Dislipidemias y prevención del ictus: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología

Practice guideline[Abstract] Objective: We present an update of the Spanish Society of Neurology's recommendations for prevention of both primary and secondary stroke in patients with dyslipidaemia. Development: We performed a systematic review to evaluate the main aspects of the management of dyslipidaemias in primary and secondary stroke prevention and establish a series of recommendations. Conclusions: In primary prevention, the patient's vascular risk should be determined in order to define target values for low-density lipoprotein cholesterol. In secondary prevention after an atherothrombotic stroke, a target value <55 mg/dL is recommended; in non-atherothombotic ischaemic strokes, given the unclear relationship with dyslipidaemia, target value should be established according to the vascular risk group of each patient. In both primary and secondary prevention, statins are the drugs of first choice, and ezetimibe and/or PCSK9 inhibitors may be added in patients not achieving the target value.[Resumen] Objetivo. Actualizar las recomendaciones de la Sociedad Española de Neurología para la prevención del ictus, tanto primaria como secundaria en pacientes con dislipidemia. Desarrollo. Se ha realizado una revisión sistemática en Pubmed evaluando los principales aspectos relacionados con el manejo de las dislipidemias en la prevención primaria y secundaria del ictus, elaborándose una serie de recomendaciones relacionadas con los mismos. Conclusiones. En prevención primaria se recomienda determinar el riesgo vascular del paciente con el fin de definir los objetivos de LDLc. En prevención secundaria tras un ictus de origen aterotrombótico se recomienda un objetivo de LDLc < 55 mg/dl, mientras que en ictus isquémicos de origen no aterotrombótico dado que su relación con dislipidemias es incierta se establecerán los objetivos en base al grupo de riesgo vascular de cada paciente. Tanto en prevención primaria como secundaria las estatinas son los fármacos de primera elección, pudiendo asociarse ezetimiba y/o inhibidores de PCSK9 en aquellos casos que no alcancen los objetivos terapéuticos

Recomendaciones de la Sociedad Española de Neurología para la prevención del ictus: actuación sobre los hábitos de vida y la contaminación atmosférica

Practice guideline[Abstract] Objective: To update the recommendations of the Spanish Society of Neurology regarding lifestyle interventions for stroke prevention. Development: We reviewed the most recent studies related to lifestyle and stroke risk, including randomised clinical trials, population studies, and meta-analyses. The risk of stroke associated with such lifestyle habits as smoking, alcohol consumption, stress, diet, obesity, and sedentary lifestyles was analysed, and the potential benefits for stroke prevention of modifying these habits were reviewed. We also reviewed stroke risk associated with exposure to air pollution. Based on the results obtained, we drafted recommendations addressing each of the lifestyle habits analysed. Conclusions: Lifestyle modification constitutes a cornerstone in the primary and secondary prevention of stroke. Abstinence or cessation of smoking, cessation of excessive alcohol consumption, avoidance of exposure to chronic stress, avoidance of overweight or obesity, a Mediterranean diet supplemented with olive oil and nuts, and regular exercise are essential measures in reducing the risk of stroke. We also recommend implementing policies to reduce air pollution.[Resumen] Objetivo. Actualizar las recomendaciones de la Sociedad Española de Neurología relativas a la actuación sobre los hábitos de vida para la prevención del ictus. Desarrollo.Se ha realizado una revisión de los estudios más recientes relacionados con los hábitos de vida y el riesgo de ictus, incluyendo ensayos clínicos aleatorizados, estudios poblacionales y meta-análisis. Se ha analizado el riesgo de ictus asociado con determinados hábitos de vida como el tabaquismo, el consumo de alcohol, el estrés, la dieta, la obesidad y el sedentarismo, y se ha revisado el potencial beneficio que la modificación de esos hábitos de vida puede aportar en la prevención del ictus. Asimismo, se ha revisado el riesgo de ictus asociado a la exposición a la contaminación atmosférica. A partir de los resultados obtenidos se han redactado unas recomendaciones sobre cada uno de los hábitos de vida analizados. Conclusiones. La actuación sobre los hábitos de vida constituye una piedra angular en la prevención primaria y secundaria del ictus. La abstinencia o cese del hábito tabáquico, el cese del consumo excesivo de alcohol, evitar la exposición a estrés crónico, evitar el sobrepeso o la obesidad, seguir una dieta mediterránea suplementada con aceite de oliva y frutos secos, y la práctica regular de actividad física son medidas fundamentales para reducir el riesgo de sufrir un ictus. Además, se aconseja desarrollar políticas encaminadas a disminuir la contaminación atmosférica

Stroke prevention in patients with type 2 diabetes or prediabetes: recommendations from the Cerebrovascular Diseases Study Group, Spanish Society of Neurology

Review[Resumen] Objetivo. Actualizar las recomendaciones de la Sociedad Española de Neurología para la prevención del ictus en pacientes con DM-2 o prediabetes, analizando las evidencias disponibles sobre el efecto del control metabólico y el posible beneficio de los antidiabéticos con beneficio vascular añadidos al tratamiento antidiabético estándar en la prevención de ictus. Desarrollo. Se han elaborado preguntas tipo PICO (Patient, Intervention, Comparison, Outcome) para identificar cuestiones prácticas para el manejo de pacientes con ictus y poder realizar recomendaciones específicas en cada una de ellas. Posteriormente se han realizado revisiones sistemáticas en Pubmed y se han seleccionado los ensayos clínicos aleatorizados que han evaluado ictus como variable independiente (principal o secundaria). Finalmente se ha elaborado metaanálisis para cada una de las preguntas PICO y se han redactado unas recomendaciones en respuesta a cada una de ellas. Conclusiones. Aunque no hay evidencia de que un mejor control metabólico reduzca el riesgo de ictus, algunas familias de antidiabéticos con beneficio vascular han mostrado reducción en el riesgo de ictus cuando se añaden al tratamiento convencional, tanto en el ámbito de prevención primaria en pacientes con DM-2 de alto riesgo vascular o con enfermedad vascular aterosclerosa establecida (agonistas GLP-1) como en prevención secundaria de ictus en pacientes con DM-2 y prediabetes (pioglitazona).[Abstract] Objective: To update the Spanish Society of Neurology's guidelines for stroke prevention in patients with type 2 diabetes or prediabetes, analysing the available evidence on the effect of metabolic control and the potential benefit of antidiabetic drugs with known vascular benefits in addition to conventional antidiabetic treatments in stroke prevention. Development: PICO-type questions (Patient, Intervention, Comparison, Outcome) were developed to identify practical issues in the management of stroke patients and to establish specific recommendations for each of them. Subsequently, we conducted systematic reviews of the PubMed database and selected those randomised clinical trials evaluating stroke as an independent variable (primary or secondary). Finally, for each of the PICO questions we developed a meta-analysis to support the final recommendations. Conclusions: While there is no evidence that metabolic control reduces the risk of stroke, some families of antidiabetic drugs with vascular benefits have been shown to reduce these effects when added to conventional treatments, both in the field of primary prevention in patients presenting type 2 diabetes and high vascular risk or established atherosclerosis (GLP-1 agonists) and in secondary stroke prevention in patients with type 2 diabetes or prediabetes (pioglitazone)

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry

Background and Purpose In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score 85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score 3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). Results Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). Conclusions Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors

Identificación de la presencia de antígenos neurales en el tejido linfoide de los pacientes con ictus y análisis de su eventual implicación patogénica en la respuesta inmune adaptativa tras el daño cerebral

Peer Reviewe

Identificación de la presencia de antígenos neurales en el tejido linfoide de los pacientes con ictus y análisis de su eventual implicación patogénica en la respuesta inmune adaptativa tras el daño cerebral

INTRODUCCION: En condiciones fisiológicas existe un drenaje de solutos y células del sistema inmune desde el sistema nervioso central hacia el tejido linfoide secundario, pudiendo desarrollarse una respuesta inmune de tipo adaptativo frente a dichos antígenos. Ciertas moléculas coadyuvantes como heat shock protein 70(Hsp-70) pueden facilitar y modular los procesos de presentación antigénica y la propia respuesta inmune. Hsp-70 es producida en gran cantidad durante la isquemia cerebral. En los pacientes con ictus isquémico podría haber una mayor llegada de antígenos cerebrales y moléculas coadyuvantes al tejido linfoide secundario que en sujetos controles y de este modo favorecerse respuestas inmunes que influyan en la evolución y pronóstico del ictus. MÉTODOS: Estudio de tejido linfoide en pacientes con ictus agudo mediante toma de biopsias de amígdala palatina y análisis de muestras de sangre, así como en sujetos control. Así mismo, toma de muestras de amígdala palatina y ganglio linfático cervical en necropsias de pacientes con ictus y necropsias control. Se estudiaron las diferentes subpoblaciones linfocitarias, marcadores de activación linfocitaria, presencia de antígenos cerebrales y la proteína Hsp-70, y estructura del tejido linfoide mediante técnicas de citometría de flujo, inmunofluorescencia y western blot, realizándose un análisis cuantitativo. Se analizó la síntesis local tanto de antígenos como Hsp-70 mediante técnica de PCR. RESULTADOS: No se observaron diferencias ni en la estructura del tejido linfoide ni en las diferentes subpoblaciones linfocitarias entre pacientes y controles. Los antígenos cerebrales y Hsp-70 se encontraron en mayor cantidad en pacientes con ictus. Ambos estaban localizados en células presentadoras de antígenos con capacidad para activar el sistema inmune. Dichas células portadoras de antígenos cerebrales se encuentran preferentemente localizadas próximas a la trama fibroreticular del tejido linfoide y podían llevar a cabo algún grado de activación linfocitaria. Los pacientes que presentaban mas antígenos neurales presentaban mejor pronostico, mientras que aquellos con mayor presencia de antígenos mielínicos tenían un mayor volumen de infarto y peor pronóstico. CONCLUSIONES: En los pacientes con ictus isquémico se observa un incremento de antígenos cerebrales en el tejido linfoide secundario. La respuesta inmune frente a ellos puede influir en la evolución y pronóstico de la enfermedad.INTRODUCTION: Under physiological conditions solutes and immune system cells drain from the central nervous system to the secondary lymphoid tissue. An immune response against these antigens can be developed. Certain adjuvant molecules as heat shock protein 70 (HSP -70) can facilitate and modulate the process of antigen presentation and the immune responses. Hsp -70 is produced in large quantities during cerebral ischemia . In patients with ischemic stroke there could be a increased arrival of brain antigens and adjuvant molecules to the secondary lymphoid tissue and this could favor the development of immune responses that could have a role in the evolution and prognosis of stroke. METHODS: We performed a biopsy of palatine tonsil to acute stroke patients and control subjects. We also obtained samples of palatine tonsil and cervical lymph node from necropsies of patients with stroke and controls. Different lymphocyte subsets, lymphocyte activation markers, presence of brain antigens and Hsp -70 protein, and lymphoid tissue structure were studied by flow cytometry, immunofluorescence and western blot techniques. RESULTS: No differences were observed in either the structure of lymphoid tissue or in different lymphocyte subpopulations between patients and controls. Brain antigens and Hsp -70 were increased in the lymphoid tissue of patients with stroke. Both were located on antigen-presenting cells with ability to activate the immune system. These antigen-presenting cells carrying brain antigens were preferably located near the fibroreticular mesh of the lymphoid tissue and performed some degree of lymphocyte activation. Patients who had more neural antigens showed better prognosis, whereas those with greater presence of myelinated antigens had an increased infarct volume and worse prognosis. CONCLUSIONS: We observed that brain antigens were increased in the secondary lymphoid tissue of stroke patients . The development of an immune response against them could influence the evolution and prognosis of the disease

Identificación de la presencia de antígenos neurales en el tejido linfoide de los pacientes con ictus y análisis de su eventual implicación patogénica en la respuesta inmune adaptativa tras el daño cerebral

[spa] INTRODUCCION: En condiciones fisiológicas existe un drenaje de solutos y células del sistema inmune desde el sistema nervioso central hacia el tejido linfoide secundario, pudiendo desarrollarse una respuesta inmune de tipo adaptativo frente a dichos antígenos. Ciertas moléculas coadyuvantes como heat shock protein 70(Hsp-70) pueden facilitar y modular los procesos de presentación antigénica y la propia respuesta inmune. Hsp-70 es producida en gran cantidad durante la isquemia cerebral. En los pacientes con ictus isquémico podría haber una mayor llegada de antígenos cerebrales y moléculas coadyuvantes al tejido linfoide secundario que en sujetos controles y de este modo favorecerse respuestas inmunes que influyan en la evolución y pronóstico del ictus. MÉTODOS: Estudio de tejido linfoide en pacientes con ictus agudo mediante toma de biopsias de amígdala palatina y análisis de muestras de sangre, así como en sujetos control. Así mismo, toma de muestras de amígdala palatina y ganglio linfático cervical en necropsias de pacientes con ictus y necropsias control. Se estudiaron las diferentes subpoblaciones linfocitarias, marcadores de activación linfocitaria, presencia de antígenos cerebrales y la proteína Hsp-70, y estructura del tejido linfoide mediante técnicas de citometría de flujo, inmunofluorescencia y western blot, realizándose un análisis cuantitativo. Se analizó la síntesis local tanto de antígenos como Hsp-70 mediante técnica de PCR. RESULTADOS: No se observaron diferencias ni en la estructura del tejido linfoide ni en las diferentes subpoblaciones linfocitarias entre pacientes y controles. Los antígenos cerebrales y Hsp-70 se encontraron en mayor cantidad en pacientes con ictus. Ambos estaban localizados en células presentadoras de antígenos con capacidad para activar el sistema inmune. Dichas células portadoras de antígenos cerebrales se encuentran preferentemente localizadas próximas a la trama fibroreticular del tejido linfoide y podían llevar a cabo algún grado de activación linfocitaria. Los pacientes que presentaban mas antígenos neurales presentaban mejor pronostico, mientras que aquellos con mayor presencia de antígenos mielínicos tenían un mayor volumen de infarto y peor pronóstico. CONCLUSIONES: En los pacientes con ictus isquémico se observa un incremento de antígenos cerebrales en el tejido linfoide secundario. La respuesta inmune frente a ellos puede influir en la evolución y pronóstico de la enfermedad.[eng] INTRODUCTION: Under physiological conditions solutes and immune system cells drain from the central nervous system to the secondary lymphoid tissue. An immune response against these antigens can be developed. Certain adjuvant molecules as heat shock protein 70 (HSP -70) can facilitate and modulate the process of antigen presentation and the immune responses. Hsp -70 is produced in large quantities during cerebral ischemia . In patients with ischemic stroke there could be a increased arrival of brain antigens and adjuvant molecules to the secondary lymphoid tissue and this could favor the development of immune responses that could have a role in the evolution and prognosis of stroke. METHODS: We performed a biopsy of palatine tonsil to acute stroke patients and control subjects. We also obtained samples of palatine tonsil and cervical lymph node from necropsies of patients with stroke and controls. Different lymphocyte subsets, lymphocyte activation markers, presence of brain antigens and Hsp -70 protein, and lymphoid tissue structure were studied by flow cytometry, immunofluorescence and western blot techniques. RESULTS: No differences were observed in either the structure of lymphoid tissue or in different lymphocyte subpopulations between patients and controls. Brain antigens and Hsp -70 were increased in the lymphoid tissue of patients with stroke. Both were located on antigen-presenting cells with ability to activate the immune system. These antigen-presenting cells carrying brain antigens were preferably located near the fibroreticular mesh of the lymphoid tissue and performed some degree of lymphocyte activation. Patients who had more neural antigens showed better prognosis, whereas those with greater presence of myelinated antigens had an increased infarct volume and worse prognosis. CONCLUSIONS: We observed that brain antigens were increased in the secondary lymphoid tissue of stroke patients . The development of an immune response against them could influence the evolution and prognosis of the disease

Presence of heat shock protein 70 in secondary lymphoid tissue correlates with stroke prognosis

Heat shock protein 70 (Hsp-70) can act as a danger signal and activate immune responses. We studied the presence of Hsp-70 in lymphoid tissue and plasma of acute stroke patients and asymptomatic controls free of neurological disease. Immunofluorescence, Western blotting, qRT-PCR and flow cytometry studies were performed. Plasma Hsp-70 concentration at day 7 was similar in patients and controls, whereas patients disclosed stronger immunoreactivity to Hsp-70 in lymphoid tissue than controls. Most Hsp-70. + cells were antigen presenting cells located in T cell zones. Stronger immunoreactivity to Hsp-70 was associated with smaller infarctions and better functional outcome. © 2014 Elsevier B.V.This work was supported by grants from the ‘Instituto de Salud Carlos III’ (ISCIII) (PI09/1313), the Spanish Ministry of Science and Innovation (SAF2011-30492), the ERANET-NEURON project (PRI-PIMNEU-2011-1342) of the European Community, and a donation by the Doctor Melchor Colet Foundation. We are indebted to IDIBAPS Biobank, Xarxa de Bancs de Tumors de Catalunya (XBTC) financed by ‘Pla Director d’Oncologia de Catalunya’ and Red Nacional de Biobancos (RNBB, ReTBioH) financed by ISCIII (RETIC RD09-0076/0038)Peer Reviewe

Monocyte subtypes predict clinical course and prognosis in human stroke

et al.The number of circulating monocytes increases after stroke. In this study, we assessed the time course and phenotype of monocyte subsets and their relationship with the clinical course and outcome in 46 consecutive stroke patients and 13 age-matched controls. The proportion of the most abundant ‘classical’ CD14highCD16− monocytes did not change after stroke, whereas that of CD14highCD16+ monocytes increased and CD14dimCD16+ monocytes decreased. CD14highCD16+ monocytes had the highest expression of TLR2, HLA-DR and the angiogenic marker, Tie-2; CD14dimCD16+ monocytes had the highest expression of costimulatory CD86 and adhesion molecule CD49d. Platelet–monocyte interactions were highest in CD14highCD16− monocytes and lowest in CD14dimCD16+ monocytes. In adjusted models, 1/CD14highCD16− monocytes were associated with poor outcome (OR: 1.38), higher mortality (OR: 1.40) and early clinical worsening (OR: 1.29); 2/CD14highCD16+ monocytes were inversely related to mortality (OR: 0.32); and 3/CD14dimCD16+ monocytes were inversely related to poor outcome (OR: 0.74) and infarction size (r=−0.45; P=0.02). These results illustrate that the predominant monocyte subtype conveys harmful effects after stroke, which include stronger interaction with platelets. Alternatively, rarer subpopulations of monocytes are beneficial with a phenotype that could promote tissue repair and angiogenesis. Therefore, monitoring of monocyte subtypes may emerge as a useful tool at the bedside for stroke patients.Peer reviewe