Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making.

Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.

Quantification of Serial Cerebral Blood Flow in Acute Stroke Using Arterial Spin Labeling.

BACKGROUND AND PURPOSE: Perfusion-weighted imaging is used to select patients with acute ischemic stroke for intervention, but knowledge of cerebral perfusion can also inform the understanding of ischemic injury. Arterial spin labeling allows repeated measurement of absolute cerebral blood flow (CBF) without the need for exogenous contrast. The aim of this study was to explore the relationship between dynamic CBF and tissue outcome in the month after stroke onset. METHODS: Patients with nonlacunar ischemic stroke underwent ≤5 repeated magnetic resonance imaging scans at presentation, 2 hours, 1 day, 1 week, and 1 month. Imaging included vessel-encoded pseudocontinuous arterial spin labeling using multiple postlabeling delays to quantify CBF in gray matter regions of interest. Receiver-operator characteristic curves were used to predict tissue outcome using CBF. Repeatability was assessed in 6 healthy volunteers and compared with contralateral regions of patients. Diffusion-weighted and T2-weighted fluid attenuated inversion recovery imaging were used to define tissue outcome. RESULTS: Forty patients were included. In contralateral regions of patients, there was significant variation of CBF between individuals, but not between scan times (mean±SD: 53±42 mL/100 g/min). Within ischemic regions, mean CBF was lowest in ischemic core (17±23 mL/100 g/min), followed by regions of early (21±26 mL/100 g/min) and late infarct growth (25±35 mL/100 g/min; ANOVA P<0.0001). Between patients, there was marked overlap in presenting and serial CBF values. CONCLUSIONS: Knowledge of perfusion dynamics partially explained tissue fate. Factors such as metabolism and tissue susceptibility are also likely to influence tissue outcome.

Posterior circulation cerebrovascular syndromes: diagnosis and management.

One in five strokes affects the posterior circulation. Diagnosing posterior circulation stroke can be challenging, as the vascular anatomy can be variable, and because presenting symptoms are often non-specific and fluctuating. Nevertheless, making the correct diagnosis is important, as these strokes have a high chance of recurrence, can be life threatening, and can lead to equally life-threatening complications. Investigation and management largely follow those for stroke in general, although some specific differences exist. These include the preferred use of MRI for diagnosing posterior fossa lesions, the management of basilar artery thrombosis, which may have a longer time window for recanalisation therapy, and the use of endovascular therapies for secondary prevention, which, so far, have not shown any benefit in the treatment of vertebral or basilar artery stenosis. In this review, we summarise the anatomy, aetiology and presentation of posterior circulation stroke, and discuss current approaches to management.

BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities.

Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a "predominantly neurodegenerative" and a "predominantly vascular" cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies.

Population-based case-control study of white matter changes on brain imaging in transient ischemic attack and ischemic stroke.

BACKGROUND AND PURPOSE: White matter changes (WMC) are a common finding on brain imaging and are associated with an increased risk of ischemic stroke. They are most frequent in small vessel stroke; however, in the absence of comparisons with normal controls, it is uncertain whether WMC are also more frequent than expected in other stroke subtypes. Therefore, we compared WMC in pathogenic subtypes of ischemic stroke versus controls in a population-based study. METHODS: We evaluated the presence and severity of WMC on computed tomography and on magnetic resonance brain imaging using modified Blennow/Fazekas scale and age-related white matter changes scale, respectively, in a population-based study of patients with incident transient ischemic attack or ischemic stroke (Oxford Vascular Study) and in a study of local controls (Oxford Project to Investigate Memory and Ageing) without history of transient ischemic attack or ischemic stroke, with stratification by stroke pathogenesis (Trial of Org10172 in Acute Stroke Treatment classification). RESULTS: Among 1601 consecutive eligible patients with first-ever ischemic events, 1453 patients had computed tomography brain imaging, 562 had magnetic resonance imaging, and 414 patients had both. Compared with 313 controls (all with computed tomography and 131 with magnetic resonance imaging) and after adjustment for age, sex, diabetes mellitus, and hypertension, moderate/severe WMC (age-related white matter changes scale) were more frequent in patients with small vessel events (odds ratio, 3.51 [95% confidence interval, 2.13-5.76]; P<0.0001) but not in large artery (odds ratio, 1.03 [95% confidence interval, 0.64-1.67]), cardioembolic (odds ratio, 0.87 [95% confidence interval, 0.56-1.34]), or undetermined (odds ratio, 0.90 [95% confidence interval, 0.62-1.30]) subtypes. Results were consistent for ischemic stroke and transient ischemic attack, for other scales, and for magnetic resonance imaging and computed tomography separately. CONCLUSIONS: In contrast to small vessel ischemic events, WMC were not independently associated with other pathogenic subtypes, suggesting that WMC are unlikely to be an independent risk factor for nonsmall vessel events.

Leukoaraiosis on MRI in patients with minimally symptomatic obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with hypertension, nocturnal blood pressure (BP) surges, and increased risk of stroke. It may therefore also be associated with a higher risk of developing leukoaraiosis. Only few data about the prevalence of leukoaraiosis in patients with OSA, and any association between degrees of severity of either condition, exist. METHODS: We studied patients who were part of a clinical trial (MOSAIC) in minimally symptomatic OSA. All patients had brain MRI (T2, FLAIR) at baseline. A single observer assessed the images for the presence and severity of leukoaraiosis (ARWMC-score). We related the extent of leukoaraiosis to the severity of OSA (measured by oxygen desaturation index [ODI]) and the presence of other vascular risk factors. RESULTS: 183 patients (156 men, 85.2%; mean age ± SD = 57.7 ± 7.4 years; median oxygen desaturation index = 9.6, interquartile range = 4.6-16.0) took part in the study. Although 135 (74%) patients had some leukoaraiosis, this was generally mild. We confirmed the well-known risk factor associations between leukoaraiosis, increasing age (p < 0.0001) and hypertension (p = 0.003), but we did not find any association between OSA and leukoaraiosis (p = 0.33), despite both conditions being associated with increasing current BP and a history of hypertension. CONCLUSION: Our data confirm the well-known association between leukoaraiosis, age and increasing BP. However, we found no association between OSA and leukoaraiosis despite some shared risk factor associations. Our findings suggest that OSA is not a strong independent risk factor for leukoaraiosis. Confounding by hypertension may explain any apparent association in previously reported studies of patients with severer OSA.

Increased cerebral arterial pulsatility in patients with leukoaraiosis: arterial stiffness enhances transmission of aortic pulsatility.

BACKGROUND AND PURPOSE: Arterial stiffening reduces damping of the arterial waveform and hence increases pulsatility of cerebral blood flow, potentially damaging small vessels. In the absence of previous studies in patients with recent transient ischemic attack or stroke, we determined the associations between leukoaraiosis and aortic and middle cerebral artery stiffness and pulsatility. METHODS: Patients were recruited from the Oxford Vascular Study within 6 weeks of a transient ischemic attack or minor stroke. Leukoaraiosis was categorized on MRI by 2 independent observers with the Fazekas and age-related white matter change scales. Middle cerebral artery (MCA) stiffness (transit time) and pulsatility (Gosling's index: MCA-PI) were measured with transcranial ultrasound and aortic pulse wave velocity and aortic systolic, diastolic, and pulse pressure with applanation tonometry (Sphygmocor). RESULTS: In 100 patients, MCA-PI was significantly greater in patients with leukoaraiosis (0.91 versus 0.73, P<0.0001). Severity of leukoaraiosis was associated with MCA-PI and aortic pulse wave velocity (Fazekas: χ(2)=0.39, MCA-PI P=0.01, aortic pulse wave velocity P=0.06; age-related white matter change: χ(2)=0.38, MCA-PI P=0.015; aortic pulse wave velocity P=0.026) for periventricular and deep white matter lesions independent of aortic systolic blood pressure, diastolic blood pressure, and pulse pressure and MCA transit time with MCA-PI independent of age. In a multivariate model (r(2)=0.68, P<0.0001), MCA-PI was independently associated with aortic pulse wave velocity (P=0.016) and aortic pulse pressure (P<0.0001) and inversely associated with aortic diastolic blood pressure (P<0.0001) and MCA transit time (P=0.001). CONCLUSIONS: MCA pulsatility was the strongest physiological correlate of leukoaraiosis, independent of age, and was dependent on aortic diastolic blood pressure and pulse pressure and aortic and MCA stiffness, supporting the hypothesis that large artery stiffening results in increased arterial pulsatility with transmission to the cerebral small vessels resulting in leukoaraiosis.

A kinetic model for vessel-encoded dynamic angiography with arterial spin labeling.

The ability to visualize blood flow in a vessel-selective manner is of importance in a range of cerebrovascular diseases. Conventional X-ray methods are invasive and carry risks to the patient. Recently, a noninvasive dynamic angiographic MRI-based technique has been proposed using vessel-encoded pseudocontinuous arterial spin labeling, yielding vessel-selective angiograms of the four main brain-feeding arteries. In this study, a novel kinetic model for the signal evolution in such acquisitions is derived and applied to healthy volunteers and to a patient with Moya-Moya disease. The model incorporates bolus dispersion, T(1) decay and radio frequency effects and is applicable to other angiographic methods based on continuous or pseudocontinuous arterial spin labeling. The model fits the data well in all subjects and yields parametric maps relating to blood volume, arrival time, and dispersion, changes to which may indicate disease. These maps are also used to generate synthesized images of blood inflow without bias from T(1) decay and radio frequency effects, greatly improving collateral vessel visibility in the patient with Moya-Moya disease. Relative volume flow rates in downstream vessels are also quantified, showing the relative importance of each feeding artery. This framework is likely to be of use in assessing collateral blood flow in patient groups.

Age-related cerebral white matter disease (leukoaraiosis): a review.

With the availability of improved brain imaging techniques, the high prevalence and clinical importance of cerebral small vessel disease have been increasingly recognised in recent years. As age is one of the most important risk factors for this condition, its prevalence is set to rise further as populations age. This may lead to an increase in the clinical consequences of white matter disease, namely cognitive decline, decreased mobility and increased stroke risk. Given the impact this will have on individuals and on healthcare systems, knowledge of the risk factors for small vessel disease, its prevention and its treatment is becoming more important. Although a lot of data are now available on the epidemiology, risk factors, clinical consequences and prognosis of leukoaraiosis, some of this information is conflicting. In this review, we summarise the current literature on cerebral small vessel disease, with an emphasis on its clinical aspects.

Maneuverability of the Scope and Instruments within Three Different Single-Incision Laparoscopic Ports: An Experimental Pilot Study.

Single-port access systems (SPASs) are currently used in human and veterinary surgeries. However, they pose technical challenges, such as instrument crowding, intra- and extracorporeal instrument collision, and reduced maneuverability. Studies comparing the maneuverability of the scopes and instruments in different SPASs are lacking. This study aimed to compare the maneuverability of three different SPASs: the Covidien SILS-port, Storz Endocone, and glove port. A clear acrylic box with artificial skin placed at the bottom was used to mimic the abdominal wall and cavity. The three SPASs were placed from below, and a 10-mm endoscope and 5-mm instrument were introduced. A motion analysis system consisting of 18 cameras and motion analysis software were used to track the movement of the endoscope and instrument, to determine the volume of the cone-shaped, three-dimensional figures over which movement was possible, with higher values indicating greater maneuverability. The Mann-Whitney U test was used for the analysis. The maneuverability of the endoscope alone was significantly higher in the glove port system than in the other two SPASs. When inserting an additional instrument, the maneuverability significantly decreased in the SILS-port and Endocone, but not in the glove port. The highest maneuverability overall was found in the glove port.

Normal cortical energy metabolism in migrainous stroke: A 31P-MR spectroscopy study.

BACKGROUND AND PURPOSE: Previous (31)P-magnetic resonance spectroscopy ((31)P-MRS) studies have shown that cerebral cortical energy metabolism is abnormal in migraine and that cortical energy reserves decrease with increasing severity and duration of aura. Migrainous infarction is a rare complication of migraine with aura, and its pathophysiology is poorly understood. We used (31)P-MRS to determine whether migrainous stroke shows similar interictal abnormalities in cortical energy metabolism as severe, prolonged aura. METHODS: We used (31)P-MRS to study patients with a diagnosis of either migrainous infarction or migraine with persistent aura without infarction (aura duration >7 days) according to International Headache Society criteria. We compared clinical presentation and metabolite ratios between patient groups. We also studied healthy controls with no history of migraine. RESULTS: Patients with persistent aura without infarction had lower phosphocreatine-phosphate (PCr/Pi) ratios (mean+/-SD, 1.61+/-0.10) compared with controls (1.94+/-0.35, P=0.011) and with patients with migrainous stroke (1.96+/-0.16, P<0.0001). These differences were present in cortical tissue only. In migrainous stroke patients, the metabolite ratios did not differ significantly from those of controls without migraine. CONCLUSIONS: The differences in cortical energy reserves between patients with migrainous stroke and in those with migraine with persistent aura suggest that the pathomechanisms of these conditions differ and that migrainous infarction does not simply represent a particularly severe form of migrainous aura. This finding supports the revised International Headache Society criteria, which now distinguish between migrainous infarction and migraine with persistent aura without infarction.

Cryptogenic stroke - How to make sense of a non-diagnostic entity.

Secondary preventive strategies in ischaemic stroke depend on the underlying aetiology. However, approximately one-third of ischaemic strokes remain unexplained, or 'cryptogenic'. There is a wide range of possible underlying causes in cryptogenic stroke, and the best approach to secondary prevention of these may differ. To date, though, the widely accepted and uniform secondary preventive strategy in this group consists of modification of vascular risk factors, and of treatment with a combination of antiplatelet therapy and antihypertensive and lipid-lowering medication. Among the potential causes for cryptogenic stroke are occult atrial fibrillation, patent foramen ovale, atrial cardiopathy, aortic arch atheroma and hypercoagulable states. While it is possible to diagnose these conditions, in individual patients there is often uncertainty over whether they have a directly causative role, are markers of disease, or are innocent bystanders. Similarly, even if the cause is found, the best secondary preventive strategies remain uncertain, which questions the benefit of extensive investigations in a clinical setting. More recently, the concept of "embolic stroke of unknown source (ESUS)" has been introduced, in the hope that anticoagulation may offer better secondary prevention than antiplatelet therapy, but trials so far have been negative. At present, there is little justification for introducing extensive new investigative strategies into the management of patients with cryptogenic stroke. Investigations should be targeted at identifying those high-risk conditions which lead to a change in management. Further investigations need to be tailored individually, according to clinical circumstances. This should include identifying patients for participation in clinical trials, as the significance and best management of many of the potential causes for cryptogenic stroke require further research.

Endovascular treatment of patients with high-risk symptomatic intracranial vertebrobasilar stenoses: long - term outcomes.

Background and purpose: We present the long-term outcome after endovascular treatment of symptomatic intracranial posterior circulation stenoses. Methods: 30 patients with symptomatic intracranial posterior circulation stenoses exceeding 70% underwent endovascular treatment between 2006 and 2012. Data regarding presentation, follow-up, procedure details, complications and imaging follow-up were reviewed. All surviving patients underwent a phone interview to establish their current Modified Ranking Scales (MRS). Results: Stenoses of the intracranial vertebral artery (24 patients) and basilar artery (6 patients) were treated with stents (10 patients), angioplasty alone (13 patients) or both (5 patients). Two procedures failed. One patient (3.3%) died after the procedure, two had stroke (6.6%) and one a subarachnoid haemorrhage without ensuing deficit. Two patients (6.7%) had asymptomatic complications (dissection and pseudoaneurysm). The median clinical follow-up time was 7 years. Of the 29 patients who survived the procedure, 6 died due to unrelated causes. Three patients (10%) had recurrent strokes and two (6.7%) a transient ischaemic attack in the posterior circulation. Two patients had subsequent middle cerebral artery strokes. Five (16.7%) patients had recurrent stenoses and three (10%) occlusions of the treated artery. Retreatment was performed in six patients, three (10%) with PTA and three (10%) with stenting. Current MRS scores were as follows: nine MRS 0, eight MRS 1, four MRS 2 and one MRS 4. Conclusions: Long-term follow-up after endovascular treatment of high-risk symptomatic intracranial posterior circulation stenoses shows few stroke recurrences. Treatment of intracranial vertebral artery stenosis may be beneficial in appropriately selected patients.

Vertebral artery stenting to prevent recurrent stroke in symptomatic vertebral artery stenosis: the VIST RCT.

BACKGROUND: Symptomatic vertebral artery (VA) stenosis has been associated with a markedly increased early risk of recurrent stroke. VA stenosis can be treated with stenting; however, there are few data from randomised controlled trials evaluating the efficacy of this treatment, and recent studies in intracranial stenosis have suggested that stenting may be associated with increased risk. OBJECTIVE: The Vertebral artery Ischaemia Stenting Trial (VIST) was established to compare the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for recently symptomatic VA stenosis. DESIGN: VIST was a prospective, randomised, open, parallel, blinded end-point clinical trial. SETTING: The trial was performed in 14 hospitals in the UK. PARTICIPANTS: Recruitment began on 23 October 2008 and follow-up ended on 1 March 2016, by which time every patient had been followed up for at least 1 year. Participants had to have symptomatic vertebral stenosis of at least 50% resulting from presumed atheromatous disease. Both patients and clinicians were aware of treatment allocation; however, an independent adjudication committee, masked to treatment allocation, assessed all primary and secondary end points. INTERVENTIONS: Participants were randomly assigned (1 : 1) to either vertebral angioplasty/stenting plus BMT (n = 91) or BMT alone (n = 88). A total of 182 patients were initially enrolled; however, three patients (two who withdrew after randomisation and one who did not attend after the initial randomisation visit) did not contribute any follow-up data and were excluded. None of these three patients had outcome events. MAIN OUTCOMES AND MEASURES: The primary end point was the occurrence of fatal or non-fatal stroke in any arterial territory during follow-up. RESULTS: The median follow-up was 3.5 (interquartile range 2.1-4.7) years. Of the 61 patients who were stented, 48 (78.7%) had extracranial stenosis and 13 (21.3%) had intracranial stenosis. No perioperative complications occurred with extracranial stenting; two strokes occurred during intracranial stenting. The primary end point occurred in five patients (including one fatal stroke) in the stent group and in 12 patients (including two fatal strokes) in the medical group (giving a hazard ratio of 0.40, 95% confidence interval 0.14 to 1.13; p = 0.08), with an absolute risk reduction of 25 strokes per 1000 person-years. LIMITATIONS: The study was underpowered because it failed to reach target recruitment. The high rate of non-confirmation of stenosis in the stented group of the trial was a second limitation. CONCLUSIONS: The trial found no difference in risk of the primary end point between the two groups. FUTURE: Post hoc analysis suggested that stenting could be associated with a reduced recurrent stroke risk in symptomatic VA and further studies are now required to confirm these findings, particularly in extracranial VA stenosis where complication rates with stenting were confirmed to be very low. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95212240. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 41. See the NIHR Journals Library website for further project information. In addition, funding for the pilot phase was provided by the Stroke Association.

About one-quarter of all strokes occur in the back of the brain, which is supplied by the vertebral and basilar arteries. An important cause of stroke is a narrowing, or stenosis, of these arteries. It is known that patients who have a minor stroke due to narrowing of a vertebral artery (VA) have a high risk of a further stroke: as much as 30% in the next year. Stenosis of the VA can be treated with stenting, in which a wire mesh is put into the narrowed artery and opens it up. Many operations to insert a vertebral stent have been carried out worldwide with good technical results; however, it is not known whether it is better to treat vertebral stenosis with stenting or only tablets. The Vertebral artery Ischaemia Stenting Trial was a randomised controlled trial comparing vertebral stenting and best medical treatment (BMT) with BMT alone in patients who had suffered a minor stroke due to vertebral stenosis. Ninety-one patients had stenting and 88 had BMT alone. Patients were followed for an average of 3.5 years. It was planned to enrol 540 patients to the trial, but recruitment was slower than expected and funding for the study was halted; therefore, recruitment was stopped at 181 patients. There was no difference in the rate of recurrent stroke between patients who had stenting and those who had BMT alone. There was some evidence that stenting might be associated with a reduced risk of recurrent stroke, but the difference was not significant. The trial was limited by the failure to recruit the anticipated sample size. The results tell us that stenting is a possible treatment for vertebral stenosis; however, further trials are required to determine whether or not it is more effective at preventing recurrent stroke than BMT alone.

Systematic review of associations between the presence of acute ischemic lesions on diffusion-weighted imaging and clinical predictors of early stroke risk after transient ischemic attack.

BACKGROUND AND PURPOSE: Early risk of stroke after a transient ischemic attack can be reliably predicted with risk scores based on clinical features of the patient and of the ischemic event, but it is unclear how these features correlate with findings on brain imaging. METHODS: We performed a systematic review of the literature and identified all previous studies which reported patient characteristics and the nature of transient ischemic attack symptoms in relation to appearances on diffusion-weighted imaging (DWI). We then performed a meta-analysis of the associations between the components of the risk scores and positive DWI. Authors were contacted for additional unpublished data. RESULTS: Nineteen studies were identified by the systematic review, and additional unpublished data were obtained from 11 of these studies. On meta-analysis, several components of the risk scores were associated with positive DWI, including symptom duration > or =60 minutes (13 studies, odds ratio [OR], 1.50; 95% CI, 1.16 to 1.96; P=0.004), dysphasia (9 studies, OR, 2.25; 95% CI, 1.57 to 3.22; P<0.001), dysarthria (8 studies, OR, 1.73; 95% CI, 1.11 to 2.68; P=0.03) and motor weakness (9 studies, OR, 2.20; 95% CI, 1.56 to 3.10; P<0.001). However patient age, sex, hypertension and diabetes were not associated with the presence of DWI lesions. From an etiologic perspective, atrial fibrillation (9 studies, OR, 2.75; 95% CI, 1.78 to 4.25; P<0.001) and ipsilateral > or =50% carotid stenosis (10 studies, OR, 1.93; 95% CI, 1.34 to 2.76; P=0.001) were associated with positive DWI. CONCLUSIONS: Presence of acute ischemic lesions on DWI correlates with several clinical features known to predict stroke risk after transient ischemic attack. Large studies (sample size >1000) will therefore be required to determine the independent prognostic value of DWI and its interactions with these clinical characteristics.

Stenting for symptomatic vertebral artery stenosis: The Vertebral Artery Ischaemia Stenting Trial.

OBJECTIVE: To compare in the Vertebral Artery Ischaemia Stenting Trial (VIST) the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for symptomatic vertebral artery stenosis. METHODS: VIST was a prospective, randomized, open-blinded endpoint clinical trial performed in 14 hospitals in the United Kingdom. Participants with symptomatic vertebral stenosis ≥50% were randomly assigned (1:1) to vertebral angioplasty/stenting plus BMT or to BMT alone with randomization stratified by site of stenosis (extracranial vs intracranial). Because of slow recruitment and cessation of funding, recruitment was stopped after 182 participants. Follow-up was a minimum of ≥1 year for each participant. RESULTS: Three patients did not contribute any follow-up data and were excluded, leaving 91 patients in the stent group and 88 in the medical group. Mean follow-up was 3.5 (interquartile range 2.1-4.7) years. Of 61 patients who were stented, stenosis was extracranial in 48 (78.7%) and intracranial in 13 (21.3%). No periprocedural complications occurred with extracranial stenting; 2 strokes occurred during intracranial stenting. The primary endpoint of fatal or nonfatal stroke occurred in 5 patients in the stent group vs 12 in the medical group (hazard ratio 0.40, 95% confidence interval 0.14-1.13, p = 0.08), with an absolute risk reduction of 25 strokes per 1,000 person-years. The hazard ratio for stroke or TIA was 0.50 (p = 0.05). CONCLUSIONS: Stenting in extracranial stenosis appears safe with low complication rates. Large phase 3 trials are required to determine whether stenting reduces stroke risk. ISRCTNCOM IDENTIFIER: ISRCTN95212240. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with symptomatic vertebral stenosis, angioplasty with stenting does not reduce the risk of stroke. However, the study lacked the precision to exclude a benefit from stenting.

Total small vessel disease score and risk of recurrent stroke: Validation in 2 large cohorts.

OBJECTIVE: In patients with TIA and ischemic stroke, we validated the total small vessel disease (SVD) score by determining its prognostic value for recurrent stroke. METHODS: Two independent prospective studies were conducted, one comprising predominantly Caucasian patients with TIA/ischemic stroke (Oxford Vascular Study [OXVASC]) and one predominantly Chinese patients with ischemic stroke (University of Hong Kong [HKU]). Cerebral MRI was performed and assessed for lacunes, microbleeds, white matter hyperintensities (WMH), and perivascular spaces (PVS). Predictive value of total SVD score for risk of recurrent stroke was determined and potential refinements considered. RESULTS: In 2,002 patients with TIA/ischemic stroke (OXVASC n = 1,028, HKU n = 974, 6,924 patient-years follow-up), a higher score was associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio [HR] per unit increase: 1.32, 1.16-1.51, p < 0.0001; c statistic 0.61, 0.56-0.65, p < 0.0001) and intracerebral hemorrhage (ICH) (HR 1.54, 1.11-2.13, p = 0.009; c statistic 0.65, 0.54-0.76, p = 0.006). A higher score predicted recurrent stroke in SVD and non-SVD TIA/ischemic stroke subtypes (c statistic 0.67, 0.59-0.74, p < 0.0001 and 0.60, 0.55-0.65, p < 0.0001). Including burden of microbleeds and WMH and adjusting the cutoff of basal ganglia PVS potentially improved predictive power for ICH (c statistic 0.71, 0.60-0.81, phet = 0.45), but not for recurrent ischemic stroke (c statistic 0.60, 0.56-0.65, phet = 0.76) on internal validation. CONCLUSIONS: The total SVD score has predictive value for recurrent stroke after TIA/ischemic stroke. Prediction of recurrence in patients with nonlacunar events highlights the potential role of SVD in wider stroke etiology.