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Background: Atrial fibrillation (AF) is one of the most prevalent causes of cryptogenic stroke. Also, apart from AF itself, structural and remodelling changes in the atria might be an underlying cause of cryptogenic stroke. We aimed to discover circulating proteins and reveal pathways altered in AF and atrial cardiomyopathy, measured by left atrial volume index (LAVI) and peak atrial longitudinal strain (PALS), in patients with cryptogenic stroke. Methods: An aptamer array (including 1310 proteins) was measured in the blood of 20 cryptogenic stroke patients monitored during 28 days with a Holter device as a case-control study of the Crypto-AF cohort. Protein levels were compared between patients with (n = 10) and without AF (n = 10) after stroke, and the best candidates were tested in 111 patients from the same cohort (44 patients with AF and 67 without AF). In addition, in the first 20 patients, proteins were explored according to PALS and LAVI values. Results: Forty-six proteins were differentially expressed in AF cases. Of those, four proteins were tested in a larger sample size. Only DPP7, presenting lower levels in AF patients, was further validated. Fifty-seven proteins correlated with LAVI, and 270 correlated with PALS. NT-proBNP was common in all the discovery analyses performed. Interestingly, many proteins and pathways were altered in patients with low PALS. Conclusions: Multiple proteins and pathways related to AF and atrial cardiomyopathy have been revealed. The role of DPP7 as a biomarker for stroke aetiology should be further explored. Moreover, the present study may be considered hypothesis-generating.

The importance of diet in preventing non-communicable diseases is well established, with polyphenol consumption suggested to impact cardiovascular disease development. Salicornia ramosissima synthesizes high amounts of phytochemicals under environmental stress. In a randomized controlled clinical trial on 90 healthy volunteers, we evaluated the safety of supplementation with 1 g of polyphenol-rich S. ramosissima extracts from salt marshes and hydroponic sources over three months. No differences in adverse effects were observed between extract-treated and placebo subjects. Salicornia extract from marshes (SM) increased glomerular filtration rate and reduced LDL cholesterol. SM treatment also modulated plasma markers related to cardiovascular disease: MERTK, Gal-9, ADM, TF, PRSS27, HAOX1, IL-18, PAPPA, TNFRSF1A, TIE2 and FGF-21 proteins were downregulated while SRC levels were upregulated. Therefore, under the studied conditions of use, Salicornia extracts consumption is safe and SM induced biochemical and proteomic changes related to cardiovascular health.

ObjectiveThe modified Centers for Disease Control and Prevention (mCDC) criteria have been proposed for diagnosing and managing stroke-associated pneumonia (SAP). The objective was to investigate the impact of SAP on stroke outcome depending on whether or not it conforms to mCDC criteria. Our secondary objective was to identify the responsible factors for antibiotic initiation in stroke patients.MethodsWe conducted a prospective, multicenter, observational study of ischemic stroke patients with moderate to severe stroke (NIHSS≥4) admitted within 24 h. For 7 days, mCDC criteria were assessed daily, and infections and antibiotics were recorded. Pneumonias were divided into those fulfilling mCDC criteria (mCDC-SAP) or not (other pneumonias, OPn). The effect of each type of pneumonia on 3-month outcome was evaluated in separated logistic regression models. Factors associated with antibiotic initiation were explored using a random forest analysis.ResultsOf the 342 patients studied, infections were diagnosed in 72 (21.6%), including 39 (11.7%) cases of pneumonia. Of them, 25 (7.5%) fulfilled mCDC criteria. Antibiotics were used in 92% of mCDC-SAP and 64.3% of OPn. In logistic regression analysis, mCDC-SAP, but not OPn, was an independent predictor of poor outcome [OR, 4.939 (1.022–23.868)]. The random forest analysis revealed that fever had the highest importance for antibiotic initiation.InterpretationThe mCDC criteria might be useful for detecting clinically relevant SAP, which is associated with poor outcomes. Isolated signs of infection were more important for antibiotic initiation than compliance with pre-defined criteria. Therefore, adherence to mCDC criteria might result in antibiotic saving without compromising clinical outcome.

El deterioro cognitivo vascular es una de las causas principales de demencia y de discapacidad en el paciente adulto. La enfermedad de pequeño vaso cerebral (EPVC) representa la etiología más frecuente. El objetivo es cuáles pueden ser los mejores test neuropsicológicos para el diagnóstico y el seguimiento del deterioro cognitivo por EPVC en poblaciones que hablam francés o español (incluyendo pacientes iletrados). Se ha realizado una revisión sistemática según la metodología PRISMA. Se ha tomado como referencia los criterios diagnósticos de deterioro cognitivo del manual DSM-5 de 2013. Como test de cribado, la escala de Mattis (validada en castellano y francés) presenta buen rendimiento diagnóstico. En pacientes iletrados de habla castellana, la mejor escala de cribado validada es el Fototest. Para la evaluación de funciones ejecutivas y atención, se han demostrado sensibles las siguientes pruebas: Test del trazo A y B, Test de los 5 dígitos, Test de los símbolos y dígitos y el Test cubos de Corsi Wechsler no verbal. Nuestra batería aplicada por neuropsicólogos puede estandarizar el diagnóstico precoz y seguimiento adecuado de la EPVC en países en los que se habla francés o español.

Introducción: Las enfermedades neurovasculares minoritarias como CADASIL, cavernomatosis múltiple familiar o arteriopatía de moyamoya requieren un abordaje diagnóstico multidisciplinario que incluya un panel genético. Métodos: Se ha realizado una revisión sistemática según la metodología PRISMA. Se ha tomado como referencia el protocolo diagnóstico empleado en la unidad de referencia CERVCO de París. Resultados: Se recomienda incluir los siguientes genes dentro del panel de enfermedad de pequeño vaso cerebral: NOTCH3, COL4A1, COL4A2, GLA, HTRA1, APP, TREX1 y LAMB1. En la cavernomatosis múltiple familiar se propone estudiar los genes KRIT1, CCM2 y PDCD10. Para el abordaje de la arteriopatía de moyamoya, los genes más interesantes serían: RNF123, BRCC3, MTCP1, GUCY1A3, ACTA2, SAMHD1, NOS3, CBL, DIAPH1 y ANO1. Si existen disecciones habría que incluir las colagenopatías en el diagnóstico diferencial. Conclusiones: Los paneles de exomas clínicos constituyen una herramienta diagnóstica fundamental en las enfermedades neurovasculares genéticas.

IntroductionCerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-β (Aβ) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aβ is also accumulated in Alzheimer’s disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins.MethodsThe study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA.ResultsWe observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS.DiscussionThis study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral β-amyloidosis.

BackgroundAtrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations.MethodsTwo hundred seventy-four subjects aged 65–75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately.ResultsAtrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665–0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654–0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively.ConclusionBlood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

Intracranial hemorrhage is a serious medical problem that requires rapid and often intensive medical care. Identifying the location and type of any hemorrhage present is a critical step in the treatment of the patient. Detection of, and diagnosis of, a hemorrhage that requires an urgent procedure is a difficult and time-consuming process for human experts. In this paper, we propose methods based on EfficientDet’s deep-learning technology that can be applied to the diagnosis of hemorrhages at a patient level and which could, thus, become a decision-support system. Our proposal is two-fold. On the one hand, the proposed technique classifies slices of computed tomography scans for the presence of hemorrhage or its lack of, and evaluates whether the patient is positive in terms of hemorrhage, and achieving, in this regard, 92.7% accuracy and 0.978 ROC AUC. On the other hand, our methodology provides visual explanations of the chosen classification using the Grad-CAM methodology.

Objective Spain’s so-called Stroke Belt is an area with high prevalence of vascular disease. We aimed to determine the prevalence of undetected obstructive sleep apnea–hypopnea syndrome (OSAHS) among patients with acute ischemic stroke (AIS) in southern Spain. Methods We conducted a cross-sectional study at the Virgen Macarena University Hospital Stroke Unit during 2018 to 2019. We included patients

Objectives The detection of cervical arterial dissection (CAD) has been rising in recent years owing to advanced imaging techniques. The aim of this study was to explore whether wide implementation of endovascular treatment for ischemic stroke has an impact on the diagnosis of CAD. Methods We included all patients with CAD diagnosed at two university hospitals in Seville, Spain from January 2015 to December 2017. We collected clinical variables and information on imaging techniques used for the diagnosis. Implementation of 24 hour/365 day mechanical thrombectomy began in Seville on 15 August 2016. We compared diagnosis rates of CAD performed before and after this date. Results We identified 41 patients with CAD. We found 13 patients diagnosed before (1.1% of all ischemic strokes) and 28 (2.2%) after implementation of neurointerventional therapy. In 17 patients, diagnosis was made in the acute phase. Dissection was not suspected according to computed tomography angiography in 11 patients owing to small dissections (n = 2) or total occlusion (n = 9). Conclusions CAD diagnoses have been rising in recent years, essentially owing to continuous improvement in imaging techniques. Rapid access to arteriography for thrombectomy is increasing the diagnoses of CAD, even in patients with a low suspicion of dissection.

Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.