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1. DNA methylation and stroke prognosis: an epigenome-wide association study

Author: Joan Jiménez-Balado, Isabel Fernández-Pérez, Cristina Gallego-Fábrega, Uxue Lazcano, Carolina Soriano-Tárraga, Marta Vallverdú-Prats, Marina Mola-Caminal, Lucía Rey-Álvarez, Adrià Macias-Gómez, Antoni Suárez-Pérez, Eva Giralt-Steinhauer, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Ángel Ois, Manel Esteller, Jaume Roquer, Israel Fernández-Cadenas, and Jordi Jiménez-Conde
Subjects: Epigenetics, Stroke outcome, Thrombospondin-2, DNA methylation, Medicine, Genetics, QH426-470
Abstract: Abstract Background and aims Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis. Methods and results To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value
Published: 2024
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2. Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis

Author: Aina Medina-Dols, Guillem Cañellas, Toni Capó, Montse Solé, Marina Mola-Caminal, Natalia Cullell, Marina Jaume, Laura Nadal-Salas, Jaume Llinàs, Lluis Gómez, Silvia Tur, Carmen Jiménez, Rosa M. Díaz, Caty Carrera, Elena Muiño, Cristina Gallego-Fabrega, Carolina Soriano-Tárraga, Laura Ruiz-Guerra, Josep Pol-Fuster, Víctor Asensio, Josep Muncunill, Aarne Fleischer, Amanda Iglesias, Eva Giralt-Steinhauer, Uxue Lazcano, Isabel Fernández-Pérez, Joan Jiménez-Balado, Marina Gabriel-Salazar, Miguel Garcia-Gabilondo, Ting Lei, Nuria-Paz Torres-Aguila, Jara Cárcel-Márquez, Jerònia Lladó, Gabriel Olmos, Anna Rosell, Joan Montaner, Anna M. Planas, Raquel Rabionet, Mar Hernández-Guillamon, Jordi Jiménez-Conde, Israel Fernández-Cadenas, and Cristòfol Vives-Bauzá
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract: Abstract Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient’s blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4–5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, β-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.
Published: 2024
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3. The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review

Author: Isabel Fernández-Pérez, Adrià Macias-Gómez, Antoni Suárez-Pérez, Marta Vallverdú-Prats, Eva Giralt-Steinhauer, Lidia Bojtos, Sílvia Susin-Calle, Ana Rodriguez-Campello, Daniel Guisado-Alonso, Joan Jimenez-Balado, Jordi Jiménez-Conde, and Elisa Cuadrado-Godia
Subjects: subarachnoid hemorrhage, intracranial aneurysm, epigenetics, DNA methylation, microRNA, circular RNA, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches.
Published: 2024
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4. High prevalence of non-alcoholic fatty liver disease in patients with a first episode of acute ischemic stroke. Impact on disability and death

Author: Lidia Canillas, Agnes Soriano-Varela, Ana Rodríguez-Campello, Eva Giralt-Steinhauer, Elisa Cuadrado-Godia, and Teresa Broquetas
Subjects: non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), fatty liver index (FLI), acute ischemic stroke, prognosis, cardiovascular event, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: IntroductionNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is associated with an increased risk of overall mortality being cardiovascular disease the most common cause of mortality. Strategies are needed to identify high risk groups for NAFLD to improve screening approaches. Moreover, there is a lack of information about the prevalence of NAFLD on patients with acute ischemic stroke (AIS) and the influence of NAFLD on the prognosis of the stroke. The aim of the study was to define the prevalence of NAFLD in patients with a first episode of AIS and the secondary aims were to evaluate the prevalence of NAFLD at different ages and its impact on the severity and prognosis of the AIS.Materials and methodsObservational study including consecutive patients admitted for the first AIS from January 2005 to May 2018. Patients with harmful alcohol intake, other liver diseases and malignancies were excluded. Sociodemographic data, cardiovascular risk factors, comorbidities, and blood test at admission were reviewed. NAFLD and liver fibrosis were assessed with the serological scores Fatty Liver Index (FLI) and Fibrosis-4 respectively. NAFLD was defined by a FLI>60. Stroke severity and prognosis were evaluated with the National Institute of Health Stroke Scale and modified Rankin Scale respectively in patients aged from 40 to 79 years old.ResultsWe included 1601 patients, 52.4% were female and median (IQR) age of 77 (66 – 83) years. The 41% of the total cohort had a FLI>60 with different prevalence according to age in decades: in 30-39 years: 35.7%; in 40-49: 47.5%; in 50-59: 51.1%, in 60-69: 56%, in 70-79: 41.4%; in 80-89: 34.9% (p
Published: 2022
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5. Door‐In–Door‐Out Time Effect on Clinical Outcome According to Reperfusion Time in Endovascular Treatment

Author: Alan Flores, Laia SeróMD, Xavier Ustrell, Anna Pellisé, Jaume Viñas, Paula Rodriguez, Angela Monterde, Gislaine Castilho de Oliveira, Carlos A. Molina, Pedro Cardona, Adrian Valls, Joan Marti‐Fabregas, Eva Giralt‐Steinhauer, Joaquín Serena, Francisco Purroy, José Zaragoza‐Brunet, Oriol Barrachina, Manuel Gomez‐Choco, Ernest Palomeras, Dolores Cocho, Josep Maria Aragonés, Claudia Pedroza, Gloria Díaz, Xavier Jimenez, Alvaro Garcia‐Tornel, Marc Ribó, and Natalia Perez de la Ossa
Subjects: door‐in door‐out time, drip and ship, endovascular treatment, onset to reperfusion time, Neurology. Diseases of the nervous system, RC346-429, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Door‐in–door‐out time (DIDO) in nonthrombectomy stroke centers is a key performance indicator in acute stroke care. Nonetheless, the relative importance of DIDO on outcome in patients transferred for endovascular treatment (EVT) is not widely known. Therefore, we aim to explore the association between DIDO and clinical outcome according to onset to reperfusion time in patients undergoing EVT. Methods Observational multicenter study including patients transferred to a thrombectomy‐capable center from a local stroke center who underwent thrombectomy. The primary outcome was favorable clinical outcome, as evaluated by a modified Rankin Scale score of 0 to 2 at 3 months. We evaluated the association between DIDO and clinical outcome according to onset to reperfusion time and factors related to shorter DIDO time. Results Among 2710 patients transferred for thrombectomy evaluation, 970 (43.8%) patients received EVT. Median baseline National Institutes of Health Stroke Scale and DIDO time were 12 (interquartile range [IQR], 6–19) and 83 minutes (IQR, 66–108), respectively. Among patients undergoing EVT, no association was found between DIDO and clinical outcome. Considering only patients treated in the early time window (onset to reperfusion time ≤240 minutes), patients with favorable outcome had a shorter DIDO (60 [IQR, 52–68] versus 73 [IQR, 61–83] minutes; P=0.013). A receiver operating characteristic curve identified a cutoff of 67 minutes of DIDO time that better predicted favorable outcome (sensitivity, 70%; specificity, 73%; area under the curve, 0.741). A multivariate analysis showed that DIDO ≤67 minutes emerged as an independent factor associated with favorable outcome (odds ratio [OR], 5.29 [95% CI, 1.38–20.27]; P=0.015). Door to computed tomography time was the only factor associated with DIDO ≤67 minutes (OR, 1.113 [95% CI, 1.018–1.261]; P=0.022) in a multivariate analysis in this time frame. Conclusions In transferred patients undergoing EVT, DIDO has a significant impact on clinical outcome, mainly in the first hours from stroke onset. A benchmark of 67 minutes in DIDO time is proposed. Shorter door to computed tomography time appears to be an independent factor associated to achieve DIDO time ≤67 minutes. Measures to optimize workflow into referral centers are warranted.
Published: 2022
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6. Identification of 20 novel loci associated with ischaemic stroke. Epigenome-wide association study

Author: Carolina Soriano-Tárraga, Uxue Lazcano, Eva Giralt-Steinhauer, Carla Avellaneda-Gómez, Ángel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Alejandra Gómez-González, Alba Fernández-Sanlés, Roberto Elosua, Israel Fernández-Cadenas, Natalia Cullell, Joan Montaner, Sebastian Moran, Manel Esteller, Jordi Jiménez-Conde, and Jaume Roquer
Subjects: ischaemic stroke, dna methylation, ewas, Genetics, QH426-470
Abstract: DNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1–2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism. To detect epigenetic variants associated with stroke occurrence and stroke subtypes. A two-stage case–control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischaemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N = 226 and N = 166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated with these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways. We identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.
Published: 2020
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7. Machine Learning Approximations to Predict Epigenetic Age Acceleration in Stroke Patients

Author: Isabel Fernández-Pérez, Joan Jiménez-Balado, Uxue Lazcano, Eva Giralt-Steinhauer, Lucía Rey Álvarez, Elisa Cuadrado-Godia, Ana Rodríguez-Campello, Adrià Macias-Gómez, Antoni Suárez-Pérez, Anna Revert-Barberá, Isabel Estragués-Gázquez, Carolina Soriano-Tarraga, Jaume Roquer, Angel Ois, and Jordi Jiménez-Conde
Subjects: aging, epigenetic clock, machine learning, vascular risk factors, stroke, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Age acceleration (Age-A) is a useful tool that is able to predict a broad range of health outcomes. It is necessary to determine DNA methylation levels to estimate it, and it is known that Age-A is influenced by environmental, lifestyle, and vascular risk factors (VRF). The aim of this study is to estimate the contribution of these easily measurable factors to Age-A in patients with cerebrovascular disease (CVD), using different machine learning (ML) approximations, and try to find a more accessible model able to predict Age-A. We studied a CVD cohort of 952 patients with information about VRF, lifestyle habits, and target organ damage. We estimated Age-A using Hannum’s epigenetic clock, and trained six different models to predict Age-A: a conventional linear regression model, four ML models (elastic net regression (EN), K-Nearest neighbors, random forest, and support vector machine models), and one deep learning approximation (multilayer perceptron (MLP) model). The best-performing models were EN and MLP; although, the predictive capability was modest (R2 0.358 and 0.378, respectively). In conclusion, our results support the influence of these factors on Age-A; although, they were not enough to explain most of its variability.
Published: 2023
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8. Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective of Chronological Age

Author: Joan Jiménez-Balado, Eva Giralt-Steinhauer, Isabel Fernández-Pérez, Lucía Rey, Elisa Cuadrado-Godia, Ángel Ois, Ana Rodríguez-Campello, Carolina Soriano-Tárraga, Uxue Lazcano, Adrià Macias-Gómez, Antoni Suárez-Pérez, Anna Revert, Isabel Estragués, Brigitte Beltrán-Mármol, Santiago Medrano-Martorell, Jaume Capellades, Jaume Roquer, and Jordi Jiménez-Conde
Subjects: white matter hyperintensities, cerebral small vessel disease, epigenetics, DNA methylation, biological age, epigenetic clock, Biology (General), QH301-705.5
Abstract: In this manuscript we studied the relationship between WMH and biological age (B-age) in patients with acute stroke. We included in this study 247 patients with acute stroke recruited at Hospital del Mar having both epigenetic (DNA methylation) and magnetic resonance imaging data. WMH were measured using a semi-automated method. B-age was calculated using two widely used methods: the Hannum and Horvath formulas. We used multiple linear regression models to interrogate the role of B-age on WMH volume after adjusting for chronological age (C-age) and other covariables. Average C-age of the sample was 68.4 (±11.8) and we observed a relatively high median WMH volume (median = 8.8 cm3, Q1–Q3 = 4.05–18.8). After adjusting for potential confounders, we observed a significant effect of B-ageHannum on WMH volume (βHannum = 0.023, p-value = 0.029) independently of C-age, which remained significant (βC-age = 0.021, p-value = 0.036). Finally, we performed a mediation analysis, which allowed us to discover that 42.7% of the effect of C-age on WMH is mediated by B-ageHannum. On the other hand, B-ageHoarvath showed no significant associations with WMH after being adjusted for C-age. In conclusion, we show for the first time that biological age, measured through DNA methylation, contributes substantially to explain WMH volumetric burden irrespective of chronological age.
Published: 2022
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9. Long-Term Stroke Recurrence after Transient Ischemic Attack: Implications of Etiology

Author: Angel Ois, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Jordi Jimenez-Conde, Carolina Soriano-Tarraga, Ana Rodríguez-Campello, Carla Avellaneda, Diego Cascales, Isabel Fernandez-Perez, and Jaume Roquer
Subjects: stroke, recurrence, ischemic attack, transient, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background and Purpose To analyze long-term stroke recurrence (SR) characteristics after transient ischemic attack (TIA) according to initial etiological classification. Methods A prospective cohort of 706 TIA patients was followed up in a single tertiary stroke center. Endpoint was SR. Etiologic subgroup was determined according to the evidence-based causative classification system. Location of TIA and SR was recorded as right, left, or posterior territory. Disability stroke recurrence (DSR) was defined as modified Rankin Scale (mRS) score >1 or a onepoint increase in those with previous mRS >1 at 3-month follow-up. Results During a follow-up of 3,493 patient-years (mean follow-up of 58.9±35.9 months), total SR was 125 (17.7%), corresponding to 3.6 recurrences per 100 patient-years. The etiology subgroups with a higher risk of SR were the unclassified (more than one cause) and large-artery atherosclerosis (LAA) categories. Of the SR cases, 88 (70.4%) had the same etiology as the index TIA; again, LAA etiology was the most frequent (83.9%). Notably, cardioaortic embolism was the most frequent cause (62.5%) of SR in the subgroup of 24 patients with undetermined TIA. Overall, SR occurred in the same territory in 74 of 125 patients (59.2%), with significant differences between etiological TIA subgroups (P=0.015). Eighty-two of 125 (65.6%) with SR had DSR, without differences between etiologies (P=0.453). Conclusions SR occurred mainly with the same etiology and location as initial TIA, although undetermined TIA was associated with a high proportion of cardioaortic embolism SR. More than half of the recurrences caused some disability, regardless of etiology.
Published: 2019
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10. Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage

Author: Eva Giralt-Steinhauer, Joan Jiménez-Balado, Isabel Fernández-Pérez, Lucía Rey Álvarez, Ana Rodríguez-Campello, Ángel Ois, Elisa Cuadrado-Godia, Jordi Jiménez-Conde, and Jaume Roquer
Subjects: intracerebral hemorrhage, genetics, epigenetics, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.
Published: 2022
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11. Diffusion-Weighted Imaging, MR Angiography, and Baseline Data in a Systematic Multicenter Analysis of 3,301 MRI Scans of Ischemic Stroke Patients—Neuroradiological Review Within the MRI-GENIE Study

Author: Mattias Drake, Petrea Frid, Björn M. Hansen, Ona Wu, Anne-Katrin Giese, Markus D. Schirmer, Kathleen Donahue, Lisa Cloonan, Robert E. Irie, Mark J. R. J. Bouts, Elissa C. McIntosh, Steven J. T. Mocking, Adrian V. Dalca, Ramesh Sridharan, Huichun Xu, Eva Giralt-Steinhauer, Lukas Holmegaard, Katarina Jood, Jaume Roquer, John W. Cole, Patrick F. McArdle, Joseph P. Broderick, Jordi Jiménez-Conde, Christina Jern, Brett M. Kissela, Dawn O. Kleindorfer, Robin Lemmens, James F. Meschia, Tatjana Rundek, Ralph L. Sacco, Reinhold Schmidt, Pankaj Sharma, Agnieszka Slowik, Vincent Thijs, Daniel Woo, Bradford B. Worrall, Steven J. Kittner, Braxton D. Mitchell, Jonathan Rosand, Polina Golland, Arne Lindgren, Natalia S. Rost, and Johan Wassélius
Subjects: stroke, imaging, MRI, phenotype, DWI, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: Magnetic resonance imaging (MRI) serves as a cornerstone in defining stroke phenotype and etiological subtype through examination of ischemic stroke lesion appearance and is therefore an essential tool in linking genetic traits and stroke. Building on baseline MRI examinations from the centralized and structured radiological assessments of ischemic stroke patients in the Stroke Genetics Network, the results of the MRI-Genetics Interface Exploration (MRI-GENIE) study are described in this work.Methods: The MRI-GENIE study included patients with symptoms caused by ischemic stroke (N = 3,301) from 12 international centers. We established and used a structured reporting protocol for all assessments. Two neuroradiologists, using a blinded evaluation protocol, independently reviewed the baseline diffusion-weighted images (DWIs) and magnetic resonance angiography images to determine acute lesion and vascular occlusion characteristics.Results: In this systematic multicenter radiological analysis of clinical MRI from 3,301 acute ischemic stroke patients according to a structured prespecified protocol, we identified that anterior circulation infarcts were most prevalent (67.4%), that infarcts in the middle cerebral artery (MCA) territory were the most common, and that the majority of large artery occlusions 0 to 48 h from ictus were in the MCA territory. Multiple acute lesions in one or several vascular territories were common (11%). Of 2,238 patients with unilateral DWI lesions, 52.6% had left-sided infarct lateralization (P = 0.013 for χ2 test).Conclusions: This large-scale analysis of a multicenter MRI-based cohort of AIS patients presents a unique imaging framework facilitating the relationship between imaging and genetics for advancing the knowledge of genetic traits linked to ischemic stroke.
Published: 2020
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12. Endothelial Progenitor Cells Predict Cardiovascular Events after Atherothrombotic Stroke and Acute Myocardial Infarction. A PROCELL Substudy.

Author: Elisa Cuadrado-Godia, Ander Regueiro, Julio Núñez, Maribel Díaz-Ricard, Susana Novella, Anna Oliveras, Miguel A Valverde, Jaume Marrugat, Angel Ois, Eva Giralt-Steinhauer, Juan Sanchís, Ginès Escolar, Carlos Hermenegildo, Magda Heras, and Jaume Roquer
Subjects: Medicine, Science
Abstract: INTRODUCTION:The aim of this study was to determine prognostic factors for the risk of new vascular events during the first 6 months after acute myocardial infarction (AMI) or atherothrombotic stroke (AS). We were interested in the prognostic role of endothelial progenitor cells (EPC) and circulating endothelial cells (CEC). METHODS:Between February 2009 and July 2012, 100 AMI and 50 AS patients were consecutively studied in three Spanish centres. Patients with previously documented coronary artery disease or ischemic strokes were excluded. Samples were collected within 24h of onset of symptoms. EPC and CEC were studied using flow cytometry and categorized by quartiles. Patients were followed for up to 6 months. NVE was defined as new acute coronary syndrome, transient ischemic attack (TIA), stroke, or any hospitalization or death from cardiovascular causes. The variables included in the analysis included: vascular risk factors, carotid intima-media thickness (IMT), atherosclerotic burden and basal EPC and CEC count. Multivariate survival analysis was performed using Cox regression analysis. RESULTS:During follow-up, 19 patients (12.66%) had a new vascular event (5 strokes; 3 TIAs; 4 AMI; 6 hospitalizations; 1 death). Vascular events were associated with age (P = 0.039), carotid IMT≥0.9 (P = 0.044), and EPC count (P = 0.041) in the univariate analysis. Multivariate Cox regression analysis showed an independent association with EPC in the lowest quartile (HR: 10.33, 95%CI (1.22-87.34), P = 0.032] and IMT≥0.9 [HR: 4.12, 95%CI (1.21-13.95), P = 0.023]. CONCLUSIONS:Basal EPC and IMT≥0.9 can predict future vascular events in patients with AMI and AS, but CEC count does not affect cardiovascular risk.
Published: 2015
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13. Dietary habits in patients with ischemic stroke: a case-control study.

Author: Ana Rodríguez-Campello, Jordi Jiménez-Conde, Ángel Ois, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Helmut Schroeder, Gemma Romeral, Mireia Llop, Carolina Soriano-Tárraga, Montserrat Garralda-Anaya, and Jaume Roquer
Subjects: Medicine, Science
Abstract: BACKGROUND AND AIMS:Diet appears to have some role in stroke development. The objective of our study was to describe the dietary habits in patients admitted with acute ischemic stroke and compare selected dietary components with healthy controls. Adherence to healthy diet behaviors was also assessed. METHODS:A case-control study of consecutive patients with acute ischemic stroke admitted to the Neurology Department of Hospital del Mar from 2007 to 2010. Patients were matched by age and sex with control subjects. A previously validated nutritional survey was administered to patients and controls. Demographic data, vascular risk factors, caloric intake and dietary nutrients were evaluated. Intention to follow a healthy diet was also assessed in both groups. RESULTS:A total of 300 acute ischemic stroke patients and 300 controls with evaluation of dietary habits. No differences were observed in vascular risk factors, except smoking habit, diabetes and ischemic heart disease. Stroke patients reported a higher caloric intake: 2444.8(1736.8-3244.5) vs 2208.7(1753.1-2860.7) Kcal, p = 0.001. After adjusting for energy intake, patients had higher intake of proteins (p
Published: 2014
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14. Global DNA methylation of ischemic stroke subtypes.

Author: Carolina Soriano-Tárraga, Jordi Jiménez-Conde, Eva Giralt-Steinhauer, Marina Mola, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Israel Fernández-Cadenas, Caty Carrera, Joan Montaner, Roberto Elosua, Jaume Roquer, GeneStroke, and “The Spanish Stroke Genetics Consortium”
Subjects: Medicine, Science
Abstract: Ischemic stroke (IS), a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA) of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA), small-artery disease (SAD), and cardio-aortic embolism (CE). A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204) were included, distributed across 3 IS subtypes: LAA (78/281, 59/204), SAD (97/281, 53/204), and CE (106/281, 89/204). In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.
Published: 2014
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15. The role of HbA1c determination in detecting unknown glucose disturbances in ischemic stroke.

Author: Jaume Roquer, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Jordi Jiménez-Conde, Carol Soriano, and Angel Ois
Subjects: Medicine, Science
Abstract: OBJECTIVES: To evaluate the usefulness of hemoglobin A1c (HbA1c) determinations during the acute ischemic stroke (IS) to identify undiagnosed glucose disturbances in a prospective series of patients with first-ever IS. METHODS: Retrospective analysis of a prospective series of first-ever IS patients. Patients with previous diagnosis of diabetes mellitus (DM) were excluded from the study. Patients were classified as non-DM (HbA1c = 126 mg/dL), prediabetes (HbA1c from 5.7% to 6.4%), and new suspected DM (HbA1c> = 6.5% independently of current blood glucose). Medical charts from hospital discharge to July 2014 of all suspected DM patients were reviewed to confirm the DM diagnosis. RESULTS: The initial cohort included 1283 patients, of which 393 were excluded because of previous DM diagnosis and 136 because HbA1c during acute stroke phase was not available. No demographic differences were observed between patients with and without HbA1c determinations. The final cohort was composed of 754 patients with first-ever IS and unknown DM history. HbA1c determination suggested new DM in 87 cases (11.5%) and detected 273 patients with prediabetes (36.2%). New DM cases were identified in all etiological stroke subtypes. After discharge, DM diagnosis was confirmed in 80.2% of patients with available follow-up. CONCLUSIONS: HbA1c determination detected both undiagnosed DM and prediabetes in IS patients without taking into account the blood glucose values during admission, and independently of etiological stroke subtype. HbA1c determination should be included in the systematic screening of all IS patients.
Published: 2014
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16. DNA isolation method is a source of global DNA methylation variability measured with LUMA. Experimental analysis and a systematic review.

Author: Carolina Soriano-Tárraga, Jordi Jiménez-Conde, Eva Giralt-Steinhauer, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Israel Fernández-Cadenas, Joan Montaner, Gavin Lucas, Roberto Elosua, Jaume Roquer, and GeneStroke “The Spanish Stroke Genetics Consortium”
Subjects: Medicine, Science
Abstract: In DNA methylation, methyl groups are covalently bound to CpG dinucleotides. However, the assumption that methyl groups are not lost during routine DNA extraction has not been empirically tested. To avoid nonbiological associations in DNA methylation studies, it is essential to account for potential batch effect bias in the assessment of this epigenetic mechanism. Our purpose was to determine if the DNA isolation method is an independent source of variability in methylation status. We quantified Global DNA Methylation (GDM) by luminometric methylation assay (LUMA), comparing the results from 3 different DNA isolation methods. In the controlled analysis (n = 9), GDM differed slightly for the same individual depending on extraction method. In the population analysis (n = 580) there were significant differences in GDM between the 3 DNA isolation methods (medians, 78.1%, 76.5% and 75.1%; p
Published: 2013
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17. Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia

Author: Álvaro García-Tornel, Alan Flores, Mikel Terceño, Pedro Cardona, Sergi Amaro, Meritxell Gomis, Josep Zaragoza, Jerzy Krupinski, Manuel Gómez-Choco, Natalia Mas, Dolores Cocho, Esther Catena, Francesc Purroy, Matias Deck, Marta Rubiera, Jorge Pagola, David Rodriguez-Luna, Jesús Juega, Noelia Rodríguez-Villatoro, Carlos A. Molina, Cristina Soro, Xavier Jimenez, Mercè Salvat-Plana, Antoni Dávalos, Tudor G Jovin, Sonia Abilleira, Natalia Pérez de la Ossa, Marc Ribó, Estela Sanjuan, Katherine Santana, Olga Maisterra, Estevo Santamarina, Marian Muchada, Sandra Boned, Antonio Palasi Franco, Marta Olivé Gadea, Matías Deck, Manuel Requena, Victoria Sala, Lucía Muñoz, Mónica Millán, Elena López-Cancio, Laura Dorado, María Hernández-Pérez, Jordi Ciurans, Daniela Samaniego, Tamara Canento, Lorena Martin, Anna Planas, Joaquin Broto, Agustín Sorrentino, Martí Paré, Nuole Zhu, Alicia Garrido, Laia Grau, Ane Miren Crespo, Silvia Presas, Miriam Almendrote, Alba Ramos, Giuseppe Lucente, Lourdes Ispierto, Manuel Lozano, Juan Luis Becerra, Marta Jiménez, Dolores Vilas Rolán, Nicolas Guanyabens, Josep Sanchez-Ojanguren, Alicia Martínez-Piñeiro, Sara Forcén, Mireia Gea, Marta Álvarez, Anna Ramos, Manuel Domínguez Lizarbe, Rubio Guerra, Irene Bragado, Andrea Arbex, Luis Rodríguez, Alejandro Bustamante, Pere Cardona Portela, Helena Quesada García, Blanca Lara Rodríguez, Nuria Cayuela, Julia Miró, Clara Marzal, Andrés Paipa, Sergio Campoy, Ana Núñez, Pablo Arroyo, Sarah Besora, Vanessa Adell, Jaume Campdelacreu, Montse Alemany Martí, Belén González, Laura Bau Vila, Marta Fiter Crespo, Anna Berbel, Ma. Cristina Villaescusa Urbaneja, Núria Guillen, Nuria Vidal, Patricia Valentina Vérez Santamaria, Diego Herrero Navarro, Marta Simó, Mercedes Falip, Elisabeth Matas, Neus Mongay Ochoa, Ariadna Gifreu, Albert Muñoz, Lucía Romero, Eduard Portell, Guillermo Hernández Perez, F. Ruiz Esteve, Silvia Teixidor, Augusto Salazar Talavera, Roser Gómez, Xabier Urra Nuin, Martha Vargas, Ángel Chamorro, Laura Llull, Arturo Renú, Salvatore Rudilosso, Raquel Sánchez del Valle, Helena Ariño, Nuria Solà, Delón la Puma, Francisco Gil, Juan Bernardo Gómez, Nuria Matos, Neus Falgàs, Sergi Borrego, Almudena Sánchez, Mircea Balasa, Carmen Montejo, Mar Guasp, David Reyes, Pablo Sánchez Cervilla, Jose Miguel Contador, Victor Augusto Vera Monge, Oscar Ramos, Alejandro Rodríguez, Ana Rodríguez Campello, Gemma Romeral Ballester, Mireia Llop Trujillano, Eva Giralt Steinhauer, Elisa Cuadrado Godia, Angel Javier Ois Santiago, Jordi Jimenez Conde, Joan Martí Fábregas, Daniel Guisado, Luís Prats, Pol Camps, Raquel Delgado, Alejandro Martínez Domeño, Rebeca Marín, David Cànovas, Jordi Estela, Marta Ros, Sonsoles Aranceta, Jordi Espinosa, Marta Rubio, Cristina Lafuente, Oriol Barrachina, Alicia Anguita, Anna Reverter, Carmen García, Gemma Sansa, Mariona Hervas, Monica Crosas, Tania Delgado, Dra Sonia Huertas Folch, Gemma Muñoz Gamito, Josep Trenado Alvarez, Teresa Subirana, Jessica Molina, Laura Comes Romero, Gemma Guardia Valls, Miriam Jover, Javier Joaquín Sotova, Sonia Mª García Sánchez, Sebastian Valenzuela, Juan José Mengual, M. Àngels Font, Mª Isabel Gómez Ruiz, Irati Zubizarreta, Susana Fernández González, Laura Gubieras, Carmen E. Cobos, Luis Mena Romo, Nuria Caballol, Luis Cano, Joaquín Serena Leal, Yolanda Silva Blas, Irene Bragado Trigo, Saima Bashir Viturro, Laura Pardo Albiñana, Montserrat Reina Garrido, Carla Marco Cazcarra, Karol Enrique Uscamaita, Fabian Márquez, Cristina Coll, Mar Irida Lloret Villlas, Berta Solano Vila, Berta Alemany Perna, Daniel López Domínguezl, Mercedes de Lera, Anna Cots Foraster, Urszula Bojaryn, Ikram Benabdelhak, Gerard Mauri Capdevila, Jordi Sanahuja Montesinos, Daniel Vázquez, José Vicente Hervás, Cristina González, Alejandro Quílez, Mikel Vicente Pascual, María Ruiz, Yolanda Riba, M. Pilar Gil Villar, Cristina García, Xavier Ustrell Roig, Mònica Baldrich Mora, Anna Pellisé Guinjoan, Judit Borras, Alba Mañé Martínez, Rafael Marés, Jaume Viñas i Gaya, Laia Seró, Paula Rodríguez, Gislaine Castilho, Angela Monterde Ortega, Silvia Reverté, Joan Josep Baiges, Gisela Martín Ozaeta, Sonia Escalante, Patricia Esteve Belloch, Iago Payo, Júlia Saura Salvado, Josep M Soler Insa, Ester Tio Vilamala, Josep Abos Navarro, Héctor Cruz Tabuenca, Tamara Canento Sánchez, Elisabet Roldán, Elsa Puiggrós Rubiol, Elisabet Franquet, Lidia Fuentes, Javier Donaire, Elena Martí, Laura Giménez, Junior Gil Vázquez, Eloisa Nieto Clara Gris Ambrós, Puri Rodríguez, José Félix Oletta, Pilar Pons Mellado, Bárbara Gómez, Vergilin Raileau, Oscar Pardina, Jordi Mercadal, María López-Diéguez, Pilar Pérez, Lourdes Gabarró, María Orriols, José Carlos Molina, Joan Josep Canet, Mireia Roca, Muriel Álvaro, Francesc Boneu, Georgina Giménez, Jaume Albà, Francesc Gibert, Jéssica Garcia, Patricia Barragan, Gustavo Jurado, Vanesa Pascual_Medicina Interna, Josep Sabaté Ortega, Joan Amaurys Martínez Solano, Víctor Fernández, Mónica Torres, Ana Belén Montero Alvaredo, Laura Redondo Parejo, Josep Maria Aragonés, Anna Bullón, Cora Loste, Paula González, Neker Bejarano, Francisco Sanchez, Gianni Lucchetti, Xavier Pla, Dr Javier Gimeno, Esteban Reynaga, Montse Barcons, Gabriel Celedón, Juan Ortiz, Dr Goran Anastasovski, Dr Oscar Mascaró, Dr Javier Diez de los Ríos, Meritxell Feliu, Anna Ribera, Cristhian Ruiz, Gerard Corominas, Dra Daniella Nunes, Claudia Roca, Nadina Latorre, Lizbeth Yataco, Maricelys Cruz, Nerea Blanco, Santiago Castejón, Claustre Pont Sunyer, Jordi Espinosa Garcia, Rodrigo Paz Martin, Albert de Luis Sanchez, Dolores Espinosa Vivas, Juan Valencia Molina, Planels Palome, Laia Tomas Chaume, Ares Villagrasa Vilella, Marco Bustamante, Anunciación Boltes, Fernando Rodríguez, Itziar Arrieta, Jordi Ciurans Molist, Barnés Andreu, Ernest Palomeras Soler, Nicolau Guanyabens Buscà, Manuel Daza López, Jordi Bigas Farreres, Virginia Casado Ruiz, Desiree Muriana Batiste, Mª Pilar Sanz Cartagena, Eulalia Cabot de Vega, Josep Bassa Real, Hector Pelaez Roman, César Socolich, Josep Mª Alonso Camp, Antonio Tomás Cano Orgaz, Mª Pilar Fossas Felip, Nicolás Morón, Sandra Bacca, Mauricio Molina, Francesc Casarramona, Lorena Elias, Muhammad Zidane Bukaei, Jose Antonio Martos Gutierrez, Judith Lopez Escuin, Cristina Olaizola, Yolexis López Vargas, Juan Jiménez Oyonarte, Rashida Soultana, Eduardo Sanjurjo Golpe, Esther Salvador, Guillem Vila, Marcos Serrano, Matilde Nuria López Claverol, Marian Lamolla, Miquel Amate, Adriana Rodriguez, Ruth Romero, Montgomery del Carpio, Ana Isabel Hernandez, Julián Martín, M Carmen Rosas, Antonio Nogueroles, Sorilandy Encarnación, Augusto Robles, Jose Antonio Herrera, Roger Gavilán, Toghrol Mameghani, Gastón Araujo, M.Angeles Garrido Morales, Enric Ramon Albert Segui, Eva Fernandez Climent, Francesc Paris Pujol, Mireia Judit Garrofé Seira, Lucía Gómez Pía, Fernando Salleres Nuñez, Cristina Aguar Peñalver, Cristina Vaz Lopes, Elisenda Ribera Tasa, Carmen Repullo Vilchez, Modesto Sánchez Zambrana, Beatriu Suescun Ribas, Inés Vilà Panés, Montserrat Vila Planavila, Alicia Vaqueiro Lorenzo, Meritxell Sabartés Guixes, Jorge Medina, David Sambrano, Javi Zamarreño, Carmen Pirela, Paola Vélez, Luis Cajamarca, Honey Pérez, Yarles Martínez, Jesus Alexander Gonçalves, Carles Regordosa, Claudia Mormeneo, Laura Griu, Maria Francia Colina, Enric Farik, Dolors Carrión Duch, Carles Badenas, Oscar Bernal, Núria Agramunt, Shyrlei Morales, Victoria Reynoso, Miguel Guerrero, Primitivo Romera Cid, Mònica Folqué, Claudia Pedroza, Adnan Hachem, Íñigo Soteras Martínez, Xavier Verdera García, Mercè López Amorós, Xavier Costa Subirós, Marta Cufí Benet, Cecile Van Eendenburg, Teresa Osuna, Dra Gina Santos, Dra Mireia Pallisera, Dr Lluís Gonzalo Oliva, Dra Gemma Sanchez, Dr Xavier Basurto, Dr Ludgi Vivoda, Dr Richard Van der Kleyn, Dra Laura Robles, Ana Cabanelas Barranco, Mª Cruz Almendros, Marc Pérez Oliveras, Amelia Fernández Álvarez, Maria Rybyeva, Antoni Viñas, Maria Barcons, Joaquim Danès Alberto Tavera, Pablo Burbano, Cintie López, David Cruz, Paula Bisbe, Nora Fernández, Juan Carlos Palacio, Eduardo Fraiz, Oriol Aguiló, Rollmy Amorodjo, John Velázquez, Elena Sánchez, Jaume Español, Judit Perez de Celis, Anna Coll, Glòria Díaz, Margarida Vergés i Sala, Mª Ángels Casas Capdevila, Yosmairy Yoselin Ferrini, Aitor Gorriz, Diego-Javier Cucurell Navarro, Dulce Velásquez, Jaume Pla Soler, Josep González, Julian David Higuera, Lina Cuellar, Liza Margarita Miniello, Lluis Pujol, Sorin Cracan, Mora Vives, M Angela, Lopez Lopez, Montse Gorchs Molist, Delofeu Anna, Silvia Solà Muñoz, Ferreres Yolanda, Carol Pujalte, Elisabeth Téllez Marín, Yolanda Font Casas, Sara Hernández Luque, Joaquim Mejias Sendra, Francesca Mellado Valero, Campos Escala, Galup De Lacanal, Lopez Diaz, Castillo Paramio, Català Estopà, Español Moreda, Calafell Majo, Carballo Almeida, Castro Naval, M Elena, Cregut Ruiz, Pere Lluis, Deulofeu Font, Fabregat Sanjuan, Joan Pere, Fontquerni Gorchs, Forés Bellés, Joan Antoni, Gomez Herrera, Juan Carlos, Hijazo Prades, Itzaina Torvisco, Marti Rovira, Obiols Gonzalez, Olive Cavero, Querol Gil, M Soledad, Rico Rodriguez, Rios Sambernardo, Ropero Molina, Jose Ramon, Sanchez Valero, Santos Arevalo, Maria Jose, Soto Garcia, Maria Angeles, Tebar Escribano, Torres Garcia, Pedro José, Verdes Carrion, M Isabel, Verge Lopez, Juan Jose, Lopez Canela, M Angeles, Lucas Guarque, Morales Alvarez, Jorge Arnulfo, Morell Fornieles, Subirats Gomez, Maria Teresa, Torello Masa, Miquel, Val Lopez, Maria Mercedes, Palmero Reyes, Juan Manuel, Rodriguez Forne, Ruana Turiel, Sanchez Gonzalez, Sebastia Gornals, Abrio Rico, Albert Gual Falip, Aznar Oliveros, Brugues Perotti, Calvet Molinero, Catells Franco, Corrales Medina, Daroca Miro, Duran Marquez, Feliu Pradas, Figueras Casanova, Garcia Tortajada, Grajera Gallego, Azahara del Mar, Las Arroyo, Dulcenombre de Jesus, Laserreta Sanz, Llambrich Vidal, Monllao Corral, Morales de la Cruz, Moreno Blanco, Orejuela Orgaz, Piñana Suazo, Pons Minguillon, Rodríguez Gómez, José Carlos, Rodriguez Pereira, Sedo Porcel, Anna, Sevil Villar, Sierra Lopez, Torres Romero, Trepat Calveres, Anna, Ventura Arnella, Acera Gil, M Teresa, Biesot Vico, Castro Galea, Rosa Maria, Escorcia Chafer, Juan Antonio, Gil Faure, Hernandez Luque, Jimenez Delgado, Mallafre Gay, M. Angel, Olivares Sanzo, Pubill Fondevila, Sabate Fort, Segovia Agámez, Antonio Carlos, Turata Longaretti, Valle Hernandez, Trayner Guixens, Aguilar Valor, Aguirre Alvarez, Alastrue Naval, Alferez Baquero, Alonso Marne, Aloy Orozco, Alvarez Colino, Alvarez Peñuela, Ameller Cirilo, Maria Vanessa, Andujar Guerrero, Estefania Remedios, Auladell Sillero, Azcarate Sorbet, Basany Genesca, Benavent Barduena, Benito Tudela, Blanch Pardo, Boluda Pla, Bonilla Gonzalez, Bru Serramalera, Burnat Andreu, Caballero Calvo-Rayo, Calvo Casellas, Camps Mombiela, Cano Bresme, Carcelen Fernandez, Caro Solà, Casasas Matavacas, Castanedo Bolado, Cerdeña Cortina, Abella Jane, Laia Collado Borrego, Colom Orri, Comellas Vilanova, Conillera Sole, Cots Torres, Cuchi Estepa, Marc de Sostoa Graell, Laura del Rio Lopez, Delgado Compte, Diaz Bueno, Diaz Maneiro, Andrea Lucia, Domenech Palau, M. Carme, Duran Carasso, Pablo Javier, El Abidi, Escoda Martin, Esteve Casanovas, Fernandez Perez, Ferre Quintero, Flores Escobar, Fontcuberta Abad, Fortes del Valle, Mª Luisa, Franco Quesada, Sara Maria, Franco Romero, Gallego Francisco, Gamiz Gala, Garcia Castañeda, Garcia Rodriguez, Casajuana Gemma, Gomez Arroyo, Gomez Girbau, Gonzalez Fernandez, Gonzalez Gonzalez, Gonzalez Lopez, Gual Obeso, Guerrero Blanco, Guillemas Roca, Guillermo Eudaldo, Sebastia Hernandez, Homar Covas, Hostench Alvarez, Huerta Royo, Ibañez Barcelo, Izquiero Cruz, Jaione Urdangarin Etxetxikia, Juárez Gimenez, Khlifi Alami, Laparra Gasco, Lara Moreales, Lasaosa Medina, Maria Lourdes, Lazaro Cava, Leon Berrar, López Maturana, Lopez Ramirez, López Romero, Lorente Marco, Lorenzo Martin, Lozano Casals, Lujan Nicola, Madrid Diaz, Jose Antonio, Maria Teresa Peris Morales, Marti Clemente, Martinez Castaño, David Natanael, Martinez Gamez, Martinez Gonzalez, Martinez Quesada, Maria de la Cabeza, Marzà Fusté, Melendo Lasheras, Miralles Mestre, Montserrat Puig Pastalle, Montserrate Vidal, Mora Mellado, Morales Ponce, Morera Cabre, Morera Vivet, Mundi Souza, Muñoz Quiles, Navea Rosa, Neira Iglesias, M Asuncion, Nuñez Manrique, Mª Pilar, Obiols Martinez, Pallares Reig, Partegas Torres, Pascual Berengueras, Perez Gamez, Perez Oset, Perez Restrepo, Maria Alejandra, Planas Yeste, Planells Mangado, Puertas Carbonell, Quinteiro Blanco, Rebollar Benavente, Recasens Fernandez, Reyes Gomez, Maria del Carmen, Roca Pou, Rodriguez Ferrer, Rodriguez Franco, Rodriguez Fuertes, Rodriguez Muñoz, Rodriguez Navarro, Roig Iniesta, Romero Gracia, Rovira Brunet, Rovira de Eugenio, Rubio Baena, Ruiz Llorens, Sala Llamazares, San Juan Alaez, Sanchez Segura, Santasusana Soldevilla, Sanz Salmeron, Segura Perez, Serra Balcells, Sorina Dumitras, Teixidor Montoya, Tena Vicente, Tierno Salinas, Ester Ines, Toledo Testa, Tomàs Figueras, Tomas Ruperez, Torrano Garcia-Penche, Torres Esparza, Vazquez Blanco, Vazquez De la Paz, Vazquez Gil, Vazquez Gonzalez, Vidal Meler, Vilalta Cots, Vilches Jimenez, Visser Fernandez, Viu Gavin, Vives Vives, Carmona Jimenez, Francisco Jose, Galobardes Vilches, Gonzalez Gomez, Jodar Manzanera, Marimon Cortes, Marrodan Orive, Martin Bosch, Martorell Lopez, Millares Roca, M Jesus, Miralles Guri, Muliterno Hernandez, Muñoz Oliva, Pons Pujol, Postius Conde, Prieto Arruñada, Quintana Mathé, Rosell Mata, Alvarin Alvarez, Arrufat Flores, Bañuelos Pago, Campo Vilar, Cardus Hidalgo, Castello Gil, Maria Gloria, Castrillo Montsesinos, Clave Garces, Comes Sanroma, Descalzo Sequi, Errando Ricol, Escudero Campillo, Maria del Mar, Fernandez Alvarez, Fernandez Gomez, Franch Espinosa, Freixes Graells, Garcia Plaza, Garcia-Marron Gallego, Hernandez Simancas, Jaraba Armas, Jimenez Ramos, Lopez Oganissian, Madrona Romero, M Rosa, Martinez Millan, Martínez Morón, Merchan Encinas, Moreno Jimenez, Muñoz Rico, Navarro Rodriguez, Nogales Ibañez, Rita Maria, Novillo Viera, Parella Torrabadella, Mari Alba, Pera Villar, Carla Montserrat, Rabella Miralles, Ramis Trilles, Ribera Ortiz, Sastre Perez, Soro Borrega, Tapia Fores, Tellez Bernad, Trenado Alvarez, Felix Martin, Herrero Perez, Lanau Fuster, Lopez Gomariz, Pardo Lozano, Quintana Altimiras, Ventosa Lopez, Almodovar Damian, Alvarez Monterroso, Arambudo Comas, Boullon Garzon, Burgos Capella, Campuzano Garcia, Maria Del Mar, Capdevila Olivas, Carre Marti, Clara Isabel, Carretero Bacaicoa, Cazorla Calderon, Chacon Osuna, Cortes Planas, Cortit Olio, Delhomme Estany, Fructuos Martinez, Garcia Lopez, Pascual Luis, Genis Amill Vallve, Gonzalez Muñoz, Hernaez Ventura, Lavernia Gimenez, Martin Rojo, Martínez Medina, Mayol Barrera, Mercader Pi, Merino Dalmau, Miguel Campodarbe, Moreno Sanchez, Francisco Javier, Penela Barrameda, Prieto Ajenjo, Rodriguez Pareja, Rodríguez Piñar, Rodriguez Tello, Romero Pereda, Sainz Saborido, Santacana Martin, Santos Martinez, Sierra Chavez, Turbau Torres, Vicente Domenech, Villena Esteo, Vives Pertegaz, Baena Gonzalez, Bagaria Pont, Beltran Sanchez, Bonet Alarcon, Borch Ballescà, Buhils Clanchet, Closa Garcia, Colomina Carril, Cristina Fernandez Sanchez, Edurne Judith Fernandez Toledo, Espases Rodriguez, Espert Resa, F Xavier, Fernández Sol, Gonzalez Lugo, Gracia Llesera, Herrada Lendinez, Juliench Liesa, Sandra Alicia, Lopez Ortega, Lopez Yuste, Lozano Villanueva, Lucia Sola Soto, Madrid Castellano, Megias Cano, Daniel Jesus, Montasell Ponce, Montesinos Sospedra, Moya Martinez, Muñoz Herrera, Ocaña Fernandez, Palau Bernal, Perez Sole, Ramon Carbonell, Ribas Lop, Rubio López, Rueda Lopez, Sabat Castaño, Sabata Lara, Salmerón Ramírez, Serra Creus, Serrano Dalmau, Sumasi Mainero, Gonzalo Gabriel, Torello Masa, Valencia Primo, Ana Maria Viñuales Muñoz, Josep Roig, and Verònica Hidalgo
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163]; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction P interaction >0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
Published: 2023

18. Factors associated with migraine aura mimicking stroke in code stroke

Author: Adrià Macias-Gómez, Antoni Suárez-Pérez, Ana Rodríguez-Campello, Eva Giralt-Steinhauer, Antía Moreira, Daniel Guisado-Alonso, Jaume Capellades, Isabel Fernández-Pérez, Jordi Jiménez-Conde, Lucía Rey, Joan Jiménez-Balado, Jaume Roquer, Ángel Ois, and Elisa Cuadrado-Godia
Subjects: Psychiatry and Mental health, Neurology (clinical), Dermatology, General Medicine
Published: 2023

19. Workflows and Outcomes in Patients With Suspected Large Vessel Occlusion Stroke Triaged in Urban and Nonurban Areas

Author: Alvaro Garcia-Tornel, Monica Millan, Marta Rubiera, Alejandro Bustamante, Manuel Requena, Laura Dorado, Marta Olivé-Gadea, Xavier Jiménez, Angels Soto, Marisol Querol, Maria Hernández-Pérez, Meritxell Gomis, Pere Cardona, Xabier Urra, Francesc Purroy, Yolanda Silva, Xavier Ustrell, Patricia Esteve, Mercè Salvat-Plana, Miquel Gallofré, Carlos Molina, Antoni Dávalos, Tudor Jovin, Sonia Abilleira, Marc Ribo, Natalia Pérez de la Ossa, Marc Ribó Jacobi, Estela Sanjuan, Katherine Santana, Noelia Rodríguez, Jorge Pagola, David Rodriguez-Luna, Olga Maisterra, Estevo Santamarina, Marian Muchada, Jesús Juega, Sandra Boned, Antonio Palasi Franco, Álvaro García -Tornel, Matías Deck, Victoria Sala, Lucía Muñoz, Mónica Millán, Elena López-Cancio, María Hernández-Pérez, Jordi Ciurans, Daniela Samaniego, Tamara Canento, Lorena Martin, Anna Planas, Joaquin Broto, Agustín Sorrentino, Martí Paré, Nuole Zhu, Alicia Garrido, Laia Grau, Ane Miren Crespo, Silvia Presas, Miriam Almendrote, Alba Ramos, Giuseppe Lucente, Lourdes Ispierto, Manuel Lozano, Juan Luis Becerra, Marta Jiménez, Dolores Vilas Rolán, Nicolas Guanyabens, Josep Sanchez-Ojanguren, Alicia Martínez-Piñeiro, Sara Forcén, Mireia Gea, Marta Álvarez, Anna Ramos, Manuel Domínguez Lizarbe, Sara, Rubio Guerra, Irene Bragado, Andrea Arbex, Luis Rodríguez, Pere Cardona Portela, Helena Quesada García, Blanca Lara Rodríguez, Nuria Cayuela, Julia Miró, Clara Marzal, Andrés Paipa, Sergio Campoy, Ana Núñez, Pablo Arroyo, Sarah Besora, Vanessa Adell, Jaume Campdelacreu, Montse Alemany Martí, Belén González, Laura Bau Vila, Marta Fiter Crespo, Anna Berbel, Ma. Cristina Villaescusa Urbaneja, Núria Guillen, Nuria Vidal, Patricia Valentina Vérez Santamaria, Diego Herrero Navarro, Marta Simó, Mercedes Falip, Elisabeth Matas, Neus Mongay Ochoa, Ariadna Gifreu, Albert Muñoz, Lucía Romero, Eduard Portell, Guillermo Hernández Perez, F. Ruiz Esteve, Silvia Teixidor, Augusto Salazar Talavera, Roser Gómez, Xabier Urra Nuin, Martha Vargas, Ángel Chamorro, Sergio Amaro, Laura Llull, Arturo Renú, Salvatore Rudilosso, Raquel Sánchez del Valle, Helena Ariño, Nuria Solà, Delón la Puma, Francisco Gil, Juan Bernardo Gómez, Nuria Matos, Neus Falgàs, Sergi Borrego, Almudena Sánchez, Mircea Balasa, Carmen Montejo, Mar Guasp, David Reyes, Pablo Sánchez Cervilla, Jose Miguel Contador, Victor Augusto Vera Monge, Oscar Ramos, Alejandro Rodríguez, Ana Rodríguez Campello, Gemma Romeral Ballester, Mireia Llop Trujillano, Eva Giralt Steinhauer, Elisa Cuadrado Godia, Angel Javier Ois Santiago, Jordi Jimenez Conde, Joan Martí Fábregas, Daniel Guisado, Luís Prats, Pol Camps, Raquel Delgado, Alejandro Martínez Domeño, Rebeca Marín, David Cànovas, Jordi Estela, Marta Ros, Sonsoles Aranceta, Jordi Espinosa, Marta Rubio, Cristina Lafuente, Oriol Barrachina, Alicia Anguita, Anna Reverter, Carmen García, Gemma Sansa, Mariona Hervas, Monica Crosas, Tania Delgado, Jerzy Krupinski, Sonia Huertas Folch, Gemma Muñoz Gamito, Josep Trenado Alvarez, Teresa Subirana, Jessica Molina, Laura Comes Romero, Gemma Guardia Valls, Miriam Jover, Javier Joaquín Sotova, Sonia Mª García Sánchez, Sebastian Valenzuela (intensivista), Manuel Gómez-Choco, Juan José Mengual, M. Àngels Font, Mª Isabel Gómez Ruiz, Irati Zubizarreta, Susana Fernández González, Laura Gubieras, Carmen E. Cobos, Luis Mena Romo, Nuria Caballol, Luis Cano, Joaquín Serena Leal, Mikel Terceño Izarra, Irene Bragado Trigo, Saima Bashir Viturro, Laura Pardo Albiñana, Montserrat Reina Garrido, Carla Marco Cazcarra, Karol Enrique Uscamaita, Fabian Márquez, Cristina Coll, Mar Irida Lloret Villlas, Berta Solano Vila, Berta Alemany Perna, Daniel López Domínguezl, Mercedes de Lera, Anna Cots Foraster, Urszula Bojaryn, Ikram Benabdelhak, Gerard Mauri Capdevila, Jordi Sanahuja Montesinos, Daniel Vázquez, José Vicente Hervás, Cristina González, Alejandro Quílez, Mikel Vicente Pascual, María Ruiz, Yolanda Riba, M. Pilar Gil Villar, Cristina García, Xavier Ustrell Roig, Mònica Baldrich Mora, Anna Pellisé Guinjoan, Judit Borras, Alba Mañé Martínez, Rafael Marés, Jaume Viñas i Gaya, Laia Seró, Alan Flores, Paula Rodríguez, Gislaine Castilho, Angela Monterde Ortega, Silvia Reverté, Josep Zaragoza, Joan Josep Baiges, Gisela Martín Ozaeta, Sonia Escalante, Iago Payo, Júlia Saura Salvado, Natalia Mas Sala, Josep M Soler Insa, Ester Tio Vilamala, Josep Abos Navarro, Héctor Cruz Tabuenca, Tamara Canento Sánchez, Elisabet Roldán, Elsa Puiggrós Rubiol, Elisabet Franquet, Lidia Fuentes, Javier Donaire, Elena Martí, Laura Giménez, Junior Gil Vázquez, Eloisa Nieto Clara Gris Ambrós, Puri Rodríguez, José Félix Oletta, Pilar Pons Mellado, Catena, Bárbara Gómez, Vergilin Raileau, Esther Catena Ruíz, Oscar Pardina, Jordi Mercadal, María López-Diéguez, Pilar Pérez, Lourdes Gabarró, María Orriols, Joan Josep Canet, Mireia Roca, Muriel Álvaro, Francesc Boneu, Georgina Giménez, Jaume Albà, Francesc Gibert, Jéssica Garcia, Patricia Barragan, Gustavo Jurado, Josep Sabaté Ortega, Joan Amaurys Martínez Solano, Víctor Fernández, Mónica Torres, Ana Belén Montero Alvaredo, Laura Redondo Parejo, Josep Maria Aragonés, Anna Bullón, Cora Loste, Paula González, Neker Bejarano, Francisco Sanchez, Gianni Lucchetti, Xavier Pla, Javier Gimeno, Esteban Reynaga, Montse Barcons, Gabriel Celedón, Juan Ortiz, Goran Anastasovski, Oscar Mascaró, Javier Diez de los Ríos, Meritxell Feliu, Anna Ribera, Cristhian Ruiz, Gerard Corominas, Daniella Nunes, Claudia Roca, Nadina Latorre, Lizbeth Yataco, Maricelys Cruz, Nerea Blanco, Santiago Castejón, Dolores Cocho Calderón, Claustre Pont Sunyer, Jordi Espinosa Garcia, Rodrigo Paz Martin, Albert de Luis Sanchez, Dolores Espinosa Vivas, Juan Valencia Molina, Gemma, Planels Palome, Laia Tomas Chaume, Ares Villagrasa Vilella, Marco Bustamante, Anunciación Boltes, Fernando Rodríguez, Itziar Arrieta, Jordi Ciurans Molist, Barnés Andreu, Ernest Palomeras Soler, Nicolau Guanyabens Buscà, Manuel Daza López, Jordi Bigas Farreres, Virginia Casado Ruiz, Desiree Muriana Batiste, Mª Pilar Sanz Cartagena, Eulalia Cabot de Vega, Josep Bassa Real, Hector Pelaez Roman, César Socolich, Josep Mª Alonso Camp, Antonio Tomás Cano Orgaz, Mª Pilar Fossas Felip, Nicolás Morón, Sandra Bacca, Mauricio Molina, Francesc Casarramona, Lorena Elias, Muhammad Zidane Bukaei, Jose Antonio Martos Gutierrez, Judith Lopez Escuin, Cristina Olaizola, Yolexis López Vargas, Juan Jiménez Oyonarte, Rashida Soultana, Eduardo Sanjurjo Golpe, Esther Salvador, Guillem Vila, Marcos Serrano, Matilde Nuria López Claverol, Marian Lamolla, Miquel Amate, Adriana Rodriguez, Ruth Romero, Montgomery del Carpio, Ana Isabel Hernandez, Julián Martín, M Carmen Rosas, Antonio Nogueroles, Sorilandy Encarnación, Augusto Robles, Jose Antonio Herrera, Roger Gavilán, Toghrol Mameghani, Gastón Araujo, M.Angeles Garrido Morales, Enric Ramon Albert Segui, Eva Fernandez Climent, Francesc Paris Pujol, Mireia Judit Garrofé Seira, Lucía Gómez Pía, Fernando Salleres Nuñez, Cristina Aguar Peñalver, Cristina Vaz Lopes, Elisenda Ribera Tasa, Carmen Repullo Vilchez, Modesto Sánchez Zambrana, Beatriu Suescun Ribas, Inés Vilà Panés, Montserrat Vila Planavila, Alicia Vaqueiro Lorenzo, Meritxell Sabartés Guixes, Jorge Medina, David Sambrano, Javi Zamarreño, Carmen Pirela, Paola Vélez, Luis Cajamarca, Honey Pérez, Yarles Martínez, Jesus Alexander Gonçalves, Carles Regordosa, Claudia Mormeneo, Laura Griu, Maria Francia Colina, Enric Farik, Dolors Carrión Duch, Carles Badenas, Oscar Bernal, Núria Agramunt, Shyrlei Morales, Victoria Reynoso, Miguel Guerrero, Primitivo Romera Cid, Mònica Folqué, Claudia Pedroza, Adnan Hachem, Íñigo Soteras Martínez, Xavier Verdera García, Mercè López Amorós, Xavier Costa Subirós, Marta Cufí Benet, Cecile Van Eendenburg, Teresa Osuna, Dra Gina Santos, Mireia Pallisera, Lluís Gonzalo Oliva, Gemma Sanchez, Xavier Basurto, Ludgi Vivoda, Richard Van der Kleyn, Laura Robles, Ana Cabanelas Barranco, Mª Cruz Almendros, Marc Pérez Oliveras, Amelia Fernández Álvarez, Maria Rybyeva, Antoni Viñas, Maria Barcons, Joaquim Danès Alberto Tavera, Pablo Burbano, Cintie López, David Cruz, Paula Bisbe, Nora Fernández, Juan Carlos Palacio, Eduardo Fraiz, Oriol Aguiló, Rollmy Amorodjo, John Velázquez, Elena Sánchez, Jaume Español, Judit Perez de Celis, Anna Coll, Glòria Díaz, Margarida Vergés i Sala, Mª Ángels Casas Capdevila, Yosmairy Yoselin Ferrini, Aitor Gorriz, Diego-Javier Cucurell Navarro, Dulce Velásquez, Jaume Pla Soler, Josep González, Julian David Higuera, Lina Cuellar, Liza Margarita Miniello, Lluis Pujol, Sorin Cracan, Mora Vives, M Angela, Lopez Lopez, null Anabel, Montse Gorchs Molist, Delofeu Anna, Silvia Solà Muñoz, Ferreres Yolanda, Carol Pujalte, Elisabeth Téllez Marín, Yolanda Font Casas, Sara Hernández Luque, Joaquim Mejias Sendra, Francesca Mellado Valero, Campos Escala, Galup De Lacanal, Lopez Diaz, Castillo Paramio, Català Estopà, Español Moreda, Calafell Majo, Carballo Almeida, Castro Naval, M Elena, Cregut Ruiz, Pere Lluis, Deulofeu Font, Fabregat Sanjuan, Joan Pere, Fontquerni Gorchs, Forés Bellés, Joan Antoni, Gomez Herrera, Juan Carlos, Hijazo Prades, Itzaina Torvisco, Marti Rovira, Obiols Gonzalez, Olive Cavero, Querol Gil, M Soledad, Rico Rodriguez, Rios Sambernardo, Ropero Molina, Jose Ramon, Sanchez Valero, Santos Arevalo, Maria Jose, Soto Garcia, Maria Angeles, Tebar Escribano, Torres Garcia, Pedro José, Verdes Carrion, M Isabel, Verge Lopez, Juan Jose, Lopez Canela, M Angeles, Lucas Guarque, Morales Alvarez, Jorge Arnulfo, Morell Fornieles, Subirats Gomez, Maria Teresa, Torello Masa, Val Lopez, Maria Mercedes, Palmero Reyes, Juan Manuel, Rodriguez Forne, Ruana Turiel, Sanchez Gonzalez, Sebastia Gornals, Abrio Rico, Albert Gual Falip, Aznar Oliveros, Brugues Perotti, Calvet Molinero, Catells Franco, Corrales Medina, Daroca Miro, Duran Marquez, Feliu Pradas, Figueras Casanova, Garcia Tortajada, Grajera Gallego, Azahara del Mar, Las Arroyo, Dulcenombre de Jesus, Laserreta Sanz, Llambrich Vidal, Monllao Corral, Morales de la Cruz, Moreno Blanco, Orejuela Orgaz, Piñana Suazo, Pons Minguillon, Rodríguez Gómez, José Carlos, Rodriguez Pereira, Sedo Porcel, Sevil Villar, Sierra Lopez, Torres Romero, Trepat Calveres, Ventura Arnella, Acera Gil, M Teresa, Biesot Vico, Castro Galea, Rosa Maria, Escorcia Chafer, Juan Antonio, Gil Faure, Hernandez Luque, Jimenez Delgado, Mallafre Gay, M. Angel, Olivares Sanzo, Pubill Fondevila, Sabate Fort, Segovia Agámez, Antonio Carlos, Turata Longaretti, Valle Hernandez, Trayner Guixens, Aguilar Valor, Aguirre Alvarez, Alastrue Naval, Alferez Baquero, Alonso Marne, Cristina, Aloy Orozco, Alvarez Colino, Alvarez Peñuela, Ameller Cirilo, Maria Vanessa, Andujar Guerrero, Estefania Remedios, Auladell Sillero, Azcarate Sorbet, Basany Genesca, Benavent Barduena, Benito Tudela, Blanch Pardo, Boluda Pla, Bonilla Gonzalez, Bru Serramalera, Burnat Andreu, Caballero Calvo-Rayo, Calvo Casellas, Camps Mombiela, Cano Bresme, Carcelen Fernandez, Caro Solà, Casasas Matavacas, Castanedo Bolado, Cerdeña Cortina, Abella Jane, Laia Collado Borrego, Colom Orri, Comellas Vilanova, Conillera Sole, Cots Torres, Cuchi Estepa, de Sostoa Graell, del Rio Lopez, Delgado Compte, Diaz Bueno, Diaz Maneiro, Andrea Lucia, Domenech Palau, M. Carme, Duran Carasso, Pablo Javier, El Abidi, Escoda Martin, Esteve Casanovas, Fernandez Perez, Ferre Quintero, Flores Escobar, Fontcuberta Abad, Fortes del Valle, Mª Luisa, Franco Quesada, Sara Maria, Franco Romero, Gallego Francisco, Gamiz Gala, Alicia, Garcia Castañeda, Garcia Rodriguez, Casajuana Gemma, Gomez Arroyo, Gomez Girbau, Gonzalez Fernandez, Gonzalez Gonzalez, Gonzalez Lopez, Gual Obeso, Guerrero Blanco, Guillemas Roca, Guillermo Eudaldo, Hernandez Sebastia, Homar Covas, Hostench Alvarez, Huerta Royo, Ibañez Barcelo, Izquiero Cruz, Jaione Urdangarin Etxetxikia, Juárez Gimenez, Khlifi Alami, Laparra Gasco, Lara Moreales, Lasaosa Medina, Maria Lourdes, Lazaro Cava, Leon Berrar, López Maturana, Lopez Ramirez, López Romero, Lorente Marco, Lorenzo Martin, Lozano Casals, Lujan Nicola, Madrid Diaz, Jose Antonio, Maria Teresa Peris Morales, Marti Clemente, Martinez Castaño, David Natanael, Martinez Gamez, Martinez Gonzalez, Martinez Quesada, Maria de la Cabeza, Marzà Fusté, Mireia, M Conillera, Melendo Lasheras, Miralles Mestre, Montserrat Puig Pastalle, Montserrate Vidal, Mora Mellado, Morales Ponce, Morera Cabre, Morera Vivet, Mundi Souza, Muñoz Quiles, Navea Rosa, Neira Iglesias, M Asuncion, Nuñez Manrique, Mª Pilar, Obiols Martinez, Pallares Reig, Partegas Torres, Pascual Berengueras, Perez Gamez, Perez Oset, Perez Restrepo, Maria Alejandra, Planas Yeste, Planells Mangado, Puertas Carbonell, Quinteiro Blanco, Rebollar Benavente, Recasens Fernandez, Reyes Gomez, Maria del Carmen, Roca Pou, Rodriguez Ferrer, Rodriguez Franco, Rodriguez Fuertes, Rodriguez Muñoz, Rodriguez Navarro, Roig Iniesta, Romero Gracia, Rovira Brunet, Rovira de Eugenio, Rubio Baena, Ruiz Llorens, Sala Llamazares, San Juan Alaez, Sanchez Segura, Santasusana Soldevilla, Sanz Salmeron, Segura Perez, Serra Balcells, Sorina Dumitras, Teixidor Montoya, Tena Vicente, Tierno Salinas, Ester Ines, Toledo Testa, Tomàs Figueras, Tomas Ruperez, Torrano Garcia-Penche, Torres Esparza, Florenc Uku, Vazquez Blanco, Vazquez De la Paz, Vazquez Gil, Vazquez Gonzalez, Vidal Meler, Vilalta Cots, Vilches Jimenez, Visser Fernandez, Viu Gavin, Vives Vives, Carmona Jimenez, Francisco Jose, Galobardes Vilches, Gonzalez Gomez, Jodar Manzanera, Marimon Cortes, Marrodan Orive, Martin Bosch, Martorell Lopez, Millares Roca, M Jesus, Miralles Guri, Muliterno Hernandez, Muñoz Oliva, Pons Pujol, Postius Conde, Prieto Arruñada, Quintana Mathé, Rosell Mata, Alvarin Alvarez, Arrufat Flores, Bañuelos Pago, Campo Vilar, Cardus Hidalgo, Castello Gil, Maria Gloria, Castrillo Montsesinos, Clave Garces, Comes Sanroma, Descalzo Sequi, Errando Ricol, Escudero Campillo, Maria del Mar, Fernandez Alvarez, Fernandez Gomez, Franch Espinosa, Freixes Graells, Garcia Plaza, Garcia-Marron Gallego, Hernandez Simancas, Jaraba Armas, Jimenez Ramos, Lopez Oganissian, Madrona Romero, M Rosa, Martinez Millan, Martínez Morón, Merchan Encinas, Moreno Jimenez, Muñoz Rico, Navarro Rodriguez, Nogales Ibañez, Rita Maria, Novillo Viera, Parella Torrabadella, Mari Alba, Pera Villar, Carla Montserrat, Rabella Miralles, Ramis Trilles, Ribera Ortiz, Sastre Perez, Soro Borrega, Tapia Fores, Tellez Bernad, Trenado Alvarez, Felix Martin, Herrero Perez, Lanau Fuster, Lopez Gomariz, Pardo Lozano, Quintana Altimiras, Ventosa Lopez, Almodovar Damian, Alvarez Monterroso, Arambudo Comas, Boullon Garzon, Burgos Capella, Campuzano Garcia, Maria Del Mar, Capdevila Olivas, Carre Marti, Clara Isabel, Carretero Bacaicoa, Cazorla Calderon, Chacon Osuna, Cortes Planas, Cortit Olio, Delhomme Estany, Fructuos Martinez, Garcia Lopez, Pascual Luis, Genis Amill Vallve, Gonzalez Muñoz, Hernaez Ventura, Lavernia Gimenez, Martin Rojo, Martínez Medina, Mayol Barrera, Mercader Pi, Merino Dalmau, Miguel Campodarbe, Moreno Sanchez, Francisco Javier, Alba Mari, Penela Barrameda, Prieto Ajenjo, Rodriguez Pareja, Rodríguez Piñar, Javier Francisco, Rodriguez Tello, Romero Pereda, Sainz Saborido, Santacana Martin, Santos Martinez, Sierra Chavez, Turbau Torres, Vicente Domenech, Villena Esteo, Vives Pertegaz, Baena Gonzalez, Bagaria Pont, Beltran Sanchez, Bonet Alarcon, Borch Ballescà, Buhils Clanchet, Closa Garcia, Colomina Carril, Cristina Fernandez Sanchez, Fernandez Toledo Edurne Judith, Espases Rodriguez, Espert Resa, F Xavier, Fernández Sol, Gonzalez Lugo, Gracia Llesera, Herrada Lendinez, Juliench Liesa, Sandra Alicia, Lopez Ortega, Lopez Yuste, Lozano Villanueva, Lucia Sola Soto, Madrid Castellano, Megias Cano, Daniel Jesus, Montasell Ponce, Montesinos Sospedra, Moya Martinez, Muñoz Herrera, Ocaña Fernandez, Palau Bernal, Perez Sole, Ramon Carbonell, Ribas Lop, Rubio López, Rueda Lopez, Sabat Castaño, Sabata Lara, Salmerón Ramírez, Serra Creus, Serrano Dalmau, Sumasi Mainero, Gonzalo Gabriel, Valencia Primo, Ana Maria Viñuales Muñoz, Josep Roig, and Verònica Hidalgo.
Subjects: Stroke, Advanced and Specialized Nursing, Treatment Outcome, Endovascular Procedures, Humans, Neurology (clinical), Cardiology and Cardiovascular Medicine, Brain Ischemia, Ischemic Stroke, Thrombectomy, Workflow
Abstract: Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95]). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
Published: 2022

20. La concentración plasmática de microARN-1-3p se asocia con fibrilación auricular subclínica en los pacientes con ictus criptogénico

Author: Begoña Benito, Anna García-Elías, Ángel Ois, Marta Tajes, Ermengol Vallès, Mireia Ble, Laia Yáñez Bisbe, Eva Giralt-Steinhauer, Ana Rodríguez-Campello, Mercè Cladellas Capdevila, Julio Martí-Almor, Jaume Roquer, and Elisa Cuadrado-Godia
Subjects: Cardiology and Cardiovascular Medicine
Published: 2022

21. Plasma levels of miRNA-1-3p are associated with subclinical atrial fibrillation in patients with cryptogenic stroke

Author: Begoña, Benito, Anna, García-Elías, Ángel, Ois, Marta, Tajes, Ermengol, Vallès, Mireia, Ble, Laia, Yáñez Bisbe, Eva, Giralt-Steinhauer, Ana, Rodríguez-Campello, Mercè, Cladellas Capdevila, Julio, Martí-Almor, Jaume, Roquer, and Elisa, Cuadrado-Godia
Subjects: Stroke, MicroRNAs, Atrial Fibrillation, Humans, Circulating MicroRNA, Heart Atria, General Medicine, Biomarkers, Ischemic Stroke
Abstract: Identifying biomarkers of subclinical atrial fibrillation (AF) is of most interest in patients with cryptogenic stroke (CrS). We sought to evaluate the circulating microRNA (miRNA) profile of patients with CrS and AF compared with those in persistent sinus rhythm.Among 64 consecutive patients with CrS under continuous monitoring by a predischarge insertable monitor, 18 patients (9 with AF and 9 in persistent sinus rhythm) were selected for high-throughput determination of 754 miRNAs. Nine patients with concomitant stroke and AF were also screened to improve the yield of miRNA selection. Differentially expressed miRNAs were replicated in an independent cohort (n=46). Biological markers were stratified by the median and included in logistic regression analyses to evaluate their association with AF at 6 and 12 months.Eight miRNAs were differentially expressed between patients with and without AF. In the replication cohort, miR-1-3p, a gene regulator involved in cardiac arrhythmogenesis, was the only miRNA to remain significantly higher in patients with CrS and AF vs those in sinus rhythm and showed a modest association with AF burden. High (= above the median) miR-1-3p plasma values, together with a low left atrial ejection fraction, were independently associated with the presence of AF at 6 and 12 months.In this cohort, plasma levels of miR-1-3p were elevated in CrS patients with subsequent AF. Our results preliminarily suggest that miR-1-3p could be a novel biomarker that, together with clinical parameters, could help identify patients with CrS and a high risk of occult AF.
Published: 2022

22. Multi-Ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke

Author: Laura Ibanez, Laura Heitsch, Caty Carrera, Fabiana H G Farias, Jorge L Del Aguila, Rajat Dhar, John Budde, Kristy Bergmann, Joseph Bradley, Oscar Harari, Chia Ling Phuah, Robin Lemmens, Alessandro A Viana Oliveira Souza, Francisco Moniche, Antonio Cabezas-Juan, Juan Francisco Arenillas, Jerzy Krupinksi, Natalia Cullell, Nuria Torres-Aguila, Elena Muiño, Jara Cárcel-Márquez, Joan Marti-Fabregas, Raquel Delgado-Mederos, Rebeca Marin-Bueno, Alejandro Hornick, Cristofol Vives-Bauza, Rosa Diaz Navarro, Silvia Tur, Carmen Jimenez, Victor Obach, Tomas Segura, Gemma Serrano-Heras, Jong Won Chung, Jaume Roquer, Carol Soriano-Tarraga, Eva Giralt-Steinhauer, Marina Mola-Caminal, Joanna Pera, Katarzyna Lapicka-Bodzioch, Justyna Derbisz, Antoni Davalos, Elena Lopez-Cancio, Lucia Muñoz, Turgut Tatlisumak, Carlos Molina, Marc Ribo, Alejandro Bustamante, Tomas Sobrino, Jose Castillo-Sanchez, Francisco Campos, Emilio Rodriguez-Castro, Susana Arias-Rivas, Manuel Rodríguez-Yáñez, Christina Herbosa, Andria L Ford, Alonso Gutierrez-Romero, Rodrigo Uribe-Pacheco, Antonio Arauz, Iscia Lopes-Cendes, Theodore Lowenkopf, Miguel A Barboza, Hajar Amini, Boryana Stamova, Bradley P Ander, Frank R Sharp, Gyeong Moon Kim, Oh Young Bang, Jordi Jimenez-Conde, Agnieszka Slowik, Daniel Stribian, Ellen A Tsai, Linda C Burkly, Joan Montaner, Israel Fernandez-Cadenas, Jin Moo Lee, Carlos Cruchaga, University of St Andrews. School of Biology, HUS Neurocenter, and Neurologian yksikkö
Subjects: ADAM23, NDAS, QH426 Genetics, ANNOTATION, Medical and Health Sciences, DISEASE, 3124 Neurology and psychiatry, SPONTANEOUS REPERFUSION, Brain Ischemia, SDG 3 - Good Health and Well-being, Genetics, Humans, 2.1 Biological and endogenous factors, genetics, Aetiology, Ischaemic stroke, QH426, METAANALYSIS, GENE-EXPRESSION, Ischemic Stroke, Medicine(all), MCC, ischaemic stroke, NEUROPROTECTION, Neurology & Neurosurgery, Human Genome, Psychology and Cognitive Sciences, 3112 Neurosciences, Neurosciences, Bayes Theorem, United States, Neuroprotection, Brain Disorders, GENOME, Stroke, SEVERITY, Neurological, LGI1, Neurology (clinical), Genome-Wide Association Study, Biotechnology, NIHSS
Abstract: Funding: This work was supported by grants from the Emergency Medicine Foundation Career Development Grant; AHA Mentored Clinical & Population Research Award (14CRP18860027); NIH/NINDS-R01-NS085419 (C.C., J.M.L.); NIH/NINDS-R37-NS107230, NIH/NINDS U24-NS107230 (J.M.L.); NIH/NINDS-K23-NS099487 (L.H.); NIH/NIA-K99-AG062723 (L.I.); Barnes-Jewish Hospital Foundation (J.M.L.); Biogen (C.C., J.M.L.); Bright Focus Foundation, US Department of Defense, Helsinki University Central Hospital; Finnish Medical Foundation; Finland government subsidiary funds; Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (grants ‘Registro BASICMAR’ Funding for Research in Health (PI051737), ‘GWALA project’ from Fondos de Investigación Sanitaria ISC III (PI10/02064, PI12/01238 and PI15/00451), JR18/00004); Fondos FEDER/EDRF Red de Investigación Cardiovascular (RD12/0042/0020); Fundació la Marató TV3; Genestroke Consortium (76/C/2011); Recercaixa’13 (JJ086116). Tomás Sobrino (CPII17/00027), Francisco Campos (CPII19/00020) and Israel Fernandez are supported by Miguel Servet II Program from Instituto de Salud Carlos III and Fondos FEDER. I.F. is also supported by Maestro project (PI18/01338) and Pre-test project (PMP15/00022) from Instituto de Salud Carlos III and Fondos Feder, Agaur; and Epigenesis project from Marató TV3 Foundation. J.C., J.M., A.D., J.M.-F., J.A. and I.F. are supported by Invictus plus Network (RD16/0019) from Instituto de Salud Carlos III and Fondos Feder. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-2013/07559-3) (I.L.-C.), Sigrid Juselius Foundation. The MEGASTROKE project received funding from sources specified at http://www.megastroke.org/acknowledgments.html. B.S., B.A. and F.S. are supported by NIH awards NS097000, NS101718, NS075035, NS079153 and NS106950. During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6h of stroke onset and NIHSS at 24h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Postprint
Published: 2022

23. Defining Minor Intracerebral Hemorrhage

Author: Uxue Lazcano, C. Avellaneda-Gómez, Raquel Delgado-Mederos, Daniel Guisado-Alonso, Angel Ois, Alejandra Gómez-González, Eva Giralt Steinhauer, Joan Martí-Fàbregas, Rosa Maria Vivanco-Hidalgo, Jordi Jimenez-Conde, Luis Prats-Sánchez, Elisa Cuadrado-Godia, Pol Camps-Renom, Ana Rodríguez-Campello, Alejandro Martínez Domeño, Jaume Roquer, and Carolina Soriano-Tárraga
Subjects: Male, Minor stroke, medicine.medical_specialty, Time Factors, NIH stroke scale, Severity of Illness Index, Disability Evaluation, Predictive Value of Tests, Modified Rankin Scale, Internal medicine, Humans, Medicine, In patient, cardiovascular diseases, Aged, Cerebral Hemorrhage, Outcome, Aged, 80 and over, Intracerebral hemorrhage, business.industry, Reproducibility of Results, Middle Aged, Prognosis, medicine.disease, University hospital, nervous system diseases, Hemorrhagic Stroke, Functional Status, Neurology, Spain, Cohort, Female, Neurology (clinical), Cutoff point, Cardiology and Cardiovascular Medicine, business
Abstract: Background and Purpose: The minor stroke concept has not been analyzed in intracerebral hemorrhage (ICH) patients. Our purpose was to determine the optimal cut point on the NIH Stroke Scale (NIHSS) for defining a minor ICH (mICH) in patients with primary ICH. Methods: An ICH was considered minor if associated with a favorable 3-month outcome (modified Rankin Scale score ≤2). For supratentorial ICH, the discovery cohort consisted of 478 patients prospectively admitted at University Hospital del Mar. Association between NIHSS at admission and 3-month outcome was evaluated with area under the curve-receiver operating characteristics (AUC-ROC) and Youden’s index to identify the optimal NIHSS cutoff point to define mICH. External validation was performed in a cohort of 242 supratentorial ICH patients from University Hospital Sant Pau. For infratentorial location, patients from both hospitals ( n = 85) were analyzed together. Results: The best NIHSS cutoff point defining supratentorial-mICH was 6 (AUC-ROC = 0.815 [0.774–0.857] in the discovery cohort and AUC-ROC = 0.819 [0.756–0.882] in the external validation cohort). For infratentorial ICH, the best cutoff point was 4 (AUC-ROC = 0.771 [0.664–0.877]). Using these cutoff points, 40.5% of all primary ICH cases were mICH. Of these, 70.2% were living independently at 3-month follow-up (72% for supratentorial ICH and 56.1% for infratentorial ICH) and 6.5% had died (5.3% for supratentorial ICH, and 14.6% for infratentorial ICH). For patients identified as non-mICH, good 3-month outcome was observed in 11.3% of cases; mortality was 51%. Conclusions: The definition of mICH using the NIHSS cutoff point of 6 for supratentorial ICH and 4 for infratentorial ICH is useful to identify good outcome in ICH patients.
Published: 2021

24. Long-term vascular events after subarachnoid hemorrhage

Author: Isabel Fernandez-Perez, Eva Giralt-Steinhauer, Elisa Cuadrado-Godia, Leopoldo Guimaraens, Elio Vivas, Jesus Saldaña, Antoni Suárez-Pérez, Adria Macias-Gomez, Anna Revert-Barbera, Isabel Estragues-Gazquez, Ana Rodríguez-Campello, Joan Jiménez-Balado, Lucia Rey-Álvarez, Jaume Roquer, Jordi Jimenez-Conde, and Angel Ois
Subjects: Cohort Studies, Neurology, Risk Factors, Incidence, Humans, Neurology (clinical), Prospective Studies, Subarachnoid Hemorrhage
Abstract: Spontaneous subarachnoid hemorrhage (SAH) long-term risk is not well known. Our aims are: describing long-term vascular event (VE) incidence rates in SAH survivors; describing VE: ischemic and/or hemorrhagic; identifying independent association of factors related to VE; and analyzing the usefulness of factors to increase predictive ability.A prospective cohort study of consecutive patients admitted to Hospital del Mar with a diagnosis of SAH (n = 566) between January 2007 and January 2020 was carried out. They were followed up until January 2021. The study endpoint was a new VE in the follow-up. We calculated both incidence rates and cumulative rates at 5 years. Cox regression survival models including vascular risk factors with and without specific data of SAH disease were developed. We analyzed ROC curves of all multivariate models.The analyzed cohort included 423 non-fatal SAH cases. Total patient-years were 2468.16 years. The average follow-up was 70.03 ± 43.14; range: 1-180 months. There were 49 VE detected in 47 patients, as 2 of them had more than 1 VE. Incidence rate was 0.020 events_per_patient/year, cumulative incidence at 5 years was 11.11%. The more frequent VE that we found were cerebrovascular (28/49), mainly ischemic (21/28). Disability after SAH and the presence of multiple aneurysms were independently associated with a VE risk and improved the predictive capacity of multivariate models (AUC 0.679 vs 0.764; p = 0.0062).We reported a low vascular risk after SAH. We have shown the usefulness of SAH factors to identify patients with a higher risk of VE.
Published: 2022

25. Increased COVID-19 mortality in people with previous cerebrovascular disease: a population-based cohort study

Author: Elisenda Martínez-Carbonell, Jaume Roquer, María Grau, Marc Boher-Massaguer, Jordi Jimenez-Conde, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Isabel Fernandez-Perez, Isaac Subirana, Ana Rodríguez-Campello, Angel Ois, Uxue Lazcano, [Lazcano U] Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Institut d'investigacions mèdiques Hospital del Mar, Barcelona, Spain. Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQuAS), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Cuadrado-Godia E, Rodríguez-Campello A, Giralt-Steinhauer E, Fernández-Pérez I, Jiménez-Conde J, Roquer J, Ois A] Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Institut d'investigacions mèdiques Hospital del Mar, Barcelona, Spain. Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Institut d'investigacions mèdiques Hospital del Mar, Barcelona, Spain. Departament de Neurologia, Hospital del Mar, Departament de Medicina i Ciències de la Vida (CEXS), Universitat Pompeu Fabra, Universitat Autònoma de Barcelona, Barcelona, Spain. [Grau M] Consorcio Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain. Department of Medicine, University of Barcelona, Spain. [Subirana I] Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Institut d'investigacions mèdiques Hospital del Mar, Barcelona, Spain. Consorcio Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain. [Martínez-Carbonell E] Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQuAS), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Boher-Massaguer M] Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQuAS), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain, and Departament de Salut
Subjects: Male, 2019-20 coronavirus outbreak, Pediatrics, medicine.medical_specialty, Subarachnoid hemorrhage, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Other subheadings::Other subheadings::/epidemiology [Other subheadings], enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares [ENFERMEDADES], COVID-19 (Malaltia) - Mortalitat, Cohort Studies, Population based cohort, Age groups, Risk Factors, Other subheadings::Other subheadings::Other subheadings::/mortality [Other subheadings], medicine, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Humans, Prospective Studies, Stroke, Advanced and Specialized Nursing, Aged, 80 and over, Otros calificadores::Otros calificadores::Otros calificadores::/mortalidad [Otros calificadores], business.industry, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders [DISEASES], Otros calificadores::Otros calificadores::/epidemiología [Otros calificadores], COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], medicine.disease, Malalties cerebrovasculars - Epidemiologia, Cerebrovascular Disorders, Ischemic stroke, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract: Background: The aim of the study was to determine the association between previous stroke and mortality after coronavirus disease 2019 (COVID-19) according to sex, age groups, and stroke subtypes. Methods: Prospective population-based cohort study including all COVID-19 positive cases between February 1 and July 31, 2020. Comorbidities and mortality were extracted using linked health administration databases. Previous stroke included transient ischemic attack, ischemic stroke, hemorrhagic stroke, spontaneous subarachnoid hemorrhage, and combined stroke for cases with more than one category. Other comorbidities were obesity, diabetes, hypertension, ischemic heart disease, atrial fibrillation, heart failure, chronic obstructive pulmonary disease, chronic kidney disease, cirrhosis, dementia, individual socioeconomic index, and deprivation index. Cases were followed up until December 31, 2020. Primary outcome was mortality of any cause after COVID-19 positivity. Cox proportional regression analysis adjusted for comorbidities was used. Stratified analyses were performed for sex and age ( Results: There were 91 629 COVID-19 cases. Previous strokes were 5752 (6.27%), of which 3887 (67.57%) were ischemic, 1237 (21.50%) transient ischemic attack, 255 (4.43%) combined, 203 (3.53%) hemorrhagic, and 170 (2.96%) subarachnoid hemorrhage. There were 9512 deaths (10.38%). Mortality was associated with previous stroke (hazard ratio [HR]=1.12 [95% CI, 1.06–1.18]; P P =0.001; women=1.09 [1.01–1.18]; P =0.023), in people P P P =0.437). Ischemic (HR=1.11 [1.05–1.18]; P =0.001), hemorrhagic (HR=1.53 [1.20–1.96]; P =0.001) and combined (HR=1.31 [1.05–1.63]; P =0.016) strokes were associated but not transient ischemic attack. Subarachnoid hemorrhage was associated only in people P =0.003). Conclusions: Previous stroke was associated with a higher mortality in people younger than 80 years. The association occurred for both ischemic and hemorrhagic stroke but not for transient ischemic attack. These data might help healthcare authorities to establish prioritization strategies for COVID-19 vaccination.
Published: 2022

26. Migraine Aura mimicking Stroke in Code Stroke. Analysis of diagnostic prediction models

Author: Adrià Macias-Gómez, Antoni Suárez-Pérez, Ana Rodríguez-Campello, Eva Giralt-Steinhauer, Antía Moreira, Daniel Guisado-Alonso, Jaume Capellades, Isabel Fernández-Pérez, Jordi Jiménez-Conde, Lucía Rey, Joan Jiménez-Baladó, Jaume Roquer, Ángel Ois, and Elisa Cuadrado-Godia
Abstract: Background: Differences between migraine with aura (MA) mimicking stroke and ischemic strokes were analyzed to create a predictive diagnostic model.Methods: Prospective cohort of code strokes attended between January 2005 and June 2020 in a tertiary hospital evaluated by a vascular neurologist. Data recorded included: Place of activation, demographics, vascular risk factors, vitals, initial blood test (glucose, blood count, electrolytes, coagulation times, D-dimer, fibrinogen and C-reactive protein), initial NIHSS, door-to-onset time, and door-to-needle time. After the vascular study, diagnosis of ischemic stroke or MA was registered. Multivariate logistic regression analyses were performed to create a predictive model. Discrimination and calibration performance were assessed. A secondary aim was to describe detailed clinical and radiological data of MA cases in order to identify new predictive factors that could be used in future studies.Results: Of 3140 code strokes attended, 2424 (77.2%) were ischemic strokes and 34 (1.1%) were MA. Migraine cases were younger, more frequently females and with low prevalence of vascular risk factors. Initial NIHSS was lower in MA cases, but no differences were seen in fibrinolysis rate (30%). Blood test showed lower levels of glucose, D-dimer, and fibrinogen in MA cases. Multivariate model showed and independent association for ischemic stroke with age [OR, (95%CI):1.09, (1.07-1.12, p65, NIHSS>6, and fibrinogen>400mg/dL) showed a good global discrimination capacity (AUC = 0.897) but a good calibration only for extreme predicted probabilities (>98% in ischemic strokes or < 10% in MA). We did not find any differential clinical or radiological factor that could be exclusive of MA.Conclusions: A predictive model including age >65, men sex, NIHSS >6 and fibrinogen >400 mg/dL showed a good discrimination, but low calibration performance to distinguish between MA and ischemic stroke. Future studies should involve migraine biomarkers in order to improve clinical decision making.
Published: 2022

27. White matter hyperintensity burden in acute stroke patients differs by ischemic stroke subtype

Author: Tatjana Rundek, Ona Wu, Ramesh Sridharan, Vincent Thijs, Marco Nardin, Daniel Woo, Bradford B. Worrall, Christina Jern, Ralph L. Sacco, Steven J. T. Mocking, Pankaj Sharma, Agnieszka Slowik, Steven J. Kittner, Anne-Katrin Giese, Braxton D. Mitchell, Elissa C. McIntosh, Jordi Jimenez-Conde, Markus D. Schirmer, Polina Golland, John W. Cole, Arne Lindgren, Robin Lemmens, Adrian V. Dalca, Eva Giralt-Steinhauer, Dawn Kleindorfer, Reinhold Schmidt, Natalia S. Rost, Jonathan Rosand, Patrick F. McArdle, Johan Wassélius, Huichun Xu, James F. Meschia, Robert E. Irie, and Kathleen L. Donahue
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, complications [Arterial Occlusive Diseases], Neurology, Arterial Occlusive Diseases, pathology [Brain Ischemia], Article, diagnostic imaging [White Matter], Brain Ischemia, Lesion, 03 medical and health sciences, Deep Learning, 0302 clinical medicine, Neuroimaging, Risk Factors, pathology [White Matter], Internal medicine, diagnostic imaging [Stroke], medicine, Humans, ddc:610, Stroke, Aged, Retrospective Studies, etiology [Stroke], Acute stroke, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, White Matter, etiology [Brain Ischemia], Magnetic Resonance Imaging, 030104 developmental biology, White matter hyperintensity, diagnostic imaging [Brain Ischemia], Ischemic stroke, Cohort, pathology [Stroke], Cardiology, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: ObjectiveTo examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS).MethodsFor the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool–based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes.ResultsPatients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18–14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001).ConclusionIn this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.
Published: 2020

28. Risk factors analysis according to regional distribution of white matter hyperintensities in a stroke cohort

Author: Jaume Capellades, Jaume Roquer, Angel Ois, Santiago Medrano-Martorell, Isabel Fernández, Carla Avellaneda, Eva Giralt-Steinhauer, Sofía González-Ortiz, Ana Rodríguez-Campello, Marta Vilas-González, Jordi Jimenez-Conde, Elisa Cuadrado-Godia, Joan Martí-Fàbregas, and Elisa Merino-Peña
Subjects: medicine.medical_specialty, behavioral disciplines and activities, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, Internal medicine, mental disorders, medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Neuroradiology, Ischemic stroke, business.industry, Leukoaraiosis, General Medicine, Odds ratio, Confidence interval, Hyperintensity, Stroke, medicine.anatomical_structure, Risk factors, 030220 oncology & carcinogenesis, Cohort, Cardiology, Etiology, Radiology, business
Abstract: The spectrum of distribution of white matter hyperintensities (WMH) may reflect different functional, histopathological, and etiological features. We examined the relationships between cerebrovascular risk factors (CVRF) and different patterns of WMH in MRI using a qualitative visual scale in ischemic stroke (IS) patients. We assembled clinical data and imaging findings from patients of two independent cohorts with recent IS. MRI scans were evaluated using a modified visual scale from Fazekas, Wahlund, and Van Swieten. WMH distributions were analyzed separately in periventricular (PV-WMH) and deep (D-WMH) white matter, basal ganglia (BG-WMH), and brainstem (B-WMH). Presence of confluence of PV-WMH and D-WMH and anterior-versus-posterior WMH predominance were also evaluated. Statistical analysis was performed with SPSS software. We included 618 patients, with a mean age of 72 years (standard deviation [SD] 11 years). The most frequent WMH pattern was D-WMH (73%). In a multivariable analysis, hypertension was associated with PV-WMH (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.29–2.50, p = 0.001) and BG-WMH (OR 2.13, 95% CI 1.19–3.83, p = 0.012). Diabetes mellitus was significantly related to PV-WMH (OR 1.69, 95% CI 1.24–2.30, p = 0.001), D-WMH (OR 1.46, 95% CI 1.07–1.49, p = 0.017), and confluence patterns of D-WMH and PV-WMH (OR 1.62, 95% CI 1.07–2.47, p = 0.024). Hyperlipidemia was found to be independently related to brainstem distribution (OR 1.70, 95% CI 1.08–2.69, p = 0.022). Different CVRF profiles were significantly related to specific WMH spatial distribution patterns in a large IS cohort. • An observational study of WMH in a large IS cohort was assessed by a modified visual evaluation. • Different CVRF profiles were significantly related to specific WMH spatial distribution patterns. • Distinct WMH anatomical patterns could be related to different pathophysiological mechanisms.
Published: 2022

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

Author: Elena Muiño, Jara Cárcel-Márquez, Caty Carrera, Laia Llucià-Carol, Cristina Gallego-Fabrega, Natalia Cullell, Miquel Lledós, José Castillo, Tomás Sobrino, Francisco Campos, Emilio Rodríguez-Castro, Mònica Millán, Lucía Muñoz-Narbona, Alejandro Bustamante, Elena López-Cancio, Marc Ribó, José Álvarez-Sabín, Jordi Jiménez-Conde, Jaume Roquer, Eva Giralt-Steinhauer, Carolina Soriano-Tárraga, Cristófol Vives-Bauza, Rosa Díaz-Navarro, Silvia Tur, Victor Obach, Juan Arenillas, Tomás Segura, Gemma Serrano-Heras, Joan Martí-Fàbregas, Raquel Delgado-Mederos, Pol Camps-Renom, Luis Prats-Sánchez, Daniel Guisado, Marina Guasch, Rebeca Marin, Alejandro Martínez-Domeño, Maria Freijo-Guerrero, Francisco Moniche, Juan Cabezas, Mar Castellanos, Jerzy Krupinsky, Daniel Strbian, Turgut Tatlisumak, Vincent Thijs, Robin Lemmens, Agnieszka Slowik, Joanna Pera, Laura Heitsch, Laura Ibañez, Carlos Cruchaga, Rajat Dhar, Jin-Moo Lee, Joan Montaner, Israel Fernández-Cadenas, on Consortium, the Consortium, Institut Català de la Salut, [Muiño E, Cárcel-Márquez J, Llucià-Carol L] Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain. [Carrera C] Laboratori de Recerca Neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Gallego-Fabrega C] Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain. Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain. [Cullell N] Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain. Stroke Pharmacogenomics and Genetics, Fundació MútuaTerrassa per la Docència i la Recerca, 08221 Terrassa, Spain. [Ribó M] Unitat d'Ictus, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Álvarez-Sabín J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Neurologia, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Instituto de Salud Carlos III, European Commission, Fundació La Marató de TV3, Agència de Gestió d'Ajuts Universitaris i de Recerca, Neurologian yksikkö, and HUS Neurocenter
Subjects: 0301 basic medicine, Oncology, Parenchymal hematoma, Genoma humano, Malalties cerebrovasculars - Tractament, Genome-wide association study, Disease, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], 3124 Neurology and psychiatry, DISEASE, 0302 clinical medicine, GWAS, Stroke, RISK, Genome-wide association study (GWAS), Genomics, General Medicine, parenchymal hematoma, 3. Good health, Meta-analysis, Medicine, DETERIORATION, Life Sciences & Biomedicine, ACUTE STROKE, medicine.medical_specialty, Genómica, education, single nucleotide variants, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::accidente cerebrovascular [ENFERMEDADES], Genetic correlation, Article, 03 medical and health sciences, Medicine, General & Internal, 32 Ciencias Médicas, Internal medicine, General & Internal Medicine, Genetic variation, medicine, Other subheadings::Other subheadings::/adverse effects [Other subheadings], cardiovascular diseases, GENOME-WIDE ASSOCIATION, Genetic association, THROMBOLYSIS, Science & Technology, técnicas de investigación::perfusión::reperfusión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Reperfusió miocardíaca - Complicacions, business.industry, Hemorrhagic transformation, medicine.disease, Hyperintensity, MODEL, hemorrhagic transformation, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Stroke [DISEASES], 030104 developmental biology, Single nucleotide variants, Investigative Techniques::Perfusion::Reperfusion [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], business, 030217 neurology & neurosurgery
Abstract: Producción Científica, 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-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases., Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - ( Projects PI 11/0176 and PI18/01338), Instituto de Salud Carlos III - (Project CM18/00198), Agencia de Gestión de Ayudas Universitarias y de Investigación (AGAUR) y Fondo Social Europeo - (Grant 2020FI_B1 00157), Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (Project CD20/00043), Instituto de Salud Carlos III - (Projects FI19/00309, CP12/03298, CPII17/00027, CPII19/00020)
Published: 2021

30. Interaction of atrial fibrillation and antithrombotics on outcome in intracerebral hemorrhage

Author: Jaume Roquer, Lluís L. Prats-Sánchez, Ana Rodríguez-Campello, Joan Martí-Fàbregas, Alejandro Martínez-Domeño, Jordi Jimenez-Conde, Elisa Cuadrado-Godia, Angel Ois, Daniel Guisado-Alonso, Rosa Maria Vivanco-Hidalgo, and Eva Giralt Steinhauer
Subjects: Male, medicine.medical_specialty, Severity of Illness Index, Internal medicine, Atrial Fibrillation, Severity of illness, Antithrombotic, medicine, Humans, Hospital Mortality, Prospective Studies, cardiovascular diseases, Prospective cohort study, Aged, Cerebral Hemorrhage, Resuscitation Orders, Aged, 80 and over, Intracerebral hemorrhage, business.industry, Age Factors, Case-control study, Anticoagulants, Atrial fibrillation, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Spain, Case-Control Studies, Cardiology, Female, Neurology (clinical), business, Platelet Aggregation Inhibitors
Abstract: ObjectiveTo analyze the clinical differences between patients with primary intracerebral hemorrhage (ICH) with and without atrial fibrillation (AF) and assess whether the effect of the antithrombotic pretreatment on outcome is modified by the presence of AF.MethodsIn this prospective observational study, researchers from 2 university hospitals included 1,106 consecutive patients with ICH. Clinical characteristics were described and stratified by presence of AF. In-hospital and 3-month mortality and 3-month disability were analyzed, considering antithrombotic pretreatment (none, antiplatelets, or oral anticoagulants) and AF (yes/no).ResultsAF was present in 21.9% of primary ICH cases. Patients with AF-ICH were older, with more vascular risk factors, more antithrombotic pretreatment, higher clinical severity, higher hematoma volume, and higher in-hospital and 3-month mortality. Do-not-resuscitate orders were applied more frequently in AF-ICH cases. After 2 different adjustment models, mortality remained significantly higher in patients with AF-ICH. However, after introducing previous antithrombotic treatment in the model, the adjusted odds ratio for 3-month mortality was 1.45 (95% confidence interval 0.74–2.85, p = 0.284) for patients with AF-ICH compared with non-AF cases. AF modified the effect of antithrombotic pretreatment on in-hospital (pint = 0.077) and 3-month mortality (pint = 0.008). Among patients without AF, antithrombotic pretreatment increased mortality; no effect was observed in patients with AF-ICH.ConclusionsPatients with AF and ICH had increased mortality; however, AF had no independent effect on mortality after adjustment for antithrombotic pretreatment. Conversely, antithrombotic pretreatment had a deleterious effect on outcome in patients with ICH without AF, but no detectable effect in patients with AF with ICH.
Published: 2019

31. PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome

Author: Christina Jern, Braxton D. Mitchell, E. Palomeras, Aina Medina-Dols, Vincent Thijs, Kistiina Rannikmae, Alejandro Bustamante, Jordi Jimenez-Conde, Tomás Segura, Caty Carrera, Rosa Maria Vivanco-Hidalgo, Victor Obach, Israel Fernandez-Cadenas, Xavier Estivill, Bradford B. Worrall, Tara M. Stanne, José Alvarez-Sabín, Gemma Serrano-Heras, Elena López-Cancio, Mar Castellanos, Catherine Sudlow, Elisa Cuadrado-Godia, Antonio Dávalos, Silvia Tur, Maria Angels Font, Ana Rodríguez-Campello, Cristina Gallego-Fabrega, Elena Muiño, Teresa García-Berrocoso, Carmen Jiménez, Marc Ribó, Laura Heitsch, Laura Ibanez, Jin-Moo Lee, Cristofol Vives-Bauza, Montserrat Solé, Pilar Delgado, Erik Lorentzen, Joan Martí-Fàbregas, Mar Freijo, Carlos A. Molina, Robin Lemmens, Carolina Soriano-Tárraga, Rosa Díaz-Navarro, Jurek Krupinski, Angel Ois, Jaume Roquer, Eva Giralt-Steinhauer, Arne Lindgren, Jane Maguire, Daniel Woo, Jonathan Rosand, Joan Montaner, Natalia Cullell, Marina Mola-Caminal, Joaquín Serena, Steven J. Kittner, Mar Hernández-Guillamon, Lucía Muñoz-Narbona, Raquel Rabionet, Natalia S. Rost, Maite Mendioroz, Carlos Cruchaga, Nuria P. Torres-Aguila, Chia-Ling Phuah, and Universitat de Barcelona
Subjects: 0301 basic medicine, Discapacitats, Isquèmia cerebral, Cardiac & Cardiovascular Systems, Neurology, Physiology, Treatment outcome, Genome-wide association study, Brain Ischemia, Brain ischemia, Disability Evaluation, 0302 clinical medicine, Gene Frequency, Risk Factors, SCALE, Stroke Rehabilitation, allele, Hematology, Cerebral ischemia, Stroke, Treatment Outcome, Phenotype, Cardiology, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, genetic variant, medicine.medical_specialty, People with disabilities, GENETICS, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, ischemic stroke, medicine, Humans, Genetic Predisposition to Disease, Allele, Allele frequency, Tight Junction Proteins, Science & Technology, genome-wide association study, business.industry, Genetic variants, genetic loci, Recovery of Function, medicine.disease, 030104 developmental biology, Cardiovascular System & Hematology, Peripheral Vascular Disease, Ischemic stroke, Cardiovascular System & Cardiology, business, 030217 neurology & neurosurgery
Abstract: Rationale: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. Methods and Results: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P =1.70×10 −9 ). Conclusions: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.
Published: 2019

32. Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome

Author: Rajat Dhar, Joan Montaner, Antoni Dávalos, Emilio Rodríguez-Castro, Katarzyna Lapicka-Bodzioch, Eva Giralt-Steinhauer, E. López-Cancio, Israel Fernandez-Cadenas, Joan Martí-Fàbregas, Turgut Tatlisumak, Jin-Moo Lee, Francisco Moniche, Carlos Cruchaga, Victor Obach, Carmen Jiménez, Lucía Muñoz-Narbona, Laura Heitsch, Joanna Pera, T. Segura, Pooja Khatri, Silva Tur, Juan Antonio Cabezas, Nuria P. Torres-Aguila, Jara Cárcel-Márquez, Alejandro Bustamante, Natalia Cullell, Jordi Jimenez-Conde, Gemma Serrano-Heras, Caty Carrera, Jonathan Rosand, Justyna Derbisz, Francisco Campos, Jaume Roquer, Jerzy Krupinski, Susana Arias-Rivas, Michael M. Binkley, José Castillo, Carol Soriano-Tarraga, Marc Ribó, Carlos A. Molina, Daniel Strbian, Juan F. Arenillas, Cristofol Vives-Bauza, Tomás Sobrino, Andria L. Ford, Rosa Díaz-Navarro, Elena Muiño, Agnieszka Slowik, Raquel Delgado-Mederos, and Laura Ibanez
Subjects: Male, medicine.medical_specialty, phenotype, Population, Ischemia, population, ischemic, Genome-wide association study, 030204 cardiovascular system & hematology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ischaemic stroke, Medicine, Humans, education, Acute ischemic stroke, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Aged, 80 and over, education.field_of_study, genome-wide association study, stroke, ischemic, business.industry, Recovery of Function, Middle Aged, medicine.disease, stroke, 3. Good health, Ischemic stroke, Cardiology, Observational study, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSS baseline – NIHSS 24hours = ΔNIHSS 6-24h ), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS 6 –24h . In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS 6–24h was examined. Finally, the association of ΔNIHSS 6 –24h with 90-day favorable outcomes (modified Rankin Scale score 0–2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4–16), and median ΔNIHSS 6 –24h was 2 (interquartile range, 0–5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS 6 –24h (R 2 =0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R 2 =0.27), but much of the variance remained unexplained. ΔNIHSS 6 –24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS 3 –24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, ΔNIHSS 6–24h , captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS 6 –24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.
Published: 2020

33. MULTI-ANCESTRY GENETIC STUDY IN 5,876 PATIENTS IDENTIFIES AN ASSOCIATION BETWEEN EXCITOTOXIC GENES AND EARLY OUTCOMES AFTER ACUTE ISCHEMIC STROKE

Author: Laura Ibanez, E. López-Cancio, Jose Castillo-Sanchez, Oh Young Bang, C. Herbosa, Joseph Bradley, Antonio Arauz, Jin-Moo Lee, Gyeong Moon Kim, Joan Montaner, Lucia Muñoz, Alejandro Bustamante, Joan Martí-Fàbregas, Francisco Moniche, Kristy Bergmann, Chia-Ling Phuah, Juan F. Arenillas, Iscia Lopes-Cendes, Laura Heitsch, Linda C. Burkly, Ellen A. Tsai, Jerzy Krupinksi, Silvia Tur, Tomás Sobrino, Susana Arias-Rivas, Raquel Delgado-Mederos, Elena Muiño, Oscar Harari, Katarzyna Lapicka-Bodzioch, Jara Cárcel-Márquez, Frank R. Sharp, Alejandro Hornick, Rajat Dhar, John P. Budde, Agnieszka Slowik, Bradley P. Ander, Robin Lemmens, Turgut Tatlisumak, Carlos Cruchaga, Antoni Dávalos, Hajar Amini, Daniel Stribian, Gemma Serrano-Heras, Justyna Derbisz, Boryana Stamova, Joanna Pera, Andria L. Ford, Carol Soriano-Tarraga, Jaume Roquer, Nuria P. Torres-Aguila, Manuel Rodríguez-Yáñez, Cristofol Vives-Bauza, Fabiana H.G. Farias, Theodore Lowenkopf, Miguel A Barboza, Alessandro A Viana Oliveira Souza, Carmen Jiménez, Marina Mola-Caminal, Antonio Cabezas-Juan, Marc Ribó, Jordi Jimenez-Conde, Tomás Segura, Caty Carrera, Eva Giralt-Steinhauer, Emilio Rodríguez-Castro, Victor Obach, Natalia Cullell, Rosa Díaz Navarro, Francisco Campos, Israel Fernandez-Cadenas, Jong-Won Chung, Carlos A. Molina, and Rebeca Marin-Bueno
Subjects: Genome-wide association study, Locus (genetics), Bioinformatics, Article, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Genetic variation, Genetics, Medicine, Humans, GRIA1, 030304 developmental biology, Genetic association, Ischemic Stroke, 0303 health sciences, biology, business.industry, ADAM23, Bayes Theorem, Genetic architecture, Neuroprotection, United States, 3. Good health, Stroke, Expression quantitative trait loci, biology.protein, business, 030217 neurology & neurosurgery, NIHSS, Genome-Wide Association Study
Abstract: During the first hours after stroke onset neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between NIH stroke scale (NIHSS) within six hours of stroke onset and NIHSS at 24h (ΔNIHSS). A total of 5,876 individuals from seven countries (Spain, Finland, Poland, United States, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of ΔNIHSS variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture than that of stroke risk. Seven loci (2p25.1, 2q31.2, 2q33.3, 4q34.3, 5q33.2, 6q26 and 7p21.1) were genome-wide significant and explained 2.1% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each loci. eQTL mapping and SMR indicate that ADAM23 (log Bayes Factor (LBF)=6.34) was driving the association for 2q33.3. Gene based analyses suggested that GRIA1 (LBF=5.26), which is predominantly expressed in brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated PARK2 (LBF=5.30) and ABCB5 (LBF=5.70) for the 6q26 and 7p21.1 loci. Human brain single nuclei RNA-seq indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a pre-synaptic protein, and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provides the first evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischemic stroke.RESEARCH INTO CONTEXTEvidence before this studyNo previous genome-wide association studies have investigated the genetic architecture of early outcomes after ischemic stroke.Added Value of this studyThis is the first study that investigated genetic influences on early outcomes after ischemic stroke using a genome-wide approach, revealing seven genome-wide significant loci. A unique aspect of this genetic study is the inclusion of all of the major ethnicities by recruiting from participants throughout the world. Most genetic studies to date have been limited to populations of European ancestry.Implications of all available evidenceThe findings provide the first evidence that genes implicating excitotoxicity contribute to human acute ischemic stroke, and demonstrates proof of principle that GWAS of acute ischemic stroke patients can reveal mechanisms involved in ischemic brain injury.
Published: 2020

34. Features of intracranial hemorrhage in cerebral venous thrombosis

Author: Robin Lemmens, Jonathan M. Coutinho, Antonio Arauz, Alessandro Pezzini, Miguel A Barboza, Nicole Hinteregger, Christian Weimar, Susanna M. Zuurbier, Sini Hiltunen, Vincent Thijs, Pieter-Jan Buyck, Joan Montaner, Carlos Garcia Esperon, Turgut Tatlisumak, Patricia Luiza Nunes Costa, J. Jiménez Conde, Jukka Putaala, K. Afifi, Irene Escudero, G Bellanger, Dimitri Renard, Eva Giralt-Steinhauer, Marc Schlamann, Thomas Gattringer, Franz Fazekas, Philippe Demaerel, ANS - Neurovascular Disorders, ACS - Atherosclerosis & ischemic syndromes, and Neurology
Subjects: Adult, Male, Cerebral veins, medicine.medical_specialty, Subarachnoid hemorrhage, Bleeding, Medizin, Hemorrhage, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Mexico, Stroke, Aged, Retrospective Studies, Venous Thrombosis, business.industry, Subdural hemorrhage, medicine.disease, Cerebral Veins, Thrombosis, Europe, Venous thrombosis, Intracranial Thrombosis, Neurology, Cerebral venous thrombosis, Female, Neurology (clinical), Radiology, business, Intracranial Hemorrhages, 030217 neurology & neurosurgery, Superior sagittal sinus
Abstract: [Background] Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage., [Aim] To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage., [Methods] We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging., [Results] We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1–3) vs. 2 (1–3) without hemorrhage, p = 0.4)., [Conclusion] The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.
Published: 2020

35. A parsimonious score with a free web tool for predicting disability after an ischemic stroke: the Parsifal Score

Author: Jaume Roquer, Joan Montaner, Natalia Cullell, Elena Muiño, Alejandro Bustamante, Jara Cárcel-Márquez, Marta Rubiera, Carlos A. Molina, Israel Fernandez-Cadenas, Nuria P. Torres-Aguila, Eva Giralt-Steinhauer, Cristina Gallego-Fabrega, Angel Ois, Jordi Jimenez-Conde, Caty Carrera, Elisa Cuadrado-Godia, Ana Rodríguez-Campello, Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, and Agència de Gestió d'Ajuts Universitaris i de Recerca
Subjects: medicine.medical_specialty, Modified Rankin Scale, Web tool, Brain Ischemia, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Disabled Persons, 030212 general & internal medicine, Stroke, Ischemic Stroke, Neuroradiology, Disability, business.industry, Prognosis, medicine.disease, Regression, Treatment Outcome, Neurology, Ischemic stroke, Cohort, Neurology (clinical), Ordered logit, business, 030217 neurology & neurosurgery, Dyslipidemia
Abstract: [Background] Most of the models to predict prognosis after an ischemic stroke include complex mathematical equations or too many variables, making them difficult to use in the daily clinic. We want to predict disability 3 months after an ischemic stroke in an independent patient not receiving recanalization treatment within the first 24 h, using a minimum set of variables and an easy tool to facilitate its implementation. As a secondary aim, we calculated the capacity of the score to predict an excellent/devastating outcome and mortality., [Methods] Eight hundred and forty-four patients were evaluated. A multivariable ordinal logistic regression was used to obtain the score. The Modified Rankin Scale (mRS) was used to estimate disability at the third month. The results were replicated in another independent cohort (378 patients). The “polr” function of R was used to perform the regression, stratifying the sample into seven groups with different cutoffs (from mRS 0 to 6)., [Results] The Parsifal score was generated with: age, previous mRS, initial NIHSS, glycemia on admission, and dyslipidemia. This score predicts disability with an accuracy of 80–76% (discovery–replication cohorts). It has an AUC of 0.86 in the discovery and replication cohort. The specificity was 90–80% (discovery–replication cohorts); while, the sensitivity was 64–74% (discovery–replication cohorts). The prediction of an excellent or devastating outcome, as well as mortality, obtained good discrimination with AUC > 0.80., [Conclusions] The Parsifal Score is a model that predicts disability at the third month, with only five variables, with good discrimination and calibration, and being replicated in an independent cohort., This work was supported by a grant from Instituto de Salud Carlos III (PI 11/0176), Generación Project, Maestro Project, INVICTUS + network, Epigenesis Project (Marató de TV3) and FEDER funds. E. Muiño is supported by a Río Hortega Contract (CM18/00198) from Instituto de Salud Carlos III. J. Cárcel-Márquez is supported by AGAUR Contract (agència de gestió d'ajuts universitaris i de recerca; FI_DGR 2019, grant number 2019_FI_B 00853). A. Bustamante is supported by a Juan Rodés Research Contract (JR16/00008) from Instituto de Salud Carlos III.
Published: 2020

36. Genomic and phenomic insights from an atlas of genetic effects on DNA methylation

Author: Carol A. Wang, Simonetta Guarrera, Avshalom Caspi, Eilis Hannon, Marta E. Alarcón-Riquelme, P. Eline Slagboom, Pooja R. Mandaviya, Koen F. Dekkers, Cheng-Jian Xu, Jari Lahti, Juan E. Castillo-Fernandez, Dan Mason, Dylan Aïssi, Jan H. Veldink, Mariona Bustamante, Melissa C. Smart, Guillermo Barturen, Zdenka Pausova, Jenny van Dongen, Jordi Jimenez-Conde, Craig E. Pennell, Gibran Hemani, Tom R. Gaunt, Camilla Schmidt Morgen, Ken K. Ong, Toni-Kim Clarke, Alexia Cardona, Susanne Lucae, René Luijk, T.J. Gorrie-Stone, Phillip E. Melton, Thorkild I. A. Sørensen, André G. Uitterlinden, Jordana T. Bell, Jouke-Jan Hottenga, Meena Kumari, Francesc Català-Moll, Jonathan Mill, Tõnu Esko, Sailalitha Bollepalli, Dorret I. Boomsma, Torben Hansen, Hongmei Zhang, Yanni Zeng, John Wright, Wilfried Karmaus, Martin Kerick, Carolina Soriano-Tárraga, Jaakko Kaprio, Miina Ollikainen, Eco J. C. de Geus, Jordi Sunyer, Therese Tillin, Juan R. González, Yvonne Awaloff, Faisal I. Rezwan, Karen Sugden, Nicholas G. Martin, Karen M Ho, Andres Metspalu, Marine Germain, Kristel R. van Eijk, Ramona A. J. Zwamborn, George Davey Smith, Judith M. Vonk, Tian Lin, Henning Tiemeier, Grant W. Montgomery, Naomi R. Wray, Rae-Chi Huang, Alfredo Iacoangeli, Wendy L. McArdle, Jean Shin, Michael Lerro, Darina Czamara, Valentina Iotchkova, David-Alexandre Trégouët, Johanna Klughammer, Elena Carnero-Montoro, Pierre-Emmanuel Morange, Andrew M. McIntosh, Gemma C Sharp, Alun D. Hughes, Carlos Ruiz-Arenas, John M. Starr, Riccardo E. Marioni, Peter M. Visscher, Nabila Kazmi, Ian J. Deary, Kathryn L. Evans, Terrie E. Moffitt, Janine F. Felix, Tomáš Paus, Ashok Kumar, Jaume Roquer, Christopher Shaw, Hannah R Elliott, Susan M. Ring, Nish Chaturvedi, Giovanni Cugliari, Ahmad Al Khleifat, Joyce B. J. van Meurs, Kimberley Burrows, Bert Brunekreef, Debbie A Lawlor, Clara Viberti, Louise Arseneault, Silva Kasela, Cilla Söderhäll, Idil Yet, Manon Bernard, Christoph Bock, Vincent W. V. Jaddoe, Felix R. Day, Diana van Heemst, Alison D. Murray, Nicholas J. Wareham, Giuseppe Matullo, John R. B. Perry, Gerard H. Koppelman, M. Arfan Ikram, Ammar Al Chalabi, Gonneke Willemsen, Richie Poulton, Daniel Lawson, Andrew D. Bretherick, Vanessa Schmoll, Carlotta Sacerdote, Annelot M. Dekker, Lili Milani, Fernando Rivadeneira, Erik Melén, John W. Holloway, Gareth E. Davies, Tom G. Richardson, Caroline L Relton, Josine L. Min, Göran Pershagen, Elisabeth B. Binder, Marian Beekman, Chris Haley, Richa Gupta, Bastiaan T. Heijmans, Ellen A. Nohr, Allan F. McRae, Matthew Suderman, Rosie M. Walker, David L. Corcoran, Katri Räikkönen, Marinus H. van IJzendoorn, Eva Giralt-Steinhauer, Leonard C. Schalkwyk, Aleksey Shatunov, and Tim D. Spector
Subjects: Genetics, Regulation of gene expression, 0303 health sciences, Natural selection, dNaM, Biology, Genetic architecture, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Genetic variation, DNA methylation, Trait, 030217 neurology & neurosurgery, DNA, 030304 developmental biology
Abstract: Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.
Published: 2020

37. Biological age is a novel biomarker to predict stroke recurrence

Author: Ana Rodríguez-Campello, C. Avellaneda-Gómez, Rosa Maria Vivanco-Hidalgo, Eva Giralt-Steinhauer, Angel Ois, Carol Soriano-Tarraga, Jordi Jimenez-Conde, Elisa Cuadrado-Godia, Uxue Lazcano, Jaume Roquer, and Alejandra Gómez-González
Subjects: medicine.medical_specialty, Aging, Neurology, Time Factors, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Risk factor, Stroke, Cause of death, Neuroradiology, business.industry, Atrial fibrillation, medicine.disease, Ischemic Attack, Transient, Spain, Child, Preschool, Cardiology, Biomarker (medicine), Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Stroke recurrence (SR) after an ischemic stroke is an important cause of death and disability. We conducted a hospital-based study to evaluate the role of biological age (b-Age: age-related DNA-methylation changes) as a risk factor for SR. We included 587 patients in the acute phase of stroke, assessed at one tertiary stroke center (Hospital del Mar: Barcelona, Spain). B-Age was estimated with 5 different methods based on DNA methylation, and Hannum’s method was the one that better performed. We analyzed the relationships between b-Age, chronological age, sex, vascular risk factors, coronary and peripheral arterial disease, atrial fibrillation, initial neurological severity assessed by National Institutes of Health Stroke Scale (NIHSS), transient ischemic attack (TIA) in the 7 days preceding the index stroke, and symptomatic atherosclerosis. Stroke recurrence definition include: new symptoms that suggest a new ischemic event had occurred within 3 months after stroke onset and worsening by four points in the initial neurological severity (measured by National Institutes of Health Stroke Scale (NIHSS) score). Logistic regression analysis associated b-Age with SR [p = 0.003; OR = 1.06 (95% CI: 1.02–1.09)], independently of chronological age [p = 0.022; OR = 0.96 (95% CI 0.94–1.00)], symptomatic atherosclerosis (stenosis > 50% in the symptomatic territory), transient ischemic attack (TIA) in the 7 days preceding the index stroke, and initial NIHSS. The b-Age of patients with SR was 2.7 years older than patients without SR. Patients with SR were biologically older than those without SR. B-Age was independently associated with high risk of developing SR.
Published: 2020

38. Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain

Author: Elena Muiño, Victor Obach, Ana Calleja, Elena López-Cancio, Reyes de Torres-Chacón, Jara Cárcel-Márquez, Joan Martí-Fàbregas, Serafí Cambray, Maria Del Mar Freijo, Jerzy Krupinski, Maria-Teresa Buongiorno, Israel Fernandez-Cadenas, Natalia Cullell, Joan Montaner, Sarah Besora, Jessica Molina, Manuel Rodríguez-Yáñez, Silvia Tur, Jonathan González-Sánchez, Cristina Gallego-Fabrega, María Hernández-Pérez, Eva Giralt-Steinhauer, Javier Sotoca, José Castillo, Nuria-Paz Torres-Aguila, Jordi Jimenez-Conde, Caty Carrera, Maria-Àngels Font, Juan Antonio Cabezas, Francisco Purroy, Fernando Mancha, Tomás Sobrino, Cristofol Vives-Bauza, Juan F. Arenillas, Luis Prats-Sánchez, Pol Camps-Renom, University of St Andrews. School of Biology, International Stroke Genetics Consortium, Consorcio español de genética del ictus, and Redes Temáticas de Investigación Cooperativa en Salud (España)
Subjects: Male, 0301 basic medicine, QH301 Biology, humanos, lcsh:Medicine, Genome-wide association study, Hemorràgia cerebral, 030204 cardiovascular system & hematology, Genoma humà, farmacogenética, 0302 clinical medicine, estudios prospectivos, Prospective Studies, lcsh:Science, Aged, 80 and over, Acenocoumarol, anciano, Multidisciplinary, Maintenance dose, Anticoagulant, Stroke, Cohort, Female, VKORC1, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, medicine.drug, medicine.medical_specialty, medicine.drug_class, NDAS, QH426 Genetics, Polymorphism, Single Nucleotide, Ictus, QH301, 03 medical and health sciences, vitamina K epóxido reductasas, Internal medicine, Vitamin K Epoxide Reductases, medicine, Humans, cardiovascular diseases, accidente cerebrovascular, QH426, CYP2C9, Cytochrome P-450 CYP2C9, Aged, business.industry, lcsh:R, Anticoagulants, 030104 developmental biology, Spain, Pharmacogenetics, estudio de asociación genómica completa, RC0321, Anticoagulants (Medicina), lcsh:Q, acenocumarol, anticoagulantes, business, Genome-Wide Association Study
Abstract: Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p, We would like to thank the International Stroke Genetics Consortium, the Spanish Stroke Genetics Consortium, and the RETICS Network INVICTUS plus (RD16/0019/0001, RD16/0019/0002, RD16/0019/0007, RD16/0019/0010, and RD16/0019/0011, RD16/0019/0017, RD16/0019/0019 and RD16/0019/0021).
Published: 2020

39. Identification of 20 novel loci associated with ischaemic stroke. Epigenome-wide association study

Author: Israel Fernandez-Cadenas, Jaume Roquer, Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Jordi Jimenez-Conde, Roberto Elosua, Angel Ois, Ana Rodríguez-Campello, Uxue Lazcano, C. Avellaneda-Gómez, Elisa Cuadrado-Godia, Manel Esteller, Natalia Cullell, Alba Fernández-Sanlés, Alejandra Gómez-González, Sebastian Moran, and Joan Montaner
Subjects: Male, 0301 basic medicine, Cancer Research, Biology, Epigenome, 03 medical and health sciences, 0302 clinical medicine, Ischaemic stroke, Genetic variation, Humans, Molecular Biology, Aged, Ischemic Stroke, EWAS, Homeodomain Proteins, Genetics, DNA methylation, Genetic variants, Middle Aged, 030104 developmental biology, Genetic Loci, 030220 oncology & carcinogenesis, Life course approach, CpG Islands, Female, Identification (biology), Research Paper
Abstract: DNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1–2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism. To detect epigenetic variants associated with stroke occurrence and stroke subtypes. A two-stage case–control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischaemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N = 226 and N = 166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated with these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways. We identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.
Published: 2020

40. Stroke Care During COVID-19 Lockdown

Author: Ana RodrÃguez-Campello, Jaume Roquer, Eva Giralt-Steinhauer, Angel Ois, Carla Avellaneda-GÃ³mez, Alejandra Gómez-González, Elisa Cuadrado-Godia, and Isabel Fernandez-Perez
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Incidence (epidemiology), Outbreak, Stroke care, medicine.disease, Emergency medicine, Medicine, business, Stroke, Acute stroke
Abstract: Background: COVID-19 outbreak and lockdown measures might have an impact in stroke This studyâ€™s aim was to analyze the incidence of acute ischemic and hemorrha
Published: 2020

41. Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis

Author: Vincent Thijs, Sini Hiltunen, Eva Giralt-Steinhauer, Alessandro Pezzini, K. Afifi, Antonio Arauz, Susanna M. Zuurbier, Thomas Gattringer, Jonathan M. Coutinho, Carlos Garcia-Esperon, G Bellanger, Joan Montaner, Jordi Jimenez-Conde, Marc Schlamann, Irene Escudero, Christian Weimar, Philippe Demaerel, Nicole Hinteregger, Franz Fazekas, Robin Lemmens, Turgut Tatlisumak, Pieter-Jan Buyck, Paolo Costa, Jukka Putaala, Miguel A Barboza, and Dimitri Renard
Subjects: Venous thrombosis, medicine.medical_specialty, Neurology, business.industry, medicine, MEDLINE, Medizin, Neurology (clinical), Radiology, medicine.disease, business, Neuroradiology
Abstract: The original version of this article unfortunately contained mistakes. The correct information is given below.
Published: 2020

42. Identification of 20 novel loci associated to ischemic stroke. Epigenome-Wide Association Study

Author: Angel Ois, Ana Rodríguez-Campello, Alejandra Gómez-González, Elisa Cuadrado-Godia, Natalia Cullell, Uxue Lazcano, Jordi Jimenez-Conde, Jaume Roquer, Carolina Soriano-Tárraga, Manel Esteller, Alba Fernández-Sanlés, Eva Giralt-Steinhauer, C. Avellaneda-Gómez, Israel Fernandez-Cadenas, Sebastian Moran, Roberto Elosua, and Joan Montaner
Subjects: Genetics, CpG site, Genetic variation, DNA methylation, Single-nucleotide polymorphism, Locus (genetics), Epigenome, Epigenetics, Methylation, Biology
Abstract: RationaleDNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1–2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism.ObjectiveTo detect epigenetic variants associated to stroke occurrence and stroke subtypes.Methods and ResultsA two-stage case-control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N=226 and N=166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated to these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways. Stratification analysis by stroke subtypes revealed distinct methylation patterns.ConclusionsWe identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.
Published: 2019
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43. Alcohol overuse and intracerebral hemorrhage: characteristics and long-term outcome

Author: C. Avellaneda-Gómez, Elisa Cuadrado-Godia, A. Zabalza de Torres, Rosa Maria Vivanco-Hidalgo, Jordi Jimenez-Conde, Eva Giralt-Steinhauer, Carolina Soriano-Tárraga, Ana Rodríguez-Campello, Jaume Roquer, M. Serra Martínez, Alejandra Gómez-González, Marina Mola-Caminal, P. de Ceballos Cerrajería, and Angel Ois
Subjects: Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Stroke care, 03 medical and health sciences, 0302 clinical medicine, Hematoma, Risk Factors, Modified Rankin Scale, Internal medicine, medicine, Humans, Prospective Studies, Risk factor, Stroke, Aged, Cerebral Hemorrhage, Aged, 80 and over, Intracerebral hemorrhage, business.industry, Smoking, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Alcoholism, Neurology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: BACKGROUND AND PURPOSE Alcohol overuse (AOu) is considered an important risk factor for spontaneous intracerebral hemorrhage (ICH). The clinical and outcome characteristics of these patients (AOu-ICH) are not well known. METHODS All patients with ICH admitted to a single university tertiary stroke center were prospectively studied from May 2005 to May 2015. Demographic profiles, radiologic characteristics and clinical outcomes of patients with acute ICH and previous AOu (>40 g/day or >300 g/week) were analyzed. RESULTS During the study period, 555 patients with spontaneous primary ICH met the inclusion criteria. A total of 81 patients (14.6%) reported AOu (24.3% of men vs. 3.1% of women; P
Published: 2018

44. Ultra-early hematoma growth in antithrombotic pretreated patients with intracerebral hemorrhage

Author: Angel Ois, Eva Giralt-Steinhauer, Carolina Soriano-Tárraga, Marina Mola-Caminal, M. Serra-Martínez, Jordi Jimenez-Conde, Elisa Cuadrado-Godia, Ana Rodríguez-Campello, Jaume Capellades, Jaume Roquer, C. Avellaneda-Gómez, and Rosa Maria Vivanco-Hidalgo
Subjects: Male, medicine.medical_specialty, medicine.drug_class, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hematoma, Interquartile range, Internal medicine, Antithrombotic, medicine, Humans, In patient, Prospective Studies, cardiovascular diseases, Aged, Cerebral Hemorrhage, Retrospective Studies, Aged, 80 and over, Intracerebral hemorrhage, business.industry, Anticoagulants, Brain, Retrospective cohort study, Middle Aged, Vitamin K antagonist, medicine.disease, Antifibrinolytic Agents, Neurology, Anesthesia, Female, Functional status, Neurology (clinical), Tomography, X-Ray Computed, business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract: Background and purpose Patients with acute intracerebral hemorrhage (ICH) pretreated with antithrombotic drugs may have increased early hematoma growth, which would increase mortality risk. The effect of antiplatelet (AP) and vitamin K antagonist (VKA) pretreatment on ultra-early hematoma growth (uHG) and its relationship with mortality in patients with acute supratentorial ICH was analyzed. Methods This is an observational retrospective study of a prospective register of 197 ICH patients with first computed tomography (CT) scan taken
Published: 2017

45. Antithrombotic pretreatment increases very-early mortality in primary intracerebral hemorrhage

Author: Eva Giralt Steinhauer, Jaume Roquer, Elisa Cuadrado Godia, Ana Rodríguez Campello, Carolina Soriano-Tárraga, Alejandra Gómez González, Rosa María Vivanco Hidalgo, Jordi Jimenez Conde, and Angel Ois
Subjects: Male, medicine.medical_specialty, Time Factors, Vitamin K, medicine.drug_class, 030204 cardiovascular system & hematology, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, Antithrombotic treatment, 0302 clinical medicine, Fibrinolytic Agents, Risk Factors, Internal medicine, Antithrombotic, Severity of illness, medicine, Humans, In patient, Prospective Studies, Prospective cohort study, Survival analysis, Aged, Cerebral Hemorrhage, Aged, 80 and over, Intracerebral hemorrhage, business.industry, Middle Aged, Vitamin K antagonist, medicine.disease, Survival Analysis, Regression Analysis, Female, Neurology (clinical), business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Objective:To analyze the effect of previous antiplatelet (AP) and vitamin K antagonist (VKA) treatments on outcome in patients with primary intracerebral hemorrhage (ICH).Methods:In this prospective observational study, we analyzed 529 patients according to antithrombotic pretreatment: none, AP, or VKA. Very-early (24-hour) death, 3-month mortality, and functional independence were analyzed.Results:Of 236 (44.6%) pretreated patients, 147 (27.8%) patients were taking AP and 89 (16.8%) VKA. Very-early death was observed in 13.4% and was increased in pretreated patients: 19.0% for AP and 27.0% for VKA treatment, compared to 6.5% in non-pretreated patients, p < 0.0001. Three-month mortality was 40.8% overall (49.7% for AP pretreated, 58.4% for VKA pretreated, and 31.1% for non-pretreated patients, p < 0.0001). The adjusted odds of very-early and 3-month mortality were 2.55 (p = 0.004) and 1.56 (p = 0.046) for AP-pretreated patients and 4.24 (p < 0.0001) and 2.34 (p = 0.01) for VKA-pretreated patients, respectively, compared with non-pretreated patients. The effect of antithrombotic pretreatment on mortality from 24 hours to 3 months was nonsignificant. At 3-month follow-up, 28.5% of patients remained functionally independent: 22.4% of AP-pretreated, 15.7% of VKA-pretreated, and 35.5% of non-pretreated patients (p < 0.0001).Conclusions:A high percentage of patients with ICH preventively treated with VKA or AP died during the first 24 hours after admission. Both treatments were predictors of very-early mortality. The final effect of antithrombotics on 3-month mortality remains significant through its strong effect on very-early mortality. Safety concerns about starting chronic antithrombotic treatment should be considered not only when VKA treatment is planned but also for AP treatment.
Published: 2017

46. Short- and long-term outcome of patients with aneurysmal subarachnoid hemorrhage

Author: Eva Giralt-Steinhauer, Jaume Roquer, Elio Vivas, Angel Ois, C. Avellaneda-Gómez, María P. García-Arnillas, Gerardo Conesa, Rosa Maria Vivanco-Hidalgo, Juan Luis Fernández-Candil, Gloria Villalba-Martínez, Carolina Soriano-Tárraga, Ana Rodríguez-Campello, Jaume Capellades, Leopoldo Guimaraens, Jordi Jimenez-Conde, and Elisa Cuadrado-Godia
Subjects: Male, medicine.medical_specialty, Subarachnoid hemorrhage, Time Factors, medicine.medical_treatment, Aneurysm, Ruptured, Neurosurgical Procedures, Article, Postoperative Complications, Modified Rankin Scale, medicine, Humans, Mechanical ventilation, Endovascular coiling, business.industry, Intracranial Aneurysm, Odds ratio, Middle Aged, Subarachnoid Hemorrhage, medicine.disease, Confidence interval, Surgery, Treatment Outcome, Spain, Number needed to treat, Female, Neurology (clinical), Neurosurgery, business
Abstract: ObjectiveTo describe short-term and 5-year rates of mortality and poor outcome in patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) who received repair treatment.MethodsIn this prospective observational study, mortality and poor outcome (modified Rankin Scale score 3–6) were analyzed in 311 patients with aSAH at 3 months, 1 year, and 5 years follow-up. Sensitivity analysis was performed according to treatment modality. In-hospital and 5-year complications were analyzed.ResultsOf 476 consecutive patients with spontaneous subarachnoid hemorrhage, 347 patients (72.9%) had aSAH. Of these, 311 (89.6%) were treated (242 endovascular, 69 neurosurgical), with a mean follow-up of 43.4 months (range, 1 to 145). Three-month, 1-year, and 5-year mortality was 18.4%, 22.9%, and 29.0%, and poor outcome was observed in 42.3%, 36.0%, and 36.0%, respectively. Adjusted poor outcome was lower in endovascular than in neurosurgical treatment at 3 months (odds ratio [OR] 0.36 [95% confidence interval [CI] 0.18-0.74]), with an absolute difference of 15.8% (number needed to treat = 6.3), and at 1 year (OR = 0.40 [95% CI 0.20-0.81]), with an absolute difference of 15.9% (number needed to treat = 6.3). Complications did not differ between the 2 procedures. However, mechanical ventilation was less frequent with the endovascular technique (OR 0.67 [95% CI 0.54–0.84]).ConclusionsPatients with aSAH treated according to current guidelines had a short-term mortality of 18.4% and 5-year mortality of 29%. The majority (64.0%) of patients remained alive without disabilities at 5-year follow-up. Patients prioritized to endovascular treatment had better outcomes than those referred to neurosurgery because endovascular coiling was not feasible.
Published: 2019

47. Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain

Author: Natalia, Cullell, Caty, Carrera, Elena, Muiño, Nuria-Paz, Torres-Aguila, Jara, Cárcel-Márquez, Jonathan, González-Sánchez, Cristina, Gallego-Fabrega, Jessica, Molina, Sarah, Besora, Javier, Sotoca, Maria-Teresa, Buongiorno, Jordi, Jiménez-Conde, Eva, Giralt-Steinhauer, Reyes, de Torres-Chacón, Joan, Montaner, Fernando, Mancha, Juan A, Cabezas, Joan, Martí-Fàbregas, Luis, Prats-Sánchez, Pol, Camps-Renom, Francisco, Purroy, Serafi, Cambray, María Del Mar, Freijo, Cristòfol, Vives-Bauzá, Silvia, Tur, Maria-Àngels, Font, Elena, López-Cancio, Maria, Hernandez-Perez, Victor, Obach, Ana, Calleja, Juan, Arenillas, Manuel, Rodríguez-Yáñez, José, Castillo, Tomas, Sobrino, Israel, Fernández-Cádenas, and Jerzy, Krupinski
Subjects: Aged, 80 and over, Male, Genetics of the nervous system, Acenocoumarol, Anticoagulants, Polymorphism, Single Nucleotide, Genome-wide association studies, Article, Stroke, Pharmacogenetics, Spain, Vitamin K Epoxide Reductases, Humans, Female, cardiovascular diseases, Prospective Studies, Aged, Cytochrome P-450 CYP2C9, Genome-Wide Association Study
Abstract: Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p
Published: 2019

48. OVERLAP BETWEEN COMPUTED TOMOGRAPHIC FEATURES OF HEMORRHAGIC CEREBRAL VENOUS THROMBOSIS AND AMYLOID ANGIOPATHY

Author: Miguel barboza Elizondo, Guillaume Bellanger, Vincent Thijs, Philippe Demaerel, Jonathan Coutinho, Thomas Gattringer, Christian Weimar, Alessandro Pezzini, Antonio Arauz, Sini Hiltunen, Eva Giralt-steinhauer, Robin Lemmens, Dimitri Renard, Irene Escudero-Martinez, Paolo Costa, Carlos Garcia Esperon, Susanna Zuurbier, and Khaled Afifi
Published: 2019

49. Abstract TP423: Risk Factors for Intracranial Hemorrhage in Cerebral Venous Thrombosis

Author: Jonathan M. Coutinho, Robin Lemmens, Sini Hiltunen, Hamed Asadi, Vincent Thijs, Yvonne Zuurbier, Alessandro Pezzini, Guillaume Bellanger, Franz Fazekas, Joan Montaner, Christian Weimar, Nicole Hinteregger, Carlos Garcia Esperon, Pieter-Jan Buyck, Turgut Tatlisumak, Leonid Churilov, Miguel A Barboza, Paolo Costa, Eva Giralt-Steinhauer, Philippe Demaerel, Dimitri Renard, Khaled Afifi, Irene Escudero, Jordi Jimenez Conde, and Thomas Gattringer
Subjects: Advanced and Specialized Nursing, Intracerebral hemorrhage, medicine.medical_specialty, Brain bleeding, business.industry, 030204 cardiovascular system & hematology, medicine.disease, 3. Good health, 03 medical and health sciences, Venous thrombosis, 0302 clinical medicine, Internal medicine, medicine, Cardiology, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Cerebral venous thrombosis is associated with intracranial hemorrhage. The occurrence of brain bleeding complicates management and is associated with worse outcomes. We aimed to identify clinical and imaging risk factors for intracerebral hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracerebral hemorrhage. Methods: We performed a retrospective analysis of an international, multicenter cohort of patients with cerebral venous thrombosis who underwent CT within 2 weeks of symptom onset and who had a subsequent confirmed diagnosis of CVT on MRV, CTV or DSA. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. Results: We recruited 260 patients with cerebral venous thrombosis from 10 institutions in Europe and Mexico. The mean age was 42 and 74% were female. Intracranial hemorrhage was found in 102 (39%). Intracerebral hemorrhage occurred in 64 (63%), small juxtacortical hemorrhage in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Combinations of these types of hemorrhage occurred in 23 (23%). Intraparenchymal hemorrhages in multiple locations occurred in 6 (6%). Older age, presence of hematological disease and superior sagittal thrombosis involvement were significantly associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracerebral hemorrhage (average number of sinuses/veins involved with hemorrhage 2.1 versus 1.9 without hemorrhage, p=0.4). Conclusion: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with the presence of intracranial hemorrhage.
Published: 2019

50. Diagnostic accuracy of noncontrast CT imaging markers in cerebral venous thrombosis

Author: Jukka Putaala, Miguel A Barboza, Pieter-Jan Buyck, Christian Weimar, Irene Escudero, Hamed Asadi, Susanna M. Zuurbier, Jonathan M. Coutinho, Philippe Demaerel, Franz Fazekas, Vincent Thijs, Jordi Jimenez Conde, Eva Giralt-Steinhauer, Carlos Garcia-Esperon, Nicole Hinteregger, Thomas Gattringer, Sini Hiltunen, Paolo Costa, Leonid Churilov, Alessandro Pezzini, Dimitri Renard, Antonio Arauz, Robin Lemmens, Turgut Tatlisumak, Joan Montaner, Neurology, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neurovascular Disorders
Subjects: Adult, Male, Computed Tomography Angiography, Medizin, Hematocrit, Sensitivity and Specificity, Magnetic resonance angiography, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Sinus Thrombosis, Intracranial, 0302 clinical medicine, D-dimer, medicine, Humans, Computed tomography angiography, Retrospective Studies, Venous Thrombosis, medicine.diagnostic_test, business.industry, Area under the curve, Phlebography, Middle Aged, medicine.disease, Thrombosis, Cerebral Veins, Confidence interval, Cerebral Angiography, Venous thrombosis, Area Under Curve, Case-Control Studies, Female, Neurology (clinical), Intracranial Thrombosis, Nuclear medicine, business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Magnetic Resonance Angiography
Abstract: [Objective] To assess the added diagnostic value of semiquantitative imaging markers on noncontrast CT scans in cerebral venous thrombosis (CVT)., [Methods] In a retrospective, multicenter, blinded, case-control study of patients with recent onset (, [Results] We enrolled 285 patients with CVT and 303 controls from 10 international centers. Sensitivity of visual impression of thrombosis ranged from 41% to 73% and specificity ranged from 97% to 100%. Attenuation measurement had an area under the curve (AUC) of 0.78 (95% confidence interval [CI] 0.74–0.81). After adjustment for hematocrit, the AUC remained 0.78 (95% CI 0.74–0.81). The analysis of attenuation ratios of affected vs unaffected sinuses had AUC of 0.83 (95% CI 0.8–0.86). Adding this imaging marker significantly improved discrimination, but sensitivity when tolerating a false-positive rate of 20% was not higher than 76% (95% CI 0.70–0.81)., [Conclusion] Semiquantitative analysis of attenuation values for diagnosis of CVT increased sensitivity but still failed to identify 1 out of 4 CVT., [Classification of evidence] This study provides Class II evidence that visual analysis of plain CT with or without attenuation measurements has high specificity but only moderate sensitivity for CVT.
Published: 2019

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