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1. Visual perception alterations in COVID-19: a preliminary study

Author

María Begona Coco-Martín, Luis Leal-Vega, Irene Alcoceba-Herrero, Ainhoa Molina-Martín, Dolores de-Fez, María José Luque, Carlos Duenas-Gutiérrez, Juan Francisco Arenillas-Lara, and David P. Pinero

Subjects
sars-cov-2, covid-19, visual perception, contrast sensitivity function, color vision, Ophthalmology, RE1-994
Abstract

AIM: To compare the visual perception (color and chromatic-achromatic contrast vision) of a small cohort of COVID-19 patients at the time of infection and after 6mo with that of a healthy population matched for sex and age. METHODS: A total of 25 patients (9 females, 16 males, mean age: 54±10y) with COVID-19 hospitalized in the COVID-19 Unit of the University Clinical Hospital of Valladolid were recruited for this preliminary study. Visual perception, as determined by monocular measurement of contrast sensitivity function (CSF) and color vision was assessed in each patient using the Optopad test. The results obtained were then compared with those of a sample of 16 age- and sex-matched healthy controls (5 females, 11 males, mean age: 50±6y) in which the same measurement procedure was repeated. Statistically significant differences between groups were assessed using the Mann-Whitney U test. Measurements were repeated after a minimum follow-up period of 6mo and statistically significant differences between the two time points in each group were assessed using the Wilcoxon signed rank test. RESULTS: Discrimination thresholds (color and chromatic-achromatic contrast vision) and their corresponding sensitivity, calculated as the inverse of the discrimination threshold, were evaluated. Analysis of the data revealed higher contrast threshold results (i.e., worse contrast sensitivity) in the COVID-19 group than in the control group for all spatial frequencies studied in the Optopad-CSF achromatic test and most of the spatial frequencies studied in the Optopad-CSF chromatic test for the red-green and blue-yellow mechanisms. In addition, color threshold results in the COVID-19 group were also significantly higher (i.e., worse color sensitivity) for almost all color mechanisms studied in the Optopad-Color test. At 6mo, most of the differences found between the groups were maintained despite COVID-19 recovery. CONCLUSION: The present results provide preliminary evidence that visual perception may be impaired in COVID-19, even when the infection has passed. Although further research is needed to determine the precise causes of this finding, analysis of CSF and color vision could provide valuable information on the visual impact of COVID-19.

Published
2023
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2. Embolic Events in Infective Endocarditis: A Comprehensive Review

Author

Gonzalo Cabezon, Paloma Pulido, Javier López Díaz, María de Miguel-Álava, Isidre Vilacosta, David García-Azorin, Adrian Lozano, Andrea Oña, Juan Francisco Arenillas, and José-Alberto San Román

Subjects
infective endocarditis, embolic events, stroke, mycotic aneurysm, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Infective endocarditis (IE) is a life-threating entity with three main complications: heart failure (HF), uncontrolled infection (UI) and embolic events (EEs). HF and UI are the main indications of cardiac surgery and have been studied thoroughly. On the other hand, much more uncertainty surrounds EEs, which have an abrupt and somewhat unpredictable behaviour. EEs in the setting of IE have unique characteristics that must be explored, such as the potential of hemorrhagic transformation of stroke. Accurately predicting which patients will suffer EEs seems to be pivotal to achieve an optimal management of the disease, but this complex process is still not completely understood. The indication of cardiac surgery in order to prevent EEs in the absence of HF or UI is in question as scientific evidence is controversial and mainly of a retrospective nature. This revision addresses these topics and try to summarize the evidence and recommendations about them.

Published
2024
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4. A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype

Author

Jara Cárcel-Márquez, Elena Muiño, Cristina Gallego-Fabrega, Natalia Cullell, Miquel Lledós, Laia Llucià-Carol, Tomás Sobrino, Francisco Campos, José Castillo, Marimar Freijo, Juan Francisco Arenillas, Victor Obach, José Álvarez-Sabín, Carlos A. Molina, Marc Ribó, Jordi Jiménez-Conde, Jaume Roquer, Lucia Muñoz-Narbona, Elena Lopez-Cancio, Mònica Millán, Rosa Diaz-Navarro, Cristòfol Vives-Bauza, Gemma Serrano-Heras, Tomás Segura, Laura Ibañez, Laura Heitsch, Pilar Delgado, Rajat Dhar, Jerzy Krupinski, Raquel Delgado-Mederos, Luis Prats-Sánchez, Pol Camps-Renom, Natalia Blay, Lauro Sumoy, Rafael de Cid, Joan Montaner, Carlos Cruchaga, Jin-Moo Lee, Joan Martí-Fàbregas, and Israel Férnandez-Cadenas

Subjects
polygenic risk score, GWAS, multi-trait analysis, stroke, ESUs, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundOccult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification.MethodsMultitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value < 5 × 10−8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort.ResultsWe found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension.ConclusionThe loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.

Published
2022
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5. Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study

Author

Javier Trigo, David García-Azorín, Álvaro Planchuelo-Gómez, Enrique Martínez-Pías, Blanca Talavera, Isabel Hernández-Pérez, Gonzalo Valle-Peñacoba, Paula Simón-Campo, Mercedes de Lera, Alba Chavarría-Miranda, Cristina López-Sanz, María Gutiérrez-Sánchez, Elena Martínez-Velasco, María Pedraza, Álvaro Sierra, Beatriz Gómez-Vicente, Juan Francisco Arenillas, and Ángel L. Guerrero

Subjects
COVID-19, Nervous system diseases, Headache disorders, secondary, Mortality, laboratory parameters, Medicine
Abstract

Abstract Introduction Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality. Methods Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis. Results During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17–0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer. Conclusion Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

Published
2020
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6. Neurological symptoms in Covid‐19 patients in the emergency department

Author

David García‐Azorín, Javier Trigo, Enrique Martínez‐Pías, Isabel Hernández‐Pérez, Gonzalo Valle‐Peñacoba, Blanca Talavera, Paula Simón‐Campo, Mercedes deLera, Alba Chavarría‐Miranda, Cristina López‐Sanz, María Gutiérrez‐Sánchez, Elena Martínez‐Velasco, María Pedraza, Álvaro Sierra, Beatriz Gómez‐Vicente, Ángel Guerrero, and Juan Francisco Arenillas

Subjects
COVID‐19, mortality, nervous system diseases, olfaction disorders, prognosis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Background Coronavirus disease 2019 (Covid‐19) might present neurological symptoms. We aimed to evaluate the frequency of them at the moment of emergency department (ED) visit and their impact in the prognosis. Methods Retrospective cohort study including all consecutive hospitalized cases between March 8th and April 11th, 2020. Covid‐19 diagnosis was confirmed by polymerase chain reaction test and/or serology. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in‐hospital all‐cause mortality by Cox‐regression log‐rank test. Results We included 576 hospitalized patients, 250 (43.3%) female, aged 67.2 years. At the moment of ED visit, 320 (55.6%) described neurological symptoms, including anosmia (146, 25.3%), myalgia (139, 24.1%), headache (137, 23.8%), and altered mental status (98, 17.0%). Neurological symptoms started the first symptomatic day in 198 (54.2%) cases. Patients with neurological symptoms presented later to the ED (7.9 versus. 6.6 days, p = .019). Only four (0.6%) cases had no typical Covid‐19 general symptoms, and only six (1.9%) had a normal laboratory results, for a sensitivity of 98.7% (95% confidence interval (CI): 96.6%–99.6%) and 98.1% (95% CI: 95.7%–99.2%), respectively. In the multivariate Cox‐regression of mortality predictors, anosmia (HR: 0.358, 95%CI: 0.140–0.916) and altered mental status (HR: 1.867, 95%CI: 1.162–3.001) were significant. Conclusion Neurological symptoms were the most frequent extrapulmonary symptoms. They were present in half of the Covid‐19 patients at the time of the ED visit. Anosmia on admission was an independent predictor of lower in‐hospital mortality and altered mental status on admission predicted in‐hospital mortality.

Published
2021
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7. Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients

Author

David García-Azorín, Enrique Martínez-Pías, Javier Trigo, Isabel Hernández-Pérez, Gonzalo Valle-Peñacoba, Blanca Talavera, Paula Simón-Campo, Mercedes de Lera, Alba Chavarría-Miranda, Cristina López-Sanz, María Gutiérrez-Sánchez, Elena Martínez-Velasco, María Pedraza, Álvaro Sierra, Beatriz Gómez-Vicente, Ángel Guerrero, David Ezpeleta, María Jesús Peñarrubia, Jose Ignacio Gómez-Herreras, Elena Bustamante-Munguira, Cristina Abad-Molina, Antonio Orduña-Domingo, Guadalupe Ruiz-Martin, María Isabel Jiménez-Cuenca, Santiago Juarros, Carlos del Pozo-Vegas, Carlos Dueñas-Gutierrez, Jose María Prieto de Paula, Belén Cantón-Álvarez, Jose Manuel Vicente, and Juan Francisco Arenillas

Subjects
SARS-CoV-2, nervous system diseases, stroke, mortality, prognosis, Neurology. Diseases of the nervous system, RC346-429
Abstract

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission.Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities.Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382–3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970–3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR.Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

Published
2020
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8. Stroke care during the COVID-19 outbreak in Spain: the experience of Spanish stroke units

Author

Francisco Purroy, Francisco Moniche, María Alonso de Leciñana, Mar Castellanos, Óscar Ayo-Martín, Ana Morales, María Dolores Fernández Pérez, Esther Gallardo Corral, Patricia Martínez Sánchez, Juan Manuel Oropesa, Soledad Pérez Sánchez, Raul Espinosa Rosso, Jose Antonio Tamayo Toledo, Roberto Valverde Moyano, Carlos Tejero Juste, Herbert Tejada Meza, Elena López-Cancio Martínez, Ignacio Casado Menéndez, M Carmen Jimenez Martinez, Antonio Medina Rodriguez, Juan Carlos López Fernandez, Enrique Jesús Palacio Portilla, Juan Francisco Arenillas Lara, Javier Tejada García, Yolanda Bravo Anguiano, Marta Ferrero Ros, Jose C Segundo Rodriguez, Pere Cardona, Jaume Roquer González, Manuel Jesus Gómez-Choco Cuesta, Joan Marti Fabregas, Joaquín Serena Leal, Sergi Amaro Delgado, Jorge Pagola, Nicolas Lopez Hernandez, Alejandro Ponz De Tienda, Cristina Soriano Soriano, José Tembl Ferrairó, Ignacio Casado Naranjo, Jose M Ramirez Moreno, Jose Luis Maciñeiras Montero, Emilio Rodríguez Castro, Joaquin Carneado Ruiz, Patricia Calleja Castaño, Jose Antonio Egido Herrero, Andres Garcia Pastor, Alicia De Felipe Mimbrera, Araceli García Tejada, Marta Guillán Rodríguez, Laura Izquierdo Esteban, Beatriz Oyanguren Rodeño, Álvaro Ximénez-Carrillo Rico, Cristina Sánchez-Vizcaíno, María Herrera Isasi, Pablo Irimia Sieira, Mar Freijo Guerrero, Maite Martínez Zabaleta, and Juan Manuel García Sánchez

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Background and purpose Spain has been heavily affected by COVID-19. Reallocation of resources for managing the outbreak might have caused a disruption in stroke care. This study analyses the impact on stroke care of reorganising the healthcare system in response to the first COVID-19 outbreak peak in Spain and the strategies adopted by Spanish stroke units to deal with this impact.Materials and methods We obtained data from a structured survey sent to the responsible of stroke units across the country. We recorded the number of strokes, stroke code activations, intravenous thrombolysis treatments and mechanical thrombectomies during February and March 2019 and 2020. We also collected information on the impact on workflow metrics and on the availability of specialised neurological care and rehabilitation treatments, the characteristics of stroke care for patients with SARS-CoV-2 infection and the impact on human resources. We compared the activity data between 2019 and 2020 and the information on activity and impact on stroke care between regions classified according to the disease incidence rate.Results Fifty-seven (75%) of all stroke units in Spain responded to the survey. There was an overall reduction in admissions for all stroke types during the outbreak’s peak and in the number of stroke code activations and intravenous thrombolysis treatments, results that were independent of the COVID-19 incidence rate. Participants reported a delay in workflow metrics and a reduction of admissions to stroke units, outpatient clinics and rehabilitation therapies. Specific pathways and protocols for managing stroke patients with SARS-CoV-2 infection have been established.Conclusion The COVID-19 outbreak has jeopardised all phases of stroke care. As a consequence, some patients with stroke did not receive adequate treatment.

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9. Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders

Author

Mar Guasp, Mireia Rosa-Justicia, Amaia Muñoz-Lopetegi, Eugenia Martínez-Hernández, Thais Armangué, Gisela Sugranyes, Heike Stein, Roger Borràs, Laia Prades, Helena Ariño, Jesús Planagumà, Elena De-La-Serna, Domingo Escudero, Sara Llufriu, Raquel Sánchez-Valle, Joan Santamaria, Albert Compte, Josefina Castro-Fornieles, Josep Dalmau, Dolores Páramo, Vicente Medrano, Virginia Casado, Nicolau Guanyabens, Eloi Giné-Servén, María Ángeles del Real, Javier Pardo, Leticia Martin-Gil, Francisco Javier Barrero-Hernández, Nuria García-Barragán, Mercè Falip, Marta Simó, Eloy Rodríguez, Juan José Ruiz Ezquerro, Luis Bataller, Gemma Safont, José Vicente-Hervàs, Luis Brieva, Ignacio Casado, Juan Carlos Portilla, Sònia Escalante, Juan Francisco Arenillas, Elena Erro, Ivonne Jericó-Pascual, Alejandro Fuerte-Hortigón, Alba Morató, Albert Saiz, Yolanda Blanco, Maria Sepúlveda, Raquel Ruiz, Laura Naranjo, Maria Rodés, Esther Aguilar, Mercè Alba, and Eva Caballero

Subjects
Anti-N-Methyl-D-Aspartate Receptor Encephalitis, Schizophrenia, Humans, Prospective Studies, Neurology (clinical), Nijmegen Breakage Syndrome, Biomarkers
Abstract

Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive-psychiatric outcomes and could serve as prognostic biomarkers.In this prospective cohort study, participants (aged 12-60 years) with anti-NMDAR encephalitis during the post-acute stage visited Hospital Clínic de Barcelona (Barcelona, Spain) on three occasions (at study entry [V1], at 6 months [V2], and at 12 months [V3]) and underwent comprehensive neuropsychiatric evaluations. Similar evaluations were done in a group of age-matched participants with schizophrenia spectrum disorders and a group of age-matched and sex-matched healthy participants also recruited from Hospital Clínic de Barcelona. We analysed differences between and within groups in the longitudinal follow-up using multilevel linear mixed-effect models, adjusting for group, age, sex, and socioeconomic status to control for possible confounding.Between Jan 1, 2017, and Sept 30, 2020, 82 participants were recruited, 28 (34%) with anti-NMDAR encephalitis, 27 (33%) with schizophrenia spectrum disorders, and 27 (33%) healthy participants. Although, by V1 (median 4 months [IQR 3-7] from disease onset), many acute-stage symptoms in participants with anti-NMDAR encephalitis had resolved (acute stage median modified Rankin Scale [mRS] score 5 [IQR 4-5] vs V1 mRS score 2 [1-2]; p0·0001), 25 (89%) participants showed deficits in at least one cognitive domain. In this group, 15 (68%) of 22 cognitive domain variables were impaired at V1, whereas only eight (36%) were altered at V3 (p=0·016). In participants with schizophrenia spectrum disorders, 11 (50%) of 22 variables (all shared with participants with anti-NMDAR encephalitis) were impaired at V1, without changes at V3. Two acute-stage features of anti-NMDAR encephalitis (ie, decreased consciousness and no improvement within the first 4 weeks of treatment) predicted cognitive domain outcomes, and a visuospatial task (ie, serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in participants with anti-NMDAR encephalitis and in those with schizophrenia spectrum disorders, but only those in individuals with anti-NMDAR encephalitis subsequently improved (p=0·031). The greatest cognitive-psychiatric improvement in participants with anti-NMDAR encephalitis occurred between V1 and V2. During this interval, four (14%) participants with anti-NMDAR encephalitis would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated.The cognitive-psychiatric symptoms of anti-NMDAR encephalitis in the post-acute stage resembled those of stabilised schizophrenia, but only those in participants with anti-NMDAR encephalitis progressively improved, predominantly during V1-V2. These findings are important for clinical trials on anti-NMDAR encephalitis and suggest that prompt cognitive-psychosocial rehabilitation might be a valuable intervention.Instituto Salud Carlos III, NEURON Network of European Funding for Neuroscience Research, National Alliance for Research in Schizophrenia and Affective Disorders, and la Caixa Health-Research Foundation.

Published
2022
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10. Investigating the Prognostic Role of Peripheral Inflammatory Markers in Mild Cognitive Impairment

Author

Comi, Giacomo Tondo, Davide Aprile, Fabiola De Marchi, Barbara Sarasso, Paola Serra, Giordana Borasio, Esther Rojo, Juan Francisco Arenillas, and Cristoforo

Subjects
neutrophil-lymphocyte ratio, cognitive impairment, dementia, neuroinflammation
Abstract

Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases. Peripheral markers of inflammation, including blood cell counts and their ratios, such as the neutrophil-to-lymphocyte ratio (NLR), have been reported as an easily accessible and reliable proxy of central nervous system inflammation. However, the role of peripheral inflammation in dementia and Mild Cognitive Impairment (MCI) still needs to be clarified. In the current study, we aimed to assess the prognostic role of the NLR and other peripheral markers of inflammation in a sample of 130 amnestic MCI, followed up for two to five years. The Mini-Mental state examination (MMSE) score at baseline and follow-up visits was used to assess global cognitive status at each visit and the degree of cognitive decline over time. Baseline peripheral markers of inflammation included blood cell counts and ratios, specifically the NLR, the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), and the systemic immune inflammation index (SII). After classifying subjects into CONVERTERS and non-CONVERTERS (respectively, patients converting to dementia and subjects showing stability at the last available follow-up), we compared peripheral markers of inflammation among groups ed correlated them with cognitive measures, testing the ability of significant factors to predict conversion to dementia. In our cohort, CONVERTERS showed lower baseline MMSE scores (p-value = 0.004) than non-CONVERTERS. In addition, CONVERTERS had statistically elevated NLR (p-value = 0.005), PLR (p-value = 0.002), and SII levels (p-value = 0.015), besides a lower number of lymphocytes (p-value = 0.004) compared with non-CONVERTERS. In a logistic regression analysis, baseline MMSE scores and NLR predicted conversion to dementia. Tertiles analysis showed that MCI with the highest NLR values had a higher conversion risk. Our study supports the hypothesis that a dysregulation of peripheral inflammation involving both lymphocytes and neutrophils may play a role in the pathogenesis of dementia, even at the early stages of neurodegeneration, as in the MCI condition.

Published
2023
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11. Intracranial atherosclerotic plaque enhancement and long-term risk of future strokes: A prospective, longitudinal study

Author

Beatriz Gómez‐Vicente, María Hernández‐Pérez, Elena Martínez‐Velasco, Margarita Rodríguez‐Velasco, Josep Munuera, Marta Rubiera, Carla Vert, Laura Dorado, Mercedes de Lera, Ana Isabel Calleja, Elisa Cortijo, Jesús Agulla, Elena López‐Cancio, and Juan Francisco Arenillas

Subjects
Radiology, Nuclear Medicine and imaging, Neurology (clinical)
Abstract

The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients.This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves.Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio1.77 had a lower survival free of events (p .05).High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.

Published
2022

12. 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

13. Educational Opportunities of Virtual Game-Based Initiatives for Students With Disabilities

Author

Adrián Martín-Gutiérrez, Luis Leal-Vega, Irene Alcoceba-Herrero, Joaquín Herrera-Medina, Juan Francisco Arenillas-Lara, and María Begoña Coco-Martín

Abstract

Digital game-based learning (DGBL) is a novel methodology implemented in many educational virtual settings to improve students´ attention, motivation, and engagement while learning. This chapter aims to provide insight into how game-based methods can enhance students' learning process with sensory, intellectual, and learning disabilities. Specifically, the key of this chapter is to assess the possibilities offered by the introduction of DGBL in educational contexts from a theoretical perspective to understand better the range of opportunities that it can mean for learning and, therefore, for the personal and professional development of people with sensory, intellectual, and learning disabilities.

Published
2022
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14. Stroke care during the COVID-19 outbreak in Spain: the experience of Spanish stroke units

Author

Francisco Purroy, Francisco Moniche, María Alonso de Leciñana, Mar Castellanos, Óscar Ayo-Martín, Ana Morales, María Dolores Fernández Pérez, Esther Gallardo Corral, Patricia Martínez Sánchez, Juan Manuel Oropesa, Soledad Pérez Sánchez, Raul Espinosa Rosso, Jose Antonio Tamayo Toledo, Roberto Valverde Moyano, Carlos Tejero Juste, Herbert Tejada Meza, Elena López-Cancio Martínez, Ignacio Casado Menéndez, M Carmen Jimenez Martinez, Antonio Medina Rodriguez, Juan Carlos López Fernandez, Enrique Jesús Palacio Portilla, Juan Francisco Arenillas Lara, Javier Tejada García, Yolanda Bravo Anguiano, Marta Ferrero Ros, Jose C Segundo Rodriguez, Pere Cardona, Jaume Roquer González, Manuel Jesus Gómez-Choco Cuesta, Joan Marti Fabregas, Joaquín Serena Leal, Sergi Amaro Delgado, Jorge Pagola, Nicolas Lopez Hernandez, Alejandro Ponz De Tienda, Cristina Soriano Soriano, José Tembl Ferrairó, Ignacio Casado Naranjo, Jose M Ramirez Moreno, Jose Luis Maciñeiras Montero, Emilio Rodríguez Castro, Joaquin Carneado Ruiz, Patricia Calleja Castaño, Jose Antonio Egido Herrero, Andres Garcia Pastor, Alicia De Felipe Mimbrera, Araceli García Tejada, Marta Guillán Rodríguez, Laura Izquierdo Esteban, Beatriz Oyanguren Rodeño, Álvaro Ximénez-Carrillo Rico, Cristina Sánchez-Vizcaíno, María Herrera Isasi, Pablo Irimia Sieira, Mar Freijo Guerrero, Maite Martínez Zabaleta, and Juan Manuel García Sánchez

Subjects
medicine.medical_specialty, Time Factors, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Clinical Neurology, 030204 cardiovascular system & hematology, Stroke care, lcsh:RC346-429, Health Services Accessibility, Workflow, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Outpatient clinic, Thrombolytic Therapy, cardiovascular diseases, Healthcare Disparities, Stroke, lcsh:Neurology. Diseases of the nervous system, Original Research, Thrombectomy, Rehabilitation, Delivery of Health Care, Integrated, business.industry, Incidence, Stroke Rehabilitation, COVID-19, Stroke units, Outbreak, Thrombolysis, medicine.disease, stroke, Spain, Health Care Surveys, Emergency medicine, Health Resources, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Background and purposeSpain has been heavily affected by COVID-19. Reallocation of resources for managing the outbreak might have caused a disruption in stroke care. This study analyses the impact on stroke care of reorganising the healthcare system in response to the first COVID-19 outbreak peak in Spain and the strategies adopted by Spanish stroke units to deal with this impact.Materials and methodsWe obtained data from a structured survey sent to the responsible of stroke units across the country. We recorded the number of strokes, stroke code activations, intravenous thrombolysis treatments and mechanical thrombectomies during February and March 2019 and 2020. We also collected information on the impact on workflow metrics and on the availability of specialised neurological care and rehabilitation treatments, the characteristics of stroke care for patients with SARS-CoV-2 infection and the impact on human resources. We compared the activity data between 2019 and 2020 and the information on activity and impact on stroke care between regions classified according to the disease incidence rate.ResultsFifty-seven (75%) of all stroke units in Spain responded to the survey. There was an overall reduction in admissions for all stroke types during the outbreak’s peak and in the number of stroke code activations and intravenous thrombolysis treatments, results that were independent of the COVID-19 incidence rate. Participants reported a delay in workflow metrics and a reduction of admissions to stroke units, outpatient clinics and rehabilitation therapies. Specific pathways and protocols for managing stroke patients with SARS-CoV-2 infection have been established.ConclusionThe COVID-19 outbreak has jeopardised all phases of stroke care. As a consequence, some patients with stroke did not receive adequate treatment.

Published
2020
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15. MULTITRAIT ANALYSIS EXPANDS GENETIC RISK FACTORS IN CARDIOEMBOLIC STROKE

Author

Jara Cárcel-Márquez, Elena Muiño, Cristina Gallego-Fabrega, Natalia Cullell, Miquel Lledós, Laia Llucià-Carol, Tomás Sobrino, Francisco Campos, José Castillo, Marimar Freijo, Juan Francisco Arenillas, Victor Obach, José Álvarez-Sabín, Carlos A. Molina, Marc Ribó, Jordi Jiménez-Conde, Jaume Roquer, Lucia Muñoz-Narbona, Elena Lopez-Cancio, Mònica Millán, Rosa Diaz-Navarro, Cristòfol Vives-Bauza, Gemma Serrano-Heras, Tomás Segura, Laura Ibañez, Laura Heitsch, Pilar Delgado, Rajat Dhar, Jerzy Krupinski, Raquel Delgado-Mederos, Luis Prats-Sánchez, Pol Camps-Renom, Natalia Blay, Lauro Sumoy, Rafael de Cid, Joan Montaner, Carlos Cruchaga, Jin-Moo Lee, Joan Martí-Fàbregas, and Israel Férnandez-Cadenas

Abstract

Background and PurposeThe genetic architecture of cardioembolic stroke (CES) is still poorly understood. Atrial fibrillation (AF) is the main cause of CES, with which it shares heritability. We aimed to discover novel loci associated with CES by performing a Multitrait Analysis of the GWAS (MTAG) with atrial fibrillation genetic data.MethodsFor the MTAG analysis we used the MEGASTROKE cohort, which comprises European patients with CES and controls (n=362,661) and an AF cohort composed of 1,030,836 subjects. Regional genetic pleiotropy of the significant results was explored using an alternative Bayesian approach with GWAS-pairwise method. A replication was performed in an independent European cohort comprising 9,105 subjects using a Genome Wide Association Study (GWAS).ResultsMTAG-CES analysis revealed 40 novel and significant loci (p-value−8) associated with CES, four of which had not previously been associated with AF. A significant replication was assessed for eight novel loci: CAV1, IGF1R, KIAA1755, NEURL1, PRRX1, SYNE2, TEX41 and WIPF1, showing a p-valueKIAA1755, a locus not previously described associated with AF. Interestingly, 51 AF risk loci were not associated with CES according to GWAS-pairwise analysis. Gene Ontology (GO) analysis revealed that these exclusive AF genes from the 51 loci participate in processes related mainly to cardiac development, whereas genes associated with AF and CES participate mainly in muscle contraction and the conduction of electrical impulses.ConclusionsWe found eight new loci associated with CES. In addition, this study provides novel insights into the pathogenesis of CES, highlighting multiple candidate genes for future functional experiments.

Published
2021
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16. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Author

Götz Thomalla, Florent Boutitie, Henry Ma, Masatoshi Koga, Peter Ringleb, Lee H Schwamm, Ona Wu, Martin Bendszus, Christopher F Bladin, Bruce C V Campbell, Bastian Cheng, Leonid Churilov, Martin Ebinger, Matthias Endres, Jochen B Fiebach, Mayumi Fukuda-Doi, Manabu Inoue, Timothy J Kleinig, Lawrence L Latour, Robin Lemmens, Christopher R Levi, Didier Leys, Kaori Miwa, Carlos A Molina, Keith W Muir, Norbert Nighoghossian, Mark W Parsons, Salvador Pedraza, Peter D Schellinger, Stefan Schwab, Claus Z Simonsen, Shlee S Song, Vincent Thijs, Danilo Toni, Chung Y Hsu, Nils Wahlgren, Haruko Yamamoto, Nawaf Yassi, Sohei Yoshimura, Steven Warach, Werner Hacke, Kazunori Toyoda, Geoffrey A Donnan, Stephen M Davis, Christian Gerloff, Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L. Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bharath Cheripelli, Tae-Hee Cho, Chi-un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B. Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M. Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K. Mueller, Keith W. Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H. Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H. Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z. Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Keizo Yasui, Toshiro Yonehara, Shinichi Yoshimura, K. Aarnio, F. Alemseged, C. Anderson, T. Ang, M.L. Archer, J. Attia, P. Bailey, A. Balabanski, A. Barber, P.A. Barber, J. Bernhardt, A. Bivard, D. Blacker, C.F. Bladin, A. Brodtmann, D. Cadilhac, B.C.V. Campbell, L. Carey, S. Celestino, L. Chan, W.H. Chang, A. ChangI, C.H. Chen, C.-I. Chen, H.F. Chen, T.C. Chen, W.H. Chen, Y.Y. Chen, C.A. Cheng, E. Cheong, Y.W. Chiou, P.M. Choi, H.J. Chu, C.S. Chuang, T.C. Chung, L. Churilov, B. Clissold, A. Connelly, S. Coote, B. Coulton, E. Cowley, J. Cranefield, S. Curtze, C. D'Este, S.M. Davis, S. Day, P.M. Desmond, H.M. Dewey, C. Ding, G.A. Donnan, R. Drew, S. Eirola, D. Field, T. Frost, C. Garcia-Esperon, K. George, R. Gerraty, R. Grimley, Y.C. Guo, G. Hankey, J. Harvey, S.C. Ho, K. Hogan, D. Howells, P.M. Hsiao, C.H. Hsu, C.T. Hsu, C.-S. Hsu, J.P. Hsu, Y.D. Hsu, Y.T. Hsu, C.J. Hu, C.C. Huang, H.Y. Huang, M.Y. Huang, S.C. Huang, W.S. Huang, D. Jackson, J.S. Jeng, S.K. Jiang, L. Kaauwai, O. Kasari, J. King, T.J. Kleinig, M. Koivu, J. Kolbe, M. Krause, C.W. Kuan, W.L. Kung, C. Kyndt, C.L. Lau, A. Lee, C.Y. Lee, J.T. Lee, Y. Lee, Y.C. Lee, C. Levi, C.R. Levi, L.M. Lien, J.C. Lim, C.C. Lin, C.H. Lin, C.M. Lin, D. Lin, C.H. Liu, J. Liu, Y.C. Lo, P.S. Loh, E. Low, C.H. Lu, C.J. Lu, M.K. Lu, J. Ly, H. Ma, L. Macaulay, R. Macdonnell, E. Mackey, M. Macleod, J. Mahadevan, V. Maxwell, R. McCoy, A. McDonald, S. McModie, A. Meretoja, S. Mishra, P.J. Mitchell, F. Miteff, A. Moore, C. Muller, F. Ng, F.C. Ng, J-L. Ng, W. O'Brian, V. O'Collins, T.J. Oxley, M.W. Parsons, S. Patel, G.S. Peng, L. Pesavento, T. Phan, E. Rodrigues, Z. Ross, A. Sabet, M. Sallaberger, P. Salvaris, D. Shah, G. Sharma, G. Sibolt, M. Simpson, S. Singhal, B. Snow, N. Spratt, R. Stark, J. Sturm, M.C. Sun, Y. Sun, P.S. Sung, Y.F. Sung, M. Suzuki, M. Tan, S.C. Tang, T. Tatlisumak, V. Thijs, M. Tiainen, C.H. Tsai, C.K. Tsai, C.L. Tsai, H.T. Tsai, L.K. Tsai, C.H. Tseng, L.T. Tseng, J. Tsoleridis, H. Tu, H.T-H. Tu, W. Vallat, J. Virta, W.C. Wang, Y.T. Wang, M. Waters, L. Weir, T. Wijeratne, C. Williams, W. Wilson, A.A. Wong, K. Wong, T.Y. Wu, Y.H. Wu, B. Yan, F.C. Yang, Y.W. Yang, N. Yassi, H.L. Yeh, J.H. Yeh, S.J. Yeh, C.H. Yen, D. Young, C.L. Ysai, W.W. Zhang, H. Zhao, L. Zhao, Katharina Althaus-Knaurer, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A. Dixit, Geoffrey Donnan, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R. Lees, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Peter Schellinger, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Rüdiger von Kummer, Joanna Wardlaw, Rebecca A. Betensky, Gregoire Boulouis, Raphael A. Carandang, William A. Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L. Ford, John Hallenbeck, Gordon J. Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Michael H. Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H. Schwamm, Eric Searls, Shlee S. Song, Sidney Starkman, Albert J. Yoo, Ramin Zand, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Monash University [Melbourne], National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], University of Heidelberg, Medical Faculty, Massachusetts General Hospital [Boston], University of Melbourne, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Royal Adelaide Hospital [Adelaide Australia], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Flanders Make [Leuven], Flanders Make, University of Newcastle [Australia] (UoN), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Vall d'Hebron University Hospital [Barcelona], University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Girona Biomedical Research Institute [Girona, Spain] (IDIBGI), Ruhr-Universität Bochum [Bochum], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Aarhus University Hospital, Cedars-Sinai Medical Center, Florey Institute of Neuroscience and Mental Health [Melbourne, Victoria, Australia], Austin Health, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], China Medical University Hospital [Taichung], Karolinska Institutet [Stockholm], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Texas at Austin [Austin], Collaborators Evaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators: Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Florent Boutitie, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bastian Cheng, Bharath Cheripelli, Tae-Hee Cho, Chi-Un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria Del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Martin Ebinger, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Matthias Endres, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Christian Gerloff, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Robin Lemmens, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-Cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K Mueller, Keith W Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Norbert Nighoghossian, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Peter Ringleb, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Vincent Thijs, Götz Thomalla, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Mayumi Fukuda-Doi, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Manabu Inoue, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Masatoshi Koga, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Kaori Miwa, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Kazunori Toyoda, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Haruko Yamamoto, Keizo Yasui, Toshiro Yonehara, Sohei Yoshimura, Shinichi Yoshimura, K Aarnio, F Alemseged, C Anderson, T Ang, M L Archer, J Attia, P Bailey, A Balabanski, A Barber, P A Barber, J Bernhardt, A Bivard, D Blacker, C F Bladin, A Brodtmann, D Cadilhac, B C V Campbell, L Carey, S Celestino, L Chan, W H Chang, A ChangI, C H Chen, C-I Chen, H F Chen, T C Chen, W H Chen, Y Y Chen, C A Cheng, E Cheong, Y W Chiou, P M Choi, H J Chu, C S Chuang, T C Chung, L Churilov, B Clissold, A Connelly, S Coote, B Coulton, E Cowley, J Cranefield, S Curtze, C D'Este, S M Davis, S Day, P M Desmond, H M Dewey, C Ding, G A Donnan, R Drew, S Eirola, D Field, T Frost, C Garcia-Esperon, K George, R Gerraty, R Grimley, Y C Guo, G Hankey, J Harvey, S C Ho, K Hogan, D Howells, P M Hsiao, C H Hsu, C T Hsu, C-S Hsu, J P Hsu, Y D Hsu, Y T Hsu, C J Hu, C C Huang, H Y Huang, M Y Huang, S C Huang, W S Huang, D Jackson, J S Jeng, S K Jiang, L Kaauwai, O Kasari, J King, T J Kleinig, M Koivu, J Kolbe, M Krause, C W Kuan, W L Kung, C Kyndt, C L Lau, A Lee, C Y Lee, J T Lee, Y Lee, Y C Lee, C Levi, C R Levi, L M Lien, J C Lim, C C Lin, C H Lin, C M Lin, D Lin, C H Liu, J Liu, Y C Lo, P S Loh, E Low, C H Lu, C J Lu, M K Lu, J Ly, H Ma, L Macaulay, R Macdonnell, E Mackey, M Macleod, J Mahadevan, V Maxwell, R McCoy, A McDonald, S McModie, A Meretoja, S Mishra, P J Mitchell, F Miteff, A Moore, C Muller, F Ng, F C Ng, J-L Ng, W O'Brian, V O'Collins, T J Oxley, M W Parsons, S Patel, G S Peng, L Pesavento, T Phan, E Rodrigues, Z Ross, A Sabet, M Sallaberger, P Salvaris, D Shah, G Sharma, G Sibolt, M Simpson, S Singhal, B Snow, N Spratt, R Stark, J Sturm, M C Sun, Y Sun, P S Sung, Y F Sung, M Suzuki, M Tan, S C Tang, T Tatlisumak, V Thijs, M Tiainen, C H Tsai, C K Tsai, C L Tsai, H T Tsai, L K Tsai, C H Tseng, L T Tseng, J Tsoleridis, H Tu, H T-H Tu, W Vallat, J Virta, W C Wang, Y T Wang, M Waters, L Weir, T Wijeratne, C Williams, W Wilson, A A Wong, K Wong, T Y Wu, Y H Wu, B Yan, F C Yang, Y W Yang, N Yassi, H L Yeh, J H Yeh, S J Yeh, C H Yen, D Young, C L Ysai, W W Zhang, H Zhao, L Zhao, Katharina Althaus-Knaurer, Martin Bendszus, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A Dixit, Geoffrey Donnan, Rainer Dziewas, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Werner Hacke, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R Lees, Didier Leys, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Catherine Oppenheim, Sven Poli, Peter Ringleb, Peter Schellinger, Stefan Schwab, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Danilo Toni, Roland Veltkamp, Rüdiger von Kummer, Nils Wahlgren, Joanna Wardlaw, Rebecca A Betensky, Gregoire Boulouis, Raphael A Carandang, William A Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L Ford, John Hallenbeck, Gordon J Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Arne Lauer, Michael H Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H Schwamm, Eric Searls, Shlee S Song, Sidney Starkman, Steven Warach, Ona Wu, Albert J Yoo, Ramin Zand, University of Newcastle [Callaghan, Australia] (UoN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CarMeN, laboratoire, Yperzeele, Laetitia, Evaluation of Unknown Onset Stroke Thrombolysis trials (EOS) investigators, UCL - SSS/IONS - Institute of NeuroScience, UCL - (MGD) Service de neurologie, Supporting clinical sciences, UZB Other, Physical Medicine and Rehabilitation, Clinical sciences, Neuroprotection & Neuromodulation, Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, Neurology, ACS - Atherosclerosis & ischemic syndromes, Graduate School, Center of Experimental and Molecular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ischemic Stroke/*diagnostic imaging/*drug therapy, Tomography, X-Ray Computed/methods, Fibrinolytic Agents/adverse effects/*therapeutic use, 030204 cardiovascular system & hematology, Ischemic Stroke/diagnostic imaging, surgery, 0302 clinical medicine, Modified Rankin Scale, 030212 general & internal medicine, 10. No inequality, Infusions, Intravenous, Stroke, Tomography, Time-to-Treatment, General Medicine, Thrombolysis, X-Ray Computed/methods, Tissue Plasminogen Activator/adverse effects, 3. Good health, [SDV] Life Sciences [q-bio], Diffusion Magnetic Resonance Imaging/methods, Treatment Outcome, Meta-analysis, Tissue Plasminogen Activator, Intravenous, medicine.medical_specialty, Infusions, Intravenous thrombolysis, Neuroimaging, Neuroscience(all), Placebo, Tissue Plasminogen Activator/adverse effects/*therapeutic use, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, medicine, Humans, ddc:610, Ischemic Stroke, business.industry, neurology, Fibrinolytic Agents/adverse effects, Odds ratio, Recovery of Function, medicine.disease, Clinical research, Diffusion Magnetic Resonance Imaging, Human medicine, business, Tomography, X-Ray Computed, Fibrinolytic agent
Abstract

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Published
2020
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17. Neutrophil–Lymphocyte ratio is associated with poor clinical outcome after mechanical thrombectomy in stroke in patients with COVID-19

Author

Fawaz Al-Mufti, Priyank Khandelwal, Tolga Sursal, Jared B. Cooper, Eric Feldstein, Krishna Amuluru, Jayaji M. Moré, Ambooj Tiwari, Amit Singla, Adam A Dmytriw, Mariangela Piano, Luca Quilici, Guglielmo Pero, Leonardo Renieri, Nicola Limbucci, Mario Martínez-Galdámez, Miguel Schüller-Arteaga, Jorge Galván, Juan Francisco Arenillas-Lara, Zafar Hashim, Sanjeev Nayak, Keith Desousa, Hai Sun, Pankaj K. Agarwalla, J Sudipta Roychowdhury, Emad Nourollahzadeh, Tannavi Prakash, Andrew R Xavier, J Diego Lozano, Gaurav Gupta, Dileep R Yavagal, Mohammad Elghanem, Chirag D. Gandhi, and Stephan A. Mayer

Subjects
General Medicine
Abstract

BackgroundThe neutrophil–lymphocyte ratio (NLR) is emerging as an important biomarker of acute physiologic stress in a myriad of medical conditions, and is a confirmed poor prognostic indicator in COVID-19.ObjectiveWe sought to describe the role of NLR in predicting poor outcome in COVID-19 patients undergoing mechanical thrombectomy for acute ischemic stroke.MethodsWe analyzed NLR in COVID-19 patients with large vessel occlusion (LVO) strokes enrolled into an international 12-center retrospective study of laboratory-confirmed COVID-19, consecutively admitted between March 1, 2020 and May 1, 2020. Increased NLR was defined as ≥7.2. Logistic regression models were generated.ResultsIncidence of LVO stroke was 38/6698 (.57%). Mean age of patients was 62 years (range 27–87), and mortality rate was 30%. Age, sex, and ethnicity were not predictive of mortality. Elevated NLR and poor vessel recanalization (Thrombolysis in Cerebral Infarction (TICI) score of 1 or 2a) synergistically predicted poor outcome (likelihood ratio 11.65, p = .003). Patients with NLR > 7.2 were 6.8 times more likely to die (OR 6.8, CI95% 1.2–38.6, p = .03) and almost 8 times more likely to require prolonged invasive mechanical ventilation (OR 7.8, CI95% 1.2–52.4, p = .03). In a multivariate analysis, NLR > 7.2 predicted poor outcome even when controlling for the effect of low TICI score on poor outcome (NLR p = .043, TICI p = .070).ConclusionsWe show elevated NLR in LVO patients with COVID-19 portends significantly worse outcomes and increased mortality regardless of recanalization status. Severe neuro-inflammatory stress response related to COVID-19 may negate the potential benefits of successful thrombectomy.

Published
2022
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18. Factores asociados al mal control de la anticoagulación con antivitamina K en pacientes con fibrilación auricular no valvular atendidos en consultas de Medicina Interna y Neurología. Estudio ALADIN

Author

M.M. Contreras Muruaga, G. Reig, J. Vivancos, A. González, P. Cardona, J.M. Ramírez-Moreno, J. Martí-Fábregas, C. Suárez Fernández, Antonio Pose, José Antonio Díaz, Manuel Rodríguez, Marta Pena, Susana Arias, Davinia Larrosa, Álvaro González, Elisa Rodríguez, Montserrat González, Dolores Fernández, Cristina Barbagelata, Natividad Raña, Santiago Freire, J. Manuel Cerqueiro, Héctor Guerrero, Laura Ramos, Leticia Álvarez, José M. de Lis, Carmen Caro, Manuel Seijo, Susana Mederer, Miguel Alberto de Zarraga, José Ferreiro, José M. Terrero, Mónica Arias, Roberto Pérez, Joaquín Sánchez, José Maciñeiras, Julián Fernández, Fernando Jaén, David Esteva, Mónica Zamora, Nuria Navarrete, Javier García, Luis Mérida, Miguel Ángel Corrales, Raúl Quirós, Jesús Cantero, Francisco Javier Barrero, Inmaculada Villegas, José Castro, Jesús Foronda, Dionisio Carrillo, Jesús Vega, José Antonio Trujillo, Manuel Montero, Ana Jurado, Carlos Sánchez, Eduardo Agüera-Morales, María Sánchez, Purificación Durán, Rafael Fernández de la Puerta, María Pérez de la Blanca, María Paz Martínez, Óscar Fernández, José Antonio Tamayo, Rafael Bustamante, Pedro Jesús Serrano, Antonio Arjona, Javier Fernández, Manuel Payan, Ricardo Gómez, Daniel Peña, Enrique Cabrerizo, Fernando Salgado, Radka Ivanova Georgieva, Antonio Gil-Núñez, Elena Bello, Fernando Díaz, Antonio Medina, Ana Castellano, Yesica Miranda, Óscar Fabre, Iluminada García Polo, Patricia Ibáñez, Clara Sainz, Fernando Sierra, Esther Aragón, Jaime Díaz, Fernando Aguilar, María Ángeles Ortega, José Antonio Egido, José Carlos Pontes, Miguel Ángel García, Francisco Cabrera, Blanca Batalla, Alex Culla, Carlos Molina, Alan Flores, Laia Seró, Marian Muchada, Pilar Meler, Sandra Boned-Riera, David Cánovas, Jordi Estela, Juli Font, Francisco Purroy, Ikram Benabdelhak, Jordi Sanahuja, Jaume Roquer, Ana Rodríguez, Ángel Ois, Elisa Cuadrado, Jordi Jiménez, Xavier Nogués, Jerzy Kuprinski, Antoni German, Daniel Irigoyen, Juan José Cara, Maria Àngels Font, Sonia Huertas, Alejandro Martínez-Domeño, Juan Antonio Arroyo, Raquel Delgado-Mederos, Manuel Jesús Gómez-Choco, Juan José Mengual, Sonia M. García, M. del Mar Castellanos, Cecile van Eedenburg, Imma Cañas, Jordi Espinosa, Santiago Montull, Helena Quesada, Xavier Ustrell, Christian Homedes, Irene Navalpotro, Jordi Casanova, Aida Pilar Lago, Carmen Morata, David Gorriz, Iván Moreno, José Tembl, Alejandro Ponz, M. José Fonseca, Raquel Chamarro, Rosario Gil, Vicente Oliver, Ana Pampliega, Arturo Artero, Francesc Puchades, Lamberto Landete, Carlos Vilar, Carmen Jiménez, Bárbara Vives, M. Dolores Moragues, Rosa Díaz, Silvia Tur, José Bernardo Escribano, César Lucas, Francisco Martínez, José Miguel Pons, Amparo Romero, David García, José Pérez, Ramón Villaverde, Salvadora Martínez, Aida Rodríguez, Carlos Tejero, Cristina Pérez, Enrique Mostacero, Covadonga Fernández, Alain Luna, Tomás Pérez, Félix González, Ana de Arce, Maite Martínez, Noemí Díez, Jaime Gállego, Beatriz Zandio, María Herrera, Nuria Aymerich, Roberto Muñoz, Javier Marta, Jorge Artal, José M. Errea, Juan José Timiraos, M. Pilar Moreno, Mar Freijo, Juan Manuel García, M. Carmen Gil, M. Ángeles Revilla, Enrique Palacio, José Luis Vázquez, María Bestué, Ana Latorre, Eva Calvo, Laura Ballester, Marta Serrano, Jesús M. Juega, M. Ángeles López, Pablo Irimia, Laura Imaz, Blanca Fuentes, Borja Enrique Sanz, Luis Beltrán, Gerardo Ruiz, Patricia Martínez, Demetrio Sánchez, Emilio Barroso, Igor Molina, Marco Antonio Budiño, Jaime Masjuan, Alicia de Felipe, Consuelo Matute, Javier Tejada, Alberto Morán, Esther Fernández, M. del Carmen Riveira, Joaquín Carnedo, Antonio Manquillo, Raquel González, José Carlos Fernández, Marta Guillan, Miguel Yebra, José M. Trejo, Jesús Saiz, Juan Carlos Martínez-Acitores, Yolanda Bravo, Juan Francisco Arenillas, Ana Calleja, Elisa Cortijo, Javier Reyes, Luis López, Pedro Luis Muñoz, M. Ángeles Fidalgo, Jacinto Hernández, José Carlos Gómez, José Carlos Morán, Sonia Gonzalo, Jorge Marrero, José Ángel Satué, Juan Carlos Belinchón, Francisco Moniche, Enrique Calderón, Irene Escudero, Javier de la Torre, Ignacio Casado, Joaquín Antón, Juan Carlos Portilla, Juan Luengo, Joan Rosal, Elena Calzado, Juan Carlos Anglada, Juan Girón, José M. Ramírez, Agustín Pijierro, Ana Roa, Jorge Romero, Mariano Aguayo, Cristina Borrachero, Gema Sanz, M. José Gómez, Miguel Ángel Rico, Antonio Cayon, Eduardo Carmona, Román Cerro, Rafael López, Alfonso Aguirre, Francisco Lozano, and José M. Rivera.

Subjects
03 medical and health sciences, 0302 clinical medicine, business.industry, Medicine, 030212 general & internal medicine, General Medicine, 030204 cardiovascular system & hematology, business, Humanities
Abstract

Resumen Objetivo Identificar los factores asociados con el mal control de la anticoagulacion con antagonistas de la vitamina K (AVK) en pacientes con fibrilacion auricular no valvular (FANV) atendidos en consultas de Neurologia y Medicina Interna de Espana. Metodos Estudio transversal, multicentrico, anidado en el estudio ALADIN, de sujetos con FANV, tratados con AVK, atendidos en consultas de Medicina Interna o Neurologia de Espana. El grado de control de la anticoagulacion se estudio mediante el metodo directo y el de Rosendaal, considerando los 6 meses previos a la inclusion. Resultados De los 1.337 pacientes incluidos en ALADIN, 750 estaban tratados con AVK, con informacion completa sobre el INR de los ultimos 6 meses en 383 pacientes. Las puntuaciones medias del indice de Charlson, CHADS2, CHA2DS2-VASc y HAS-BLED fueron 1,94 ± 1,54; 3,10 ± 1,26; 4,63 ± 1,54 y 2,20 ± 0,90, respectivamente. El 46,2% y el 47,0% de los pacientes presentaban un control adecuado de la anticoagulacion por los metodos directo y Rosendaal, respectivamente. El control inadecuado de la anticoagulacion se asocio por el metodo directo con diabetes (OR: 2,511; IC 95%: 1,144-5,659), antecedentes de INR inestable (OR: 35,371; IC 95%: 15,058-83,083) y la realizacion de > 6 controles en los ultimos 6 meses (OR: 4,747; IC 95%: 2,094-10,759), y por el metodo de Rosendaal, con los antecedentes de INR inestable (p Conclusiones Pese al alto riesgo tromboembolico, solo estaban bien controlados algo mas de la mitad. Los factores asociados al mal control de la anticoagulacion fueron la diabetes, INR inestable, > 6 controles de INR y el HAS-BLED.

Published
2018
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19. [Analysis of factors associated with the comprehensive recovery of stroke patients at acute hospital discharge]

Author

Verónica, Olmedo Vega, Mª José, Aguilar Idáñez, and Juan Francisco, Arenillas Lara

Subjects
Adult, Aged, 80 and over, Male, Age Factors, Stroke Rehabilitation, Recovery of Function, Rural Health, Middle Aged, Health Services Accessibility, Patient Discharge, Logistic Models, Socioeconomic Factors, Residence Characteristics, Spain, Quality of Life, Humans, Female, Healthcare Disparities, Aged, Follow-Up Studies
Abstract

Stroke is a public health problem of the first magnitude, being the first cause of disability in Spain. Although the fundamental role of psychophysical rehabilitation is known in patients suffering from this pathology, little is known about the integral and functional recovery of this type of patient. The Public Health Systems pay for or manage part of the treatment, but never its entirety. The aim of our study was to identify the factors that hinder access to the different treatments and care that allow the functional recovery of stroke patients.Bivariate correlational descriptive analysis was performed on a sample of 102 stroke patients, over 30 years of age, admitted to the University Clinical Hospital of Valladolid, who required comprehensive rehabilitation upon discharge from hospital. Additionally, a multivariable analysis (logistic regression) was carried out to adjust results and eliminate confusing variables.The study showed that the factors initially associated with access to total rehabilitation were age (p0.001), place of residence (p0.001), marital status (p=0.007) and the existence of family support (p=0.01). Sex (p=0.18) and income (p=0.62) were not statistically significant. Age and place of residence (rural or urban) were the explanatory factors for access to comprehensive rehabilitation (values adjusted for all other variables p0.001 were obtained).The results show the existence of very unequal access variables to comprehensive rehabilitation, with the consequences of loss of quality of life and impossibility of functional recovery that this implies, both for stroke patients of advanced age and for patients residing in rural areas.El ictus es un problema de Salud Pública de primera magnitud, siendo la primera causa de discapacidad en España. A pesar de que se conoce el papel fundamental de la rehabilitación psicofísica en los pacientes que sufren esta patología, poco se conoce sobre la recuperación integral y funcional de este tipo de pacientes. Los Sistemas Públicos de Salud costean o gestionan parte del tratamiento, pero nunca su totalidad. El objetivo de nuestro estudio fue identificar los factores que dificultan el acceso a los diferentes tratamientos y cuidados que permiten la recuperación funcional del paciente con ictus.Se realizó análisis descriptivo correlacional bivariable de una muestra de 102 pacientes con ictus, mayores de 30 años, ingresados en el Hospital Clínico Universitario de Valladolid, que precisaban una rehabilitación integral al alta hospitalaria. Adicionalmente, se realizó un análisis multivariable (regresión logística) para ajustar resultados y eliminar variables confusoras.El estudio evidenció que los factores inicialmente asociados al acceso a la rehabilitación total fueron la edad (p0,001), el lugar de residencia (p0,001), el estado civil (p=0,007) y la existencia de apoyo familiar (p=0,01). El sexo (p=0,18) y los ingresos económicos (p=0,62) no presentaron asociación estadísticamente significativa. La edad y el lugar de residencia (rural o urbano) fueron los factores explicativos del acceso a la rehabilitación integral (se obtuvieron valores ajustados al resto de variables de p0,001).Los resultados muestran la existencia de variables de acceso muy desigual a la rehabilitación integral, con las consecuencias de pérdida de calidad de vida e imposibilidad de recuperación funcional que ello implica, tanto para pacientes de ictus de edad avanzada como para pacientes que residen en el medio rural.

Published
2019

21. [Intracranial atherosclerosis]

Author

Pablo, Del Saz-Saucedo, José Francisco, Maestre-Moreno, and Juan Francisco, Arenillas-Lara

Subjects
Clinical Protocols, Risk Factors, Practice Guidelines as Topic, Humans, Intracranial Arteriosclerosis, Prognosis
Abstract

Until recently, intracranial atheromatosis was a probably underdiagnosed clinicopathological entity that was rarely studied in depth. In the last years the advance and expansion in the use of non-invasive diagnostic tools have led intracranial atheromatosis to the front page among the most prevalent causes of stroke worldwide. Important efforts have been accomplished with the aim of identifying markers of poor outcome, which, besides the underlying mechanisms of cerebral ischemia in these patients, are the most important factors on which clinical and therapeutic decisions should be based. To date, the therapeutic armamentarium is scarce and far from optimun, regarding medical and endovascular measures. In this review we address the most important aspects of the natural history and cure treatment of intracranial atheromatosis.

Published
2008

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