Dyslipidemias and stroke prevention: Recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology.

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.

Dislipidemias y prevención del ictus: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología / Dyslipidemias and stroke prevention: recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology

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 función del 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. (AU)

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. (AU)

Recommendations of the Spanish Society of Neurology for the prevention of stroke. Interventions on lifestyle and air pollution.

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.

Prevención de ictus en pacientes con hipertensión arterial: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología / Stroke prevention in patients with arterial hypertension: Recommendations of the Spanish Society of Neurology's Stroke Study Group

Objetivo: Actualizar las recomendaciones de la Sociedad Española de Neurología para la prevención de ictus, tanto primaria como secundaria, en pacientes con hipertensión arterial.DesarrolloSe han planteado diferentes preguntas para identificar cuestiones prácticas para el manejo de la presión arterial (PA) en prevención de ictus, analizando cuál debe ser el objetivo de control de la presión arterial y cuáles son los fármacos más adecuados en prevención primaria, cuándo iniciar el tratamiento antihipertensivo después de un ictus, cuáles son las cifras que debemos alcanzar y qué fármacos son los más adecuados en prevención secundaria de ictus. Se ha realizado una revisión sistemática en Pubmed analizando los principales ensayos clínicos para dar respuesta a estas preguntas y se han elaborado unas recomendaciones.ConclusionesEn prevención primaria se recomienda iniciar tratamiento antihipertensivo con cifras de PA > 140/90 mmHg, con un objetivo de control de PA < 130/80 mmHg. En prevención secundaria de ictus se recomienda iniciar tratamiento antihipertensivo pasada la fase aguda (primeras 24 h) con un objetivo de control de PA < 130/80 mmHg, siendo preferible el empleo de ARA-II o diuréticos solos o en combinación con IECA. (AU)

Objective: To update the recommendations of the Spanish Society of Neurology on primary and secondary stroke prevention in patients with arterial hypertension.DevelopmentWe proposed several questions to identify practical issues for the management of blood pressure (BP) in stroke prevention, analysing the objectives of blood pressure control, which drugs are most appropriate in primary prevention, when antihypertensive treatment should be started after a stroke, what levels we should aim to achieve, and which drugs are most appropriate in secondary stroke prevention. We conducted a systematic review of the PubMed database and analysed the main clinical trials to address these questions and establish a series of recommendations.ConclusionsIn primary stroke prevention, antihypertensive treatment should be started in patients with BP levels > 140/90 mmHg, with a target BP of < 130/80 mmHg. In secondary stroke prevention, we recommend starting antihypertensive treatment after the acute phase (first 24 hours), with a target BP of < 130/80 mmHg. The use of angiotensin-II receptor antagonists or diuretics alone or in combination with angiotensin-converting enzyme inhibitors is preferable. (AU)

Stroke prevention in patients with arterial hypertension: Recommendations of the Spanish Society of Neurology's Stroke Study Group.

OBJECTIVE: To update the recommendations of the Spanish Society of Neurology on primary and secondary stroke prevention in patients with arterial hypertension. DEVELOPMENT: We proposed several questions to identify practical issues for the management of blood pressure (BP) in stroke prevention, analysing the objectives of blood pressure control, which drugs are most appropriate in primary prevention, when antihypertensive treatment should be started after a stroke, what levels we should aim to achieve, and which drugs are most appropriate in secondary stroke prevention. We conducted a systematic review of the PubMed database and analysed the main clinical trials to address these questions and establish a series of recommendations. CONCLUSIONS: In primary stroke prevention, antihypertensive treatment should be started in patients with BP levels >  140/90 mmHg, with a target BP of < 130/80 mmHg. In secondary stroke prevention, we recommend starting antihypertensive treatment after the acute phase (first 24 hours), with a target BP of < 130/80 mmHg. The use of angiotensin-II receptor antagonists or diuretics alone or in combination with angiotensin-converting enzyme inhibitors is preferable.

Recomendaciones de la Sociedad Española de Neurología para la prevención del ictus. Actuación sobre los hábitos de vida y la contaminación atmosférica / Recommendations of the Spanish Society of Neurology for the prevention of stroke. Interventions on lifestyle and air pollution

Objetivo: Actualizar las recomendaciones de la Sociedad Española de Neurología relativas a la actuación sobre los hábitos de vida para la prevención del ictus.DesarrolloSe 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 metaanálisis. 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, también 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.ConclusionesLa 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, así como 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. (AU)

Objective: To update the recommendations of the Spanish Society of Neurology regarding lifestyle interventions for stroke prevention.DevelopmentWe 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.ConclusionsLifestyle 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. (AU)

Prevención de ictus en pacientes con diabetes mellitus tipo 2 o prediabetes. Recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología / Stroke prevention in patients with type 2 diabetes or prediabetes. Recommendations from the Cerebrovascular Diseases Study Group, Spanish Society of Neurology

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.DesarrolloSe 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.ConclusionesAunque 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). (AU)

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.DevelopmentPICO-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.ConclusionsWhile 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). (AU)

Use of cardiovascular polypills for the secondary prevention of cerebrovascular disease. / Uso de la polipíldora cardiovascular en la prevención secundaria de la enfermedad cerebrovascular.

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.

B-type natriuretic peptide over N-terminal pro-brain natriuretic peptide to predict incident atrial fibrillation after cryptogenic stroke.

BACKGROUND AND PURPOSE: B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT-proBNP. The aim was to determine and directly compare the validity of the two biomarkers as a tool to predict AF and guide prolonged cardiac monitoring in cryptogenic stroke patients. METHODS: Non-lacunar acute ischaemic stroke (<72 h) patients over 55 years of age with cryptogenic stroke after standard evaluation were included in the Crypto-AF study and blood was collected. BNP and NT-proBNP levels were determined by automated immunoassays. AF was assessed by 28 days' monitoring. Highest (optimizing specificity) and lowest (optimizing sensitivity) quartiles were used as biomarker cut-offs to build predictive models adjusted by sex and age. The integrated discrimination improvement index (IDI) and DeLong test were used to compare the performance of the two biomarkers. RESULTS: From 320 patients evaluated, 218 were included in the analysis. AF was detected in 50 patients (22.9%). NT-proBNP (P < 0.001) and BNP (P < 0.001) levels were higher in subjects with AF and their levels correlated (r = 0.495, P < 0.001). BNP showed an increased area under the curve (0.720 vs. 0.669; P = 0.0218) and a better predictive capacity (IDI = 3.63%, 95% confidence interval 1.36%-5.91%) compared to NT-proBNP. BNP performed better than NT-proBNP in a specific model (IDI = 3.7%, 95% confidence interval 0.87%-6.5%), whilst both biomarkers performed similarly in the case of a sensitive model. CONCLUSIONS: Both BNP and NT-proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT-proBNP, especially in terms of specificity.

Stroke prevention in patients with type 2 diabetes or prediabetes. Recommendations from the Cerebrovascular Diseases Study Group, Spanish Society of Neurology. / Prevención de ictus en pacientes con diabetes mellitus tipo 2 o prediabetes. Recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología.

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).

Dyslipidemias and stroke prevention: recommendations of the Study Group of Cerebrovascular Diseases of the Spanish Society of Neurology. / Dislipidemias y prevención del ictus: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología.

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 <55mg/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.

The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study: Subclinical cervico-cerebral stenosis and middle cerebral artery pulsatility index as predictors of long-term incident cognitive impairment.

BACKGROUND AND AIMS: We aimed to study subclinical non-invasive vascular markers as predictors of incident long-term cognitive impairment in a longitudinal population-based study. METHODS: The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study is a population-based study that included a random sample of 933 Caucasian subjects (mean age 66 years, 64% male) with a moderate-high vascular risk and without history of stroke or dementia. Subclinical carotid and intracranial stenosis was assessed at baseline visit by cervical and transcranial color-coded duplex (TCCD) and confirmed by magnetic resonance angiography. Cervico-cerebral stenosis (CCS) was defined as the presence of extra and/or intracranial stenosis >50%. Baseline middle cerebral artery pulsatility index (MCA-PI) was measured bilaterally by TCCD, and mean PI of both sides was considered for analyses. Subjects were followed-up to determine incident long-term cognitive impairment (mild cognitive impairment or dementia). RESULTS: After a median of 7.16 [6.91-7.75] years of follow-up, 91 subjects (9.7%) developed cognitive impairment, 27 of them mild cognitive impairment, and 64 dementia. Incidence of cognitive impairment was significantly higher among subjects with subclinical CCS (21.4% versus 9% in those without CCS) and among those with mean MCA-PI>1 (13.5% versus 7.4% in those with MCA-PI<1). In multivariate Cox regression analyses, both CCS and MCA-PI>1 were independently associated with incident cognitive impairment with HR of 2.07 [1.11-3.88] and 1.58 [1.02-2.46], respectively. CONCLUSIONS: Subclinical cervico-cerebral stenosis and higher MCA-PI are non-invasive neurosonological markers of incident long-term cognitive impairment in our population.

Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

Large vessel occlusion is independently associated with atrial fibrillation detection.

BACKGROUND AND PURPOSE: Covert paroxysmal atrial fibrillation (pAF) is the most frequent cause of cardiac embolism. Our goal was to discover parameters associated with early pAF detection with intensive cardiac monitoring. METHOD: Crypto-AF was a multicentre prospective study (four Comprehensive Stroke Centres) to detect pAF in non-lacunar cryptogenic stroke continuously monitored within the first 28 days. Stroke severity, infarct pattern, large vessel occlusion (LVO) at baseline, electrocardiography analysis, supraventricular extrasystolia in the Holter examination, left atrial volume index and brain natriuretic peptide level were assessed. The percentage of pAF detection and pAF episodes lasting more than 5 h were registered. RESULTS: Out of 296 patients, 264 patients completed the monitoring period with 23.1% (61/264) of pAF detection. Patients with pAF were older [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08], they had more haemorrhagic infarction (OR 4.03, 95% CI 1.44-11.22), they were more likely to have LVO (OR 4.29, 95% CI 2.31-7.97) (P < 0.0001), they had a larger left atrial volume index (OR 1.03, 95% CI 1.01-1.1) (P = 0.0002) and they had a higher level of brain natriuretic peptide (OR 1.01, 95% CI 1.0-1.1). Age and LVO were independently associated with pAF detection (OR 1.06, 95% CI 1.00-1.16, and OR 4.58, 95% CI 2.27- 21.38, respectively). Patients with LVO had higher cumulative incidence of pAF (log rank P < 0.001) and more percentage of pAF > 5 h [29.6% (21/71) vs. 8.3% (12/144); OR 4.62, 95% CI 2.11-10.08; P < 0.001]. In a mean follow-up of 26.82 months (SD 10.15) the stroke recurrence rate was 4.6% (12/260). CONCLUSIONS: Large vessel occlusion in cryptogenic stroke emerged as an independent marker of pAF.

How predictors and patterns of stroke recurrence after a TIA differ during the first year of follow-up.

The highest risk of subsequent stroke after a TIA occurs within the first week after the index event. However, the risk of stroke recurrence (SR) remains high during the first year of follow-up. We studied the temporal pattern and predictors of SR (at 7 days and from 7 days to 1-year follow-up). Between April 2008 and December 2009, we included 1,255 consecutive TIA patients from 30 Spanish stroke centers (PROMAPA study). We determined the short-term (at 7 days) and long-term (from 8 days to 1 year) risk of SR. Patients who underwent short-term recurrence and long-term recurrence were compared with regard to clinical findings, vascular territories, and etiology. Enough information (clinical variables and extracranial vascular imaging) was assessed in 1,137 (90.6 %) patients. The 7-day stroke risk was 2.6 %. 32 (3.0 %) patients had an SR after 7-day follow-up. Multiple TIA (HR 3.50, 1.67-7.35, p = 0.001) and large artery atherosclerosis (HR 2.51, 1.17-5.37, p = 0.018) were independent predictors of early SR, whereas previous stroke (HR 1.40, 1.03-1.92, p = 0.034) and coronary heart disease (2.65, 1.28-5.50, p = 0.009) were independent predictors of late SR. Notoriously, 80 % of SR happened in the same territory of the index TIA at 7-day follow-up, whereas only 38 % during the long-term follow-up (p < 0.001). Different predictors of SR were identified throughout the follow-up period. Moreover, the ischemic mechanism differed in early and late stroke recurrences.

Ankle-brachial index in screening for asymptomatic carotid and intracranial atherosclerosis.

OBJECTIVE: To evaluate usefulness of ankle-brachial index (ABI) in the screening for asymptomatic cervico-cerebral atherosclerosis (CCA) against traditional vascular risk assessment. METHODS: This study included a random population sample of 933 Caucasians without prior cardiovascular disease but with a moderate and high vascular risk (REGICOR score 5-9% and ≥ 10%). Presence and degree of CCA was evaluated by color-coded duplex and significant stenosis >50% (SCCA) confirmed by MRA. RESULTS: Prevalence of significant carotid and/or intracranial stenosis was 6% in the whole population, but increased up to 25% among those subjects with ABI ≤ 0.9 regardless of REGICOR score. Using REGICOR ≥ 10%, the likelihood ratio (LR) for the detection of SCCA was 1.8, while using ABI ≤ 0.90 the LR was 6.0. After multivariate regression analysis, low ABI was independently associated with SCCA whereas REGICOR score was not. Less than 40% of subjects with SCCA were taking antiplatelet drugs or statins at the moment of diagnosis. CONCLUSION: ABI emerged as a useful and simple tool in identifying asymptomatic SCCA in our population. This finding may be important for improving stroke primary prevention strategies.

Predictive value of ankle-brachial index and PAI-1 in symptomatic intracranial atherosclerotic disease recurrence.

BACKGROUND AND PURPOSE: We prospectively examine the single and combined predictive value of biological and clinical markers in recurrent strokes related to intracranial atherosclerotic disease (ICAD). METHODS: In 73 ICAD first-ever stroke patients, ankle-brachial index (ABI) was assessed three months after TIA or stroke together with CRP, Lp-PLA2, ICAM-1, E-selectin and PAI-1 measurements. Appearance of new TIA/stroke was assessed every 6 months. RESULTS: After a median follow-up of 22.4 months, 13 patients (17.8%) suffered a new stroke or TIA. Risk of new cerebrovascular events (CVEs) was associated with lowered ABI (p=0.011), baseline PAI-1>22.52 ng/ml (<0.001), E-selectin>24.75 ng/ml (p = 0.008) and ICAM-1>205 ng/ml (p = 0.029). The combination of PAI-1 with ABI or ESRS reclassified 55.4% (p<0.005) and 48.3% (p<0.05) of patients between low, high and very high-risk categories. CONCLUSIONS: This tentative study shows that ABI and PAI-1 are associated with the risk of new CVEs in symptomatic ICAD patients, and their combination might improve identification of patients at higher risk.

Immune reconstitution inflammatory syndrome and natalizumab-Is it possible before removing the drug?

Multiple sclerosis (MS) patients treated with natalizumab have a significant reduction in annualized relapse rate; in these patients, a relapse is uncommon but not unexpected. In contrast, the appearance of a severe exacerbation is striking and requires the differential diagnosis with progressive multifocal leukoencephalopathy. Here, we describe a case of a 22-year-old woman with relapsing-remitting MS who developed an unexpected response after the patient׳s fifth natalizumab infusion with an aggressive radiological and clinical evolution. Changing the patient׳s treatment to fingolimod resulted in the absence of new clinical relapses and the absence of active lesions on brain magnetic resonance images (MRI) during the first 12 months of follow-up. We hypothesize that the appearance of natalizumab antibodies in this patient triggered lymphocyte migration to the central nervous system in a rebound phenomenon; this is similar to what occurs during immune reconstitution inflammatory syndrome (IRIS) after removal of natalizumab.

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

BACKGROUND: Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. METHODS: We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. RESULTS: Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. CONCLUSION: Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis.