Association of neonatal inflammatory markers and perinatal stroke subtypes.

OBJECTIVE: To examine the relationship between neonatal inflammatory cytokines and perinatal stroke using a systems biology approach analyzing serum and blood-spot cytokines from 47 patients. METHODS: This was a population-based, controlled cohort study with prospective and retrospective case ascertainment. Participants were recruited through the Alberta Perinatal Stroke Project. Stroke was classified as neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or periventricular venous infarction (PVI). Biosamples were stored blood spots (retrospective) and acute serum (prospective). Controls had comparable gestational and maternal ages. Sixty-five cytokines were measured (Luminex). Hierarchical clustering analysis was performed to create heat maps. The Fisher linear discriminant analysis was used to create projection models to determine discriminatory boundaries between stroke types and controls. RESULTS: A total of 197 participants were analyzed (27 with NAIS, 8 with APPIS, 12 with PVI, 150 controls). Cytokines were quantifiable with quality control measures satisfied (standards testing, decay analysis). Linear discriminant analysis had high accuracy in using cytokine profiles to separate groups. Profiles in participants with PVI and controls were similar. NAIS separation was accurate (sensitivity 77%, specificity 97%). APPIS mapping was also distinguishable from NAIS (sensitivity 86%, specificity 99%). Classification tree analysis generated similar diagnostic accuracy. CONCLUSIONS: Unique inflammatory biomarker signatures are associated with specific perinatal stroke diseases. Findings support an acquired pathophysiology and suggest the possibility that at-risk pregnancies might be identified to develop prevention strategies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that differences in acute neonatal serum cytokine profiles can discriminate between patients with specific perinatal stroke diseases and controls.

Reclassification of Ischemic Stroke Etiological Subtypes on the Basis of High-Risk Nonstenosing Carotid Plaque.

Background and Purpose- Carotid artery plaque with <50% luminal stenosis may be an underappreciated stroke mechanism. We assessed how many stroke causes might be reclassified after accounting for nonstenosing plaques with high-risk features. Methods- We included patients enrolled in the Cornell Acute Stroke Academic Registry from 2011 to 2015 who had anterior circulation infarction, magnetic resonance imaging of the brain, and magnetic resonance angiography of the neck. High-risk plaque was identified by intraplaque hemorrhage ascertained from routine neck magnetic resonance angiography studies using validated methods. Infarct location was determined from diffusion-weighted imaging. Intraplaque hemorrhage and infarct location were assessed separately in a blinded fashion by a neuroradiologist. We used the McNemar test for matched data to compare the prevalence of intraplaque hemorrhage ipsilateral versus contralateral to brain infarction. We reclassified stroke subtypes by including large-artery atherosclerosis as a cause if there was intraplaque hemorrhage ipsilateral to brain infarction, regardless of the degree of stenosis. Results- Among the 1721 acute ischemic stroke patients registered in the Cornell Acute Stroke Academic Registry from 2011 to 2015, 579 were eligible for this analysis. High-risk plaque was more common ipsilateral versus contralateral to brain infarction in large-artery atherosclerotic (risk ratio [RR], 3.7 [95% CI, 2.2-6.1]), cryptogenic (RR, 2.1 [95% CI, 1.4-3.1]), and cardioembolic strokes (RR, 1.7 [95% CI, 1.1-2.4]). There were nonsignificant ipsilateral-contralateral differences in high-risk plaque among lacunar strokes (RR, 1.2 [95% CI, 0.4-3.5]) and strokes of other determined cause (RR, 1.5 [95% CI, 0.7-3.3]). After accounting for ipsilateral high-risk plaque, 88 (15.2%) patients were reclassified: 38 (22.6%) cardioembolic to multiple potential etiologies, 6 (8.5%) lacunar to multiple, 3 (15.8%) other determined cause to multiple, and 41 (20.8%) cryptogenic to large-artery atherosclerosis. Conclusions- High-risk carotid plaque was more prevalent ipsilateral to brain infarction across several ischemic stroke subtypes. Accounting for such plaques may reclassify the etiologies of up to 15% of cases in our sample.

Small obliquely oriented cortical cerebellar infarctions are associated with cardioembolic stroke.

BACKGROUND: A revised classification of cerebellar infarctions (CI) may uncover unrecognized associations with etiologic stroke subtypes. We hypothesized that obliquely oriented small cortical cerebellar infarction (SCCI) representing end zone infarctions on MRI would be associated with cardiac embolism. METHODS: We retrospectively analyzed consecutive stroke patients recruited between January-December 2016 in our center. Analyzed baseline characteristics: sex, age, cardiovascular risk factors, history of stroke or atrial fibrillation (AF). TOAST classification was used for determining stroke subtype. Acute infarction location (anterior/posterior/mixed anterior-posterior circulation), acute uni- or multiterritorial infarction, and acute or chronic CI/SCCI/non-SCCI were assessed by MRI, and vertebrobasilar stenosis/occlusion by vessel imaging. Pre-specified analysis was also performed in patients without known high cardioembolic risk (known AF history or acute multiterritorial infarction). RESULTS: We included 452 patients (CI in 154, isolated SCCI in 55, isolated non-SCCI in 50, and mixed SCCI/non-SCCI in 49). Both SCCI and non-SCCI were associated with AF history (SCCI, p = 0.021; non-SCCI, p = 0.004), additional acute posterior circulation infarction (p < 0.001 both CI-subtypes), multiterritorial infarctions (SCCI, p = 0.003; non-SCCI, p < 0.001) and cardioembolic more frequent than large-artery atherosclerosis origin (p < 0.001 for both CI-subtypes). SCCI was associated with older age (p < 0.001), whereas non-SCCI was associated with stroke history (p = 0.036) and vertebrobasilar stenosis/occlusion (p = 0.002). SCCI were older (p = 0.046) than non-SCCI patients, had less frequently prior stroke (p < 0.001), and more frequent cardioembolic infarction (p = 0.025). In patients without known high cardioembolic risk (n = 348), SCCI was strongly associated with subsequent cardioembolism diagnosis (OR 3.00 [CI 1.58-5.73, p < 0.001]). No such association was present in non-SCCI. CONCLUSIONS: Acute or chronic SCCI are strongly associated with a cardioembolic origin.

Imaging of Brain Infarctions: Beyond the Usual Territories.

In this review, our intension is to present imaging features of several categories of uncommon cases of brain infarctions including infarctions associated with neurovascular variants, infarctions along small arterial territories, and brainstem stroke syndromes. Infarctions associated with neurovascular variants include azygos anterior cerebral artery territory infarction and artery of Percheron infarction. In the second group, we discuss anterior choroidal artery infarction and artery of Heubner infarction. The third group highlights brainstem stroke syndromes, including Claude and Benedikt syndromes due to midbrain infarction; Foville, Marie Foix, and locked-in syndromes due to pontine infarction; and Dejerine (medial medullary), bilateral medial medullary, and Wallenberg (lateral medullary) syndromes.

A retrospective study of branch atheromatous disease: Analyses of risk factors and prognosis.

The theory of branch atheromatous disease (BAD) has been commonly underused in clinical practice and research since it was proposed in 1989. In this study, we sought to explore clinical characteristics of its substypes and biomarkers for prognosis of BAD. A total of 176 consecutive patients with BAD were classified into two groups: paramedianpontine artery group (PPA group, n=70) and lenticulostriate artery group (LSA group, n=106). Bivariate analyses were used to explore the relationship between white matter hyperintensities (WMHs), National Institutes of Health Stroke Scale (NIHSS) scores and prognosis evaluated by the modified Rank Scale (mRS) at 6th month after stroke. The differences in prevalence of diabetes mellitus and a history of ischemic heart disease were statistically significant between PPA group and LSA group (χ 2=8.255, P=0.004; χ 2=13.402, P<0.001). The bivariate analyses demonstrated a positive correlation between NIHSS and poor prognosis in patients with BAD and in the two subtype groups, and a positive correlation between WMHs and poor prognosis in the PPA group. It is concluded that a significantly higher prevalence of diabetes mellitus and a history of ischemic heart disease exist in the PPA group than in the LSA group. In addition, high grades of NIHSS scores imply poor prognosis in patients with BAD and in the two subtype groups. Moreover, WMHs are a positive predictor for poor prognosis in patients in the PPA group.

Etiologic Subtypes of Watershed Infarcts.

BACKGROUND: Two types of watershed infarcts (WI) are recognized. Internal WI are usually attributed to either severe stenosis in large arteries or acute hypotensive events, whereas external WI are thought to be caused by embolism. The aim of this study was to determine the etiologic background and prognosis of external and internal WI in our patients. METHODS: We reviewed the medical records and diffusion-weighted images of the patients who were admitted to our stroke unit with acute ischemic stroke between January 2012 and November 2014. The demographics, clinical features, radiologic investigations, and other etiologic tests of the patients with internal or external WI were recorded. We determined etiologic stroke subtypes according to the automated Causative Classification System. RESULTS: Fifty-three patients with WI were detected in our registry. Twenty-two (41.5%) of them were women. The mean age was 69 ± 12.8 (33-98) years. Twenty-one (39.6%) patients had external WI: 7 (33.3%) of them had large-artery atherosclerosis (LAA), 8 (38.1%) patients had cardioembolism, 3 (14.3%) patients had stroke due to other causes (vasculitis; n = 3), and etiologic subtype was undetermined in 3 patients (14.3%). Thirty-two (60.4%) patients had internal WI: 21 (65.6.%) of them had LAA, 5 (15.6%) patients had cardioembolism, 3 (9.4%) patients had stroke due to other causes (aneurysm; n = 1, hypercoagulability due to chronic myeloid leukemia; n = 1, vasculitis; n = 1), and etiologic subtype of 3 (9.4%) patients remained cryptogenic. LAA was significantly associated with internal WI (P = .024). Hypertension was more common in patients with internal WI (P = .035). CONCLUSIONS: In this series, cardioembolism was the most common etiologic subtype in the patients with external WI, whereas internal WI were significantly associated with LAA. Uncommon causes should also be investigated in cryptogenic patients.

Hypertension before and after posterior circulation infarction: analysis of data from the South London Stroke Register.

BACKGROUND: Postmortem data have shown that blood pressure before death correlates more closely with a narrowing of the vertebral arteries than any other vessel studied. This study explores a possible association between hypertension, both before and after posterior circulation infarction (POCI) compared to anterior circulation infarction (ACI). METHODS: Patients with a first-ever stroke enrolled in the South London Stroke Register between 2000 and 2006 were included. Chi-square tests and multivariable logistic regression were used to compare risk factors including hypertension, sex, smoking history, diabetes, and hypercholesterolemia in patients with POCI compared to ACI. Chi-square testing was used to compare the incidence of newly diagnosed hypertension after POCI and ACI. Absolute blood pressure readings recorded before stroke and 7 days after stroke were also compared between groups. RESULTS: On multivariable analysis, POCI was significantly associated with male sex (odds ratio [OR] 2.24; 95% confidence interval [CI] 1.55-3.22; P < .001) and hypertension (OR 1.69; 95% CI 1.15-2.50; P = .008). After stroke, patients with POCI were more likely to be newly diagnosed with hypertension during a 1-year follow-up period (OR 2.15; 95% CI 1.20-3.86; P = .009) and as an inpatient (OR 3.27; 95% CI 1.49-7.13; P = .002). Systolic blood pressure was significantly higher in the POCI group before stroke (152 v 146 mm Hg; P = .027). Diastolic blood pressure was significantly higher 7 days poststroke (81 v 74 mm Hg; P = .01) in patients not previously diagnosed with hypertension. CONCLUSIONS: This study has shown a significant association between hypertension before and after POCI compared to ACI. We believe further investigation with brainstem imaging and recordings of sympathetic nervous system activity after stroke is warranted.

Border zone infarcts: pathophysiologic and imaging characteristics.

Border zone or watershed infarcts are ischemic lesions that occur in characteristic locations at the junction between two main arterial territories. These lesions constitute approximately 10% of all brain infarcts and are well described in the literature. Their pathophysiology has not yet been fully elucidated, but a commonly accepted hypothesis holds that decreased perfusion in the distal regions of the vascular territories leaves them vulnerable to infarction. Two types of border zone infarcts are recognized: external (cortical) and internal (subcortical). To select the most appropriate methods for managing these infarcts, it is important to understand the underlying causal mechanisms. Internal border zone infarcts are caused mainly by hemodynamic compromise, whereas external border zone infarcts are believed to result from embolism but not always with associated hypoperfusion. Various imaging modalities have been used to determine the presence and extent of hemodynamic compromise or misery perfusion in association with border zone infarcts, and some findings (eg, multiple small internal infarcts) have proved to be independent predictors of subsequent ischemic stroke. A combination of several advanced techniques (eg, diffusion and perfusion magnetic resonance imaging and computed tomography, positron emission tomography, transcranial Doppler ultrasonography) can be useful for identifying the pathophysiologic process, making an early clinical diagnosis, guiding management, and predicting the outcome.

Diabetes mellitus and risk of stroke and its subtypes among Japanese: the Japan public health center study.

BACKGROUND AND PURPOSE: Although diabetes mellitus has been recognized as a risk factor for ischemic stroke, evidence is limited for ischemic stroke subtypes among Asians. METHODS: A survey was conducted of a total of 13 129 men and 22 528 women aged 40 to 69 years at baseline. During the median 12.0-year follow-up, there were 526 incidences of ischemic strokes (259 lacunar infarctions, 91 large-artery occlusive, and 140 embolic infarctions). RESULTS: The risk of ischemic stroke for both sexes was approximately 2 to 4 times higher for diabetic subjects than for those with normal glucose levels. Significant excess risks of lacunar and embolic infarction for both sexes and of large-artery occlusive infarctions for women were also observed in diabetic subjects. Diabetes mellitus was not associated with risk of intraparenchymal or subarachnoid hemorrhage for either sex. CONCLUSIONS: Diabetes mellitus is a significant risk factor for ischemic stroke and all subtypes of ischemic stroke for middle-aged Japanese.

Silent brain infarcts, leukoaraiosis, and long-term prognosis in young ischemic stroke patients.

OBJECTIVE: To investigate prognostic relevance of silent brain infarcts (SBIs) and leukoaraiosis (LA) in young patients with ischemic stroke. METHODS: This observational cohort study included consecutive MRI-scanned patients aged 15 to 49 with first-ever ischemic stroke treated at Helsinki University Central Hospital (1994-2007) with long-term follow-up data available. Outcome measures were 1) nonfatal or fatal ischemic stroke, 2) composite vascular endpoint, and 3) death from any cause. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and Bamford criteria allowed for stroke subtyping. Number of SBIs was categorized into none, single, or multiple. LA fell into groups of none, mild, or moderate to severe (validated visual rating scale). RESULTS: The 655 patients (mean age 40.0 ± 8.0 years) included were followed for a mean 8.7 ± 3.8 years (survivors). Of the 86 (13.1%) patients with SBIs, 46 had single and 40 had multiple SBIs. In the 50 (7.6%) patients with LA, these changes were mild in 21 and moderate to severe in 29. In Cox regression analysis, multiple SBIs independently raised the risk for recurrent ischemic stroke (odds ratio 2.48; 95% confidence interval 1.24-4.94) adjusted for age, gender, risk factors, stroke etiology, and LA. After further adjustment for initial stroke severity, TOAST and Bamford subgroups, and presence of SBIs, moderate to severe LA increased the risk for death (3.43; 1.58-7.42). Neither SBIs nor LA associated with the composite vascular endpoint. CONCLUSIONS: MRI-defined SBIs and LA are prognostically valuable in young adults after their first-ever ischemic stroke.

Wide variation in definition, detection, and description of lacunar lesions on imaging.

BACKGROUND AND PURPOSE: Variation in the definition of lacunar lesions on imaging and difficulties in their detection may be hampering lacunar stroke research. We assessed literature definitions of imaging lacunar lesions and the definitions and detection of lacunar lesions among small-vessel disease researchers. METHODS: We assessed definitions of imaging lacunar lesion in 50 randomly selected articles from 3 stroke-related journals and an online survey of small-vessel disease researchers. In the literature review, we assessed clinical/imaging definitions of lacunar stroke. In the survey, we assessed lacunar lesion detection, effects of lesion appearance, background white matter lesions, and provision of relevant data. RESULTS: Among 50 articles, imaging definitions were varied and often limited; size was stated in 21 of 43 (49%) studies of acute and in 9 of 20 (45%) studies of old lesions and site in 18 (42%) and 4 (20%), respectively. Clinical definitions also varied, and images were read mostly by nonradiologists. Among 56 survey respondents, multiple descriptions were used for recent and old, symptomatic and asymptomatic, lesions on imaging. Most agreed on definitions for site (98%) and "old lacunar infarct" (61%) size. Cavitated (vs noncavitated) lesions were usually identified as lacunar lesions; with increasing white matter lesions, however, noncavitated lesions were very unlikely to be identified, even with prior imaging available (7.8%). CONCLUSIONS: Imaging definitions of lacunar lesions vary widely, in part due to variation in lesion detection and classification. A consensus for imaging definitions of small-vessel disease features would be helpful.

Nineteen-year trends in risk factors, clinical characteristics and prognosis in lacunar infarcts.

BACKGROUND: Cardiovascular risk factors, clinical features and early outcome of first-ever cerebral lacunar infarcts from 1986 to 2004, using the Sagrat Cor Hospital of Barcelona Stroke Registry, were assessed and compared with data from patients with nonlacunar infarction. METHODS: The study population consisted of 566 patients with lacunar infarct and 1,516 patients with nonlacunar infarct. Secular trends for the periods 1986-1992, 1993-1998 and 1999-2004 were analyzed. RESULTS: Age and the percentage of very old patients (≥85 years old) increased significantly (p < 0.001) throughout the time period. There was a significant decrease in the percentage of patients with hypertension, but the percentage of patients with chronic obstructive pulmonary disease increased. The use of brain magnetic resonance imaging (MRI) also increased significantly. The median length of hospital stay decreased significantly. CONCLUSIONS: Significant changes over a 19-year period included an increase in the patients' age, frequency of very old patients (≥85 years old) and use of MRI studies, whereas the frequency of hypertension and length of hospital stay decreased.

Endothelial activation in lacunar stroke subtypes.

BACKGROUND AND PURPOSE: Lacunar stroke (LS) can be subtyped according to the absence (isolated lacunar infarct [ILA]) or presence of concomitant white matter lesions (WML) and/or asymptomatic lacunar infarcts. Endothelial activation is thought to play a pivotal role in the subtype with WML and/or asymptomatic lacunar infarcts. The aim of this study was to evaluate whether endothelial activation is associated with WML and/or asymptomatic lacunar infarcts in LS patients. Here, we determined levels of circulating blood markers of endothelial function in LS patients. METHODS: In 149 patients, all of whom had brain-MRI, levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA-PAI-1 complex, von Willebrand factor, tissue factor, thrombomodulin, and coagulation factor VIII were determined. Levels of blood markers were related to subtypes of LS and adjusted for age, gender, and vascular risk factors. RESULTS: In subtypes of LS, tPA activity was increased in patients with WML (0.79 IU/mL vs 0.44 IU/mL for ILA; P=0.02) and PAI-1-antigen levels were lowest in patients with WML (27.5 ng/mL vs 44.0 ng/mL for ILA; P=0.02). The association between WML and PAI-1 remained significant after multivariable analysis (OR, 0.99; 95% CI, 0.98-1.00 per ng/mL change of PAI-1; P=0.04). CONCLUSIONS: We found further evidence for the hypothesis of endothelial activation in the subtype of LS caused by a diffuse small vessel vasculopathy, as we found higher levels of tPA in patients with concomitant extensive WML than in those with ILA. Second, low levels of PAI-1 were associated with WML. We postulate that differences in activity of components of the fibrinolytic system might contribute to WML development.

Prevalence of silent myocardial ischemia in single and multiple lacunar infarcts and large vessel disease stroke.

BACKGROUND AND PURPOSE: The relationships between single (SLI) and multiple lacunar infarcts (MLI) and occult coronary artery disease (CAD) have not yet been sufficiently evaluated. We aimed to investigate the prevalence of silent CAD in patients with SLI, MLI and large vessel disease (LVD) stroke, and to identify factors associated with its presence. METHODS: We enrolled 125 patients who had suffered their first non-cardioembolic ischemic stroke but had no documented history of CAD. According to their pathologies, these patients were assigned to one of three groups: MLI (n=21), SLI (n=50) or LVD (n=54). Asymptomatic CAD was detected by myocardial perfusion SPECT imaging. RESULTS: Silent CAD was detected in 40 patients (32% of the total); of those that experienced CAD, 15 (30%) were from the SLI group, 7 (33%) had MLI, and 18 (33%) had an LVD stroke. Differences between the groups were not significant. During a median follow-up of 48 months, the overall stroke recurrence was 8.8%; the stroke recurrence rates for each subgroup were 6% in patients with SLI, 7% in LVD and 19% in MLI. Mortality was higher in patients from the MLI and LVD groups (26% and 14%, respectively) than in those from the SLI group (6%; p=0.02). We found no relationships between the various risk factors and silent CAD. CONCLUSIONS: In this exploratory study, SPECT imaging results revealed that the prevalence of abnormal myocardial perfusion was similar in patients with either single or multiple lacunar infarcts and those that had experienced large vessel disease stroke.

Metabolic syndrome relates to lacunar stroke without white matter lesions: a study in first-ever lacunar stroke patients.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of three or more of the following risk factors: obesity, elevated blood pressure, elevated triglyceride level, elevated glucose level, and low high-density lipoprotein level. Lacunar infarcts (LS) account for 25% of all ischemic strokes and are small, deeply located brain infarcts. Two different subtypes exist, which are distinguished by the presence of concomitant white matter lesions (WML) on brain imaging. We determined the prevalence of MetS in LS and the association between MetS with LS subtypes in a series of first-ever LS patients. METHODS: We included 92 patients with a first-ever LS, and 92 patients with a first-ever atheroslerotic cortical stroke (CS) matched for age and sex. LS subtypes were defined according to presence of concomitant WML. We defined MetS retrospectively according to previously defined standards. RESULTS: 35.9% of LS patients and 45.7% of CS patients had MetS (OR 0.67; 95% CI 0.37-1.20). MetS was more prevalent in LS without WML than in LS with WML (44.4 and 23.7%, respectively; OR 2.98; 95% CI 1.04-8.47). Similarly, MetS related more to CS compared to LS with WML (OR 2.56; 95% CI 1.03-6.37). CONCLUSION: MetS relates more strongly to LS without WML and to CS, than to LS with WML. Our results suggest a different underlying mechanism between LS without WML and CS, and lacunar stroke with WML.

Associations of clinical stroke misclassification ('clinical-imaging dissociation') in acute ischemic stroke.

BACKGROUND: Up to 20% of lacunar infarcts are clinically misdiagnosed as cortical infarcts and vice versa. The reasons for this discrepancy are unclear. We assessed clinical and imaging features which might explain this 'clinical-imaging dissociation' (C-ID). METHODS: Patients with an acute stroke syndrome (cortical or lacunar) underwent magnetic resonance imaging including diffusion-weighted imaging (DWI). We recorded DWI-positive infarcts and proximity to cortex for small subcortical infarcts. We examined factors associated with C-ID. RESULTS: 137 patients with a mild cortical or lacunar syndrome had an acute ischemic lesion on DWI. Of these, 21/93 (23%) with a cortical syndrome had an acute lacunar infarct and 7/44 (16%) with a lacunar syndrome had an acute cortical infarct. From 72 patients with an acute lacunar infarct on DWI, lesion proximity to cortex (odds ratio (OR) 14.5, 95% confidence interval (CI) 1.61-130.1), left hemisphere location (OR 8.95, 95% CI 1.23-64.99) and diabetes (OR 17.1, 95% CI 1.49-196.16) predicted C-ID. On multivariate analysis of all 137 patients, C-ID was associated with diabetes (OR 7.12, 95% CI 1.86-27.2). CONCLUSIONS: C-ID occurs in a fifth of patients with mild stroke. Lacunar infarcts lying close to cortex are more likely to cause cortical symptoms. Diabetes is associated with any clinical-imaging mismatch. Stroke misclassification which can arise with clinical classification alone should be minimized in research by verification with high-sensitivity imaging.

Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinct lacunar arteriopathy?

BACKGROUND AND PURPOSE: Differences in risk factor profiles between lacunar and other ischemic stroke subtypes may provide evidence for a distinct lacunar arteriopathy, but existing studies have limitations. We overcame these by pooling individual data on 2875 patients with first-ever ischemic stroke from 5 collaborating prospective stroke registers that used similar, unbiased methods to define risk factors and classify stroke subtypes. METHODS: We compared risk factors between lacunar and nonlacunar ischemic strokes, altering the comparison groups in sensitivity analyses, and incorporated these data into a meta-analysis of published studies. RESULTS: Unadjusted and adjusted analyses gave similar results. We found a lower prevalence of cardioembolic source (adjusted odds ratio, 0.33; 95% CI, 0.24 to 0.46), ipsilateral carotid stenosis (odds ratio, 0.21; 95% CI, 0.14 to 0.30), and ischemic heart disease (odds ratio, 0.75; 95% CI, 0.58 to 0.97) in lacunar compared with nonlacunar patients but no difference for hypertension, diabetes, or any other risk factor studied. Results were robust to sensitivity analyses and largely confirmed in our meta-analysis. CONCLUSIONS: Hypertension and diabetes appear equally common in lacunar and nonlacunar ischemic stroke, but lacunar stroke is less likely to be caused by embolism from the heart or proximal arteries, and the lower prevalence of ischemic heart disease in lacunar stroke provides additional support for a nonatherosclerotic arteriopathy causing many lacunar ischemic strokes. Our findings have implications for how clinicians classify ischemic stroke subtypes and highlight the need for additional research into the specific causes of and treatments for lacunar stroke.

Differences between ischemic stroke subtypes in vascular outcomes support a distinct lacunar ischemic stroke arteriopathy: a prospective, hospital-based study.

BACKGROUND AND PURPOSE: Whether and how the arterial pathology underlying lacunar ischemic stroke differs from the atherothrombotic processes causing most other ischemic strokes is still debated. Different risks of recurrent stroke and MI after lacunar versus nonlacunar ischemic stroke may support a distinct lacunar arteriopathy. METHODS: We prospectively followed a hospital-based cohort of 809 first-ever ischemic stroke patients for 1 to 4 years. We compared risks of death, recurrent stroke, and MI in patients with lacunar versus nonlacunar stroke, and performed an updated meta-analysis of recurrent stroke subtype patterns. RESULTS: During 1725 person-years of follow-up, 109 patients had a recurrent stroke and 31 had MI. All patients at baseline, and 93% with recurrent stroke, had brain imaging and more than half with recurrent stroke had diffusion-weighted MRI. Overall, there was no difference in recurrence risk after lacunar vs nonlacunar stroke, although there was a trend toward a lower recurrence risk in the early weeks after lacunar stroke. Lacunar recurrence was more likely after lacunar than nonlacunar stroke (OR, 6.5; 95% CI, 2.4-17.5; updated meta-analysis OR, 6.8; 95% CI, 4.2-11.2). MI risk was nonsignificantly lower after lacunar than nonlacunar stroke (rate ratio, 0.5; 95% CI, 0.2-1.1; rate ratio after excluding patients with previous ischemic heart disease: 0.3; 95% CI, 0.1-0.9). CONCLUSIONS: Our finding of a trend toward a lower MI risk after lacunar vs nonlacunar stroke and confirmation of both a lower early recurrence risk after lacunar stroke and a tendency of recurrent stroke subtypes to "breed true" support the notion of a distinct nonatherothrombotic lacunar arteriopathy.

Ischemic lesion typing on computed tomography perfusion and computed tomography angiography in hyperacute ischemic stroke: a preliminary study.

The ability to rapidly and accurately evaluate the location and extent of hyperacute brain ischemia is of major clinical importance. Herein, we aimed to develop imaging criteria to classify the ischemic lesion by computed tomography (CT) perfusion (CTP) and CT angiography (CTA) in hyperacute ischemic stroke patient. Non-contrast-enhanced CT, CTP and CTA were performed in patients with symptoms of hyperacute stroke lasting <8 hours. According to the volume of infarct core, ischemic penumbra and vessel status, three ischemic lesion types were defined. Twenty-six patients were included in our study. Among them, ten patients were classified into severe group, 15 patients were classified into mild group and one patient was classified into reversible group. In acute stroke patients, the ischemic lesion typing may assist in individualizing therapeutic decisions for patients by possibly extending the window for giving thrombolytics beyond the current 3 hour limit.