Early automated cerebral edema assessment following endovascular therapy: impact on stroke outcome.

BACKGROUND: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome. METHODS: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis. RESULTS: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32). CONCLUSIONS: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes.

Ischaemic stroke patients present sex differences in gut microbiota.

BACKGROUND: Gut microbiota plays a role in the pathophysiology of ischaemic stroke (IS) through the bidirectional gut-brain axis. Nevertheless, little is known about sex-specific microbiota signatures in IS occurrence. METHODS: A total of 89 IS patients and 12 healthy controls were enrolled. We studied the taxonomic differences of the gut microbiota between men and women with IS by shotgun metagenomic sequencing. To evaluate the causal effect of several bacteria on IS risk, we performed a two-sample Mendelian randomisation (MR) with inverse-variance weighting (IVW) using genome-wide association analysis (GWAS) summary statistics from two cohorts of 5959 subjects with genetic and microbiota data and 1,296,908 subjects with genetic and IS data, respectively. RESULTS: α-Diversity analysis measured using Observed Species (p = 0.017), Chao1 (p = 0.009) and Abundance-based Coverage Estimator (p = 0.012) indexes revealed that IS men have a higher species richness compared with IS women. Moreover, we found sex-differences in IS patients in relation to the phylum Fusobacteria, class Fusobacteriia, order Fusobacteriales and family Fusobacteriaceae (all Bonferroni-corrected p < 0.001). MR confirmed that increased Fusobacteriaceae levels in the gut are causally associated with an increased risk of IS (IVW p = 0.02, ß = 0.32). CONCLUSIONS: Our study is the first to indicate that there are gut microbiome differences between men and women with IS, identifying high levels of Fusobacteriaceae in women as a specific risk factor for IS. Incorporating sex stratification analysis is important in the design, analysis and interpretation of studies on stroke and the gut microbiota.

Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis.

Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an 18F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(-)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(-). In a multivariable logistic regression analysis, the levels of LDL(-), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15-25.44, p < 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26-44.83, p < 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21-95.93, p < 0.033), indicating that an increased proportion of LDL(-) is associated with vulnerable atherosclerotic plaque.

Serum from Stroke Patients with High-Grade Carotid Stenosis Promotes Cyclooxygenase-Dependent Endothelial Dysfunction in Non-ischemic Mice Carotid Arteries.

Atherosclerosis is responsible for 20% of ischemic strokes, and severe carotid stenosis is associated with a higher incidence of first-ever and recurrent strokes. The release of pro-inflammatory mediators into the blood in severe atherosclerosis may aggravate endothelial dysfunction after stroke contributing to impair disease outcomes. We hypothesize that environments of severe carotid atherosclerotic disease worsen endothelial dysfunction in stroke linked to enhanced risk of further cerebrovascular events. We mounted nonischemic common carotid arteries from 2- to 4-month-old male Oncins France 1 mice in tissue baths for isometric contraction force measurements and exposed them to serum from men with a recent ischemic stroke and different degrees of carotid stenosis: low- or moderate-grade stenosis (LMGS; < 70%) and high-grade stenosis (HGS; ≥ 70%). The results show that serum from stroke patients induced an impairment of acetylcholine relaxations in mice carotid arteries indicative of endothelium dysfunction. This effect was more pronounced after incubation with serum from patients with a recurrent stroke or vascular death within 1 year of follow-up. When patients were stratified according to the degree of stenosis, serum from HGS patients induced more pronounced carotid artery endothelial dysfunction, an effect that was associated with enhanced circulating levels of IL-1ß. Mechanistically, endothelial dysfunction was prevented by both nonselective and selective COX blockade. Altogether, the present findings add knowledge on the understanding of the mechanisms involved in the increased risk of stroke in atherosclerosis and suggest that targeting COX in the carotid artery wall may represent a potential novel therapeutic strategy for secondary stroke prevention.

Plasma sICAM-1 as a Biomarker of Carotid Plaque Inflammation in Patients with a Recent Ischemic Stroke.

18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) identifies carotid plaque inflammation and predicts stroke recurrence in patients with atherothrombotic stroke. The aim of the study was to identify plasma inflammatory biomarkers associated with plaque inflammation according to 18F-FDG uptake. We conducted a prospective study of consecutive adult patients with a recent (< 7 days) anterior circulation ischemic stroke and at least one atherosclerotic plaque in the ipsilateral internal carotid artery. We included 64 patients, 57.8% of whom showed a carotid stenosis ≥ 50%. All patients underwent an early (< 15 days from inclusion) 18F-FDG PET, and a blood sample was obtained at days 7 ± 1 from the stroke. The plasma concentration of 16 inflammation-related molecules was analyzed in a Luminex using xMAP technology. Multivariable linear regression was used to assess the association between plasma biomarkers and the standardized uptake value (SUV) of 18F-FDG uptake. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and fractalkine (FKN) were independently associated with plaque inflammation (ß = 0.121, 95% CI 0.061-0.181, p < 0.001; ß = 0.144, 95% CI 0.012-0.276, p = 0.033; ß = 0.136, 95% CI 0.037-0.235, p = 0.008). In a multivariable logistic regression analysis, sICAM-1 was associated with SUVmax ≥ 2.85 (OR = 1.02, 95% CI 1.00-1.03, p = 0.020). Multivariable Cox regression was used to assess the association between biomarkers and stroke recurrence. sICAM-1 was associated with stroke recurrence (HR = 1.03, 95% CI 1.00-1.05, p = 0.002). In summary, elevated concentrations of sICAM-1 were associated with carotid plaque inflammation and an increased risk of stroke recurrence in patients with recent ischemic stroke and carotid atherosclerosis.

Biological Age Acceleration Is Lower in Women With Ischemic Stroke Compared to Men.

BACKGROUND: Stroke onset in women occurs later in life compared with men. The underlying mechanisms of these differences have not been established. Epigenetic clocks, based on DNA methylation (DNAm) profiles, are the most accurate biological age estimate. Epigenetic age acceleration (EAA) measures indicate whether an individual is biologically younger or older than expected. Our aim was to analyze whether sexual dichotomy at age of stroke onset is conditioned by EAA. METHODS: We used 2 DNAm datasets from whole blood samples of case-control genetic studies of ischemic stroke (IS), a discovery cohort of 374 IS patients (N women=163, N men=211), from GRECOS (Genotyping Recurrence Risk of Stroke) and SEDMAN (Dabigatran Study in the Early Phase of Stroke, New Neuroimaging Markers and Biomarkers) studies and a replication cohort of 981 IS patients (N women=411, N men=570) from BASICMAR register. We compared chronological age, 2 DNAm-based biomarkers of aging and intrinsic and extrinsic epigenetic age acceleration EAA (IEAA and extrinsic EAA, respectively), in IS as well as in individual IS etiologic subtypes. Horvath and Hannum epigenetic clocks were used to assess the aging rate. A proteomic study using the SOMAScan multiplex assay was performed on 26 samples analyzing 1305 proteins. RESULTS: Women present lower Hannum-extrinsic EAA values, whereas men have higher Hannum-extrinsic EAA values (women=-0.64, men=1.24, P=1.34×10-2); the same tendency was observed in the second cohort (women=-0.57, men=0.79, P=0.02). These differences seemed to be specific to cardioembolic and undetermined stroke subtypes. Additionally, 42 blood protein levels were associated with Hannum-extrinsic EAA (P<0.05), belonging to the immune effector process (P=1.54×10-6) and platelet degranulation (P<8.74×10-6) pathways. CONCLUSIONS: This study shows that sex-specific underlying biological mechanisms associated with stroke onset could be due to differences in biological age acceleration between men and women.

Endothelial Progenitor Cells Count after Acute Ischemic Stroke Predicts Functional Outcome in Patients with Carotid Atherosclerosis.

OBJECTIVES: Circulating Endothelial Progenitor Cells (EPCs) predict cardiovascular outcomes in patients with coronary disease. However, the predictive value of EPCs after ischemic stroke is not well established. We aimed to study the prognostic role of EPCs in patients with acute ischemic stroke and carotid atherosclerosis, focusing on post-stroke functional outcome and stroke recurrences. MATERIALS AND METHODS: We studied consecutive adult patients with an acute (<7 days) anterior circulation ischemic stroke and carotid atherosclerosis. Cardioembolic strokes were excluded. We measured circulating EPCs by flow cytometry (CD34+/CD133+/KDR+) at inclusion (7±1 days after stroke) and at one year of follow-up. At three months and at one year we registered the modified Rankin Scale score, stroke recurrences and coronary syndromes during the follow-up. RESULTS: We studied 80 patients with a mean age of 74.3±10.4 years. We divided the population in tertiles according to the EPCs count. At three months we observed a favorable outcome in 25/36 (69.4%) patients in the lowest, 19/22 (86.4%) in the medium and 21/22 (95.5%) in the highest tercile (p=0.037). In the multivariable analysis a higher EPCs count was associated with favorable functional outcome after adjusting for age and baseline NIHSS score (OR=3.61, 95%CI 1.34-9.76; p=0.011). This association persisted at one year of follow-up. We did not find association between counts of EPCs and stroke recurrence. CONCLUSIONS: In patients with acute ischemic stroke and carotid atherosclerosis, a higher count of EPCs was associated with favorable functional outcome in the mid and long-term follow-up. Counts of EPCs did not predict stroke recurrences.

RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis.

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10-8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10-8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-ß, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.

Violencia de parejas gays y en hombres que tienen sexo con hombres: una revisión sistemática exploratoria / Violence between Gay Couples and Men who have Sex with other Men: a Systematic Exploratory Review / Violência entre casais gays e em homens que fazem sexo com home revisão sistemática exploratória

Resumen La violencia en parejas de gays y hombres que tienen sexo con otros hombres es un problema grave que ha ido captando la atención de la comunidad científica internacional, por ello esta revisión sistemática explora las conceptualizaciones de la violencia en estas parejas, así como la prevalencia de los tipos de violencia y factores asociados en diversos estudios. Siguiendo un protocolo PRISMA se realizó una búsqueda en bases de datos como Scopus, Clarivate, EBSCO, Science Direct, Scielo y La Referencia. Del total de 292 referencias iniciales, se analizaron, mediante un proceso de depuración dividida en cuatro fases, 19 artículos que cumplieron con los criterios de inclusión (publicaciones realizadas entre 2000 y 2019, con acceso abierto y texto completo). Entre los principales resultados destacó la falta de homogeneidad en la definición de la violencia, así como sus subtipos, la mayor representación de muestras estadounidenses, que la violencia psicológica fue la más estudiada y que el análisis y detección de factores protectores fue prácticamente inexistente. Se discuten los resultados e implicaciones priorizando la necesidad de mayores estudios en la región latinoamericana.

Abstract Violence between gay couples and men who have sex with other men is a serious problem that has captured the international scientific community's attention. For this reason, this systematic exploratory review explores these couples' conceptualization of violence, as well as the prevalence of types of violence and associated factors in various studies. Databases, such as Scopus, Clarivate, EBSCO, Science Direct, Scielo and La Referencia, were searched following a PRISMA protocol. Of 292 total initial references, 19 articles, which complied with inclusion criteria (publications between 2000 and 2019 with open access and full text), were analyzed by means of a debugging process divided into four phases. Among the main results, the lack of homogeneity in definitions of violence, as well as their subtypes, higher representation of samples from the United States, the fact that psychological violence was studied most, and that protective factor analysis and detection were practically nonexistent stood out. The results and implications are discussed, prioritizing the need for more studies in Latin America.

Resumo A violência entre casais gays e homens que fazem sexo com homens é um problema grave que vem chamando a atenção da comunidade científica internacional, portanto, esta revisão sistemática explora as conceituações da violência nesses casais, bem como a prevalência de tipos de violência e fatores associados em vários estudos. Seguindo um protocolo PRISMA, foi realizada uma busca em bases de dados como Scopus, Clarivate, EBSCO, Science Direct, Scielo e La Referencia. Do total de 292 referências iniciais foram analisados19 artigos que atenderam aos critérios de inclusão (publicações realizadas entre 2000 e 2019, com acesso aberto e texto completo), após um processo de depuração dividida em quatro fases. Dentre os principais resultados, destacou-se a falta de homogeneidade na definicão da violência e seus subtipos, a maior representatividade de amostras americanas, a violência psicológica como o tipo mais estudado e a inexistência de análise e detecção de fatores de proteção. Os resultados, e implicações são discutidos, priorizando a necessidade de novos estudos na região da América Latina.

Clinical and radiological characteristics and outcome of wake-up intracerebral hemorrhage.

There is little information on the characteristics of patients with wake-up intracerebral hemorrhage (WU-ICH). We aimed to evaluate frequency and relevant differences between WU-ICH and while-awake (WA) ICH patients. This is a retrospective study of a prospective database of consecutive patients with spontaneous ICH, who were classified as WU-ICH, WA-ICH or UO-ICH (unclear onset). We collected demographic, clinical and radiological data, prognostic and therapeutic variables, and outcome [(neurological deterioration, mortality, functional outcome (favorable when modified Rankin scale score 0-2)]. From a total of 466 patients, 98 (25.8%) were classified as UO-ICH according to the type of onset and therefore excluded. We studied 368 patients (mean age 73.9 ± 13.8, 51.4% men), and compared 95 (25.8%) WU-ICH with 273 (74.2%) WA-ICH. Patients from the WU-ICH group were significantly older than WA-ICH (76.9 ± 14.3 vs 72.8 ± 13.6, p = 0.01) but the vascular risk factors were similar. Compared to the WA-ICH group, patients from the WU-ICH group had a lower GCS score or a higher NIHSS score and a higher ICH score, and were less often admitted to a stroke unit or intensive care unit. There were no differences between groups in location, volume, rate of hematoma growth, frequency of intraventricular hemorrhage and outcome. One in five patients with spontaneous ICH are WU-ICH patients. Other than age, there are no relevant differences between WU and WA groups. Although WU-ICH is associated with worse prognostic markers vital and functional outcome is similar to WA-ICH patients.

MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation.

OBJECTIVE: We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI. METHODS: Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses. RESULTS: We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4). CONCLUSION: Patients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke. CLINICALTRIALSGOV IDENTIFIER: NCT02238470.

Transcranial diffuse optical assessment of the microvascular reperfusion after thrombolysis for acute ischemic stroke.

In this pilot study, we have evaluated bedside diffuse optical monitoring combining diffuse correlation spectroscopy and near-infrared diffuse optical spectroscopy to assess the effect of thrombolysis with an intravenous recombinant tissue plasminogen activator (rtPA) on cerebral hemodynamics in an acute ischemic stroke. Frontal lobes of five patients with an acute middle cerebral artery occlusion were measured bilaterally during rtPA treatment. Both ipsilesional and contralesional hemispheres showed significant increases in cerebral blood flow, total hemoglobin concentration and oxy-hemoglobin concentration during the first 2.5 hours after rtPA bolus. The increases were faster and higher in the ipsilesional hemisphere. The results show that bedside optical monitoring can detect the effect of reperfusion therapy for ischemic stroke in real-time.

Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke.

We investigated whether pre-treatment with statins is associated with surrogate markers of amyloid and hypertensive angiopathies in patients who need to start long-term oral anticoagulation therapy. A prospective multicenter study of patients naive for oral anticoagulants, who had an acute cardioembolic stroke. MRI was performed at admission to evaluate microbleeds, leukoaraiosis and superficial siderosis. We collected data on the specific statin compound, the dose and the statin intensity. We performed bivariate analyses and a logistic regression to investigate variables associated with microbleeds. We studied 470 patients (age 77.5 ± 6.4 years, 43.7% were men), and 193 (41.1%) of them received prior treatment with a statin. Microbleeds were detected in 140 (29.8%), leukoaraiosis in 388 (82.5%) and superficial siderosis in 20 (4.3%) patients. The presence of microbleeds, leukoaraiosis or superficial siderosis was not related to pre-treatment with statins. Microbleeds were more frequent in patients with prior intracerebral hemorrhage (OR 9.7, 95% CI 1.06-90.9) and in those pre-treated antiplatelets (OR 1.66, 95% CI 1.09-2.53). Prior treatment with statins was not associated with markers of bleeding-prone cerebral angiopathies in patients with cardioembolic stroke. Therefore, previous statin treatment should not influence the decision to initiate or withhold oral anticoagulation if these neuroimaging markers are detected.

Risk factors are different for deep and lobar remote hemorrhages after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Remote parenchymal haemorrhage (rPH) after intravenous thrombolysis is defined as hemorrhages that appear in brain regions without visible ischemic damage, remote from the area of ischemia causing the initial stroke symptom. The pathophysiology of rPH is not clear and may be explained by different underlying mechanisms. We hypothesized that rPH may have different risk factors according to the bleeding location. We report the variables that we found associated with deep and lobar rPH after intravenous thrombolysis. METHODS: This is a descriptive study of patients with ischemic stroke who were treated with intravenous thrombolysis. These patients were included in a multicenter prospective registry. We collected demographic, clinical and radiological data. We evaluated the number and distribution of cerebral microbleeds (CMB) from Magnetic Resonance Imaging. We excluded patients treated endovascularly, patients with parenchymal hemorrhage without concomitant rPH and stroke mimics. We compared the variables from patients with deep or lobar rPH with those with no intracranial hemorrhage. RESULTS: We studied 934 patients (mean age 73.9±12.6 years) and 52.8% were men. We observed rPH in 34 patients (3.6%); 9 (0.9%) were deep and 25 (2.7%) lobar. No hemorrhage was observed in 900 (96.6%) patients. Deep rPH were associated with hypertensive episodes within first 24 hours after intravenous thrombolysis (77.7% vs 23.3%, p<0.001). Lobar rPH were associated with the presence of CMB (53.8% vs 7.9%, p<0.001), multiple (>1) CMB (30.7% vs 4.4%, p = 0.003), lobar CMB (53.8% vs 3.0%, p<0.001) and severe leukoaraiosis (76.9% vs 42%, p = 0.02). CONCLUSIONS: A high blood pressure within the first 24 hours after intravenous thrombolysis is associated with deep rPH, whereas lobar rPH are associated with imaging markers of amyloid deposition. Thus, our results suggest that deep and lobar rPH after intravenous thrombolysis may have different mechanisms.

Remote Intracerebral Hemorrhage After Intravenous Thrombolysis: Results From a Multicenter Study.

BACKGROUND AND PURPOSE: Remote parenchymal hemorrhage (rPH) after intravenous thrombolysis with recombinant tissue-type plasminogen activator may be associated with cerebral amyloid angiopathy, although supportive data are limited. We aimed to investigate risk factors of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator. METHODS: This is an observational study of patients with ischemic stroke who were treated with intravenous thrombolysis with recombinant tissue-type plasminogen activator and were included in a multicenter prospective registry. rPH was defined as any extraischemic hemorrhage detected in the follow-up computed tomography. We collected demographic, clinical, laboratory, radiological, and outcome variables. In the subset of patients who underwent a magnetic resonance imaging examination, we evaluated the distribution and burden of cerebral microbleeds, cortical superficial siderosis, leukoaraiosis, and recent silent ischemia in regions anatomically unrelated to the ischemic lesion that caused the initial symptoms. We compared patients with rPH with those without rPH or parenchymal hemorrhage. Independent risk factors for rPH were obtained by multivariable logistic regression analyses. RESULTS: We evaluated 992 patients (mean age, 74.0±12.6 years; 52.9% were men), and 408 (41%) of them underwent a magnetic resonance imaging. Twenty-six patients (2.6%) had a rPH, 8 (0.8%) had both rPH and PH, 58 (5.8%) had PH, and 900 (90.7%) had no bleeding complication. Lobar cerebral microbleeds (odds ratio, 8.0; 95% confidence interval, 2.3-27.2) and recent silent ischemia (odds ratio, 4.8; 95% confidence interval, 1.6-14.1) increased the risk of rPH. CONCLUSIONS: The occurrence of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator in patients with ischemic stroke is associated with lobar cerebral microbleeds and multiple ischemic lesions in different regions.

The H-ATOMIC Criteria for the Etiologic Classification of Patients with Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: There are no generally accepted criteria for the etiologic classification of intracerebral hemorrhage (ICH). For this reason, we have developed a set of etiologic criteria and have applied them to a large number of patients to determine their utility. METHODS: The H-ATOMIC classification includes 7 etiologic categories: Hypertension, cerebral Amyloid angiopathy, Tumour, Oral anticoagulants, vascular Malformation, Infrequent causes and Cryptogenic. For each category, the etiology is scored with three degrees of certainty: Possible(3), Probable(2) and Definite(1). Our aim was to perform a basic study consisting of neuroimaging, blood tests, and CT-angio when a numerical score (SICH) suggested an underlying structural abnormality. Combinations of >1 etiologic category for an individual patient were acceptable. The criteria were evaluated in a multicenter and prospective study of consecutive patients with spontaneous ICH. RESULTS: Our study included 439 patients (age 70.8 ± 14.5 years; 61.3% were men). A definite etiology was achieved in 176 (40.1% of the patients: Hypertension 28.2%, cerebral Amyloid angiopathy 0.2%, Tumour 0.2%, Oral anticoagulants 2.2%, vascular Malformation 4.5%, Infrequent causes 4.5%). A total of 7 patients (1.6%) were cryptogenic. In the remaining 58.3% of the patients, ICH was attributable to a single (n = 56, 12.7%) or the combination of ≥2 (n = 200, 45.5%) possible/probable etiologies. The most frequent combinations of etiologies involved possible hypertension with possible CAA (H3A3, n = 38) or with probable CAA (H3A2, n = 29), and probable hypertension with probable OA (H2O2, n = 27). The most frequent category with any degree of certainty was hypertension (H1+2+3 = 80.6%) followed by cerebral amyloid angiopathy (A1+2+3 = 30.9%). CONCLUSIONS: According to our etiologic criteria, only about 40% patients received a definite diagnosis, while in the remaining patients ICH was attributable to a single possible/probable etiology or to more than one possible/probable etiology. The use of these criteria would likely help in the management of patients with ICH.

"It sounds like...": A natural language processing approach to detecting counselor reflections in motivational interviewing.

The dissemination and evaluation of evidence-based behavioral treatments for substance abuse problems rely on the evaluation of counselor interventions. In Motivational Interviewing (MI), a treatment that directs the therapist to utilize a particular linguistic style, proficiency is assessed via behavioral coding-a time consuming, nontechnological approach. Natural language processing techniques have the potential to scale up the evaluation of behavioral treatments such as MI. We present a novel computational approach to assessing components of MI, focusing on 1 specific counselor behavior-reflections, which are believed to be a critical MI ingredient. Using 57 sessions from 3 MI clinical trials, we automatically detected counselor reflections in a maximum entropy Markov modeling framework using the raw linguistic data derived from session transcripts. We achieved 93% recall, 90% specificity, and 73% precision. Results provide insight into the linguistic information used by coders to make ratings and demonstrate the feasibility of new computational approaches to scaling up the evaluation of behavioral treatments.

Circulating endothelial progenitor cells and the risk of vascular events after ischemic stroke.

BACKGROUND AND PURPOSE: We evaluated the hypothesis that the number of circulating EPC could be associated with the risk of stroke recurrence (SR) or vascular events (VE) after an ischemic stroke. METHODS: We studied prospectively consecutive patients with cerebral infarction within the first 48 hours after the onset. We recorded demographic factors, vascular risk factors, previous Rankin scale (RS) score, and etiology. We analyzed EPC counts by flow cytometry in blood collected at day 7 and defined EPC as CD34+/CD133+/KDR+ cells. Mean follow-up was 29.3 ± 16 months. We evaluated SR as well as VE. Patients were classified as to the presence or absence of EPC in the circulation (either EPC+ or EPC-). Bivariate analyses, Kaplan-Meier survival curves and Cox regression models were used. RESULTS: We included 121 patients (mean age 70.1±12.6 years; 65% were men). The percentage of EPC+ patients was 47.1%. SR occurred in 12 (9.9%) and VE in 18 (14.9%) patients. SR was associated significantly with a worse prior RS score, previous stroke and etiology, but not with EPC count. VE were associated significantly with EPC-, worse prior RS score, previous stroke, high age, peripheral artery disease and etiology. Cox regression model showed that EPC- (HR 7.07, p=0.003), age (HR 1.08, p=0.004) and a worse prior RS score (HR 5.8, p=0.004) were associated significantly with an increased risk of VE. CONCLUSIONS: The absence of circulating EPC is not associated with the risk of stroke recurrence, but is associated with an increased risk of future vascular events.

Advancing methods for reliably assessing motivational interviewing fidelity using the motivational interviewing skills code.

The current paper presents novel methods for collecting MISC data and accurately assessing reliability of behavior codes at the level of the utterance. The MISC 2.1 was used to rate MI interviews from five randomized trials targeting alcohol and drug use. Sessions were coded at the utterance-level. Utterance-based coding reliability was estimated using three methods and compared to traditional reliability estimates of session tallies. Session-level reliability was generally higher compared to reliability using utterance-based codes, suggesting that typical methods for MISC reliability may be biased. These novel methods in MI fidelity data collection and reliability assessment provided rich data for therapist feedback and further analyses. Beyond implications for fidelity coding, utterance-level coding schemes may elucidate important elements in the counselor-client interaction that could inform theories of change and the practice of MI.

Prognostic value of plasma ß-amyloid levels in patients with acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: It has been proposed that the deposition of the ß-amyloid peptide (Aß) in the brain parenchyma and brain blood vessels has deleterious effects. We tested the hypothesis that the levels of plasma Aß are related to the outcome in patients with intracerebral hemorrhage. METHODS: In a multicenter study, we prospectively included patients with spontaneous intracerebral hemorrhage within the first 24 hours after onset. At admission, we measured plasma Aß40 and Aß42 levels using ELISA techniques. Also, we recorded age, sex, vascular risk factors, National Institutes of Health Stroke Scale score, presence of intraventricular hemorrhage, localization, cause, and volume of the hematoma. We obtained the modified Rankin scale and defined a unfavorable outcome as modified Rankin scale >2 at 3 months. Bivariate and multivariate regression analyses were performed. RESULTS: We studied 160 patients (mean age, 73.8±11.3 years; 59.4% of them were men). A favorable outcome was observed in 64 (40%) of the patients. In the bivariate analyses, unfavorable outcome was associated with high age, female sex, diabetes mellitus, presence of intraventricular hemorrhage, high blood glucose, high National Institutes of Health Stroke Scale score, high volume, and high plasma levels of Aß42 and Aß40. The multivariate analysis showed that increased age (odds ratio, 1.07; 95% confidence interval, 1.035-1.21; P<0.0001), high admission National Institutes of Health Stroke Scale score (odds ratio, 1.29, 95% confidence interval, 1.17-1.42; P<0.0001), presence of diabetes mellitus (odds ratio, 4.15; 95% confidence interval, 1.21-14.1; P=0.02), and Aß42 levels >9.7 pg/mL (odds ratio, 4.11; 95% confidence interval, 1.65-10.1; P=0.02) were independently associated with an increased likelihood of an unfavorable outcome. CONCLUSIONS: High levels of plasma Aß42 in patients with acute intracerebral hemorrhage are associated with a poor functional prognosis.