Ambient air pollution, covert cerebrovascular disease and cognition: results from the ISSYS study.

BACKGROUND AND PURPOSE: Although air pollution (AP) has been associated with stroke and dementia, data regarding its relationship with covert cerebrovascular disease (cCVD) and cognition over time are sparse. The aim of this study was to explore these relationships. METHODS: A prospective population-based study of 976 stroke-free and non-demented individuals living in Barcelona, Spain, was conducted during 2010-2016. A land use regression model was used to estimate the exposure of each participant to AP: NOx, NO2, PM2.5, PM10, PMcoarse and PM2.5 absorbance. Cognitive function and cCVD were assessed at baseline (n = 976) and 4 years after (n = 317). Multivariate-adjusted models were developed. RESULTS: At baseline, 99 participants (10.1%) had covert brain infarcts and 91 (9.3%) had extensive periventricular white matter hyperintensities (WMHs). Marked subcortical WMH progression was seen in 19.7%; the incidence of other covert cerebrovascular lessons ranged between 5% and 6% each. PM2.5 was related to higher odds of having a covert brain infarct (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.06-4.60). PM2.5 absorbance was related to higher odds of having extensive subcortical WMHs (OR 1.72; 95% CI 1.13-2.60), whereas NO2 was related to higher odds of having extensive subcortical (OR 1.66; 95% CI 1.17-2.35) or periventricular (OR 1.96; 95% CI 1.10-3.50) WMHs and to higher odds of developing marked subcortical WMH progression (OR 1.40; 95% CI 1.05-1.90). NOx was related to incident cerebral microbleeds (OR 1.36; 95% CI 1.04-1.79). There was no association between AP and cognition. CONCLUSIONS: Air pollutant predicts the presence and accumulation of cCVD. Its impact on cognitive impairment remains to be determined.

Ventilation time and prognosis after stroke thrombectomy: the shorter, the better!

BACKGROUND AND PURPOSE: The aim was to investigate the clinical impact of the duration of artificial ventilation in stroke patients receiving mechanical thrombectomy (MT) under general anaesthesia. METHODS: All consecutive ischaemic stroke patients who had been treated at our centre with MT for anterior circulation large vessel occlusion under general anaesthesia were identified over an 8-year period. Ventilation time was analysed as a continuous variable and patients were grouped into extubation within 6 h ('early'), 6-24 h ('delayed') and >24 h ('late'). Favourable outcome was defined as modified Rankin Scale scores of 0-2 at 3 months post-stroke. Pneumonia rate and reasons for prolonged ventilation were also assessed. RESULTS: Amongst 447 MT patients (mean age 69.1 ± 13.3 years, 50.1% female), the median ventilation time was 3 h. 188 (42.6%) patients had a favourable 3-month outcome, which correlated with shorter ventilation time (Spearman's rho 0.39, P < 0.001). In patients extubated within 24 h, early compared to delayed extubation was associated with improved outcome (odds ratio 2.40, 95% confidence interval 1.53-3.76, P < 0.001). This was confirmed in multivariable analysis (P = 0.01). A longer ventilation time was associated with a higher rate of pneumonia during neurointensive care unit/stroke unit stay (early/delayed/late extubation: 9.6%/20.6%/27.7%, P < 0.01). Whilst stroke-associated complications represented the most common reasons for late extubation (>24 h), delayed extubation (6-24 h) was associated with admission outside of core working hours (P < 0.001). CONCLUSIONS: Prolonged ventilation time after stroke thrombectomy independently predicts unfavourable outcome at 3 months and is associated with increased pneumonia rates. Therefore, extubation should be performed as early as safely possible.

Ventilator autotriggering : An underestimated phenomenon in the determination of brain death.

BACKGROUND: Ventilator autotriggering (VAT) may induce uncertainty in diagnosing brain death because it may falsely suggest a central respiratory drive in brain-dead patients where no intrinsic respiratory efforts exist. Since the lack of international standardization of brain death criteria contributes to the loss of potential donor organs, it is important to be aware of this phenomenon, which is a not well-known confounder in the process of diagnosing brain death. METHODS: The national official recommendations or guidelines for the determination of brain death and organ transplantation of 15 selected European countries (including all 8 member states of the Eurotransplant network) were evaluated with respect to VAT. In addition, a literature search (PubMed, Google Scholar) using the term "ventilator autotriggering", synonyms or similar content-related wording was carried out. RESULTS: The VAT phenomenon was mentioned in 3 of the 15 official recommendations and guidelines on diagnosing brain death. The causes and management of VAT are presented in different ways in the reviewed official recommendations and guidelines. CONCLUSION: The phenomenon of VAT is inconsistently addressed in the national guidelines and recommendations for the determination of brain death and should, therefore, be included in future harmonized brain death codes. Detection and correction of VAT should be implemented as early as possible by a structured procedure. Additional training and information on this phenomenon should be made available to the entire intensive care unit staff.

Assessment of enlarged perivascular spaces and their relation to target organ damage and mild cognitive impairment in patients with hypertension.

BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVS) have been recently considered a feature of cerebral small vessel disease. They have been related to aging, hypertension and dementia but their relationship with hypertension related variables (i.e. target organ damage, treatment compliance) and mild cognitive impairment (MCI) is not fully elucidated. Our aims were to investigate the relation between basal ganglia (BG) and centrum semiovale (CSO) EPVS with vascular risk factors, hypertension related variables and MCI. METHODS: In all, 733 hypertensive individuals free of stroke and dementia from the Investigating Silent Strokes in Hypertensives, a magnetic resonance imaging Study (ISSYS) underwent brain magnetic resonance imaging and cognitive testing to diagnose MCI or normal cognitive aging. RESULTS: The numbers of participants presenting high grade (>10) EPVS at the BG and CSO were 23.3% and 40.0%, respectively. After controlling for vascular risk factors, high grade BG EPVS were associated with age (odds ratio 1.68; 95% confidence interval 1.37, 2.06), poor antihypertensive compliance (1.49; 1.03, 2.14) and the presence of microalbuminuria (1.95; 1.16, 3.28), whereas in the CSO only age (1.38; 1.18, 1.63) and male sex were associated with EPVS (1.73; 1. 24, 2.42). MCI was diagnosed in 9.3% of the participants and it was predicted by EPVS in the BG (1.87; 1.03, 3.39) but not in the CSO. This last association was greatly attenuated after correction for lacunes and white matter hyperintensities. CONCLUSIONS: Basal ganglia EPVS are associated with the presence of microalbuminuria and poor adherence to antihypertensive drugs. The BG EPVS relation with MCI is not independent of the presence of other cerebral small vessel disease markers.

New limits on intrinsic charm in the nucleon from global analysis of parton distributions.

We present a new global QCD analysis of parton distribution functions, allowing for possible intrinsic charm (IC) contributions in the nucleon inspired by light-front models. The analysis makes use of the full range of available high-energy scattering data for Q^{2}≳1 GeV^{2} and W^{2}≳3.5 GeV^{2}, including fixed-target proton and deuteron cross sections at lower energies that were excluded in previous global analyses. The expanded data set places more stringent constraints on the momentum carried by IC, with ⟨x⟩_{IC} at most 0.5% (corresponding to an IC normalization of ∼1%) at the 4σ level for Δχ^{2}=1. We also critically assess the impact of older EMC measurements of F_{2}^{c} at large x, which favor a nonzero IC, but with very large χ^{2} values.

Phase II/III clinical trial to assess the tolerability and immunological effect of a new updosing phase of Dermatophagoides mix-based immunotherapy.

BACKGROUND: Immunologically enhanced subcutaneous specific immunotherapy (SCIT) has been developed with a fast and simplified updosing phase containing equal parts of the house dust mites (HDM) Dermatophagoides pteronyssinus and Dermatophagoides farinae (Dermatophagoides mix) adsorbed on aluminum hydroxide. OBJECTIVE: To evaluate the tolerability and immunological impact of the updosing phase of this new allergen extract formulation. MATERIAL AND METHODS: We performed a multicenter, open-label, single-arm, phase II/III clinical trial. The inclusion criteria were a clinical history of rhinitis/conjunctivitis due to HDM (with/without asthma) and sensitization to HDM (positive specific IgE and skin prick test). Five updosing injections of Dermatophagoides mix (300, 600, 3000, 6000, and 15000 SQ+) were administered at weekly intervals with 1 maintenance injection (15000 SQ+) 2 weeks after the last updosing injection. Two days after each visit, patients were contacted by telephone to follow up on any adverse events. IgE-blocking factor, IgG4, and immediate skin reactivity were evaluated. RESULTS: The sample comprised 102 patients (mean [SD] age, 29.3 [7.7] years; male, 52.9%). There were 117 adverse drug reactions (ADR): 101 were local, regardless of reaction size, in 48 (47.1%) patients and 7 were systemic (all grade I) in 5 (4.9%) patients. All ADRs were mild, except for 1, which was moderate. Six weeks of treatment led to statistically significant increases in IgE-blocking factor and IgG4, as well as a significant reduction in immediate skin reactivity. CONCLUSION: This new updosing phase of Dermatophagoides mix-based immunotherapy had a good tolerability profile and induced a significant immunological effect.

Clinical-Hematological Changes and Predictors of Severity in Acute Food Protein-Induced Enterocolitis Syndrome Reactions at Oral Food Challenge: A Multicenter Observational Study.

BACKGROUND: Oral food challenge (OFC) is the criterion standard for diagnosis of acute food protein-induced enterocolitis syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-hematological changes and predictors of severity of FPIES reactions at OFC. METHODS: This was an observational multicenter prospective study. Children aged 0 to 18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centers in Spain and Italy. OFC outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed on the basis of published "2017 FPIES Consensus" criteria. Clinical characteristics were recorded, and full blood cell count was done at baseline, reaction onset, and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: A total of 81 children had positive OFC (mild in 11% [9 of 81], moderate in 61% [49 of 81], and severe in 28% [23 of 81]). Increase in neutrophils and reduction in eosinophils, basophils, and lymphocytes were observed (P < .05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed that a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not sex, age, culprit food, cumulative dose, and previous reaction severity) was associated with reduced odds of severe reaction compared with giving multiple doses in a single day. CONCLUSIONS: Distinct hematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may be associated with a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Universal pre-mixing dry-film stickers capable of retrofitting existing microfluidics.

Integrating microfluidic mixers into lab-on-a-chip devices remains challenging yet important for numerous applications including dilutions, extractions, addition of reagents or drugs, and particle synthesis. High-efficiency mixers utilize large or intricate geometries that are difficult to manufacture and co-implement with lab-on-a-chip processes, leading to cumbersome two-chip solutions. We present a universal dry-film microfluidic mixing sticker that can retrofit pre-existing microfluidics and maintain high mixing performance over a range of Reynolds numbers and input mixing ratios. To attach our pre-mixing sticker module, remove the backing material and press the sticker onto an existing microfluidic/substrate. Our innovation centers around the multilayer use of laser-cut commercially available silicone-adhesive-coated polymer sheets as microfluidic layers to create geometrically complex, easy to assemble designs that can be adhered to a variety of surfaces, namely, existing microfluidic devices. Our approach enabled us to assemble the traditional yet difficult to manufacture "F-mixer" in minutes and conceptually extend this design to create a novel space-saving spiral F-mixer. Computational fluid dynamic simulations and experimental results confirmed that both designs maintained high performance for 0.1 < Re < 10 and disparate input mixing ratios of 1:10. We tested the integration of our system by using the pre-mixer to fluorescently tag proteins encapsulated in an existing microfluidic. When integrated with another microfluidic, our pre-mixing sticker successfully combined primary and secondary antibodies to fluorescently tag micropatterned proteins with high spatial uniformity, unlike a traditional pre-mixing "T-mixer" sticker. Given the ease of this technology, we anticipate numerous applications for point-of-care devices, microphysiological-systems-on-a-chip, and microfluidic-based biomedical research.

Brain natriuretic peptide is associated with worsening and mortality in acute stroke patients but adds no prognostic value to clinical predictors of outcome.

BACKGROUND: At the present time, the determination of the outcome of stroke patients is based on the analysis of clinical and neuroimaging data. The use of prognostic blood biomarkers could aid in decision-making processes, e.g. admitting patients to specialized stroke units. Although the prognostic role of natriuretic peptides has been studied in heart failure and coronary diseases, the value of brain natriuretic peptide (BNP) is less known within the field of strokes. OBJECTIVE: We aimed to study the relationship between plasma levels of BNP and acute neurological worsening or mortality after stroke in a large cohort of patients (investigating both ischemic and hemorrhagic disease). METHODS: Consecutive stroke patients (ischemic and hemorrhagic) admitted to the Stroke Unit of our University Hospital within 24 h of the onset of symptoms were included. Stroke severity was assessed according to the National Institutes of Health Stroke Scale (NIHSS) at admission and at discharge. Neurological worsening was defined as an increase of 4 or more points in the NIHSS score or death during the patient's stay at the Stroke Unit. Blood samples were drawn upon admission to measure plasma levels of BNP (Biosite Inc., San Diego, Calif., USA). Statistical analysis was performed using SPSS 15.0 and R software. RESULTS: Altogether, 896 patients were included in the study. BNP plasma levels were higher among patients who deteriorated the most over time (n = 112; 90.5 vs. 61.2 ng/l; p = 0.006) or died (n = 83; 118.2 vs. 60.9 ng/l; p < 0.001). Multivariate logistic regression analysis indicated that plasma BNP level was an independent predictor of neurological worsening [BNP >56.7 ng/l; odds ratio (OR) = 1.64; p = 0.04] and death after stroke (BNP >65.3 ng/l; OR = 1.97; p = 0.034). Adding BNP level to other well-known clinical predictors of bad outcome did not significantly increase the predictive value. CONCLUSIONS: Plasma levels of BNP measured during the acute phase of stroke are associated both with early neurological worsening and mortality. However, this biological information does not supply prognostic information which would add to clinical variables, which limits its use as a biomarker. Further investigation and systematic reviews are needed to clarify the role of natriuretic peptides in stroke outcome.

Serotonin receptor, SERT mRNA and correlations with symptoms in males with alcohol dependence and suicide.

OBJECTIVE: This study tested the hypothesis that abnormalities in components of the serotonin (5HT) system in the prefrontal cortex are associated with suicide in alcohol-dependent subjects. Second, we assessed the relationship of lifetime impulsivity and mood symptoms with prefrontal cortex 5-HT measures. METHOD: Tissue was obtained from Brodmann's areas (BA) 9 and 24 in postmortem samples of individuals who were alcohol dependent with suicide (n = 5), alcohol dependent without suicide (n = 9) and normal controls (n = 5). Serotonin receptor (5HT) and serotonin reuptake transporter (SERT) mRNA were measured. Interviews with next of kin estimated lifetime impulsivity and mood symptoms in the last week of life. RESULTS: Serotonin receptor 1A (5HT1A) mRNA in BA 9 was elevated in the alcohol dependence without suicide group compared with controls. In the alcohol dependence with suicide group, anxiety symptoms were associated with decreased BA 24 SERT mRNA and depressive symptoms with BA 9 5HT1A mRNA expression. In the alcohol dependent only group impulsivity is correlated with increased BA 9, and BA 24 serotonin receptor 2A mRNA. CONCLUSION: Our data suggest region-specific change, rather than global serotonin blunting is involved in alcohol dependence and suicide. It also suggests that symptoms are differentially influenced by prefrontal cortex serotonin receptor mRNA levels.

Molecular typing of adenovirus circulating in a Colombian paediatric population with acute respiratory infection.

Human adenoviruses (HAdV) cause a broad spectrum of diseases including acute respiratory infection (ARI), and are responsible for 5% of cases requiring hospitalization in children aged <5 years in Colombia; however, little is known about the circulating types, partly due to the lack of reliable typing tests. In order to evaluate a VA gene PCR-sequencing approach for identification of HAdV circulating types in a Colombian population, 52 nasopharyngeal aspirates/swabs from children with ARI were processed. After a BLAST analysis, matches with species B (41/48, 85·42%), C (6/48, 12·5%), and D (1/48, 2·08%) were found; and at the type level, type 3 (22/48, 45·83%) was the most frequent. This initial effort to expand our knowledge about the molecular epidemiology of HAdV circulating in Bogota, Colombia, showed that HAdV-B was the predominant circulating species in the study period and reports, for the first time in Colombia, the presence of HAdV-D in a respiratory sample.

The gender gap in stroke: a meta-analysis.

UNLABELLED: Several studies have indicated that gender differences might exist in stroke. OBJECTIVES AND METHODS: Our goal was to perform a comprehensive meta-analysis in order to evaluate and quantify stroke gender disparities through a systematic search of relevant articles published up to October 2009 and addressing gender related differences in ischemic stroke risk factors, stroke subtype and severity, diagnostic tests, and acute phase and secondary prevention treatments. RESULTS: Forty-five articles were included in the analysis, representing a total of 673,935 patients. Women were globally older than men (+5.2 years) and suffered more hypertension (P = 0.017) and atrial fibrillation (P < 0.001), although they were less likely to drink alcohol (P < 0.001), smoke cigarettes (P < 0.001), present hyperlipidemia (P = 0.033) or diabetes (P = 0.003) than men. Baseline stroke severity was not different between genders. Women suffered more cardioembolic strokes, while men had more atherothrombotic strokes. Moreover, women were less likely to receive stroke-related treatments, such as antiplatelets (P < 0.001), statins (P < 0.001), and tPA (P < 0.001) than men. Although meta-regression did not identify age or stroke etiology as sources of heterogeneity, caution should be taken as that analysis was possible only for gender differences in secondary prevention with antiplatelets because of limited data for other end points. CONCLUSIONS: Gender differences have been identified on the risk factors profile and diagnostic and therapeutic management of patients with ischemic stroke. Active measures should thus be taken to avoid bias in clinical practice.

[Spontaneous resolution of a paraparesis due to a dorsolumbar epidural haematoma associated with subarachnoid anaesthesia and postoperative analgesia using an epidural catheter]. / Resolución espontánea de paraparesia por hematoma epidural dorsolumbar asociado a anestesia subaracnoidea y analgesia postoperatoria mediante catéter epidural.

Spinal epidural haematoma after neuroaxial anaesthesia is a rare but serious complication. Most cases are attributed to anticoagulant therapy or bleeding tendency. It presents as an acute spinal cord compression and usually requires emergency surgical decompression. The interval between the onset of clinical signs and surgical evacuation is very important, influencing the neurological prognosis. We report a case of a spinal epidural haematoma after epidural analgesia in a patient who was treated with low molecular weight heparin for thrombo-prophylaxis in the perioperative period. In some cases, such as the one reported here, good neurological recovery can be achieved with conservative management.

A panel of biomarkers including caspase-3 and D-dimer may differentiate acute stroke from stroke-mimicking conditions in the emergency department.

BACKGROUND AND AIMS: At present, a rapid and widely available diagnostic test for stroke remains elusive. The aim of this study was to examine the predictive value of a panel of blood-borne biochemical markers for stroke diagnosis. DESIGN: Consecutive patients with strokes or stroke-mimicking conditions (mimics) were evaluated within 24 h from symptom onset (915 strokes and 90 mimics). Blood samples were analysed by enzyme-linked immunosorbent assay for C-reactive protein, d-dimer, soluble receptor for advanced glycation end products (sRAGE), metalloproteinase 9 (MMP-9), S100B, brain natriuretic peptide, caspase-3, neurotrophin-3, chimerin and secretagogin. RESULTS: The main independent predictors of stroke versus mimics were caspase-3 >1.96 ng mL(-1) [odds ratio (OR) = 3.32; 95% confidence interval (CI) 1.88-5.88, P < 0.0001], d-dimer >0.27 µg mL(-1) (OR = 2.97; 95% CI 1.72-5.16, P = 0.0001), sRAGE >0.91 ng mL(-1) (OR = 2.19; 95% CI 1.26-3.83, P = 0.006), chimerin <1.11 ng mL(-1) (OR = 0.4; 95% CI 0.19-0.81, P = 0.011), secretagogin <0.24 ng mL(-1) (OR = 0.51; 95% CI 0.27-0.97, P = 0.041) and MMP-9 > 199 ng mL(-1) (OR = 1.66; 95% CI 1.01-2.73, P = 0.046). The model's predictive probability of stroke when the six biomarkers are above/below these cut-off levels was 99.01%. The best combination of biomarkers in the model was caspase-3 and d-dimer. Moreover, a model developed for samples obtained within the first 3 h showed high sensitivity (Se) and specificity (Sp) (threshold at 25th percentile: Se 0.87, Sp 0.55; threshold at 75th percentile: Se 0.28, Sp 0.99). CONCLUSIONS: A combination of biomarkers including caspase-3 and d-dimer appears to be the most promising to achieve a rapid biochemical diagnosis of stroke. If replicated, this approach could be used as a tool for urgent referral of stroke patients to hospitals in which acute treatments are available.

In-hospital stroke: a multi-centre prospective registry.

BACKGROUND: in-hospital strokes (IHS) are relatively frequent. Avoidable delays in neurological assessment have been demonstrated. We study the clinical characteristics, neurological care and mortality of IHS. METHODS: multi-centre 1-year prospective study of IHS in 13 hospitals. Demographic and clinical characteristics, admission diagnosis, quality of care, thrombolytic therapy and mortality were recorded. RESULTS: we included 273 IHS patients [156 men; 210 ischaemic strokes (IS), 37 transient ischaemic attacks (TIA) and 26 cerebral haemorrhages]. Mean age was 72 ± 12 years. Cardiac sources of embolism were present in 138 (50.5%), withdrawal of antithrombotic drugs in 77 (28%) and active cancers in 35 (12.8%). Cardioembolic stroke was the most common subtype of IS (50%). Reasons for admission were programmed or urgent surgery in 70 (25%), cardiac diseases in 50 (18%), TIA or stroke in 30 (11%) and other medical illnesses in 71 (26%). Fifty-two per cent of patients were evaluated by a neurologist within 3 h of stroke onset. Thirty-three patients received treatment with tPA (15.7%). Thirty-one patients (14.7%) could not be treated because of a delay in contacting the neurologist. During hospitalization, 50 patients (18.4%) died, 41 of them because of the stroke or its complications. CONCLUSIONS: cardioembolic IS was the most frequent subtype of stroke. Cardiac sources of embolism, active cancers and withdrawal of antithrombotic drugs constituted special risk factors for IHS. A significant proportion of patients were treated with thrombolysis. However, delays in contacting the neurologist excluded a similar proportion of patients from treatment. IHS mortality was high, mostly because of stroke.

No evidence of APP point mutation and locus duplication in individuals with cerebral amyloid angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a well-established cause of lobar intracerebral hemorrhage (ICH). Familial forms of CAA are because of mutations in the gene encoding the beta-amyloid precursor protein (APP) and duplications of this gene can cause early-onset Alzheimer's disease associated with CAA. However, the contribution of APP genetic variants in the development of sporadic CAA remains unknown. METHODS: The presence of genetic variants in the APP was examined in 78 patients with CAA-related ICH by sequencing exons 16 and 17 coding the ß-amyloid protein and analyzing the presence of possible duplications of APP by microsatellite analysis and quantitative PCR. RESULTS: We did not identify any pathogenic mutation or chromosomal duplication of APP. CONCLUSIONS: Our results suggest that APP genetic variants, point mutations and locus duplication, are not a common cause of CAA-related ICH in the Spanish population.

Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients.

BACKGROUND: The biologic agents causing leukoaraiosis are unknown. Our aim was to study the genetic basis of leukoaraiosis. METHODS: We analyzed 212 single nucleotide polymorphisms (SNPs) in 142 patients with ischaemic stroke, generating a total of 30,104 genotypes. Seventy-nine subjects (55.6%) presented leukoaraiosis measured by the Fazekas scale and 69 (48.6%) by ARWMC scale. We analyzed the presence of synergic associations between SNPs using the hfcc software. Finally, functional studies were performed in 56 subjects. The Ingenuity Pathways software (ipa) was used to examine the role of the identified genes. RESULTS: Six SNPs were associated with leukoaraiosis using both measuring scales. After logistic regression adjusted for leukoaraiosis risk factors, the rs2252070 of MMP13 (OR = 4.9, 95%CI: 1.34-17.9, P = 0.016), rs662 of PON1 (OR = 0.37, 95%CI: 0.15-0.87, P = 0.024) and rs1800779 of NOS3 (OR = 3.9, 95%CI: 1.38-11.38, P = 0.01) were independently associated with leukoaraiosis under a dominant/recessive model and the rs2290608 of IL5RA (OR = 0.46, 95%CI: 0.25-0.85, P = 0.013) and rs669 of A2M (OR = 2.5, 95%CI: 1.36-4.83, P = 0.004) under an additive model. Computational analysis showed a synergic association of rs10497212-AA of ITGB6 and rs2290608-GG of IL5RA with leukoaraiosis using both scales. (i) ARWMC (P = 1.3 × 10(-4) ) and (ii) Fazekas (P = 4.5 × 10(-5) ). Functional studies showed that the rs669 SNP was associated with plasma levels of A2M (P = 0.012) and A2M levels with leukoaraiosis in Fazekas scale (P = 0.02). ipa analysis revealed that the genes associated with leukoaraiosis were involved in blood-brain barrier (BBB) homeostasis. CONCLUSIONS: Amongst patients with ischaemic stroke, several genes associated with BBB homeostasis could be involved with a higher risk of leukoaraiosis.

[Aneurysmal subarachnoid hemorrhage: group of study of cerebrovascular pathology of the Spanish society of neurosurgery management guideline]. / Hemorragia subaracnoidea aneurismática: guía de tratamiento del grupo de patología vascular de la sociedad Española de neurocirugía.

An actualized revision of the most important aspects of aneurismal subarachnoid hemorrhage is presented from the guidelines previously published by the group of study of cerebrovascular pathology of the Spanish Society of Neurosurgery. The proposed recommendations should be considered as a general guide for the management of this pathological condition. However, they can be modified, even in a significant manner according to the circumstances relating each clinical case and the variations in the therapeutic and diagnostic procedures available in the center attending each patient.