Characteristics of stroke units and stroke teams in Spain in 2018. Pre2Ictus project

Introduction: The aim of this work is to describe the characteristics of stroke units and stroketeams in Spain.Method: We performed a cross-sectional study based on an ad hoc questionnaire designed by5 experts and addressed to neurologists leading stroke units/teams that had been operationalfor ≥ 1 year. Results: The survey was completed by 43 stroke units (61% of units in Spain) and 14 stroketeams. The mean (SD) number of neurologists assigned to each unit/team is 4±3. 98% of strokeunits (and 38% of stroke teams) have a neurologist on-call available 24hours, 365 days. 98% ofstroke units (79% of stroke teams) have specialised nurse, 95% of units (71% of stroke teams) auxiliary personnel, 86% of units (71% of stroke teams) social worker, 81% of stroke units (71%of stroke teams) have a rehabilitation physician and 81% of stroke units (86% of stroke teams) aphysiotherapist. Most stroke units (80%) have 4-6 beds with continuous non-invasive monitoring.The mean number of unmonitored beds is 14 (8) for stroke units and 12 (7) for stroke teams.The mean duration of non-invasive monitoring is 3 (1) days. All stroke units and 86% of stroke teams have intravenous thrombolysis available, and 81% of stroke units and 21% of stroke teamsare able to perform mechanical thrombectomy, whereas the remaining centres have referral pathways in place. Telestroke systems are available at 44% of stroke units, providing supportto a mean of 4 (3) centres. Activity is recorded in clinical registries by 77% of stroke units and 50% of stroke teams, but less than 75% of data is completed in 25% of cases. Conclusions: Most stroke units/teams comply with the current recommendations. The syste-matic use of clinical registries should be improved to further improve patient care.Introducción: El objetivo del trabajo es describir las características de las unidades y equipos de ictus en España. Método: Estudio transversal basado en un cuestionario ad hoc, diseñado por 5 expertos y dirigido a los neurólogos responsables de las unidades de ictus (UI) y los equipos de ictus (EI) conal menos un año de funcionamiento. Resultados: Participaron 43 UI (61% del total) y 14 EI. La media (±DE) de neurólogos adscritos a las UI/EI fue de 4 ± 3. El 98% de las UI frente al 38% de los EI cuentan con neurólogo de guardia 24 h los 365 días. Disponen de enfermería especializada un 98% de las UI frente al 79% de los EI,de médico rehabilitador un 81% frente al 71% y de trabajador social un 86% frente al 71%. Lamayoría de las UI (80%) tienen 4-6 camas con monitorización continua no invasiva. El número medio de camas no monitorizadas de las UI es de 14 ± 8 y de 12 ± 7 en los EI. La estancia mediade los pacientes en las camas monitorizadas de las UI es de 3 ± 1 días. Todas las UI y el 86% de los EI pueden realizar trombólisis intravenosa; el 81% de las UI y el 21% de los EI pueden realizar trombectomía mecánica y el resto de los centros tiene posibilidad de derivación. El 44% de las UI dispone de un sistema de teleictus, que da servicio a 4 ± 3 centros. La actividad se recoge sistemáticamente en el 77% de las UI y en el 50% de los EI, pero su cumplimentación es < 75% en un 25% de los casos. Conclusiones: La mayoría de las UI y de los EI cumple las recomendaciones actuales. Para seguir mejorando la atención del paciente, resulta necesario optimizar el registro sistemático de su actividad

Circulating extracellular vesicle proteins and microRNA profiles in subcortical and cortical-subcortical ischaemic stroke

In order to investigate the role of circulating extracellular vesicles (EVs), proteins, and microRNAs as damage and repair markers in ischaemic stroke depending on its topography, subcor-tical (SC), and cortical-subcortical (CSC) involvement, we quantified the total amount of EVs using an enzyme-linked immunosorbent assay technique and analysed their global protein content using proteomics. We also employed a polymerase chain reaction to evaluate the circulating microRNA profile. The study included 81 patients with ischaemic stroke (26 SC and 55 CSC) and 22 healthy controls (HCs). No differences were found in circulating EV levels between the SC, CSC, and HC groups. We detected the specific expression of C1QA and Casp14 in the EVs of patients with CSC ischaemic stroke and the specific expression of ANXA2 in the EVs of patients with SC involvement. Patients with CSC ischaemic stroke showed a lower expression of miR-15a, miR-424, miR-100, and miR-339 compared with those with SC ischaemic stroke, and the levels of miR-339, miR-100, miR-199a, miR-369a, miR-424, and miR-15a were lower than those of the HCs. Circulating EV proteins and microRNAs from patients with CSC ischaemic stroke could be considered markers of neurite outgrowth, neurogenesis, inflammation process, and atherosclerosis. On the other hand, EV proteins and microRNAs from patients with SC ischaemic stroke might be markers of an anti-inflammatory process and blood–brain barrier disruption reduction.This work was sponsored by a grant from Miguel Servet (CP15/00069; CPII20/00002 to María Gutiérrez-Fernández), Miguel Servet (CP20/00024 to Laura Otero-Ortega), a predoctoral fellowship (FI17/00188 to Mari Carmen Gómez-de Frutos; FI18/00026 to Fernando Laso-García), a Sara Borrell postdoctoral fellowship (CD19/00033 to María Pérez-Mato), a Río Hortega (CM20/00047 to Elisa Alonso-López) and the INVICTUS PLUS network grant (RD16/0019/0005) from the Carlos III Health Institute Health Care Research Fund and was co-funded by the European Regional Development Fund (ERDF)

The role of ultrasound as a diagnostic and therapeutic tool in experimental animal models of stroke: A review

Ultrasound is a noninvasive technique that provides real-time imaging with excellent resolution, and several studies demonstrated the potential of ultrasound in acute ischemic stroke monitoring. However, only a few studies were performed using animal models, of which many showed ultrasound to be a safe and effective tool also in therapeutic applications. The full potential of ultrasound application in experimental stroke is yet to be explored to further determine the limitations of this technique and to ensure the accuracy of translational research. This review covers the current status of ultrasound applied to monitoring and treatment in experimental animal models of stroke and examines the safety, limitations, and future perspectives.This research was funded by the Carlos III Health Institute Health Care Research Fund grant number FIS PI16/01052 and cofunded by the European Regional Development Fund (ERDF)–Miguel Servet (CP15/00069, CPII20/00002 to María Gutiérrez–Fernández; CP20/00024 to Laura Otero–Ortega) and predoctoral fellowship (FI17/00188 to Mari Carmen Gómez–de Frutos, FI18/00026 to Fernando Laso–García) and the INVICTUS PLUS Spanish Network (RD16/0019/0005) of the Carlos III Health Institute (ISCIII)

Similarities and differences in extracellular vesicle profiles between ischaemic stroke and myocardial infarction

Extracellular vesicles (EVs) are involved in intercellular signalling through the transfer of molecules during physiological and pathological conditions, such as ischaemic disease. EVs might therefore play a role in ischaemic stroke (IS) and myocardial infarction (MI). In the present study, we analysed the similarities and differences in the content of circulating EVs in patients with IS and MI. This prospective observational study enrolled 140 participants (81 patients with IS, 37 with MI and 22 healthy controls [HCs]). We analysed the protein and microRNA content from EVs using proteomics and reverse transcription quantitative real-time polymerase chain reaction and compared it between the groups. In the patients with IS and MI, we identified 14 common proteins. When comparing IS and MI, we found differences in the protein profiles (apolipoprotein B, alpha-2-macroglobulin, fibronectin). We also found lower levels of miR-340 and miR-424 and higher levels of miR-29b in the patients with IS and MI compared with the HCs. Lastly, we found higher miR-340 levels in IS than in MI. In conclusion, proteomic and miRNA analyses suggest a relationship between circulating EV content and the patient’s disease state. Although IS and MI affect different organs (brain and heart) with distinct histological characteristics, certain EV proteins and miRNAs appear to participate in both diseases, while others are present only in patients with ISThis work was sponsored by a grant from Miguel Servet (CP15/00069 to María Gutiérrez- Fernández), a predoctoral fellowship (FI17/00188 to Mari Carmen Gómez-de Frutos;FI18/00026 to Fernando Laso-García), a Sara Borrell postdoctoral fellowship (CD19/00033 to María Pérez-Mato), the INVICTUS PLUS network grant (RD16/0019/0005) from the Carlos III Health Institute Health Care Research Fund and was co-funded by the European Regional Development Fund (ERDF) and Juan de la Cierva postdoctoral fellowship (IJCI-2017-33505 to Laura Otero-Ortega, Spanish State Research Agency) and the Spanish Ministry of Science and Innovatio

Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease’s pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease’s pathological processes. Purpose: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. Results: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen β chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. Conclusion: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MSfor reflecting the disease stateWe greatly appreciate the support of Morote Traducciones S.L. for their editing assistance. This work was sponsored by a grant from Miguel Servet (CP20/00024 to Laura Otero-Ortega), Miguel Servet (CPII20/00002 to María Guti´errez-Fernández), a predoctoral fellowship (FI18/00026 to Fernando Laso-García), a Río-Hortega grant (CM22/00065 to Gabriel Torres Iglesias and CM20/00047 to Elisa Alonso-Lopez) and byResearch Project (PI21/00918) from the Instituto de Salud Carlos III and co-funded by the European Union and by a grant CA1/RSUE/2021-00753 to Dolores Piniella funded by Ministerio de Universidades, Plan de Recuperacion, ´ Transformacion ´ y Resiliencia y la Universidad Autónoma de Madri

DUbbing language-therapy CINEma-based in aphasia post-stroke (DULCINEA): study protocol for a randomized crossover pilot trial

Communication is one of the most important predictors of social reintegration after stroke. Approximately 15–42% of stroke survivors experience post-stroke aphasia. Helping people recover from aphasia is one of the research priorities after a stroke. Our aim is to develop and validate a new therapy integrating dubbing techniques to improve functional communication. Methods: The research project is structured as three work packages (WP). WP1: development of the dubbed language cinema-based therapy: Two research assistants (a speech therapist and a dubbing actor) will select the clips, mute specific words/sentences in progressive speech difficulty, and guide patients to dub them across sessions. Words to be dubbed will be those considered to be functionally meaningful by a representative sample of aphasic patients and relatives through an online survey. WP2: a randomized, crossover, interventional pilot study with the inclusion of 54 patients with post-stroke non-fluent aphasia. Patients will be treated individually in 40-min sessions twice per week for 8 weeks. Primary outcomes will be significant pre/post differences in scores in the Communicative Activity Log (CAL) questionnaire and Boston Diagnostic Aphasia Examination (BDAE) administered by a psychologist blinded to the patients’ clinical characteristics. Secondary outcomes: General Health Questionnaire (GHQ)-12, Stroke Aphasia Quality of Life Scale (SAQOL-39), Western Aphasia Battery Revised (WAB-R), and the Stroke Aphasic Depression Questionnaire (SADQ10). WP3: educational activities and dissemination of results. WP3 includes educational activities to improve public knowledge of aphasia and dissemination of the results, with the participation of the Spanish patients’ association Afasia Activa. Discussion: This pilot clinical trial will explore the efficacy of a new therapeutic tool based on dubbing techniques and computer technology to improve functional communication of patients suffering from post-stroke aphasia with the use of standardized test assessmentThis study is promoted by Blanca Fuentes and the Research Foundation of La Paz University Hospital, which hosts a research consortium joined by the Department of Neurology at La Paz University Hospital, the Department of Psychology at Comillas Pontifical University, and the patients’ association Afasia Activa. This project has received funding from “la Caixa” Banking Foundation under the project code HR18-00026. Funder is not involved in any of the following processes: design of the trial, data collection, analysis, or interpretation of data nor than in writing the manuscrip

Alberta Stroke Program Early CT Score applied to CT angiography source images is a strong predictor of futile recanalization in acute ischemic stroke

The final publication is available at Springer via http://dx.doi.org/10.1007/s00234-016-1652-7Introduction Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization. Methods Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, timelapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability). Results Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT+MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3–0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5–1.2). A score ≤5 in CTA-SIASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %). Conclusions CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapie

Intravenous thrombolytic treatment in the oldest old

Background and Purpose. Intravenous thrombolysis using tissue plasminogen activator is safe and probably effective in patients >80 years old. Nevertheless, its safety has not been specifically addressed for the oldest old patients (≥85 years old, OO). We assessed the safety and effectiveness of thrombolysis in this group of age. Methods. A prospective registry of patients treated with intravenous thrombolysis. Patients were divided in two groups (<85 years and the OO). Demographic data, stroke aetiology and baseline National Institute Health Stroke Scale (NIHSS) score were recorded. The primary outcome measures were the percentage of symptomatic intracranial haemorrhage (SICH) and functional outcome at 3 months (modified Rankin Scale, mRS). Results. A total of 1,505 patients were registered. 106 patients were OO [median 88, range 85–101]. Female sex, hypertension, elevated blood pressure at admission, cardioembolic strokes and higher basal NIHSS score were more frequent in the OO. SICH transformation rates were similar (3.1% versus 3.7%, P = 1.00). The probability of independence at 3 months (mRS 0–2) was lower in the OO (40.2% versus 58.7%, P = 0.001) but not after adjustment for confounding factors (adjusted OR, 0.82; 95% CI, 0.50 to 1.37; P = 0.455). Three-month mortality was higher in the OO (28.0% versus 11.5%,P < 0.001). Conclusion. Intravenous thrombolysis for stroke in OO patients did not increase the risk of SICH although mortality was higher in this groupThis work is part of the Spanish collaborative research network RENEVAS (Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, RD06/0026/008, RD07/0026/2003

Brain and immune system-derived extracellular vesicles mediate regulation of complement system, extracellular matrix remodeling, brain repair and antigen tolerance in Multiple sclerosis

Background: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease's pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease's pathological processes. Purpose: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. Results: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen β chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. Conclusion: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MS for reflecting the disease state.This work was sponsored by a grant from Miguel Servet (CP20/00024 to Laura Otero-Ortega), Miguel Servet (CPII20/00002 to María Gutiérrez-Fernández), a predoctoral fellowship (FI18/00026 to Fernando Laso-García), a Río-Hortega grant (CM22/00065 to Gabriel Torres Iglesias and CM20/00047 to Elisa Alonso-López) and by Research Project (PI21/00918) from the Instituto de Salud Carlos III and co-funded by the European Union and by a grant CA1/RSUE/2021-00753 to Dolores Piniella funded by Ministerio de Universidades, Plan de Recuperación, Transformación y Resiliencia y la Universidad Autónoma de Madrid.S

Long-term anticoagulation in secondary ischemic stroke prevention: The prospective multicenter RESTAIC registry

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence.This study was supported by grants from the Foundation for Biomedical Research of La Paz University Hospital (PI 1131