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Introduction: Spinal cord infarction is a rare disease with a high rate of morbidity. Its diagnosis can be challenging and controversy remains regarding the best treatment. Few case series have been published. Methods: We conducted a retrospective review of cases of spinal cord infarction attended in a tertiary hospital from 1999 to 2020. Aetiology and clinical, imaging, and prognostic features were assessed. Results: Forty-one patients (58.5% men, mean [standard deviation] age 61 [17] years) were included in the study. Thirty-one patients (75.6%) presented vascular risk factors. Motor deficits were recorded in 39 (95.1%), pain in 20 (48.8%), sensory deficits in 33 (80.4%), and autonomic dysfunction in 24 (58.5%). MRI was performed in 37 (90.2%) patients. Diffusion-weighted images were available for 12 patients, with 10 showing diffusion restriction. The thoracic region was the most frequently affected (68.2%). Vascular imaging studies were performed in 33 patients (80.4%). The most frequent aetiologies were aortic dissection (6 cases), atherosclerosis demonstrated by vascular imaging (6 cases), fibrocartilaginous embolism (6 cases), surgery (5 cases), and hypotension (4 cases). Aetiology was undetermined in 12 patients (29.3%), although 9 of these presented vascular risk factors. At the end of the follow-up period (median, 24 months; interquartile range, 3–70), 12 patients (29.2%) were able to walk without assistance. Vascular risk factors and paraparesis were significantly associated with poorer prognosis (P

Introduction: Thrombectomy in the carotid artery territory was recently shown to be effective up to 24 hours after symptoms onset. Methods: We conducted a retrospective review of a prospective registry of patients treated at our stroke reference centre between November 2016 and April 2019 in order to assess the safety and effectiveness of mechanical thrombectomy performed beyond 6 hours after symptoms onset in patients with acute ischaemic stroke and large vessel occlusion in the carotid artery territory. Results: Data were gathered from 59 patients (55.9% women; median age, 71 years). In 33 cases, stroke was detected upon awakening; 57.6% of patients were transferred from another hospital. Median baseline NIHSS score was 16, and median ASPECTS score was 8, with 94.9% of patients presenting > 50% of salvageable tissue. Satisfactory recanalisation was achieved in 88.1% of patients, beyond 24 hours after onset in 5 cases. At 90 days of follow-up, 67.8% were functionally independent; those who were not were older and presented higher prevalence of atrial fibrillation, greater puncture-to-recanalisation time, and higher NIHSS scores, both at baseline and at discharge. Conclusion: In our experience, mechanical thrombectomy beyond 6 hours was associated with good 90-day functional outcomes. Age, NIHSS score, puncture-to-recanalisation time, and presence of atrial fibrillation affected functional prognosis. The efficacy of the treatment beyond 24 hours after onset merits study. Resumen: Introducción: La eficacia de la trombectomía mecánica en territorio carotídeo en las primeras 24 horas se ha probado con trabajos publicados recientemente. Métodos: Revisión retrospectiva a partir de un registro prospectivo en nuestro centro de referencia de ictus para valorar la eficacia y seguridad del tratamiento endovascular realizado más allá de las 6 horas de evolución de los síntomas en pacientes con ictus isquémico agudo y oclusión de gran vaso en territorio carotídeo, entre noviembre de 2016 y abril de 2019. Resultados: Se recopilaron datos de 59 pacientes (55,9% mujeres, mediana de edad 71 años). Treinta y tres pacientes fueron detectados al despertar. El 57,6% de los casos fueron traslados secundarios. La mediana de NIHSS basal fue 16. La mediana del ASPECTS fue 8 y el 94,9% de los pacientes presentó > 50% de tejido salvable. El 88,1% de los pacientes logró una recanalización satisfactoria, en 5 pacientes después de 24 horas de evolución. El 67,8% de los casos logró la independencia funcional a los 90 días de seguimiento. Los pacientes que no lograron la independencia funcional presentaban mayor edad, mayor proporción de fibrilación auricular, mayor tiempo punción-recanalización y mayor puntuación NIHSS, tanto basal como al alta. Conclusión: En nuestra experiencia la trombectomía mecánica después de las 6 horas se asoció con buenos resultados de funcionalidad a los 90 días. La edad, la puntuación NIHSS, el tiempo punción-recanalización y la prevalencia de fibrilación auricular fueron factores determinantes en el pronóstico funcional. La eficacia de este tratamiento por encima de las 24 horas merece ser estudiada.

Introduction: There is little control of cardiovascular (CV) risk factors in secondary prevention after an ischaemic stroke, in part due to a lack of adherence to treatment. The CV polypill may contribute to proper treatment adherence, which is necessary for CV disease prevention. This study aimed to establish how and in what cases the CV polypill should be administered. Methods: A group of 8 neurologists drafted consensus recommendations using structured brainstorming and based on their experience and a literature review. Results: These recommendations are based on the opinion of the participating experts. The use of the CV polypill is beneficial for patients, healthcare professionals, and the health system. Its use is most appropriate for atherothrombotic stroke, lacunar stroke, stroke associated with cognitive impairment, cryptogenic stroke with CV risk factors, and silent cerebrovascular disease. It is the preferred treatment in cases of suspected poor adherence, polymedicated patients, elderly people, patients with polyvascular disease or severe atherothrombosis, young patients in active work, and patients who express a preference for the CV polypill. Administration options include switching from individual drugs to the CV polypill, starting treatment with the CV polypill in the acute phase in particular cases, use in patients receiving another statin or an angiotensin ii receptor antagonist, or de novo use if there is suspicion of poor adherence. Nevertheless, use of the CV polypill requires follow-up on the achievement of the therapeutic objectives to make dose adjustments. Conclusions: This document is the first to establish recommendations for the use of the CV polypill in cerebrovascular disease, beyond its advantages in terms of treatment adherence. Resumen: Introducción: El control de los factores de riesgo cardiovascular (CV) en la prevención secundaria tras un ictus isquémico es bajo, en parte debido a la falta de adherencia terapéutica. La polipíldora CV puede contribuir a la buena cumplimentación del adecuado tratamiento para la prevención cerebrovascular. El objetivo fue establecer cómo y en qué casos se debería administrar. Métodos: Un grupo de 8 neurólogos redactaron recomendaciones consensuadas mediante una técnica de brainstorming estructurado, basándose en su experiencia y en una revisión bibliográfica. Resultados: Los resultados atienden a la opinión de los expertos. El uso de la polipíldora CV tiene ventajas para pacientes, profesionales sanitarios y para el sistema de salud. Las situaciones clínicas más adecuadas para su uso son el ictus aterotrombótico, el lacunar, el asociado a deterioro cognitivo, el criptogénico con factores de riesgo CV y la enfermedad cerebrovascular silente. Su uso preferente incluye la sospecha de mal cumplimiento, a los pacientes polimedicados, ancianos, polivasculares o con alta carga aterotrombótica, jóvenes activos laboralmente y pacientes con preferencias por la polipíldora CV. Las opciones de administración incluyen el paso de fármacos individuales a la polipíldora CV, el inicio directo desde la fase aguda en casos particulares, a los pacientes con otra estatina o con un antagonista del receptor de la angiotensina ii, o de novo si hubiera sospecha de mala adherencia. No obstante, su uso implica realizar seguimiento del cumplimiento de los objetivos terapéuticos para ajustar la dosis. Conclusiones: Este documento es el primero en establecer recomendaciones de uso de la polipíldora CV en enfermedad cerebrovascular, aparte de sus ventajas sobre la adherencia.

Introduction: Organisational capacity in terms of resources and care circuits to shorten response times in new stroke cases is key to obtaining positive outcomes. This study compares therapeutic approaches and treatment outcomes between traditional care centres (with stroke teams and no stroke unit) and centres with stroke units. Methods: We conducted a prospective, quasi-experimental study (without randomisation of the units analysed) to draw comparisons between 2 centres with stroke units and 4 centres providing traditional care through the neurology department, analysing a selection of agreed indicators for monitoring quality of stroke care. A total of 225 patients participated in the study. In addition, self-administered questionnaires were used to collect patients’ evaluations of the service and healthcare received. Results: Centres with stroke units showed shorter response times after symptom onset, both in the time taken to arrive at the centre and in the time elapsed from patient's arrival at the hospital to diagnostic imaging. Hospitals with stroke units had greater capacity to respond through the application of intravenous thrombolysis than centres delivering traditional neurological care. Conclusion: Centres with stroke units showed a better fit to the reference standards for stroke response time, as calculated in the Quick study, than centres providing traditional care through the neurology department. Resumen: Introducción: La capacidad organizativa en términos de recursos y circuitos asistenciales que permiten acortar el tiempo de respuesta ante un nuevo caso de ictus es clave para obtener un buen resultado. En este estudio se compararon el abordaje terapéutico y los resultados del tratamiento de centros de asistencia tradicional (equipos de ictus, sin Unidad de Ictus) y con Unidad de Ictus. Métodos: Estudio de tipo prospectivo, cuasiexperimental (sin aleatorización de las unidades analizadas) para realizar comparaciones entre 2 centros con Unidad de Ictus y 4 centros con atención tradicional por Neurología, sobre una selección de indicadores consensuados para monitorizar la calidad de la atención en ictus. Participaron 225 pacientes. Además, se utilizaron cuestionarios autoadministrados para recoger la valoración del servicio y la asistencia sanitaria recibida por parte de los pacientes. Resultados: Los centros con Unidad de Ictus mostraron menores tiempos de respuesta tras el inicio de los síntomas, tanto al tiempo para llegar al centro, como para el diagnóstico por imagen considerando la hora de llegada del paciente al hospital. La capacidad de respuesta para aplicar tratamiento con trombólisis intravenosa fue mayor entre los hospitales con Unidad de Ictus frente a los centros con atención tradicional por Neurología. Conclusión: Los centros con Unidad de Ictus mostraron un mejor ajuste a los estándares de tiempos de respuesta de referencia en el ictus, calculados en el estudio Quick frente a los centros con atención tradicional por Neurología. Keywords: Patient-centred care, Emergency care, Care quality, Hospital, Stroke, Quality indicators, Palabras clave: Atención centrada en el paciente, Atención urgente, Calidad asistencial, Hospital, Ictus, Indicadores de calidad

Objective: This study proposes a set of quality indicators for care outcomes in patients with acute cerebral infarction. These indicators are understandable and relevant from a clinical viewpoint, as well as being acceptable and feasible in terms of time required, ease of data capture, and interpretability. Method: The method consisted of reaching consensus among doctors after having reviewed the literature on quality indicators in stroke. We then designed and conducted a field study to assess the understandability and feasibility of the set of indicators. Results: Consensus yielded 8 structural indicators, 5 process indicators, and 12 result indicators. Additionally, standards of reference were established for each indicator. Conclusion: This set of indicators can be used to monitor the quality care for stroke patients, identify strengths, and potentially to identify areas needing improvement. Resumen: Objetivo: Mediante este estudio se propone un conjunto de indicadores de calidad del resultado en la atención con infarto cerebral agudo. El conjunto de indicadores se caracteriza por ser comprensible, relevante desde el punto de vista clínico-asistencial, aceptable y factible en términos de tiempos de dedicación, facilidad de captura del dato y sencillez de su interpretación. Método: Tras la revisión de la literatura sobre indicadores de calidad en ictus, se llevó a cabo una metodología de consenso entre profesionales. Posteriormente, se diseñó y ejecutó un estudio de campo para valorar su comprensión y factibilidad. Resultados: Se han consensuado 8 indicadores de estructura, 5 de proceso y 12 de resultado. Además, se han establecido estándares de referencia para cada uno. Conclusión: Este conjunto de indicadores permite monitorizar el nivel de calidad de la atención sanitaria, identifican fortalezas y posibilita la identificación de áreas de mejora en la atención a los pacientes con ictus. Keywords: Patient-centred care, Emergencies, Care quality, Consensus, Stroke, Quality indicators, Palabras clave: Atención centrada en el paciente, Atención urgente, Calidad asistencial, Consenso, Ictus, Indicadores de calidad

Introduction: Cervical artery dissection (CAD) is responsible for up to 20% of all ischaemic strokes in patients younger than 45. The benefits of acute-phase reperfusion therapy in these patients have yet to be confirmed. Methods: We conducted a retrospective review of patients with CAD admitted to a comprehensive stroke centre between 2010 and 2015. We recorded baseline clinical characteristics, treatments, functional outcomes, and mortality. Results: We identified 35 cases of CAD (23 carotid/12 vertebral); mean age was 43.5 ± 9.5 years and 67.7% were men. Ten patients (32.3%) had a history of trauma. The most frequent risk factors were arterial hypertension (29%) and smoking (35.5%). The most common clinical presentation was ischaemic stroke (29 patients, 93.5%). The median baseline National Institute of Health Stroke Scale score was 6 (range, 0-41). The most frequently used diagnostic method was CT angiography (74.2%), followed by MRI (64.5%) and digital subtraction angiography (45.6%). Seven patients (22.6%) were treated with intravenous fibrinolysis and 11 (35.5%) with endovascular treatment plus intravenous fibrinolysis; at 3 months, functional independence (modified Rankin Scale scores 0-2) was achieved by 57.1% and 63.6% of these cases, respectively. One patient died (3.2%). Conclusions: In our sample, the most common form of presentation of CAD was ischaemic stroke. Reperfusion therapy seems to be a safe and effective option for these patients, and outcomes resemble those of other patients with ischaemic stroke. Larger comparative studies are necessary to better assess response to reperfusion therapy in acute ischaemic stroke. Resumen: Introducción: Las disecciones de arteriales cervicales (DAC) provocan hasta el 20% de los ictus isquémicos en menores de 45 años. El beneficio de los tratamientos de reperfusión en fase aguda no está plenamente clarificado. Métodos: Revisión retrospectiva de pacientes con DAC ingresados en un centro terciario de ictus desde 2010 hasta 2015. Recogemos las características basales, clínicas, los tratamientos, el pronóstico funcional y la mortalidad. Resultados: Se registraron 35 DAC (23 carotídeas/12 vertebrales). La edad media fue de 43,5 ± 9,5 años y el 67,7% fueron varones. En 10 casos (32,3%) hubo antecedente de un traumatismo. Los factores de riesgo más frecuentes fueron la hipertensión arterial (29%) y el tabaquismo (35,5%). La presentación clínica más frecuente fue el infarto cerebral en 29 pacientes (93,5%). La mediana de puntuación National Institute of Health Stroke Scale basal fue de 6 (0-41). El método diagnóstico más empleado fue la angio-TC (74,2%), seguido de resonancia magnética (64,5%) y arteriografía cerebral (45,6%). Siete pacientes (22,6%) fueron tratados con fibrinólisis intravenosa y 11 (35,5%) con tratamiento endovascular (TEV) ± fibrinólisis intravenosa. A los 3 meses, la independencia funcional (escala de Rankin 0-2) fue del 57,1% y del 63,6%, respectivamente. Falleció un paciente (3,2%). Conclusiones: La forma de presentación más frecuente de la DAC fue el infarto cerebral. Estos casos pueden beneficiarse de terapias de reperfusión, con un pronóstico similar al resto de enfermos con ictus isquémicos. Se requieren registros más extensos para conocer mejor la respuesta a los tratamientos de reperfusión en fase aguda en este grupo de pacientes. Keywords: Ischaemic stroke, Carotid artery dissection, Vertebral artery dissection, Cervical artery dissection, Intravenous fibrinolysis, Endovascular treatment, Palabras clave: Ictus isquémico, Disección carotídea, Disección vertebral, Disección arterial cervical, Fibrinólisis intravenosa, Tratamiento endovascular

Introduction: Intracranial haemorrhages (ICHs) represent a severe and frequently lethal complication in patients treated with vitamin K antagonists (VKA). The purpose of our study is to describe the factors and clinical features associated with mortality in these patients. Methods: We conducted an observational, retrospective, multi-centre study based on prospective stroke registries in Spain. We included all patients admitted to neurology departments during a 1-year period who met the following inclusion criteria: being 18 or older, having a diagnosis of ICH, and receiving VKA. Clinical and radiological parameters and 3-month outcomes were analysed. Results: A total of 235 patients from 21 hospitals were included. Mortality rate at 90 days was 42.6%. Bivariate analysis showed a significant association between death and the following factors: median NIHSS score at admission (5 [IQR = 9] vs 17 [IQR = 14] points, P

Introduction: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). Methods: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the e-mail address during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients’ demographic and clinical data, number of queries, reason for consultation, and actions taken. Results: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71 ± 10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive. Conclusions: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting. Resumen: Introducción: La problemática de los trastornos del movimiento (TM) es compleja y la duración y frecuencia de las consultas presenciales puede estar limitada por problemas de espacio y tiempo. Analizamos el funcionamiento de un servicio de atención por correo electrónico institucional para médicos de Atención Primaria (MAP) y pacientes en la Unidad de Trastornos del Movimiento (UTM). Métodos: Se revisaron retrospectivamente los correos electrónicos enviados y recibidos en un periodo de 4 meses, un año tras su implantación. La dirección se proporcionaba en consulta y mediante sesiones informativas a los MAP del área. Se analizaron datos clínicos y demográficos de los pacientes, tipo de interlocutor, número de consultas, motivo y actuaciones derivadas de ellas. Resultados: Del 1 de enero al 30 de abril de 2015 se recibieron 137 correos de 63 pacientes (43% varones; edad 71 ± 10,5 años) diagnosticados de enfermedad de Parkinson (76%), parkinsonismos atípicos (10%) y otros (14%), y se enviaron 116 respuestas. En 20 casos (32%) fueron redactados por el paciente, en 38 (60%) por sus familiares y en 5 (8%) por MAP. Los motivos de consulta fueron clínicos en 50 casos (80%): deterioro clínico (16; 32%), nuevos síntomas (14; 28%), efectos secundarios o dudas sobre medicación (20; 40%). Como consecuencia, se adelantó una cita programada en 9 casos (14%), mientras que el resto se solucionaron por correo electrónico. En 13 (20%), el motivo de consulta fue burocrático: relacionado con citas (11, 85%) y solicitud de informe (2, 15%). La satisfacción fue generalizada, sin constituir una sobrecarga asistencial excesiva para los facultativos responsables. Conclusiones: La implantación de una consulta por correo electrónico es factible en UTM, facilita la comunicación médico-paciente y la continuidad asistencial con Atención Primaria. Keywords: E-consult, Email-based consultation, Telemedicine, Electronic consultation, Parkinson's disease, Palabras clave: Consulta electrónica, Atención por mail, Telemedicina, Atención electrónica, Parkinson

Background: The development of endovascular techniques has put Interventional Neuroradiology (INR) as the first-option treatment in the majority of vascular diseases of the central nervous system. Scientific societies in developed countries have created standard procedures for training and accreditation for a safe practice in these procedures. Discussion: In Spain, we are waiting for the development of the legislation on the accreditation for specialists which will establish the official formative model to achieve an accreditation in INR. Until this moment comes, it is necessary to establish standards that define desirable minimums for the formative period in INR. Radiology specialists as well as neurologists and neurosurgeons will have access to INR accreditation. Specific requirements for the hospitals that wish to offer this technique and training should also be defined. Conclusion: The Spanish Group of Interventional Neuroradiology, the Spanish Society of Neuroradiology, the Spanish Group of Cerebrovascular Diseases, the Spanish Society of Neurology and the Spanish Society of Neurosurgery have approved the content of this document and will create a committee in order to put into practice the accreditation of formative centres and INR specialists. Resumen: Introducción: El desarrollo de las técnicas endovasculares ha colocado a la Neurorradiología Intervencionista-Neurointervencionismo (NRI-NI) como una alternativa de primera elección para el tratamiento de gran parte de las enfermedades vasculares del sistema nervioso central. Al no disponer de programas formativos en NRI-NI normalizados, las sociedades científicas de los países desarrollados han creado estándares de formación y acreditación para la práctica segura de estos procedimientos. Desarrollo: En España, estamos a la espera del desarrollo legislativo de las Áreas de Capacitación Específicas que establecerán el modelo formativo oficial para los especialistas que deseen formarse en NRI-NI. Hasta que llegue ese momento, se hace pertinente disponer de unos estándares que definan los mínimos deseables para el periodo formativo en NRI-NI al que puedan acceder especialistas no solo de la Radiología, sino también de la Neurocirugía, y la Neurología, así como los requisitos exigibles a los hospitales que realizan esta actividad y quieran impartir dicha formación. Conclusiones: Para poner en práctica la acreditación de centros formativos y la acreditación de los centros formadores y especialistas formados en NRI-NI, el Grupo Español de Neurorradiología Intervencionista (GENI), la Sociedad Española de Neurorradiología (SENR), el Grupo de Estudio de Enfermedades Cerebrovasculares (GEECV) de la Sociedad Española de Neurología (SEN) y el grupo experto en enfermedades vasculares de la Sociedad Española de Neurocirugía (SENEC), han aprobado el contenido de este documento de consenso y crearán un comité acreditador. Keywords: Interventional Neuroradiology-Neurointervention, Stroke, Cerebrovascular diseases, Endovascular treatment, Formative period, Interventional specialist, Palabras clave: Neurorradiología intervencionista-Neurointervencionismo, ictus, enfermedades cerebrovasculares, tratamiento endovascular, plan de formación, neurointervención

Introduction: The minimum basic dataset is the largest available hospital care administrative database that is used in clinical studies and hospital management in association with diagnosis-related groups (DRGs). In 2011, the quality of the national MBDS in hospital discharges was audited, in order to assess its reliability. This paper presents a sub-analysis of the results from that analysis which are referred to cerebrovascular disease (CVD). Methods: Using all discharge reports from the Spanish MBDS in 2009, a representative sample was obtained by stratified sampling and 11 209 records were evaluated. Outcome indicators were obtained to measure any differences observed between the national MBDS being evaluated and the hospital's original MBDS. Analysis of codes for CVD as a primary diagnosis was performed for ICD-9-CM diagnostic categories 430 through 438. We evaluated error rates in the selection and classification of main diagnoses, as well as in DRG assignment. Results: There were 397 discharges of cases of CVD which included 21 different DRGs. Diagnostic coding showed a concordance rate of 81.87%; the selection error rate was 2.26% and the classification error rate was 15.87%. The error rate in the DRG was 16.12% and associated with the greatest impact on the mortality risk level. Conclusions: While the errors we observed must be taken into account, data suggest that the quality of the MBDS for CVD is sufficient to ensure delivery of valid information. The hospital discharge registry serves as a valuable tool for use in studies of this disease. Resumen: Introducción: El conjunto mínimo básico de datos (CMBD) es la mayor base de datos clínico-administrativa hospitalaria disponible, empleada en estudios clínicos y en gestión hospitalaria, a través de los grupos relacionados con el diagnóstico (GRD). En 2011 se acometió una auditoría de la calidad del CMBD en las altas hospitalarias, a fin de evaluar su fiabilidad. Este trabajo constituye un subanálisis de los resultados, referidos a enfermedad cerebrovascular (ECV). Métodos: De todas las altas del CMBD estatal del 2009, se obtuvo una muestra representativa, evaluándose 11.209 historias clínicas. Los indicadores de resultado se obtuvieron como medida de las diferencias observadas entre el CMBD evaluado y el CMBD original del hospital. El análisis de la codificación de la ECV como diagnóstico principal se realizó sobre las categorías diagnósticas CIE-9-MC 430-438. Se evaluaron las tasas de error en la selección y clasificación del diagnóstico principal, así como en la asignación del GRD. Resultados: Se observaron 397 altas por ECV, incluyendo 21 GRD diferentes. La codificación mostró una concordancia del 81,87%, siendo la tasa de error de selección del 2,26% y de error de clasificación del 15,87%. La tasa de error en los GRD fue del 16,12%, con mayor repercusión sobre el nivel de riesgo de mortalidad. Conclusiones: Si bien los errores observados deben ser considerados, los resultados obtenidos indican que la calidad del CMBD en la ECV permite garantizar la obtención de información válida. El registro de altas hospitalarias puede ser una herramienta valiosa a la hora de acometer estudios sobre esta enfermedad. Keywords: Quality, Spain's minimum basic dataset, Cerebrovascular disease, Diagnosis-related groups, Stroke, Registries, Palabras clave: Calidad, Conjunto mínimo básico de datos, Enfermedad cerebrovascular, Grupos relacionados con el diagnóstico, Ictus, Registros

Introduction: The Spanish Health System's stroke care strategy (EISNS) is a consensus statement that was drawn up by various government bodies and scientific societies with the aim of improving quality throughout the care process and ensuring equality among regions. Our objective is to analyse existing healthcare resources and establish whether they have met EISNS targets. Material and methods: The survey on available resources was conducted by a committee of neurologists representing each of Spain's regions; the same committee also conducted the survey of 2008. The items included were the number of stroke units (SU), their resources (monitoring, neurologists on call 24 hours/7 days, nurse ratio, protocols), SU bed ratio/100 000 inhabitants, diagnostic resources (cardiac and cerebral arterial ultrasound, advanced neuroimaging), performing intravenous thrombolysis, neurovascular interventional radiology (neuro VIR), surgery for malignant middle cerebral artery (MCA) infarctions and telemedicine availability. Results: We included data from 136 hospitals and found 45 Stroke Units distributed unequally among regions. The ratio of SU beds to residents ranged from 1/74 000 to 1/1 037 000 inhabitants; only the regions of Cantabria and Navarre met the target. Neurologists performed 3237 intravenous thrombolysis procedures in 83 hospitals; thrombolysis procedures compared to the total of ischaemic strokes yielded percentages ranging from 0.3% to 33.7%. Hospitals without SUs showed varying levels of available resources. Neuro VIR is performed in every region except La Rioja, and VIR is only available on a 24 hours/7 days basis in 17 cities. Surgery for malignant MCA infarction is performed in 46 hospitals, and 5 have telemedicine. Conclusion: Stroke care has improved in terms of numbers of participating hospitals, the increased use of intravenous thrombolysis and endovascular procedures, and surgery for malignant MCA infarction. Implementation of SUs and telemedicine remain insufficient. The availability of diagnostic resources is good in most SUs and irregular in other hospitals. Regional governments should strive to ensure better care and territorial equality, which would achieve the EISNS objectives. Resumen: Introducción: La Estrategia del Ictus del Sistema Nacional de Salud (EISNS) fue un documento de consenso entre las distintas administraciones y sociedades científicas que se desarrolló con el objetivo de mejorar la calidad del proceso asistencial y garantizar la equidad territorial. Nuestro objetivo fue analizar los recursos asistenciales existentes y si se había cumplido el objetivo de la EISNS. Material y métodos: La encuesta sobre los recursos disponibles se realizó por un comité de neurólogos de cada una de las comunidades autónomas (CC.AA), los cuales también realizaron la encuesta de 2008. Los ítems incluidos fueron el número de Unidades de Ictus (UI), su dotación (monitorización, neurólogo 24 h/7 días, ratio enfermería, protocolos), ratio cama UI/100.000 habitantes, recursos diagnósticos (ecografía cardíaca y arterial cerebral, neuroimagen avanzada), realización de trombolisis intravenosa, intervencionismo neurovascular (INV), cirugía del infarto maligno de la arteria cerebral media (ACM) y disponibilidad de la telemedicina. Resultados: Se incluyeron datos de 136 hospitales. Existen 45 UI distribuidas de un modo desigual. La relación cama de UI por habitantes y comunidad autónoma osciló entre 1/74.000 a 1/1.037.000 habitantes, cumpliendo el objetivo solo Cantabria y Navarra. Se realizaron por neurólogos 3.237 trombolisis intravenosas en 83 hospitales, con un porcentaje respecto del total de ictus isquémico entre el 0,3 y el 33,7%. Los hospitales sin UI tenían una disponibilidad variable de recursos. Se realiza INV en todas las CC.AA salvo La Rioja, la disponibilidad del INV 24 h/7 días solo existe en 17 ciudades. Hay 46 centros con cirugía del infarto maligno de la ACM y 5 con telemedicina. Conclusión: La asistencia al ictus ha mejorado en cuanto al incremento de hospitales participantes, la mayor aplicación de trombolisis intravenosa y procedimientos endovasculares, también en la cirugía del infarto maligno de la ACM, pero con insuficiente implantación de UI y de la telemedicina. La disponibilidad de recursos diagnósticos es buena en la mayoría de las UI, e irregular en el resto de hospitales. Las distintas CC.AA deben avanzar para garantizar el mejor tratamiento y equidad territorial, y así conseguir el objetivo de la EISNS. Keywords: Stroke unit, Stroke treatment, Stroke facilities survey, Thrombolysis, Palabras clave: Unidad de ictus, Tratamiento ictus, Encuesta recursos, Trombolisis

Objective: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. Materials and methods: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. Results: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100, 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. Conclusions: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes. Resumen: Objetivo: Actualización de la guía para el diagnóstico y tratamiento de la hemorragia subaracnoidea de la Sociedad Española de Neurología. Material y métodos: Revisión y análisis de la bibliografía existente. Se establecen recomendaciones en función del nivel de evidencia que ofrecen los estudios revisados. Resultados: La causa más frecuente de hemorragia subaracnoidea espontánea (HSA) es la rotura de un aneurisma cerebral. Su incidencia se sitúa en torno 9 casos por 100.000 habitantes/año y supone un 5% de todos los ictus. La hipertensión arterial y el tabaquismo son sus principales factores de riesgo. Se ha de realizar el tratamiento en centros especializados. Se debe considerar el ingreso en unidades de ictus de aquellos pacientes con HSA y buena situación clínica inicial (grados I y II en la escala de Hunt y Hess). Se recomienda la exclusión precoz de la circulación del aneurisma. El estudio diagnóstico de elección es la tomografía computarizada (TC) craneal sin contraste. Si esta es negativa y persiste la sospecha clínica se aconseja realizar una punción lumbar. Los estudios de elección para identificar la fuente de sangrado son la resonancia magnética (RM) y la angiografía. Los estudios ultrasonográficos son útiles para el diagnóstico y seguimiento del vasoespasmo. Se recomienda el nimodipino para la prevención de la isquemia cerebral diferida. La terapia hipertensiva y el intervencionismo neurovascular pueden plantearse para tratar el vasoespasmo establecido. Conclusiones: La HSA es una enfermedad grave y compleja que debe ser atendida en centros especializados, con suficiente experiencia para abordar el proceso diagnóstico y terapéutico. Keywords: Subarachnoid haemorrhage, Cerebral aneurysm, Diagnosis, Vasospasm, Delayed cerebral ischaemia, Rebleeding, Medical treatment, Palabras clave: Hemorragia subaracnoidea, Aneurisma cerebral, Diagnóstico, Vasoespasmo, Isquemia cerebral diferida, Resangrado, Tratamiento médico

Background and objective: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischemic stroke (IS) and Transient Ischaemic Attack (TIA). Methods: We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. Results: In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70–99%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. Conclusions: We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient. Resumen: Fundamento y objetivo: Actualizar las guías terapéuticas del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isquémico (II) y ataque isquémico transitorio (AIT). Métodos: Revisión de evidencias disponibles sobre la prevención del ictus isquémico y AIT en función del subtipo etiológico. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia. Resultados: En el II de origen aterotrombótico reducen el riesgo de recurrencias el tratamiento antiagregante y los procedimientos revascularizadores en casos seleccionados de estenosis carotidea ipsilateral (70-99%). La prevención de II de origen cardioembólico (fibrilación auricular, valulopatías, prótesis valvulares y en infarto de miocardio con trombo mural) se basa en el uso de anticoagulantes orales. En el II de origen inhabitual, las terapias preventivas dependerán dela etiología; en la trombosis venosa cerebral la anticoagulación oral es eficaz. Conclusiones: Se concluye con recomendaciones de práctica clínica en prevención de ictus isquémico y AIT adaptadas al subtipo etiológico de II que ha presentado el paciente. Keywords: Guidelines, Ischaemic stroke, Transient ischemic attack, Prevention, Palabras clave: Guía de práctica clínica, Ictus isquémico, Ataque isquémico transitorio, Prevención

Introduction: Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. Development: Organised systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12–24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so-called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. Conclusion: Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated. Resumen: Introducción: Actualización de la guía para el tratamiento del infarto cerebral agudo de la Sociedad Española de Neurología basada en la revisión y análisis de la bibliografía existente sobre el tema. Se establecen recomendaciones en base al nivel de evidencia que ofrecen los estudios revisados. Desarrollo: Los sistemas de asistencia urgente extrahospitalaria se organizarán para asegurar la atención especializada de los pacientes y el ingreso en unidades de ictus (UI). Deben aplicarse cuidados generales para mantener la homeostasis (tratar la tensión arterial sistólica > 185 mmHg o diastólica > 105 mmHg, evitar hiperglucemia > 155 mg/dl y controlar la temperatura, tratando con antitérmicos cifras > 37,5 °C), y prevenir y tratar las complicaciones. La craniectomía descompresiva debe ser considerada en casos seleccionados de oedema cerebral maligno. La trombólisis intravenosa con rtPA se administrará en las primeras 4,5 horas en pacientes sin contraindicación. La trombólisis intraarterial farmacológica puede indicarse en las primeras 6 horas de evolución y la trombectomía mecánica hasta las 8 horas. En el territorio posterior la ventana puede ampliarse hasta 12–24 horas. No hay evidencias para recomendar el uso rutinario de los fármacos denominados neuroprotectores. Se recomienda la anticoagulación en pacientes con trombosis de senos venosos. Se aconseja el inicio precoz de rehabilitación. Conclusiones: El tratamiento del infarto cerebral se basa en la atención especializada en UI, la aplicación urgente de cuidados generales y el tratamiento trombolítico intravenoso en las primeras 4,5 horas. La recanalización intraarterial farmacológica o mecánica pueden ser útiles en casos seleccionados. Terapias de protección y reparación cerebral están en desarrollo. Keywords: Cerebral infarct, Ischaemic stroke, Thrombolysis, Brain protection, Stroke units, Cerebral venous thrombosis, Palabras clave: Infarto cerebral, Ictus isquémico, Trombólisis, Cerebroprotección, Unidades de ictus, Trombosis venosa cerebral

Introduction: Patients with stroke associated with non-valvular atrial fibrillation (NVAF) are a specific group, and their disease has a considerable social and economic impact. The primary objective of the CONOCES study, the protocol of which is presented here, is to compare the costs of stroke in NVAF patients to those of patients without NVAF in Spanish stroke units from a societal perspective. Materials and methods: CONOCES is an epidemiological, observational, naturalistic, prospective, multicentre study of the cost of the illness in a sample of patients who have suffered a stroke and were admitted to a Spanish stroke unit. During a 12-month follow-up period, we record sociodemographic and clinical variables, score on the NIH stroke scale, level of disability, degree of functional dependency according to the modified Rankin scale, and use of healthcare resources (hospitalisation at the time of the first episode, readmissions, outpatient rehabilitation, orthotic and/or prosthetic material, medication for secondary prevention, medical check-ups, nursing care and formal social care services). Estimated monthly income, lost work productivity and health-related quality of life measured with the generic EQ-5D questionnaire are also recorded. We also administer a direct interview to the caregiver to determine loss of productivity, informal care, and caregiver burden. Results and conclusions: The CONOCES study will provide more in-depth information about the economic and clinical impact of stroke according to whether or not it is associated with NVAF. Resumen: Introducción: Los pacientes con ictus asociado a fibrilación auricular no valvular (FANV) constituyen un grupo específico con gran repercusión social y económica. El objetivo principal del estudio CONOCES, cuyo protocolo se presenta en ese trabajo, es comparar los costes del infarto cerebral en los pacientes con FANV frente a los pacientes sin FANV en el ámbito sanitario español ingresados en unidades de ictus, utilizando la perspectiva de la sociedad. Materiales y métodos: CONOCES es un estudio epidemiológico, observacional, naturalístico, prospectivo y multicéntrico de los costes de la enfermedad, en una muestra de pacientes que ha sufrido un ictus establecido e ingresado en una unidad de ictus, en el ámbito sanitario español. El periodo de seguimiento será de 12 meses. Se recogerán variables sociodemográficas, clínicas, la escala de ictus del NIH, el nivel de discapacidad, el grado de dependencia funcional mediante la escala de Rankin modificada y el consumo de recursos sanitarios (hospitalización en el primer episodio, reingresos, rehabilitación ambulatoria, material ortoprotésico, medicación para la prevención secundaria, consultas médicas, atención de enfermería, servicios sociales de atención formal). También se registrará la renta mensual estimada, la pérdida de productividad laboral y la calidad de vida relacionada con la salud con el cuestionario genérico EQ-5D. Por último se entrevistará directamente al cuidador para conocer la pérdida de productividad, los cuidados informales prestados y la sobrecarga del cuidador. Resultados y conclusiones: La aportación del estudio CONOCES permitirá profundizar en las diferencias del impacto tanto económico como clínico del ictus en función de su asociación con la FANV. Keywords: Stroke, Atrial fibrillation, Healthcare costs, Social costs, Disability, Quality of life, Palabras clave: Ictus, Fibrilación auricular, Costes sanitarios, Costes sociales, Discapacidad, Calidad de vida

Intracerebral haemorrhage accounts for 10% to 15% of all strokes, however it has a poor prognosis with higher rates of morbidity and mortality. Neurological deterioration is often observed during the first hours from onset, and determines the poor prognosis. Intracerebral haemorrhage, therefore, is a neurological emergency which must be diagnosed and treated properly as soon as possible. In this guide we review the diagnostic procedures and factors that influence the prognosis of patients with intracerebral haemorrhage and we establish recommendations for the therapeutic strategy, systematic diagnosis, acute treatment and secondary prevention for this condition. Resumen: La hemorragia intracerebral sólo representa entre el 10 y el 15% de todos los ictus, sin embargo condiciona un peor pronóstico, con unas tasas más elevadas de morbilidad y mortalidad. Es frecuente que durante las primeras horas tras el inicio de los síntomas se produzca un empeoramiento clínico, lo cual condiciona un peor pronóstico, por lo que la hemorragia intracerebral constituye una emergencia neurológica en la que debe realizarse un diagnóstico y tratamiento adecuado de manera precoz. En esta guía realizamos una revisión de los procedimientos diagnósticos y los factores que influyen en el pronóstico de los pacientes con hemorragia intracerebral y establecemos unas recomendaciones para la estrategia asistencial, sistemática diagnóstica, tratamiento en fase aguda y prevención secundaria en la hemorragia intracerebral. Keywords: Intracerebral haemorrhage, Guidelines, Stroke, Palabras clave: Hemorragia intracerebral, Guías, Ictus

Objective: To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA). Methods: We reviewed available evidence on risk factors and means of modifying them to prevent IS and TIA. Levels of evidence and recommendation grades are based on the classification of the Centre for Evidence-Based Medicine. Results: This first section summarises the recommendations for action on the following factors: blood pressure, diabetes, lipids, tobacco and alcohol consumption, diet and physical activity, cardio-embolic diseases, asymptomatic carotid stenosis, hormone replacement therapy (HRT) and contraceptives, hyperhomocysteinemia, prothrombotic states and sleep apnea syndrome. Conclusions: Changes in lifestyle and pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia, according to criteria of primary and secondary prevention, are recommended for preventing IS. Resumen: Objetivo: Actualizar las guías terapéuticas del Comité ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isquémico (II) y ataque isquémico transitorio (AIT). Métodos: Revisión de evidencias disponibles sobre los factores de riesgo y la oportunidad de su modificación para prevenir el ictus isquémico y AIT. Los niveles de evidencia y grados de recomendación se han basado en la clasificación del Centro de Medicina Basada en la Evidencia. Resultados: En esta primera parte se resumen las recomendaciones sobre la actuación sobre los siguientes factores: presión arterial, DM, lípidos plasmáticos, consumo de tabaco y alcohol, dieta y actividad física, cardiopatías embolígenas, estenosis carotídea asintomática, terapia hormonal sustitutiva y anticonceptivos, hiperhomocisteinemía, estados protrombóticos y síndrome de apnea del sueño. Conclusiones: La modificación de los estilos de vida y el tratamiento farmacológico de la hipertensión arterial, diabetes méllitus y dislipemia según criterios de prevención primaria y secundaria se recomiendan en la prevención de ictus isquémico. Keywords: Guidelines, Ischaemic stroke, Transient ischaemic attack, Prevention, Palabras clave: Guías de práctica clínica, Prevención de ictus, Ictus, Ataque isquémico transitorio

Background: PRACTIC is an observational, epidemiological, multi-centre, prospective registry of patients admitted to the emergency room with acute stroke. We aim to study the impact of admission to a specialised neurology ward, either a Stroke Unit or by a Stroke Team, on several outcomes. Methods: Ten consecutive acute stroke patients admitted to the emergency room of 88 different hospitals of all levels of care in all regions of Spain were included. Only patients who gave informed consent were studied. Oxfordshire Community Stroke Project, TOAST subtypes and modified Rankin Scale (mRS) were determined. At six months, stroke or any other vascular recurrence was recorded. Results: From a total of 864 patients, 729 (84.4%) were admitted; 555 (76.1%) in a specialised neurology ward (SNW) and 174 (23.9%) in a general medicine ward. Patients admitted in a SNW were younger and had higher rates of transient ischemic attack (TIA) or intracerebral haemorrhage (ICH). Regarding outcomes, patients admitted to an SNW had lower rate of hospital complications (35.5 vs 50.6%; P

Introduction: Epilepsy is a very common disease in Spain. There is a great lack of information on real epidemiological data and the patient impact of this disease. The objective of the Spanish Foundation for Neurological Diseases (FEEN) report is to collect epidemiological data, morbidity, mortality and costs of this disease in Spain. Development: A search was carried out in Medline on publications up to 2010, as well as a review of data published by the Spanish National Statistics Institute (INE). There are about 400,000 patients with epilepsy in Spain. Approximately 5–10% of the population will experience a seizure in their lifetime, and up to 20% of these will have recurrent seizures. Using hospital discharge report data, hospital admissions for epilepsy are around 35 patients per 100,000 patients. Mortality risk in epileptic patients is two or three times higher than in non-epileptics. The mean total annual cost of drug-resistant epilepsy patient in Spain is 6935 euros. The total cost of epilepsy according to data from the year 2000 could be around 5% of the total health budget. Conclusions: It is very important to maintain disease registers. This initiative should be encouraged by the patient associations and scientific societies. This report confirms that epilepsy has a great social and health impact on the population. Resumen: Introducción: La epilepsia es una enfermedad muy prevalente en España. Existe un gran vacío de información sobre los datos epidemiológicos reales de esta enfermedad así como la repercusión que esta enfermedad produce sobre el paciente. El objetivo de la Fundación Española de Enfermedades Neurológicas con este informe es recoger los datos epidemiológicos, de morbi-mortalidad y coste que de esta enfermedad existen en nuestro país. Desarrollo: Se ha realizado una búsqueda en Medline sobre lo publicado hasta 2010 y una revisión de los datos publicados por el Instituto Nacional de Estadística. En España hay alrededor de 400.000 pacientes con epilepsia. Aproximadamente el 5–10% de la población experimentará una crisis a lo largo de su vida y hasta un 20% de éstos tendrán crisis recurrentes. Los ingresos hospitalarios por epilepsia suponen 35 pacientes por cada 100.000 enfermos dados de alta en un hospital. Un paciente epiléptico tiene dos o tres veces más riesgo de morir que un no epiléptico. El total del coste medio de recursos anual de un paciente farmacorresistente en España es de 6.935 euros. El coste total de la epilepsia prevalente según datos del 2000 puede suponer alrededor del 5% del presupuesto total de Sanidad. Conclusiones: La epilepsia supone un gran impacto socio-sanitario en la población española. La promoción de registros sobre enfermedades y su repercusión sobre los pacientes debe ser una iniciativa que debe propulsarse desde las sociedades científicas y de pacientes. Keywords: Epilepsy, Cost, Disability, Epidemiology, Mortality, Spain, Palabras clave: Epilepsia, Coste, Discapacidad, Epidemiología, Mortalidad, España

Introduction: Stroke is currently a major social health problem. For this reason, the Spanish Ministry of Health approved the Stroke National Strategy (SNS) in 2008 to improve the prevention, treatment and rehabilitation of stroke patients. This plan intends to guarantee 24-h, 365-days neurological assistance in the whole country by the end of 2010. Our aim was to analyze the situation of stroke assistance in Spain in 2009. Material and methods: A committee of neurologists practicing in the different autonomous communities (AC), and who had not participated in the preparation of the SNS, was created. A national survey was performed including the number of stroke units (SU) and their characteristics (monitoring, 24-h/7-day on-call neurology service, nursing staff ratio and the use of protocols), bed ratio of SU/100,000 people, availability of intravenous thrombolysis therapy, neurovascular intervention (NI) and telemedicine. Results: We included data from 145 hospitals. There are 39 SUs in Spain, unevenly distributed. The ratio between SU bed/number of people/AC varied from 1/75,000 to 1/1,037,000 inhabitants; Navarra and Cantabria met the goal. Intravenous thrombolysis therapy is used in 80 hospitals; the number of treatments per AC was between 7 and 536 in 2008. NI was performed in 63% of the AC, with a total of 28 qualified hospitals (although only 1 hospital performed it 24 h, 7 days a week in 2009). There were 3 hospitals offering clinical telemedicine services. Conclusions: Assistance for stroke patients has improved in Spain compared to previous years, but there are still some important differences between the AC that must be eliminated to achieve the objectives of the SNS. Resumen: Introducción: El ictus constituye un importante problema sociosanitario. Por ese motivo, el Ministerio de Sanidad aprobó en 2008 la Estrategia Nacional en Ictus (ENI) con el objetivo de mejorar la prevención, tratamiento y rehabilitación del paciente con ictus. Se pretende garantizar una atención neurológica en todo el país y a cualquier hora del día para final del 2010. Nuestro objetivo fue analizar la situación de la atención al ictus en España en el año 2009. Material y métodos: Se constituyó un comité de neurólogos de las diferentes CC. AA. que no hubieran participado en la ENI. Se elaboró una encuesta nacional que recogió el número de unidades de ictus (UI) y la dotación (monitorización, guardia de neurología 24 h/7 días, ratio de enfermería y existencia de protocolos), ratio cama UI/100.000 habitantes, presencia de trombólisis iv, intervencionismo neurovascular (INV) y telemedicina. Resultados: Se incluyeron datos de 145 hospitales. Existen 39 UI distribuidas de un modo desigual. La relación cama de UI/número de habitantes/comunidad autónoma osciló entre 1/75.000 a 1/1.037.000 habitantes, cumpliendo el objetivo Navarra y Cantabria. Se realiza trombólisis iv en 80 hospitales, el número osciló entre 7-536 tratamientos/CC. AA. durante el año 2008. Se realiza INV en el 63% de las CC. AA., teniendo 28 centros capacitados, aunque sólo 1 la realizaba en 2009 las 24 h/7 día. Existen 3 centros con telemedicina. Conclusiones: La asistencia al ictus ha mejorado en España respecto a unos años atrás, pero todavía existen importantes desigualdades por CC. AA. que deberían superarse si se quiere cumplir el objetivo de la ENI. Keywords: Stroke, Stroke thrombolysis, Stroke unit, Facilities survey, Palabras clave: Ictus, Unidades de ictus, Trombólisis, Encuesta recursos

Introduction: The Spanish Stroke Group published the “Plan for stroke healthcare delivery” in 2006 with the aim that all stroke patients could receive the same degree of specialized healthcare according to the stage of their disease, independently of where they live, their age, gender or ethnicity. This Plan needs to be updated in order to introduce new developments in acute stroke. Material and methods: A committee of 19 neurologists specialized in neurovascular diseases representing different regions of Spain evaluated previous experience with this Plan and the available scientific evidence according to published literature. Results and conclusions: The new organized healthcare system must place emphasis on the characteristics of the different care levels with promotion of reference stroke hospitals, set up less restrictive stroke code activation criteria that include new therapeutic options, establish new standard measures for endovascular treatment and develop tele-medicine stroke networks. Resumen: Introducción: El Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología publicó en el año 2006 el Plan de Atención Sanitaria del Ictus (PASI) con el objetivo de elaborar un sistema organizado de atención al ictus que de respuesta a las necesidades de cada enfermo y optimice la utilización de los recursos sanitarios. Este plan pretendía garantizar la equidad en la atención sanitaria del paciente con ictus. La Estrategia Nacional en Ictus del Sistema Nacional de Salud aprobada en el año 2008, recogió en gran medida el tipo de modelo organizativo sanitario del PASI. Sin embargo, en el tiempo transcurrido desde su publicación, han aparecido nuevos avances en el tratamiento de la fase aguda del infarto cerebral que obligan a realizar una revisión del mismo. Fuentes: Un comité de 19 neurólogos especialistas en patología neurovascular y representativos de las diferentes comunidades autónomas han revisado el PASI con el objetivo de incorporar los nuevos avances del tratamiento en la fase aguda del infarto cerebral. Esta revisión se ha basado en una revisión de la literatura científica y en la experiencia acumulada con el plan anterior. Desarrollo: El nuevo modelo organizativo propuesto debe hacer hincapié en las características de los diferentes niveles asistenciales con la potenciación de Hospitales de Referencia, establecer nuevos criterios de activación del Código Ictus menos restrictivos que contemplen las nuevas posibilidades terapéuticas, establecer medidas organizativas para la implantación del intervencionismo neurovascular y permitir la utilización del recurso técnico de la Telemedicina. Keywords: Stroke, Stroke healthcare, Reference Stroke Hospitals, Stroke code, Interventional treatment of acute stroke, Tele-medicine, Palabras clave: Ictus, Atención sanitaria al ictus, Hospitales de Referencia, Código ictus, Intervencionismo neurovascular, Telemedicina

Background and purpose: Endovascular therapies in acute ischaemic stroke may offer benefits to patients that are not eligible for standard use of intravenous tissue activator plasminogen (iv t-PA) or when this is not effective. Our aim is to present the initial experience in with endovascular techniques in the Community of Madrid. Methods: We present data from our registry of acute ischaemic strokes treated with endovascular re-perfusion therapies in five University Hospitals in Madrid (Spain) during the period 2005–2009. We recorded demographic data, vascular risk factors, risk severity with the NIHSS (National Institute of Health Stroke Scale), endovascular techniques, complications and mortality rates. Functional outcome and neurological disability at 90 days was defined by the modified Rankin scale (mRs). Results: A total of 41 patients were treated with endovascular therapies. Mean age was 58.6 ± 19.9, and 56.1% were males. Of those 22 patients had an anterior circulation stroke and 19 had a posterior circulation stroke. Baseline NIHSS score was: median, 17 [range, 2–34]; 7 patients had previously received IV t-PA. The following endovascular techniques were performed: mechanical disruption (26 patients), intra-arterial infusion of t-PA (26 patients), angioplasty and stenting (5 patients), mechanical use of MERCI device (3 patients). Partial or total re-canalization was achieved in 32 patients (78%). Only one patient had a symptomatic cerebral haemorrhage. Three months after stroke, 53.6% of the patients were independent (mRs = 2) and overall mortality rate was 19.5%. Conclusions: Acute ischaemic stroke is a potentially treatable medical emergency within the first hours after the onset of symptoms. Stroke endovascular procedures constitute an alternative for patients with IV t-PA exclusion criteria or when this is not effective. Resumen: Introducción y objetivos: El intervencionismo neurovascular (INV) en la fase aguda del ictus isquémico es una alternativa válida en los casos en que la trombólisis intravenosa está contraindicada o cuando no ha sido efectiva. Nuestro objetivo es presentar la experiencia inicial del INV en la Comunidad de Madrid. Métodos: Registro prospectivo de ictus isquémicos tratados con INV en la Comunidad de Madrid (2005–2009). Se recogen variables epidemiológicas, factores de riesgo y gravedad del ictus mediante la NIHSS (National Institute of Health Stroke Scale). Registramos el tipo de técnica, la situación funcional a los 3 meses, mediante la escala de Rankin modificada (eRm), complicaciones hemorrágicas y mortalidad. Resultados: Se incluyó a 41 pacientes. La media±desviación estándar de edad fue 58,6 ± 19,9 años; el 56,1%, varones. Hubo 22 pacientes con ictus de circulación anterior y 19, de circulación posterior. La mediana de la puntuación NIHSS basal fue 17 [intervalo, 2–34]; 7 pacientes recibieron trombólisis intravenosa previa. Las técnicas utilizadas fueron: interrupción mecánica (26 pacientes), trombólisis intraarterial (26 pacientes), angioplastia/ stent (5 pacientes), extracción mecánica mediante dispositivo MERCI (Mechanical Embolus Removal in Cerebral Ischemia) (3 pacientes). Se consiguió una recanalización parcial o total en 32 pacientes (78%). Un paciente presentó una transformación hemorrágica sintomática (2,4%). Al cabo de 3 meses el 53,6% de los pacientes eran independientes (eRm = 2) y la mortalidad general fue del 19,5%. Conclusiones: El ictus isquémico es una emergencia médica tratable en las primeras horas. El INV es una alternativa terapéutica factible y útil en los casos de contraindicación o ineficacia de la trombólisis intravenosa. Keywords: Ischaemic stroke, Thrombolysis, Endovascular procedures, Cerebral infarction, Intra-arterial thrombolysis, Tissue plasminogen activator, Palabras clave: Ictus isquémico, Trombólisis, Intervencionismo neurovascular, Infarto cerebral, Trombólisis intraarterial, Activador del plasminógeno tisular

Introduction: The COVID-19 pandemic has resulted in complete saturation of healthcare capacities, making it necessary to reorganise healthcare systems. In this context, we must guarantee the provision of acute stroke care and optimise code stroke protocols to reduce the risk of SARS-CoV-2 infection and rationalise the use of hospital resources. The Madrid Stroke multidisciplinary group presents a series of recommendations to achieve these goals. Methods: We conducted a non-systematic literature search using the keywords “stroke” and “COVID-19” or “coronavirus” or “SARS-CoV-2.” Our literature review also included other relevant studies known to the authors. Based on this literature review, a series of consensus recommendations were established by the Madrid Stroke multidisciplinary group and its neurology committee. Results: These recommendations address 5 main objectives: (1) coordination of action protocols to ensure access to hospital care for stroke patients; (2) recognition of potentially COVID-19-positive stroke patients; (3) organisation of patient management to prevent SARS-CoV-2 infection among healthcare professionals; (4) avoidance of unnecessary neuroimaging studies and other procedures that may increase the risk of infection; and (5) safe, early discharge and follow-up to ensure bed availability. This management protocol has been called CORONA (Coordinate, Recognise, Organise, Neuroimaging, At home). Conclusions: The recommendations presented here may assist in the organisation of acute stroke care and the optimisation of healthcare resources, while ensuring the safety of healthcare professionals. Resumen: Introducción: La pandemia por COVID-19 ha obligado a una reorganización de los sistemas sanitarios y ha comportado una saturación excepcional de sus recursos. En este contexto es vital asegurar la atención al ictus agudo y optimizar los procesos asistenciales del código ictus para reducir el riesgo de contagios y racionalizar el uso de recursos hospitalarios. Para ello, desde el Grupo Multidisciplinar Ictus Madrid proponemos una serie de recomendaciones. Métodos: Revisión bibliográfica no sistemática de las publicaciones disponibles con los términos «stroke» y «COVID-19» o «coronavirus» o «SARS-CoV-2», así como otras conocidas por los autores. En base a esta se redacta un documento de recomendaciones que es sometido a consenso por el Grupo Multidisciplinar Ictus Madrid y su Comité de Neurología. Resultados: Las recomendaciones se estructuran en cinco líneas fundamentales: 1) coordinar la actuación para garantizar el acceso a la asistencia hospitalaria de los pacientes con ictus; 2) reconocer a los pacientes con ictus potencialmente infectados por COVID-19, 3) organización adecuada para garantizar la protección de los profesionales sanitarios frente al riesgo de contagio por COVID-19, 4) en la realización de neuroimagen y otros procedimientos que conlleven contactos de riesgo de infección COVID-19 hay que procurar reducirlos y asegurar la protección, y 5) alta y seguimiento seguros procurando optimizar la ocupación hospitalaria. Resumimos el procedimiento de forma esquemática con el acrónimo CORONA (COordinar, Reconocer, Organizar, Neuroimagen, Alta). Conclusiones: Estas recomendaciones pueden servir de apoyo para la organización del sistema sanitario en la atención al ictus agudo y la optimización de sus recursos, garantizando la protección de sus profesionales.

Background: Tapping speed (TS) correlates with baseline disability scales in people with multiple sclerosis (pwMS)., Objective: The study aimed to address if progression independent of relapse activity (PIRA) could be predicted by first-month measurement of TS., Methods: Prospective study including pwMS in one referral MS center. Consecutive patients were included and keys/second (Keys/s) were passively measured each day using an in-house smartphone application for 1 month. Median, mean, and maximum keys/s were obtained. Multivariate logistic regression models (including keys/s, age, sex, and baseline disability scores) were obtained for prediction of a PIRA event after 1 year., Results: Overall, 59 patients were included in the final analysis (64.4% women, median age of 44.5 years). However, 10 patients presented a PIRA event, without differences regarding baseline characteristics between PIRA and no-PIRA groups. PIRA group presented lower median keys/s (2 vs 4 keys/s, p = 0.002) and mean keys/s (2.8 vs 4.6, p = 0.008), while maximum keys/s were similar ( p = 0.32). A median ⩽ 3 keys/s was independently associated with PIRA (aOR = 16.8, p = 0.03), as did a mean ⩽ 3.7 keys/s (aOR = 17, p = 0.02). These differences were not detected regarding other variables analyzed., Conclusion: Low median or mean keys/s obtained during initial month of assessment were indicative of a PIRA event within the next year., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.L.C-G. has received honorary for speaking engagements or consulting services from Biogen, Bayer, Bial, Bristol Myers Squibb, Johnson & Johnson, Roche, and Sanofi Genzyme. R.S.A. has received honorary for speaking engagements from Johnson & Johnson. E.M. received research grants, travel support, or honoraria for speaking engagements from Biogen, Merck, Novartis, Roche, Almirall, Janssen, Bristol Myers Squibb, and Sanofi Genzyme. F.R.J. has received honorary for speaking engagements or consulting services from Bial, Biogen, Johnson & Johnson, and Sanofi Genzyme. S.S.d.l.M. received payment for lecturing or travel expenses from Merck Serono, Biogen, Sanofi Genzyme, Roche, Janssen, and Novartis. L.C-F. received speaker fees and travel support, and served on advisory boards by Biogen, Sanofi, Merck, Bayer, Novartis, Roche, Teva, Celgene, Ipsen, Biopas, and Almirall. L.M.V. received research grants, travel support, or honoraria for speaking engagements from Biogen, Merck, Novartis, Roche, Sanofi Genzyme, Celgene, and Bristol Myers Squibb. The remaining authors have no conflicts of interest to declare.

Objective: To evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage., Methods: Single-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded., Results: Fifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77-0.98, p=0.022). Larger studies are needed to validate these results., Conclusion: COVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients., Competing Interests: SS received research grants, travel support or honoraria for speaking engagements from Almirall, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. EM received research grants, travel support or honoraria for speaking engagements from Almirall, Biogen, Janssen, Merck, Novartis, Roche, and Sanofi-Genzyme. JC-G has received honorary for speaking engagements or consulting services from Biogen, Bayer, Bial, Bristol-Myers, Johnson&Johnson and Sanofi-Genzyme. FR-J has received honorary for speaking engagements or consulting services from Bial, Biogen, Johnson&Johnson and Sanofi-Genzyme. RS-A has received honorary for speaking engagements from Johnson&Johnson. LC-F received speaker fees, travel support, and/or served on advisory boards by Almirall, Bayer, Biogen, Biopas, Bristol Myers Squibb, Celgene, Ipsen, Janssen, Merck, Novartis, Roche, Sanofi and Teva. LV received research grants, travel support or honoraria for speaking engagements from Biogen, Bristol Myers Squibb, Merck, Novartis, Roche and Sanofi-Genzyme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sainz de la Maza, Rodero-Romero, Monreal, Chico-García, Villarrubia, Rodríguez-Jorge, Fernández-Velasco, Sainz-Amo, Costa-Frossard, Masjuan and Villar.)

Introduction: Alemtuzumab is a highly effective pulsed immune reconstitution therapy for multiple sclerosis (MS)., Aim: To evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS who have been treated with Alemtuzumab over the course of 2 years., Methods: This prospective study involved MS patients treated with Alemtuzumab at a referral MS center. Both sNfL and sGFAP were analyzed at baseline and then again at 6, 12, and 24 months post-treatment using the single molecule array (SiMoA) technique. We also recruited matched healthy controls (HCs) for comparison., Results: The study included 46 patients (with a median age of 34.2 [Interquartile range (IQR), 28.7-42.3] years, 27 of which were women [58%]) and 76 HCs. No differences in demographic characteristics were observed between patients and HC. The median disease duration was 6.22 (IQR, 1.56-10.13) years. The median annualized relapse rate before treatment was 2 (IQR, 1-3). At baseline, sNfL and sGFAP levels were higher in MS patients (median of 18.8 [IQR, 10.7-52.7] pg/ml and 158.9 [IQR, 126.9-255.5] pg/ml, respectively) when compared to HC (6.11 [IQR, 2.03-8.54] pg/ml and 91.0 [72.6-109] pg/ml, respectively) (p<0.001 for both comparisons). The data indicates that 80% of patients had high (≥10 pg/ml) sNfL values at baseline. We observed a significant decrease in sNfL levels at 6 (65%, p = 0.02), 12 (70.8%, p<0.001), and 24 (78.1%, p<0.001) months. sNfL reached similar levels to HC only after 24 months of Alemtuzumab treatment. During the follow-up period, no changes were identified in the sGFAP values., Conclusion: Alemtuzumab leads to the normalization of sNfL values in MS patients after 2 years of treatment, with no apparent effect on sGFAP values., Competing Interests: RS-A reported receiving research travel support from Roche and Janssen outside the submitted work. EM reported receiving research grants, travel support, or honoraria for speaking engagements from Biogen, Sanofi, Merck, Novartis, Almirall, Roche, Bristol Myers Squibb, and Janssen outside the submitted work. JF reported receiving research travel support from Roche and Janssen outside the submitted work. SM reported receiving personal fees from Almirall, Bristol Myers Squibb, and Teva outside the submitted work and receiving compensation for lectures or travel expenses from Merck Serono, Biogen, Sanofi Genzyme, Roche, Janssen, and Novartis. JC reported receiving personal fees from Sanofi outside the submitted work and receiving speaker honoraria from Biogen Idec and Sanofi. FR reported receiving personal fees from Sanofi outside the submitted work and receiving speaker honoraria from Biogen Idec and Sanofi. LF reported receiving speaker fees and travel support and/or serving on advisory boards for Biogen, Sanofi, Merck, Bayer, Novartis, Roche, Teva, Celgene, Ipsen, Biopas, Bristol Myers Squibb, Janssen, and Almirall. LV reported receiving grants and personal fees from Merck, Roche, Sanofi Genzyme, Bristol Myers Squibb, Celgene, Biogen, and Novartis outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sainz-Amo, Rodero Romero, Monreal, Chico García, Fernández Velasco, Villarrubia, Veiga González, Sainz de la Maza, Rodríguez Jorge, Masjuan, Costa-Frossard and Villar.)

The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.

Introduction: This study aimed to describe and analyze the rate of clot migration of vessel thrombosis to distal segments in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis (IVT) with tenecteplase (TNK) and alteplase (ALT) before mechanical thrombectomy (MT). In addition, we aimed to determine the relationship between thrombus migration and functional prognosis., Methods: This study followed the STROBE reporting guidelines. We performed a retrospective analysis of a series of patients from November 2017 to April 2023 with an AIS with thrombosis on CT imaging, treated with IVT (TNK or ALT, split into two distinct groups) prior to mechanical thrombectomy., Results: Two hundred and fifty-six patients with large vessel occlusion (LVO) were included. Ninety-six had received TNK. One hundred and sixty had received ALT. Of the 96 TNK patients, 25 experienced either complete recanalization ( n  = 3) or thrombus migration ( n  = 22). Of the 160 ALT patients, 20 experienced either complete recanalization ( n  = 6) or thrombus migration ( n  = 14). The difference being statistically substantial for the thrombus migration rate (OR = 3.61, 95% confidence interval: 1.63; 7.98). Migration to an irretrievable very distal segment occurred in four (4%) patients with TNK and in three patients (2%) with ALT ( p  > 0.05). Thrombus migration was not significantly associated to a different functional prognosis, measured through Rankin scale after 3 months (OR = 0.44, 95% confidence interval: 0.17; 1.12)., Conclusion: The use of TNK over ALT as a fibrinolytic agent is associated with a higher thrombus migration rate. The migration of thrombi to distal segments, which are theoretically less accessible for mechanical thrombectomy, did not result in worse clinical outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the phase 2 PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), asundexian, an oral factor XIa inhibitor, did not increase the risk of hemorrhagic transformation (HT). In this secondary analysis, we aimed to investigate the frequency, types, and risk factors of HT on brain magnetic resonance imaging (MRI)., Methods: This was a secondary analysis of the PACIFIC-STROKE trial. Patients with mild-to-moderate acute noncardioembolic ischemic stroke were randomly assigned to asundexian or placebo plus guideline-based antiplatelet therapy. Brain MRIs were required at baseline (≤120 hours after stroke onset) and at 26 weeks or end-of-study. HT was defined using the Heidelberg classification and classified as early HT (identified on baseline MRI) or late HT (new HT by 26 weeks) based on iron-sensitive sequences. Multivariable logistic regression models were used to test factors that are associated with early HT and late HT, respectively., Results: Of 1745 patients with adequate baseline brain MRI (mean age, 67 years; mean National Institutes of Health Stroke Scale score, 2.8), early HT at baseline was detected in 497 (28.4%). Most were hemorrhagic infarctions (hemorrhagic infarction type 1: 15.2%; HI2: 12.7%) while a few were parenchymal hematomas (parenchymal hematoma type 1: 0.4%; parenchymal hematoma type 2: 0.2%). Early HT was more frequent with longer symptom onset-to-MRI interval. Male sex, diabetes, higher National Institutes of Health Stroke Scale large (>15 mm) infarct size, cortical involvement by infarct, higher number of acute infarcts, presence of chronic brain infarct, cerebral microbleed, and chronic cortical superficial siderosis were independently associated with early HT in the multivariable logistic regression model. Of 1507 with follow-up MRI, HT was seen in 642 (42.6%) overall, including 361 patients (23.9%) with late HT (new HT: 306; increased grade of baseline HT: 55). Higher National Institutes of Health Stroke Scale, large infarct size, cortical involvement of infarct, and higher number of acute infarcts predicted late HT., Conclusions: About 28% of patients with noncardioembolic stroke had early HT, and 24% had late HT detectable by MRI. Given the high frequency of HT on MRI, more research is needed on how it influences treatment decisions and outcomes., Competing Interests: Disclosures Dr Caso reports consulting for Boehringer Ingelheim, a grant from Daichi Sankyo, and other funding from EVER Neuro Pharma. Dr Christensen reports being employed by the Capital Region of Denmark, and consulting for Alexion Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Daichi Sankyo, and Medtronic. Dr Connolly reports grants from AtriCure Inc and Pfizer and consulting for Bristol Myers Squibb, Daichi Sankyo, and Javelin Ventures. Dr Khatri reports grants from the National Institutes of Health; a grant from Johnson and Johnson Health Care Systems; royalties from UpToDate; consulting for Basking Biosciences, Lumosa, and Shinogi Inc; and other funding from Translational Sciences. Dr Chen reports no disclosures, or their institutions received financial support from Bayer for participation in the PACIFIC-Stroke trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke).

Introduction: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in patients with MS., Methods: Single-center prospective study in patients with MS. We passively assessed TS during first week, measured by an "in house" smartphone application. Reliability was assessed by intraclass correlation coefficient (ICC). Correlations between median and maximum keys/s of first week of assessment and baseline disability measures were explored., Results: One-hundred three patients were included: 62.1 % women, with a median (IQR) age of 47 (40.4-54.8) years-old and an EDSS score of 3.0 (2.0-4.0). Distribution by MS subtypes was: 77.7 % relapsing-remitting MS (RRMS), 17.5 % secondary-progressive MS (SPMS) and 4.9 % primary-progressive MS (PPMS). ICC during first week was 0.714 (p < 0.00001). Both median and maximum keys/s showed a negative correlation with Expanded Disability Status Score, 9-hole peg test and timed 25-foot walk and a positive correlation with Processing Speed Test CogEval® raw and Z-score. Median and maximum keys/s were lower in patients diagnosed with SPMS than in RRMS. Both measures of tapping speed were associated with MS phenotype independently of age., Conclusion: TS measured through our application is reliable and correlates with baseline disability scales., Competing Interests: Declaration of competing interest The authors report no relevant conflict of interest regarding the current study. JLCG has received honorary for speaking engagements or consulting services from Biogen, Bayer, Bial, Bristol-Myers, Johnson&Johnson and Sanofi-Genzyme. RSA has received honorary for speaking engagements from Johnson&Johnson. EM received research grants, travel support or honoraria for speaking engagements from Biogen, Merck, Novartis, Roche, Almirall, Janssen, Bristol-Myers Squibb, and Sanofi-Genzyme. FRJ has received honorary for speaking engagements or consulting services from Bial, Biogen, Johnson&Johnson and Sanofi-Genzyme. SSM received payment for lecturing or travel expenses from Merck-Serono, Biogen, Sanofi-Genzyme, Roche, Janssen, and Novartis. LMV received research grants, travel support or honoraria for speaking engagements from Biogen, Merck, Novartis, Roche, Sanofi- Genzyme, Celgene and Bristol-Myers Squib. LCF received speaker fees, travel support, and/or served on advisory boards by Biogen, Sanofi, Merck, Bayer, Novartis, Roche, Teva, Celgene, Ipsen, Biopas, Almirall. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort., Methods: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression., Results: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery., Conclusions: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation., Competing Interests: Disclosures Dr Coutinho reports grants paid to his institution from Boehringer Ingelheim and Bayer. Dr Uyttenboogaart reports grants from Hartstichting and ZonMw. Dr Werring reports grant funding from the Stroke Association and British Heart Foundation, speaking honoraria from Bayer, speaking and chairing honoraria from Alexion and NovoNordisk, and consultancy fees from Alnylam, Bayer, and NovoNordisk. Dr Aguiar de Sousa reports personal fees for AstraZeneca, Organon, and Johnson & Johnson advisory board participation, travel support from Boehringer Ingelheim, DSMB participation for the SECRET trial (University of British Columbia), and speaking fees from Bayer and Bial. Dr Ferro reports personal fees from Bayer. The other authors report no conflicts.

Background: Exploratory analysis of the phase 2 PACIFIC-Stroke (Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334-Non-Cardioembolic Stroke) randomized trial suggested that asundexian, an oral factor XIa inhibitor, prevents recurrent stroke and transient ischemic attacks in patients with atherosclerotic stroke. In this post hoc exploratory analysis, we hypothesized that asundexian would be more effective in patients enrolled with large, multiple, or cortical acute infarcts on magnetic resonance imaging than in patients enrolled with a single small subcortical acute infarct, and asundexian would prevent incident cortical covert infarcts., Methods: In this placebo-controlled double-blinded randomized controlled trial, patients with mild-to-moderate noncardioembolic ischemic stroke were assigned to asundexian (10, 20, or 50 mg once daily) or placebo, in addition to antiplatelet therapy. Brain magnetic resonance imagings were required within 72 hours of randomization and repeated at 26 weeks or at discontinuation of the study drug., Results: Of 1808 randomized patients, 1780 (98.5%) had interpretable baseline magnetic resonance imagings, of which 1628 (91.5%) had ≥1 diffusion-weighted imaging positive acute infarcts. Magnetic resonance imaging follow-up was obtained in 1439 patients, of whom 1358 had no symptomatic stroke during the trial period. Compared with placebo, asundexian 50 mg daily conferred a trend toward reduced risk of recurrent ischemic stroke or incident covert infarcts (hazard ratio, 0.71 [95% CI, 0.45-1.11]) and recurrent ischemic stroke or transient ischemic attack (secondary outcome; hazard ratio, 0.59 [95% CI, 0.33-1.06]) that was not evident in patients with single small subcortical infarcts (hazard ratios, 1.14 [95% CI, 0.62-2.10] and 0.93 [95% CI, 0.28-3.06]). Incident cortical covert infarcts were reduced in patients taking asundexian 50 mg, but the difference was not statistically significant (crude incidence ratio, 0.56 [95% CI, 0.28-1.12])., Conclusions: These exploratory, unconfirmed results suggest that asundexian may prevent new embolic infarcts but not small artery occlusion. The hypothesis that subtypes of covert brain infarcts respond differently to anticoagulant prevention should be tested in future trials., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04304508., Competing Interests: Disclosures Except for Dr Chen, all authors reported financial support from Bayer AG for participation in the PACIFIC-Stroke trial (Program of Anticoagulation via Inhibition of FXIa by the Oral Compound BAY 2433334—Non-Cardioembolic Stroke), paid either to them or their institution. Drs Mundl and Colorado are employees of Bayer AG. Dr Caso additionally reports honoraria and travel support from Boehringer Ingelheim and EVER Pharma and participated in a Data Safety Board, Steering Committee of Pacific AF and Stroke, paid to ARS Umbria. Dr Connolly additionally reports research grants and consulting fees from Boehringer Ingelheim, Bristol Myers Squibb, Sanofi Aventis, and Boston Scientific; consulting fees from Portola; and honoraria from Boehringer Ingelheim and Bristol Myers Squibb. The other authors report no conflicts.

Acute ischemic stroke constitutes a health challenge with great social impact due to its high incidence, with the social dependency that it generates being an important source of inequality. The lack of treatments serving as effective neuroprotective therapies beyond thrombolysis and thrombectomy is presented as a need. With this goal in mind, our research group's collaborative studies into cerebral ischemia and subsequent reperfusion concluded that there is a need to develop compounds with antioxidant and radical scavenger features. In this review, we summarize the path taken toward the identification of lead compounds as potential candidates for the treatment of acute ischemic stroke. Evaluations of the antioxidant capacity, neuroprotection of primary neuronal cultures and in vivo experimental models of cerebral ischemia, including neurological deficit score assessments, are conducted to characterize the biological efficacy of the various neuroprotective compounds developed. Moreover, the initial results in preclinical development, including dose-response studies, the therapeutic window, the long-term neuroprotective effect and in vivo antioxidant evaluation, are reported. The results prompt these compounds for clinical trials and are encouraging regarding new drug developments aimed at a successful therapy for ischemic stroke.

Introduction: The immunoglobulin kappa free light chain (KFLC) index has been proposed as a potentially suitable alternative to oligoclonal IgG bands (OCGB) for diagnosing multiple sclerosis (MS), offering automation and reduced processing time. However, there is no consensus on the preferred approach or how to combine both techniques., Methods: This prospective cohort study aimed to determine the best utilization of OCGB and KFLC index in patients with a clinically isolated syndrome (CIS) followed for at least two years. OCGB and KFLC were assessed using isoelectric focusing and immunoblotting and turbidimetry, respectively. Sensitivity, specificity, and accuracy for diagnosing MS were calculated for each method., Results: The study included 371 patients, with 260 (70.1 %) being women, and a median age of 34.9 (27.8 - 43.9) years. Using a cut-off value of 6.1, the KFLC index demonstrated a sensitivity and specificity of 86.3% and 93.9%, respectively. The sensitivity of OCGB (95.3%) was higher (p < 0.001 vs. KFLC index) and the specificity (100%) was comparable to that of the KFLC index (p = 0.5). The concordance between the methods was not uniform across all patients, with 97.8% agreement in patients with KFLC index ≥ 6.1 and 56.0 % in patients with KFLC index < 6.1. In patients with a KFLC index < 6.1, OCGB still identified 75.0 % of MS patients due to its higher sensitivity. An algorithm using the KFLC index as a screening tool and OCGB as an alternative for patients with a negative KFLC index result achieved an accuracy of 96.3 %., Discussion: Combining the KFLC index and OCGB can provide an easily reproducible and accurate method for diagnosing MS, with OCGB primarily reserved for patients with a KFLC index < 6.1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Monreal, Fernández-Velasco, García-Soidán, Sainz de la Maza, Espiño, Villarrubia, Rodríguez-Jorge, Chico-García, Sainz-Amo, Masjuan, Costa-Frossard and Villar.)

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated ( p -value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p -value = 2.3 × 10 -2 , se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = -0.04, p -value = 1.3 × 10 -3 , se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p -value = 3.6 × 10 -4 , se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p -value = 1.0 × 10 -2 , se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.

This single-center study included 68 multiple sclerosis (MS) patients who received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from one of several approved vaccine preparations in Spain. Blood samples were collected one to three months after the second dose of the vaccine had been administered. Cellular immune responses to the vaccine were assessed using QuantiFERON analysis, and peripheral blood mononuclear cell subsets were assayed using flow cytometry. Response associated with higher percentages of total lymphocytes, naïve CD4+ T-cells ( p = 0.028), CD8+ T-cells ( p = 0.013), and, mostly, naïve CD8+ T-cells ( p = 0.0003). These results were confirmed by analyzing absolute numbers ( p = 0.019; p = 0.002, and p = 0.0003, respectively). Naïve CD8 T-cell numbers higher than 17 cells/μL were closely associated with an optimal cellular response to SARS-CoV-2 vaccination (odds ratio: 24.0, confidence interval: 4.8-460.3; p = 0.0001). This finding clearly shows that independent of the treatment received, higher numbers of naïve CD8+ T-cells yield a strong cellular response to SARS-CoV-2 vaccines in MS patients. If this finding is validated with other viruses/vaccines, it could provide a good tool for identifying MS patients undergoing treatment who will develop strong cellular responses to anti-virus vaccines.

Introduction: Spinal cord infarction is a rare disease with a high rate of morbidity. Its diagnosis can be challenging and controversy remains regarding the best treatment. Few case series have been published., Methods: We conducted a retrospective review of cases of spinal cord infarction attended in a tertiary hospital from 1999 to 2020. Aetiology and clinical, imaging, and prognostic features were assessed., Results: Forty-one patients (58.5% men, mean [standard deviation] age 61 [17] years) were included in the study. Thirty-one patients (75.6%) presented vascular risk factors. Motor deficits were recorded in 39 (95.1%), pain in 20 (48.8%), sensory deficits in 33 (80.4%), and autonomic dysfunction in 24 (58.5%). MRI was performed in 37 (90.2%) patients. Diffusion-weighted images were available for 12 patients, with 10 showing diffusion restriction. The thoracic region was the most frequently affected (68.2%). Vascular imaging studies were performed in 33 patients (80.4%). The most frequent aetiologies were aortic dissection (6 cases), atherosclerosis demonstrated by vascular imaging (6 cases), fibrocartilaginous embolism (6 cases), surgery (5 cases), and hypotension (4 cases). Aetiology was undetermined in 12 patients (29.3%), although 9 of these presented vascular risk factors. At the end of the follow-up period (median, 24 months; interquartile range, 3-70), 12 patients (29.2%) were able to walk without assistance. Vascular risk factors and paraparesis were significantly associated with poorer prognosis (P < .05)., Discussion: Spinal cord infarction may present diverse aetiologies, with the cause remaining undetermined in many patients. Long-term functional prognosis is poor, and depends on baseline characteristics and clinical presentation. MRI, and especially diffusion-weighted sequences, is useful for early diagnosis., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Transient cerebral ischemia induces neuronal degeneration, followed in time by secondary delayed neuronal death that is strongly correlated with a permanent inhibition of protein synthesis in vulnerable brain regions, while protein translational rates are recovered in resistant areas. In the translation-regulation initiation step, the eukaryotic initiation factor (eIF) 4E is a key player regulated by its association with eIF4E-binding proteins (4E-BPs), mostly 4E-BP2 in brain tissue. In a previous work, we identified dihydropyrimidinase-related protein 2 (DRP2) as a 4E-BP2-interacting protein. Here, using a proteomic approach in a model of transient cerebral ischemia, a detailed study of DRP2 was performed in order to address the challenge of translation restoration in vulnerable regions. In this report, several DRP2 isoforms that have a specific interaction with both 4E-BP2 and eIF4E were identified, showing significant and opposite differences in this association, and being differentially detected in resistant and vulnerable regions in response to ischemia reperfusion. Our results provide the first evidence of DRP2 isoforms as potential regulators of the 4E-BP2-eIF4E association that would have consequences in the delayed neuronal death under ischemic-reperfusion stress. The new knowledge reported here identifies DRP2 as a new target to promote neuronal survival after cerebral ischemia.

Introduction: Thrombectomy in the carotid artery territory was recently shown to be effective up to 24 hours after symptoms onset., Methods: We conducted a retrospective review of a prospective registry of patients treated at our stroke reference centre between November 2016 and April 2019 in order to assess the safety and effectiveness of mechanical thrombectomy performed beyond 6 hours after symptoms onset in patients with acute ischaemic stroke and large vessel occlusion in the carotid artery territory., Results: Data were gathered from 59 patients (55.9% women; median age, 71 years). In 33 cases, stroke was detected upon awakening; 57.6% of patients were transferred from another hospital. Median baseline NIHSS score was 16, and median ASPECTS score was 8, with 94.9% of patients presenting > 50% of salvageable tissue. Satisfactory recanalisation was achieved in 88.1% of patients, beyond 24 hours after onset in 5 cases. At 90 days of follow-up, 67.8% were functionally independent; those who were not were older and presented higher prevalence of atrial fibrillation, greater puncture-to-recanalisation time, and higher NIHSS scores, both at baseline and at discharge., Conclusion: In our experience, mechanical thrombectomy beyond 6 hours was associated with good 90-day functional outcomes. Age, NIHSS score, puncture-to-recanalisation time, and presence of atrial fibrillation affected functional prognosis. The efficacy of the treatment beyond 24 hours after onset merits study., (Copyright © 2021. Published by Elsevier España, S.L.U.)

Background: This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs)., Methods: Single-center observational longitudinal study including 102 patients with MS who consecutively received vaccination against SARS-CoV-2. Serum samples were collected at baseline and after receiving the second dose of the vaccine. Specific Th1 responses following in vitro stimulation with spike and nucleocapsid peptides were analyzed by quantifying levels of IFN-γ. Serum IgG-type antibodies against the spike region of SARS-CoV-2 were studied by chemiluminescent microparticle immunoassay., Results: Patients undergoing fingolimod and anti-CD20 therapies had a markedly lower humoral response than those treated with other DMTs and untreated patients. Robust antigen-specific T-cell responses were detected in all patients except those treated with fingolimod, who had lower IFN-γ levels than those treated with other DMTs (25.8 pg/mL vs. 868.7 pg/mL, p = 0.011). At mid-term follow-up, a decrease in vaccine-induced anti-SARS-CoV-2 IgG antibodies was observed in all subgroups of patients receiving DMTs, although most patients receiving induction DMTs or natalizumab and non-treated patients remained protected. Cellular immunity was maintained above protective levels in all DMT subgroups except the fingolimod subgroup., Conclusions: SARS-CoV-2 vaccines induce robust and long-lasting humoral and cell-mediated specific immune responses in most patients with MS.

Importance: The value of serum neurofilament light chain (sNfL) levels for predicting long-term disability in patients with multiple sclerosis (MS) remains controversial., Objective: To assess whether high sNfL values are associated with disability worsening in patients who underwent their first demyelinating MS event., Design, Setting, and Participants: This multicenter cohort study included patients who underwent their first demyelinating event suggestive of MS at Hospital Universitario Ramón y Cajal (development cohort; June 1, 1994, to September 31, 2021, with follow-up until August 31, 2022) and 8 Spanish hospitals (validation cohort; October 1, 1995, to August 4, 2020, with follow-up until August 16, 2022)., Exposures: Clinical evaluations at least every 6 months., Main Outcomes and Measures: The main outcomes were 6-month confirmed disability worsening (CDW) and an Expanded Disability Status Scale (EDSS) score of 3. Levels of sNfL were measured in blood samples obtained within 12 months after disease onset using a single molecule array kit. The cutoffs used were sNfL level of 10 pg/mL and a standardized score (z score) of 1.5. Multivariable Cox proportional hazards regression models were used to evaluate outcomes., Results: Of the 578 patients included in the study, 327 were in the development cohort (median age at sNfL analysis, 34.1 years [IQR, 27.2-42.7 years]; 226 female [69.1%]) and 251 patients were in the validation cohort (median age at sNfL analysis, 33.3 years [IQR, 27.4-41.5 years]; 184 female [73.3%]). The median follow-up was 7.10 years (IQR, 4.18-10.0 years). Levels of sNfL greater than 10 pg/mL were independently associated with higher risk of 6-month CDW and an EDSS of 3 in the development cohort (6-month CDW: hazard ratio [HR], 2.39; 95% CI, 1.39-4.12; P = .002; EDSS of 3: HR, 4.12; 95% CI, 2.18-7.77; P < .001) and the validation cohort (6-month CDW: HR, 1.61; 95% CI, 1.07-2.42; P = .02; EDSS of 3: HR, 2.03; 95% CI, 1.23-3.33; P = .005). Highly effective disease-modifying treatments were associated with lower risks of 6-month CDW and an EDSS of 3 in patients with high baseline sNfL values., Conclusions and Relevance: This cohort study found that high sNfL values obtained within the first year of disease were associated with long-term disability worsening in MS, suggesting that sNfL level measurement may help identify optimal candidates for highly effective disease-modifying treatments.

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes.

Background: Assessing bleeding risk during the decision-making process of starting oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients is essential. Several bleeding risk scores have been proposed for vitamin K antagonist users but, few studies have focused on validation of these bleeding risk scores in patients taking direct oral anticoagulants (DOACs). The aim was to compare the predictive ability of HAS-BLED and ORBIT bleeding risk scores in AF patients taking rivaroxaban in the EMIR ('Estudio observacional para la identificación de los factores de riesgo asociados a eventos cardiovasculares mayores en pacientes con fibrilación auricular no valvular tratados con un anticoagulante oral directo [Rivaroxaban]) Study., Methods and Results: EMIR Study was an observational, multicenter, post-authorization, and prospective study that involved AF patients under OAC with rivaroxaban at least 6 months before enrolment. We analysed baseline clinical characteristics and adverse events after 2.5 years of follow-up and validated the predictive ability of HAS-BLED and ORBIT scores for major bleeding (MB) events.We analysed 1433 patients with mean age of 74.2 ± 9.7 (44.5% female). Mean HAS-BLED score was 1.6 ± 1.0 and ORBIT score was 1.1 ± 1.2. The ORBIT score categorised a higher proportion of patients as 'low-risk' (87.1%) compared with 53.5% using the HAS-BLED score. There were 33 MB events (1.04%/year) and 87 patients died (2.73%/year). Both HAS-BLED and ORBIT had a good predictive ability for MB{Area under the curve (AUC) 0.770, [95% confidence interval (CI) 0.693-0.847; P <0.001] and AUC 0.765 (95% CI 0.672-0.858; P <0.001), respectively}. There was a non-significant difference for discriminative ability of the two tested scores (P = 0.930) and risk reclassification in terms of net reclassification improvement (NRI) -5.7 (95% CI -42.4-31.1; P = 0.762). HAS-BLED score showed the best calibration and ORBIT score showed the largest mismatch in calibration, particularly in higher predicted risk patients., Conclusion: In a prospective real-world AF population under rivaroxaban from EMIR registry, the HAS-BLED score had good predictive performance and calibration compared with ORBIT score for MB events. ORBIT score presented worse calibration than HAS-BLED in this DOAC treated population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)