Early Neurologic Deterioration after Stroke Depends on Vascular Territory and Stroke Etiology.
ABSTRACT: Early neurologic deterioration (END) occurs in up to one-third of patients with ischemic stroke and is associated with poor outcomes. The purpose of the present study was to determine which stroke etiologies and vascular distributions pose a greater threat of END in stroke patients.Using a single-center registry of prospectively maintained clinical data, adult ischemic stroke patients admitted (July 2008 to June 2014) within 48 hours of symptom onset were evaluated according to stroke etiology and vascular distribution using diffusion-weighted MRI. Major stroke etiologies were divided into cardioembolic, large vessel, small vessel, other, unknown source, and multiple possible etiologies. END was defined as a worsening of 2 or more points on the National Institutes of Health Stroke Scale during a 24-hour period of hospitalization. Crude and backward stepwise regression models were generated to associate stroke etiology and vascular distribution with END.Of the included 961 patients (median age 65 years, 47% female, 72% non-White), 323 (34%) experienced END. Strokes involving the internal carotid artery (ICA) were associated with a threefold higher odds of END in stepwise regression models (OR 3.0, 95% CI 1.4-6.6, P=0.006). Among stroke etiologies, those with unclear mechanisms had the lowest odds of END in the fully adjusted model (OR 0.6, 95% CI 0.4-1.0, P=0.029).In our single-center cohort of patients, ICA infarctions were independently associated with END whereas strokes of unknown etiology were least often associated with END. Larger cohorts are necessary to determine which steps, if any, can be taken to prevent END in these vulnerable populations.
Project description:Population-based studies have estimated that about 15% of ischemic strokes are caused by large-vessel cerebrovascular disease. We determined the types of large-vessel atherosclerosis responsible for ischemic strokes in a population-based stroke study.Patients with first-ever or recurrent ischemic stroke in the Greater Cincinnati area were identified during 2005 at all local hospitals. Study physicians assigned ischemic stroke subtypes. Overall event rates and incidence rates for first-ever events were calculated, and age-, race- and sex-adjusted to the 2000 US population.There were 2,204 ischemic strokes, including 365 strokes of large-vessel subtype (16.6% of all ischemic strokes). Extracranial internal carotid artery (ICA) stenosis was associated with 8.0% of all ischemic strokes, while extracranial ICA occlusion and intracranial atherosclerosis were each associated with 3.5% of strokes. The annual rate of first-ever and recurrent stroke attributed to extracranial ICA was 13.4 (11.4-15.4) per 100,000 persons. We conservatively estimate that about 41,000 strokes may be attributed to extracranial ICA stenosis annually in the United States.Large-vessel atherosclerosis is an important cause of stroke, with extracranial ICA stenosis being significantly more common than extracranial ICA occlusion or intracranial atherosclerotic disease.
Project description:Ischemic stroke can be classified depending on its etiology as cardioembolic (CE), large-vessel atheroesclerotic (LAA), lacunar, other or cryptogenic. Our aim was to identify gene expression changes that could differentiate CE and LAA stroke in order to guide the optimal secondary treatment . Overall design: Blood from 26 ischemic stroke patients (18 CE and 8 LAA) was collected into EDTA tubes within the first 4.5h after the onset of neurological symptoms. After centrifugation, buffy coat was mixed with RNAlater solution and preserved at -80°C until RNA isolation. In order to obtain a common signature and to avoid interindividual variability, equal amounts of RNA from individual samples were pooled based on their stroke etiology and according to clinical characteristics: 18 CE strokes were divided among 7 different pools and 8 LAA strokes among 4 pools.
Project description:BACKGROUND AND PURPOSE:Most cryptogenic strokes are thought to have an embolic source. We sought to determine whether cryptogenic strokes are associated with visceral infarcts, which are usually embolic. METHODS:Among patients prospectively enrolled in CAESAR (Cornell Acute Stroke Academic Registry), we selected those with a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. Our exposure variable was adjudicated stroke subtype per the Trial of ORG 10172 in Acute Stroke Treatment classification. Our outcome was renal or splenic infarction as assessed by a single radiologist blinded to stroke subtype. We used Fisher exact test and multiple logistic regression to compare the prevalence of visceral infarcts among cardioembolic strokes, strokes of undetermined etiology, and noncardioembolic strokes (large- or small-vessel strokes). RESULTS:Among 227 patients with ischemic stroke and a contrast-enhanced abdominal computed tomographic scan, 59 had a visceral infarct (35 renal and 27 splenic). The prevalence of visceral infarction was significantly different among cardioembolic strokes (34.2%; 95% confidence interval [CI], 23.7%-44.6%), strokes of undetermined etiology (23.9%; 95% CI, 15.0%-32.8%), and strokes from large-artery atherosclerosis or small-vessel occlusion (12.5%; 95% CI, 1.8%-23.2%; P=0.03). In multiple logistic regression models adjusted for demographics and vascular comorbidities, we found significant associations with visceral infarction for both cardioembolic stroke (odds ratio, 3.5; 95% CI, 1.2-9.9) and stroke of undetermined source (odds ratio, 3.3; 95% CI, 1.1-10.5) as compared with noncardioembolic stroke. CONCLUSIONS:The prevalence of visceral infarction differed significantly across ischemic stroke subtypes. Cardioembolic and cryptogenic strokes were associated with a higher prevalence of visceral infarcts than noncardioembolic strokes.
Project description:Determining the cause of stroke is considered one of the main objectives in evaluating a stroke patient in clinical practice. However, ischemic stroke is a heterogeneous disorder and numerous underlying disorders are implicated in its pathogenesis. Although progress has been made in identifying individual stroke etiology, in many cases underlying mechanisms still remain elusive. Since secondary prevention strategies are tailored toward individual stroke mechanisms, patients whose stroke etiology is unknown may not receive optimal preventive treatment. Cardioembolic stroke is commonly defined as cerebral vessel occlusion by distant embolization arising from thrombus formation in the heart. It accounts for the main proportion of ischemic strokes, and its share to stroke etiology is likely to rise even further in future decades. However, it can be challenging to distinguish cardioembolism from other possible etiologies. As personalized medicine advances, stroke researchers' focus is increasingly drawn to etiology-associated biomarkers. They can provide deeper insight regarding specific stroke mechanisms and can help to unravel previously undetected pathologies. Furthermore, etiology-associated biomarkers could play an important role in guiding future stroke prevention strategies. To achieve this, broad validation of promising candidate biomarkers as well as their implementation in well-designed randomized clinical trials is necessary. This review focuses on the most-promising candidates for diagnosis of cardioembolic stroke. It discusses existing evidence for possible clinical applications of these biomarkers, addresses current challenges, and outlines future perspectives.
Project description:Stroke is one of the main causes of death and disability in the world. Cardioembolic etiology accounts for approximately one fifth of all ischemic strokes whereas 25-30% remains undetermined even after an advanced diagnostic workup. Despite there is not any biomarker currently approved to distinguish cardioembolic stroke among other etiologies in clinical practice the use of biomarkers represents a promising valuable complement to determine stroke etiology reducing the number of cryptogenic strokes and aiding in the prescription of the most appropriated primary and secondary treatments in order to minimize therapeutic risks and to avoid recurrences. In this review we present an update about specific cardioembolic stroke-related biomarkers at a protein, transcriptomic and genetic level. Finally, we also focused on reported biomarkers associated with atrial fibrillation (a cardiac illness strongly related with cardioembolic stroke subtype) thus with a potential to become biomarkers to detect cardioembolic stroke in the future.
Project description:We examined practice patterns of inpatient testing to identify stroke etiologies and treatable risk factors for acute ischemic stroke recurrence.We identified stroke cases and related diagnostic testing from four 1-year study periods (July 1993 to June 1994, 1999, 2005, and 2010) of the Greater Cincinnati/Northern Kentucky Stroke Study. Patients aged ?18 years were included. We focused on evaluation of extracranial arteries for carotid stenosis and assessment of atrial fibrillation because randomized controlled trials supported treatment of these conditions for stroke prevention across all 4 study periods. In each study period, we also recorded stroke etiology, as determined by diagnostic testing and physician adjudication. An increasing proportion of stroke patients received assessment of both extracranial arteries and the heart over time (50%, 58%, 74%, and 78% in the 1993-1994, 1999, 2005, and 2010 periods, respectively; P<0.0001 for trend), with the most dramatic individual increases in echocardiography (57%, 63%, 77%, and 83%, respectively). Concurrently, we observed a decrease in strokes of unknown etiology (47%, 48%, 41%, and 38%, respectively; P<0.0001 for trend). We also found a significant increase in strokes of other known causes (32%, 25%, 45% and 59%, respectively; P<0.0001 for trend).Stroke workup for treatable causes of stroke are being used more frequently over time, and this is associated with a decrease in cryptogenic strokes. Future study of whether better determination of treatable stroke etiologies translates to a decrease in stroke recurrence at the population level will be essential.
Project description:OBJECTIVE:The cause of stroke remains unknown or cryptogenic in many patients. We sought to determine whether gene expression signatures in blood can distinguish between cardioembolic and large-vessel causes of stroke, and whether these profiles can predict stroke etiology in the cryptogenic group. METHODS:A total of 194 samples from 76 acute ischemic stroke patients were analyzed. RNA was isolated from blood and run on Affymetrix U133 Plus2.0 microarrays. Genes that distinguish large-vessel from cardioembolic stroke were determined at 3, 5, and 24 hours following stroke onset. Predictors were evaluated using cross-validation and a separate set of patients with known stroke subtype. The cause of cryptogenic stroke was predicted based on a model developed from strokes of known cause and identified predictors. RESULTS:A 40-gene profile differentiated cardioembolic stroke from large-vessel stroke with >95% sensitivity and specificity. A separate 37-gene profile differentiated cardioembolic stroke due to atrial fibrillation from nonatrial fibrillation causes with >90% sensitivity and specificity. The identified genes elucidate differences in inflammation between stroke subtypes. When applied to patients with cryptogenic stroke, 17% are predicted to be large-vessel and 41% to be cardioembolic stroke. Of the cryptogenic strokes predicted to be cardioembolic, 27% were predicted to have atrial fibrillation. INTERPRETATION:Gene expression signatures distinguish cardioembolic from large-vessel causes of ischemic stroke. These gene profiles may add valuable diagnostic information in the management of patients with stroke of unknown etiology though they need to be validated in future independent, large studies.
Project description:HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke.
Project description:Lacunar stroke is common, but the etiology of the small vessel abnormality is unknown. Retinal vessels share ontogeny, size, and physiologic characteristics with cerebral small vessels, and retinopathy is associated with stroke. We compared retinal microvessel appearance as a surrogate for cerebral small vessels in patients with lacunar and large artery cortical ischemic stroke.We prospectively recruited patients with lacunar ischemic stroke and cortical stroke controls. We took digital retinal photographs of each eye. We assessed central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) diameters and arteriovenous ratios (AVRs) using semiautomated computer software methods and quantified arteriovenous nicking and focal arteriolar narrowing.Among 212 patients (105 lacunar, 107 cortical strokes) of mean age 68 years (SD 12 years), AVR was decreased (0.76 vs 0.78, p = 0.03) and CRVE was increased (44.9 pixels/218 microm vs 42.8 pixels/208 microm, p = 0.01) in lacunar patients compared with cortical patients, but CRAE did not differ (33.2 pixels/161 microm vs 33.7 pixels/163 microm, p = 0.4). On multivariable analysis, increased CRVE was associated with lacunar stroke subtype (p = 0.03) and younger age (p < 0.001) after correcting for other vascular risk factors. Arteriovenous nicking and focal arteriolar narrowing did not differ between ischemic stroke subtypes.Retinal venules are wider and arteriovenous ratios are smaller in patients with lacunar strokes compared with those in patients with cortical strokes.
Project description:Randomized trials support carotid endarterectomy (CEA) in asymptomatic patients with ?60% internal carotid artery (ICA) stenosis. The widely referenced Society for Radiologists in Ultrasound Consensus Statement on carotid duplex ultrasound (CDUS) imaging indicates that an ICA peak systolic velocity (PSV) ?230 cm/s corresponds to a ?70% ICA stenosis, leading to the potential conclusion that asymptomatic patients with an ICA PSV ?230 cm/s would benefit from CEA. Our goal was to determine the natural history stroke risk of asymptomatic patients who might have undergone CEA based on consensus statement PSV of ?230 cm/s but instead were treated medically based on more conservative CDUS imaging criteria.All patients who underwent CDUS imaging at our institution during 2009 were retrospectively reviewed. The year 2009 was chosen to ensure extended follow-up. Asymptomatic patients were included if their ICA PSV was ?230 cm/s but less than what our laboratory considers a ?80% stenosis by CDUS imaging (PSV ?430 cm/s, end-diastolic velocity ?151 cm/s, or ICA/common carotid artery PSV ratio ?7.5). Study end points included freedom from transient ischemic attack (TIA), freedom from any stroke, freedom from carotid-etiology stroke, and freedom from revascularization.Criteria for review were met by 327 patients. Mean follow-up was 4.3 years, with 85% of patients having >3-year follow-up. Four unheralded strokes occurred during follow-up at <1, 17, 25, and 30 months that were potentially attributable to the index carotid artery. Ipsilateral TIA occurred in 17 patients. An additional 12 strokes occurred that appeared unrelated to ipsilateral carotid disease, including hemorrhagic events, contralateral, and cerebellar strokes. Revascularization was undertaken in 59 patients, 1 for stroke, 12 for TIA, and 46 for asymptomatic disease. Actuarial freedom from carotid-etiology stroke was 99.7%, 98.4%, and 98.4% at 1, 3, and 5 years, respectively. Freedom from TIA was 98%, 96%, and 95%, freedom from any stroke was 99%, 96%, and 93%, and freedom from revascularization was 95%, 86%, and 81% at 1, 3, and 5 years, respectively.Patients with intermediate asymptomatic carotid stenosis (ICA PSV 230-429 cm/s) do well with medical therapy when carefully monitored and intervened upon using conservative CDUS criteria. Furthermore, a substantial number of patients would undergo unnecessary CEA if consensus statement CDUS thresholds are used to recommend surgery. Current velocity threshold recommendations should be re-evaluated, with potentially important implications for upcoming clinical trials.