ICH). We aimed to determine their prevalence, clinical neuroimaging spectrum, and future ICH risk.
This was a multicenter retrospective cohort study of 172 CAA patients. Clinical, imaging, and follow-up data were collected. We classified TFNE into: predominantly positive symptoms ("aura-like" spreading paraesthesias/positive visual phenomena or limb jerking) and predominantly negative symptoms ("transient ischemic attack-like" sudden-onset limb weakness, dysphasia, or visual loss). We pooled our results with all published cases identified in a systematic review.
In our multicenter cohort, 25 patients (14.5%; 95% confidence interval, 9.6%-20.7%) had TFNE. Positive and negative symptoms were equally common (52% vs 48%, respectively). The commonest neuroimaging features were leukoaraiosis (84%), lobar ICH (76%), multiple lobar cerebral microbleeds (58%), and superficial cortical siderosis/convexity subarachnoid hemorrhage (54%). The CAA patients with TFNE more often had superficial cortical siderosis/convexity subarachnoid hemorrhage (but not other magnetic resonance imaging features) compared with those without TFNE (50% vs 19%; P=0.001). Over a median period of 14 months, 50% of TFNE patients had symptomatic lobar ICH. The meta-analysis showed a risk of symptomatic ICH after TFNE of 24.5% (95% confidence interval, 15.8%-36.9%) at 8 weeks, related neither to clinical features nor to previous symptomatic ICH.
TFNE are common in CAA, include both positive and negative neurological symptoms, and may be caused by superficial cortical siderosis/convexity subarachnoid hemorrhage. TFNE predict a high early risk of symptomatic ICH (which may be amenable to prevention). Blood-sensitive magnetic resonance imaging sequences are important in the investigation of such episodes.
[Show abstract][Hide abstract] ABSTRACT: Cerebral microbleeds (CMBs) have emerged as an important new imaging manifestation of sporadic cerebral small vessel diseases - mainly hypertensive arteriopathy and cerebral amyloid angiopathy - which are highly prevalent in the elderly and have a critical role in vascular cognitive impairment and dementia. With the development of MRI techniques that are exquisitely sensitive to the products of bleeding, including T2*-weighted gradient-recalled echo (T2*-GRE) and susceptibility-weighted imaging (SWI), CMBs have been detected in ever-increasing numbers of patients, including those with vascular cognitive impairment and dementia, as well as in population-based samples of healthy elderly people. Our increased ability to image CMBs and hence to see the development and progression of cerebral small vessel disease raises many clinical and pathophysiological questions about the mechanisms, diagnosis and monitoring of cognitive impairment. In order to tackle these questions, it is important to be able to reliably detect, define and map CMBs in the brains of elderly people. In this review, we consider radiological detection methods, criteria for defining CMBs (including a practical approach to the identification of CMB "mimics"), and the use of standardised rating scales. We also briefly discuss the potential for automatically detecting and quantitatively mapping CMBs in future.
[Show abstract][Hide abstract] ABSTRACT: Vascular cognitive impairment causes significant disability in the elderly and is common following ischaemic stroke. Although the underlying mechanisms and prognostic factors remain unclear, small vessel diseases are known to contribute. Cerebral microbleeds (CMBs) are a magnetic resonance imaging (MRI) manifestation of small vessel diseases and may contribute to vascular cognitive impairment, particularly frontal-executive functions. We hypothesized that baseline CMBs would predict long-term cognitive outcome, specifically frontal-executive function.
A cohort of consecutive patients found to have CMBs when first referred to a stroke clinic, together with a CMB-free control group matched for age, gender and clinicoradiological characteristics, were invited for follow-up cognitive assessment a median of 5.7 years later. MRI and detailed cognitive assessment (including current intellectual function, verbal memory, visual memory, naming skills, perceptual functions, frontal-executive functions; and speed and attention) were performed at baseline and follow-up. Patients were classified (blinded to MRI and clinical data) as impaired or unimpaired in each domain using predefined criteria. We compared the prevalence of cognitive impairments in each domain at baseline and follow-up and investigated clinical and radiological predictors [including baseline CMBs and white matter changes (WMCs)] of frontal-executive cognitive impairment.
Of the original cohort of 55 patients, 13 died without follow-up. Twenty-six of the surviving patients (9 with, 17 without baseline CMBs) agreed to follow-up neuropsychological assessment; 21 of these patients had a repeat MRI scan. The median number of cognitive domains impaired increased, regardless of the presence of baseline CMBs (with baseline CMBs: median 3, range 0-5 at follow-up vs. median 2, range 0-2 at baseline, p = 0.016; without CMBs: median 1.0, range 0-5 at follow-up vs. median 0, range 0-5 at baseline, p = 0.035). Frontal-executive impairment at follow-up was more prevalent in patients with baseline CMBs than in those without (78 vs. 29%, p = 0.038). The presence of baseline CMBs predicted frontal-executive impairment at follow-up (OR 8.40, 95% CI 1.27-55.39, p = 0.027). Fifty percent of patients with CMBs versus 8% of patients without baseline CMBs developed new CMBs (p = 0.047). The severity of WMCs increased; the difference was statistically significant only in patients without baseline CMBs (p = 0.027). There were no new cortical infarcts.
In stroke clinic patients, CMBs are consistently associated with frontal-executive impairment; baseline CMBs are associated with frontal-executive impairment at follow-up after 5.7 years. The presence of CMBs has prognostic relevance for long-term cognitive outcome in stroke clinic patients, and may help to optimally target preventive strategies in individuals at highest risk of cognitive decline.
[Show abstract][Hide abstract] ABSTRACT: Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (<3 months after intracerebral haemorrhage) using diffusion-weighted imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02-1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15-12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in other intracerebral haemorrhage types. Ischaemic brain lesions are associated with white matter changes and cerebral microbleeds, suggesting that they result from an occlusive small-vessel arteriopathy. Diffusion-weighted imaging lesions contribute to the overall burden of vascular-related brain damage in intracerebral haemorrhage, and may be a useful surrogate marker of ongoing ischaemic injury from small-vessel damage.
[Show abstract][Hide abstract] ABSTRACT: Quantitative magnetisation transfer imaging (qMTI) is an extension of conventional MT techniques and allows the measurement of parameters that reflect tissue ultrastructure through the properties of macromolecule-bound protons; these include the bound proton fraction and the relaxation times of free and bound proton pools. It has been used in multiple sclerosis and Alzheimer's disease, and has shown changes in some of the parameters, particularly the bound proton fraction. The purpose of this pilot study was to assess whether qMTI could distinguish between gliomas and normal brain tissue, and provide proof of principle for its use in tumour characterisation. Eight subjects [three men, five women; mean age, 44 years; range, 27-66 years; seven World Health Organization (WHO) Grade II, one Grade III] with biopsy-proven glioma were imaged with a structural MRI protocol that included three-dimensional qMTI. qMTI parameters were extracted from regions of interest selected from different tumour components visible on conventional MR sequences, normal-appearing peritumoral tissue and distant normal-appearing white matter. All patients gave informed consent and the study was approved by the Local Research Ethics Committee. Almost all of the qMTI parameters detected abnormalities in both glioma and the peritumoral region relative to the distant white matter. In particular, the bound proton fraction was reduced significantly from 6.0 percentage units (pu) [standard deviation (SD), 0.5 pu] in normal-appearing white matter to 1.7 pu (SD = 0.5 pu) in solid tumour and 2.2 pu (SD = 0.5 pu) in peritumoral areas. This work shows that qMTI reveals abnormalities, not only in glioma, but also in the apparently normal tissue surrounding the conventionally defined tumour. Thus, qMTI shows promise for tumour characterisation and for studying tumour boundaries. These preliminary data justify larger studies in a range of different tumour types and grades.
NMR in Biomedicine 06/2011; 24(5):492-8. DOI:10.1002/nbm.1614 · 3.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cerebral microbleeds, visible on gradient-recalled echo (GRE) T2* MRI, have generated increasing interest as an imaging marker of small vessel diseases, with relevance for intracerebral bleeding risk or brain dysfunction.
Manual rating methods have limited reliability and are time-consuming. We developed a new method for microbleed detection using automated segmentation (MIDAS) and compared it with a validated visual rating system. In thirty consecutive stroke service patients, standard GRE T2* images were acquired and manually rated for microbleeds by a trained observer. After spatially normalizing each patient's GRE T2* images into a standard stereotaxic space, the automated microbleed detection algorithm (MIDAS) identified cerebral microbleeds by explicitly incorporating an "extra" tissue class for abnormal voxels within a unified segmentation-normalization model. The agreement between manual and automated methods was assessed using the intraclass correlation coefficient (ICC) and Kappa statistic. We found that MIDAS had generally moderate to good agreement with the manual reference method for the presence of lobar microbleeds (Kappa = 0.43, improved to 0.65 after manual exclusion of obvious artefacts). Agreement for the number of microbleeds was very good for lobar regions: (ICC = 0.71, improved to ICC = 0.87). MIDAS successfully detected all patients with multiple (≥2) lobar microbleeds.
MIDAS can identify microbleeds on standard MR datasets, and with an additional rapid editing step shows good agreement with a validated visual rating system. MIDAS may be useful in screening for multiple lobar microbleeds.
PLoS ONE 03/2011; 6(3):e17547. DOI:10.1371/journal.pone.0017547 · 3.23 Impact Factor