[Clinical profile and non-recreational methamphetamine abuse (shabu) among stroke patients in the Philippine population]. / Perfil clínico y abuso de metanfetamina no recreativa (shabú) entre los pacientes con ictus en la población filipina.

INTRODUCTION: Chronic non-recreational use of methamphetamine (shabu) is increasing among the Filipino population in Barcelona. The Asian population presents a different stroke pattern, with a higher incidence of haemorrhage, and different vascular risk factors and health behaviours. The objective of this study is to describe the stroke profile and incidence of methamphetamine use in patients of Filipino origin admitted to our centre. PATIENTS AND METHODS: Demographic data, vascular risk factors, clinical data and prognosis were recorded. Methamphetamine exposure was analysed in plasma samples collected on admission, which were then analysed by liquid chromatography-mass spectrometry. RESULTS: Of a total of 6,418 stroke patients, 73 (1.1%) were identified as being of Filipino origin. The mean age was 54.4 ± 12.1 years, 54% were male and the stroke was ischaemic in 64.4% of cases. Arterial hypertension was the main risk factor. Ten (13.7%) patients tested positive for methamphetamine and amphetamine. These results confirm recent substance use prior to the stroke, mostly in men (80%). In patients who were consumers, 60% had a haemorrhagic stroke, with a poor functional prognosis at three months in 55.6% of patients. CONCLUSIONS: In our setting, patients of Filipino ethnicity admitted for stroke related to the consumption of shabu belonged a younger age bracket, with a lower prevalence of vascular risk factors and a predominance of the haemorrhagic subtype. Methamphetamine testing in Filipino stroke patients is recommended due to the high prevalence of methamphetamine use in our country.

TITLE: Perfil clínico y abuso de metanfetamina no recreativa (shabú) entre los pacientes con ictus en la población filipina.Introducción. En la población filipina de Barcelona está aumentando el consumo crónico no recreativo de metanfetaminas (shabú). La población asiática presenta un patrón de ictus diferente, con mayor incidencia de hemorragias, y diferentes factores de riesgo vascular y conductas de salud. El objetivo es describir el perfil de ictus e incidencia de consumo de metanfetaminas en pacientes de origen filipino ingresados en nuestro centro. Pacientes y métodos. Se registraron datos demográficos, factores de riesgo vascular, datos clínicos y pronóstico. Se analizó la exposición a metanfetamina en muestras de plasma recogidas en el ingreso, que se analizaron por cromatografía líquida-espectrometría de masas. Resultados. Del total de 6.418 pacientes con ictus, se identificó a 73 pacientes filipinos (1,1%). La edad media era de 54,4 ± 12,1 años, el 54% eran hombres y el ictus era isquémico en el 64,4%. La hipertensión arterial fue el principal factor de riesgo. Diez (13,7%) pacientes dieron positivo a metanfetamina y anfetamina. Estos resultados confirman un consumo reciente de sustancias previo al ictus, principalmente en hombres (80%). En pacientes consumidores, un 60% presentaba un ictus hemorrágico, con mal pronóstico funcional a tres meses en el 55,6% de los pacientes. Conclusiones. En nuestro medio, los pacientes de etnia filipina ingresados por ictus en relación con consumo de shabú presentaron un perfil de edad más joven, con menor prevalencia de factores de riesgo vascular y predominio del subtipo hemorrágico. Se recomienda la determinación de metanfetamina en los pacientes filipinos con ictus debido a la alta prevalencia del consumo de metanfetamina en nuestro país.

Perfil clínico y abuso de metanfetamina no recreativa (shabú) entre los pacientes con ictus en la población filipina / Clinical profile and non-recreational methamphetamine abuse (shabu) among stroke patients in the Philippine population

Introducción En la población filipina de Barcelona está aumentando el consumo crónico no recreativo de metanfetaminas (shabú). La población asiática presenta un patrón de ictus diferente, con mayor incidencia de hemorragias, y diferentes factores de riesgo vascular y conductas de salud. El objetivo es describir el perfil de ictus e incidencia de consumo de metanfetaminas en pacientes de origen filipino ingresados en nuestro centro. Pacientes y métodos Se registraron datos demográficos, factores de riesgo vascular, datos clínicos y pronóstico. Se analizó la exposición a metanfetamina en muestras de plasma recogidas en el ingreso, que se analizaron por cromatografía líquida-espectrometría de masas. Resultados Del total de 6.418 pacientes con ictus, se identificó a 73 pacientes filipinos (1,1%). La edad media era de 54,4 ± 12,1 años, el 54% eran hombres y el ictus era isquémico en el 64,4%. La hipertensión arterial fue el principal factor de riesgo. Diez (13,7%) pacientes dieron positivo a metanfetamina y anfetamina. Estos resultados confirman un consumo reciente de sustancias previo al ictus, principalmente en hombres (80%). En pacientes consumidores, un 60% presentaba un ictus hemorrágico, con mal pronóstico funcional a tres meses en el 55,6% de los pacientes. Conclusiones En nuestro medio, los pacientes de etnia filipina ingresados por ictus en relación con consumo de shabú presentaron un perfil de edad más joven, con menor prevalencia de factores de riesgo vascular y predominio del subtipo hemorrágico. Se recomienda la determinación de metanfetamina en los pacientes filipinos con ictus debido a la alta prevalencia del consumo de metanfetamina en nuestro país. (AU)

INTRODUCTION Chronic non-recreational use of methamphetamine (shabú) is increasing among the Filipino population in Barcelona. The Asian population presents a different stroke pattern, with a higher incidence of haemorrhage, and different vascular risk factors and health behaviours. The objective of this study is to describe the stroke profile and incidence of methamphetamine use in patients of Filipino origin admitted to our centre. PATIENTS AND METHODS Demographic data, vascular risk factors, clinical data and prognosis were recorded. Methamphetamine exposure was analysed in plasma samples collected on admission, which were then analysed by liquid chromatography-mass spectrometry. RESULTS Of a total of 6,418 stroke patients, 73 (1.1%) were identified as being of Filipino origin. The mean age was 54.4 ± 12.1 years, 54% were male and the stroke was ischaemic in 64.4% of cases. Arterial hypertension was the main risk factor. Ten (13.7%) patients tested positive for methamphetamine and amphetamine. These results confirm recent substance use prior to the stroke, mostly in men (80%). In patients who were consumers, 60% had a haemorrhagic stroke, with a poor functional prognosis at three months in 55.6% of patients. CONCLUSIONS In our setting, patients of Filipino ethnicity admitted for stroke related to the consumption of shabú belonged a younger age bracket, with a lower prevalence of vascular risk factors and a predominance of the haemorrhagic subtype. Methamphetamine testing in Filipino stroke patients is recommended due to the high prevalence of methamphetamine use in our country. (AU)

Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Biological Age Acceleration Is Lower in Women With Ischemic Stroke Compared to Men.

BACKGROUND: Stroke onset in women occurs later in life compared with men. The underlying mechanisms of these differences have not been established. Epigenetic clocks, based on DNA methylation (DNAm) profiles, are the most accurate biological age estimate. Epigenetic age acceleration (EAA) measures indicate whether an individual is biologically younger or older than expected. Our aim was to analyze whether sexual dichotomy at age of stroke onset is conditioned by EAA. METHODS: We used 2 DNAm datasets from whole blood samples of case-control genetic studies of ischemic stroke (IS), a discovery cohort of 374 IS patients (N women=163, N men=211), from GRECOS (Genotyping Recurrence Risk of Stroke) and SEDMAN (Dabigatran Study in the Early Phase of Stroke, New Neuroimaging Markers and Biomarkers) studies and a replication cohort of 981 IS patients (N women=411, N men=570) from BASICMAR register. We compared chronological age, 2 DNAm-based biomarkers of aging and intrinsic and extrinsic epigenetic age acceleration EAA (IEAA and extrinsic EAA, respectively), in IS as well as in individual IS etiologic subtypes. Horvath and Hannum epigenetic clocks were used to assess the aging rate. A proteomic study using the SOMAScan multiplex assay was performed on 26 samples analyzing 1305 proteins. RESULTS: Women present lower Hannum-extrinsic EAA values, whereas men have higher Hannum-extrinsic EAA values (women=-0.64, men=1.24, P=1.34×10-2); the same tendency was observed in the second cohort (women=-0.57, men=0.79, P=0.02). These differences seemed to be specific to cardioembolic and undetermined stroke subtypes. Additionally, 42 blood protein levels were associated with Hannum-extrinsic EAA (P<0.05), belonging to the immune effector process (P=1.54×10-6) and platelet degranulation (P<8.74×10-6) pathways. CONCLUSIONS: This study shows that sex-specific underlying biological mechanisms associated with stroke onset could be due to differences in biological age acceleration between men and women.

Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis.

The original version of this article unfortunately contained mistakes. The correct information is given below.

A parsimonious score with a free web tool for predicting disability after an ischemic stroke: the Parsifal Score.

BACKGROUND: Most of the models to predict prognosis after an ischemic stroke include complex mathematical equations or too many variables, making them difficult to use in the daily clinic. We want to predict disability 3 months after an ischemic stroke in an independent patient not receiving recanalization treatment within the first 24 h, using a minimum set of variables and an easy tool to facilitate its implementation. As a secondary aim, we calculated the capacity of the score to predict an excellent/devastating outcome and mortality. METHODS: Eight hundred and forty-four patients were evaluated. A multivariable ordinal logistic regression was used to obtain the score. The Modified Rankin Scale (mRS) was used to estimate disability at the third month. The results were replicated in another independent cohort (378 patients). The "polr" function of R was used to perform the regression, stratifying the sample into seven groups with different cutoffs (from mRS 0 to 6). RESULTS: The Parsifal score was generated with: age, previous mRS, initial NIHSS, glycemia on admission, and dyslipidemia. This score predicts disability with an accuracy of 80-76% (discovery-replication cohorts). It has an AUC of 0.86 in the discovery and replication cohort. The specificity was 90-80% (discovery-replication cohorts); while, the sensitivity was 64-74% (discovery-replication cohorts). The prediction of an excellent or devastating outcome, as well as mortality, obtained good discrimination with AUC > 0.80. CONCLUSIONS: The Parsifal Score is a model that predicts disability at the third month, with only five variables, with good discrimination and calibration, and being replicated in an independent cohort.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Ultra-early continuous cardiac monitoring improves atrial fibrillation detection and prognosis of patients with cryptogenic stroke.

BACKGROUND AND PURPOSE: Subclinical atrial fibrillation (AF) is known to underlie a number of cases of cryptogenic stroke (CrS). However, there is need to define the most effective strategy for AF detection. The diagnostic usefulness was analysed of a strategy based on ultra-early continuous monitoring in patients with CrS in terms of AF detection, oral anticoagulation treatment and stroke recurrence, in comparison to a standard outpatient strategy. METHODS: Patients with ischaemic stroke of undetermined origin and confirmed to be cryptogenic after extensive work-up were searched for AF with (i) a conventional strategy (historical cohort, n = 101) with serial electrocardiograms and 24-h Holter monitoring or (ii) an ultra-early monitoring strategy with insertable cardiac monitor (ICM) implanted before discharge (prospective cohort, n = 90). AF episodes lasting >1 min, anticoagulant treatment and stroke recurrence were recorded. RESULTS: During admission, AF was similarly detected in both cohorts (24% of patients). After discharge (mean follow-up 30 ± 10 months), AF detection rates were 17/80 (21.3%) and 38/65 (58.5%) for patients in the conventional versus the ultra-early ICM group (P < 0.001). Up to 41% of AF cases in the ICM cohort were detected within the first month. Oral anticoagulation was initiated in 37.6% versus 65.5% (P < 0.001) and stroke recurrence was recorded in 10.9% versus 3.3% (P 0.04) in the conventional versus the ICM cohort. CONCLUSIONS: Pre-discharge ICM implant allows detection of AF during follow-up in up to 58% of selected patients with CrS. Compared to a conventional strategy, ultra-early ICM implant results in higher anticoagulation rates and a decrease in stroke recurrence.

Estudio descriptivo de los stroke mimics después de un estudio neurovascular completo / Description of stroke mimics after complete neurovascular assessment

Introducción: Un porcentaje de casos diagnosticados inicialmente como infartos isquémicos son de causa no cerebrovascular o stroke mimics (SM). Los datos publicados al respecto son heterogéneos y, generalmente, con cohortes pequeñas. Objetivo: Nuestro objetivo es establecer qué enfermedades cursan como SM, definir sus características epidemiológicas y clínicas e identificar el porcentaje de casos tratados con fibrinólisis. Métodos: Registro prospectivo de los eventos considerados cerebrovasculares desde junio del 2005 a abril del 2015, analizando datos demográficos, factores de riesgo cardiovascular, activación de Código Ictus e ingreso, severidad (NIHSS), destino al alta, morbilidad (mRS) y tratamiento recibido. Se han comparado los ictus isquémicos con los SM. Se excluyeron las hemorragias intracraneales, subaracnoideas y las causas de SM detectables en la TC inicial. Resultados: Sobre 4.570 casos, 404 (8,8%) son SM. Los pacientes con SM son más jóvenes (70,3 vs. 74 años, p < 0,0001), tienen menos factores de riesgo cardiovascular y fibrilación auricular (13 vs. 34%, p < 0,0001), una menor puntuación en NIHSS (2 vs. 4, p < 0,0001) y menos afasia (9,4 vs. 19,6%, p < 0,02) y disfagia (1,2 vs. 17%, p < 0,0001). En los SM se activan menos códigos ictus (28 vs. 40%, p < 0,0001) y requieren menos días de ingreso (4,9 vs. 7,8; p<0,0001) y menos ingresos en la unidad de ictus (47 vs. 60%, p < 0,0001). Los SM son dados de alta a domicilio con mayor frecuencia (95 vs. 62%, p < 0,0001) y con menor discapacidad (mRS 0-2; 76 vs. 54%, p < 0,0001). Un 4,7% de los SM recibieron fibrinólisis. La primera causa de SM fueron las crisis epilépticas (26%). Conclusiones: Los SM supusieron el 8,8% de los ingresos con diagnóstico inicial de ictus isquémico. Los SM tienen características demográficas, clínicas y pronósticas diferentes, siendo la epilepsia la etiología más frecuente. Pese a recibir atención urgente especializada, 19 pacientes (4,7%) fueron trataron con fibrinólisis

Introduction: A considerable percentage of events initially diagnosed as ischaemic stroke have non-cerebrovascular causes; these are called stroke mimics (SM). Currently available evidence about these events is heterogeneous and comes from studies with small samples. Objective:The purpose of our study is to identify conditions that may present as SM, define their epidemiological and clinical characteristics, and determine the percentage of cases of SM treated with intravenous fibrinolysis. Methods: Prospective study including all patients admitted to a tertiary university hospital between June 2005 and April 2015 with a diagnosis of acute stroke. We analysed demographic data, cardiovascular risk factors, time from code stroke activation to admission, stroke severity (NIHSS), final destination after discharge, degree of disability (mRS), and treatment. We compared SM and ischaemic strokes. We ruled out patients with intracranial haemorrhage, subarachnoid haemorrhage, or other causes of SM that may be detected on the baseline CT scan. Results: Four hundred four of the 4,570 included patients (8.8%) were found to have SM. Patients with SM were younger (70.3 vs. 74, P <. 0001), less likely to exhibit cardiovascular risk factors and atrial fibrillation (13 vs. 34%, P < .0001), scored lower on the NIHSS at baseline (2 vs. 4, P<.0001), and included fewer cases of aphasia (9.4 vs. 19.6%, P < .02) and dysphagia (1.2 vs. 17%, P < .0001) than patients with stroke. SM caused fewer code stroke activations (28 vs. 40%, P < .0001). Patients with SM required shorter hospital stays (4.9 vs. 7.8 days, P < .0001), were less frequently admitted to the stroke unit (47 vs. 60%, P < .0001) and more frequently discharged home (95 vs. 62%, P < .0001), and had better outcomes (mRS scores 0-2; 76 vs. 54%, P <. 0001). Intravenous fibrinolysis was administered to 4.7% of these patients. Epileptic seizures were the most frequent cause of SM (26%). Conclusions: In our sample, 8.8% of all diagnoses of ischaemic stroke were SM. These events have different demographic, clinical, and prognostic characteristics; epilepsy is the most common aetiology. Despite receiving specialised emergency care, 19 patients with SM (4.7%) were treated with intravenous fibrinolysis

Description of stroke mimics after complete neurovascular assessment. / Estudio descriptivo de los stroke mimics después de un estudio neurovascular completo.

INTRODUCTION: A considerable percentage of events initially diagnosed as ischaemic stroke have non-cerebrovascular causes; these are called stroke mimics (SM). Currently available evidence about these events is heterogeneous and comes from studies with small samples. OBJECTIVE: The purpose of our study is to identify conditions that may present as SM, define their epidemiological and clinical characteristics, and determine the percentage of cases of SM treated with intravenous fibrinolysis. METHODS: Prospective study including all patients admitted to a tertiary university hospital between June 2005 and April 2015 with a diagnosis of acute stroke. We analysed demographic data, cardiovascular risk factors, time from code stroke activation to admission, stroke severity (NIHSS), final destination after discharge, degree of disability (mRS), and treatment. We compared SM and ischaemic strokes. We ruled out patients with intracranial haemorrhage, subarachnoid haemorrhage, or other causes of SM that may be detected on the baseline CT scan. RESULTS: Four hundred four of the 4,570 included patients (8.8%) were found to have SM. Patients with SM were younger (70.3 vs. 74, P<.0001), less likely to exhibit cardiovascular risk factors and atrial fibrillation (13 vs. 34%, P<.0001), scored lower on the NIHSS at baseline (2 vs. 4, P<.0001), and included fewer cases of aphasia (9.4 vs. 19.6%, P<.02) and dysphagia (1.2 vs. 17%, P<.0001) than patients with stroke. SM caused fewer code stroke activations (28 vs. 40%, P<.0001). Patients with SM required shorter hospital stays (4.9 vs. 7.8 days, P<.0001), were less frequently admitted to the stroke unit (47 vs. 60%, P<.0001) and more frequently discharged home (95 vs. 62%, P<.0001), and had better outcomes (mRS scores 0-2; 76 vs. 54%, P<.0001). Intravenous fibrinolysis was administered to 4.7% of these patients. Epileptic seizures were the most frequent cause of SM (26%). CONCLUSIONS: In our sample, 8.8% of all diagnoses of ischaemic stroke were SM. These events have different demographic, clinical, and prognostic characteristics; epilepsy is the most common aetiology. Despite receiving specialised emergency care, 19 patients with SM (4.7%) were treated with intravenous fibrinolysis.

Alcohol overuse and intracerebral hemorrhage: characteristics and long-term outcome.

BACKGROUND AND PURPOSE: Alcohol overuse (AOu) is considered an important risk factor for spontaneous intracerebral hemorrhage (ICH). The clinical and outcome characteristics of these patients (AOu-ICH) are not well known. METHODS: All patients with ICH admitted to a single university tertiary stroke center were prospectively studied from May 2005 to May 2015. Demographic profiles, radiologic characteristics and clinical outcomes of patients with acute ICH and previous AOu (>40 g/day or >300 g/week) were analyzed. RESULTS: During the study period, 555 patients with spontaneous primary ICH met the inclusion criteria. A total of 81 patients (14.6%) reported AOu (24.3% of men vs. 3.1% of women; P < 0.0001; mean age, 63 years old for AOu vs. 74 years old for non-AOu; P < 0.0001). Of the classic cardiovascular risk factors, only smoking was associated with AOu (63% vs. 12.2% of non-AOu; P < 0.0001). Initial severity and hematoma volume were similar in both groups, with no observed differences in stroke care or in-hospital medical complications. Patients with AOu had worse outcome (modified Rankin Scale score, 3-6 points) than patients without AOu at 3 months [odds ratio (OR), 2.50; 95% confidence interval (CI), 1.32-4.75; P = 0.005] and 12 months (OR, 2.47; 95% CI, 1.23-5.00; P = 0.011). A similar trend was observed at 5 years (OR, 2.48; 95% CI, 0.96-6.39; P = 0.059). CONCLUSIONS: Alcohol overuse was present in 14.6% of patients with ICH, who were predominantly male, smokers and a mean of 11 years younger than the non-AOu group. Despite a lack of differences in initial clinical severity, stroke care and early medical complications, patients with AOu had worse short- and long-term outcomes.

Brainstem leukoaraiosis independently predicts poor outcome after ischemic stroke.

BACKGROUND AND PURPOSE: Increased supratentorial white matter hyperintensities volume (S-WMHV) has been reported to be a predictor of worse outcome in patients with acute ischemic stroke (AIS). However, few studies have focused on less common locations, such as brainstem white matter hyperintensities (B-WMH), and their relationship to S-WMHV. This study aimed to examine whether B-WMH affect clinical outcome after AIS or transient ischemic attack (TIA). METHODS: Based on magnetic resonance imaging evidence, B-WMH were evaluated in 313 prospectively identified patients with AIS/TIA and registered as absent or present. Standardized S-WMHV was quantified using a validated volumetric image analysis and natural log-transformed (Log_S-WMHV). Poor outcome was defined as a modified Rankin Scale score of 3-6 at 3 months after the index event. RESULTS: Brainstem white matter hyperintensities were detected in 57 (18.2%) patients. In unadjusted analyses for outcome, the presence of B-WMH was associated with worse outcome, compared with patients without B-WMH (P = 0.034). In multivariate analysis controlling for age, atrial fibrillation, stroke severity, reperfusion therapies and Log_S-WMHV, only B-WMH [odds ratio (OR), 2.46; P = 0.021] and stroke severity (OR, 1.23; P < 0.001) remained independently associated with unfavourable 90-day modified Rankin Scale score. Patients with B-WMH were older (OR, 1.06; P < 0.001) and tended to have more hyperlipidaemia (OR, 2.21; P = 0.023) and peripheral arterial disease (OR, 2.57; P = 0.031). CONCLUSIONS: Brainstem white matter hyperintensities are an independent predictor of poor outcome after AIS/TIA and this relationship persists after adjustment for important prognostic factors. Our results also show that leukoaraiosis in this location identifies patients with a specific risk factor profile, suggesting differences in the underlying pathogenesis.

Ultra-early hematoma growth in antithrombotic pretreated patients with intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Patients with acute intracerebral hemorrhage (ICH) pretreated with antithrombotic drugs may have increased early hematoma growth, which would increase mortality risk. The effect of antiplatelet (AP) and vitamin K antagonist (VKA) pretreatment on ultra-early hematoma growth (uHG) and its relationship with mortality in patients with acute supratentorial ICH was analyzed. METHODS: This is an observational retrospective study of a prospective register of 197 ICH patients with first computed tomography (CT) scan taken <6 h from ICH symptom onset. ICH volume was calculated by the ABC/2 formula and uHG by the baseline ICH volume/onset-to-CT time (ml/h) formula. The uHG analysis took into account the patient's pretreatment (none, AP or VKA) and the relationship between uHG and very-early (first 24 h) and 3-month mortality. RESULTS: In the pretreatment group, 50 (25.4%) patients were treated with AP and 37 (18.8%) with VKA. The median (interquartile range 25-75) uHG was 19.7 ml/h (2.9-44.8) for AP pretreated patients, 16.2 ml/h (5.1-42.5) for VKA pretreated patients and 8.4 ml/h (2.4-21.8) for non-pretreated patients, P = 0.019. The uHG was higher in patients with very-early [42.1 ml/h (20.1-79.6)] and total 3-month mortality [28.0 ml/h (15.8-52.5)] compared with survivors [3.9 ml/h (1.5-10.4)], P < 0.0001. Adjusted by ICH severity and previous functional status, uHG was an independent factor related to very-early (P = 0.028) and total 3-month mortality (P = 0.014). CONCLUSIONS: Patients pretreated with antithrombotics have much higher uHG, which would explain the increased mortality in these patients compared to untreated patients.

Sex-related differences in abdominal obesity impact on ischemic stroke risk.

BACKGROUND AND PURPOSE: The objective of our study was to evaluate sex differences in the impact of weight and abdominal obesity on the risk of ischemic stroke. METHODS: We included 388 patients with ischemic stroke (aged <75 years) assessed consecutively in our hospital and 732 controls matched by age and sex. Vascular risk factors and anthropometric data (waist circumference, weight and height) were recorded. The impact of three anthropometric variables [body mass index (BMI), waist circumference and waist to height ratio] on ischemic stroke risk was calculated. These variables were divided into quartiles for a comprehensive comparison between cases and controls, stratified by sex and adjusted in logistic regression by age and vascular risk factors. Further logistic regression using dummy variables was performed to evaluate the association between BMI-adjusted abdominal obesity and stroke risk. RESULTS: Increased BMI was not associated with increased stroke risk overall or in women, but was a protective factor in men [P = 0.03; odds ratio (OR), 0.59 (0.37-0.94)]. Abdominal obesity was a risk factor for stroke in women, in both waist circumference [P < 0.001; OR, 5.79 (3.10-10.85)] and waist to height ratio [P < 0.001; OR, 3.61 (1.99-6.54)] analyses, but was not significant in men. When considered independently of BMI, abdominal obesity was a risk factor in both sexes, but the strength of the association was significantly higher in women. CONCLUSIONS: Increased BMI was related to a lower risk of stroke in men. Abdominal obesity was associated with ischemic stroke in women. The impact of abdominal obesity on stroke risk differs by sex.

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is not only an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina Human Methylation 450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n = 645) and validation in the Framingham Offspring Study (n = 2,542). Fourteen CpG sites located in nine genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP and SLC7A11) and 2 intergenic regions showed differential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation related to total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP and SLC7A11). These CpGs explained 0.7%, 9.5% and 18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genes SREBF2 and SREBF1 was inversely associated with methylation of their corresponding CpGs (P-value = 0.0042 and 0.0045, respectively) in participants of the GOLDN study (n = 98). In turn, SREBF1 expression was directly associated with HDL cholesterol (P-value = 0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1 and CPT1A were also associated with lipid profile. Further research is warranted to functionally validate these new loci and assess the causality of new and established associations between these differentially methylated loci and lipid metabolism.

Assessing long-term effects of eslicarbazepine acetate on lipid metabolism profile, sodium values and liver function tests.

INTRODUCTION: Older dibenzazepines with a carboxamide substitution have been demonstrated to cause deleterious effects on lipid metabolism profile, as well as frequent hyponatremia. The aim of our study is to assess the effects of eslicarbazepine acetate, a novel AED, on lipid metabolism profile, sodium values and liver function tests, as well as to compare them with previous effects of carbamazepine and oxcarbazepine. METHODS: This report describes a retrospective cohort study of 108 patients who were treated with eslicarbazepine. Of these patients, 52% had switched to eslicarbazepine from prior treatment with carbamazepine or oxcarbazepine. Laboratory values concerning lipid metabolism profile, liver function tests and sodium were assessed before and after beginning/switching treatment. Patients who began treatment or whose treatment for dyslipidemia was modified during the study period were excluded from the analysis. Co-medications that could impact lipid metabolism profile, sodium or hepatic function were kept stable during the study period. RESULTS: The mean total cholesterol of the entire group decreased significantly from prior pathological to normal values after beginning/switching treatment. The percentage of patients with pathological values decreased. Patients switching from prior carboxamides also showed significant reductions in mean LDL and triglycerides. Patients beginning treatment without prior carboxamides did not develop dyslipidemia after titration. A tendency for an increased percentage of patients with hyponatremia was detected in both groups. CONCLUSIONS: Compared with older carboxamides, eslicarbazepine acetate exhibits a safer profile related to lipid metabolism. No relevant changes were detected in liver function tests. Consequently, a vascular risk factor could be avoided in patients with chronic epilepsy, while hyponatremia still needs to be ruled out. Prospective studies are still needed.

Aproximación al conocimiento de las bases genéticas del ictus. Consorcio español de genética del ictus / Exploring the genetic basis of stroke. Spanish stroke genetics consortium

El presente artículo revisa la evolución de los estudios en genética del ictus desde la aproximación por gen candidato hasta los recientes estudios de genome wide association. Se destaca la complejidad de esta afección por sus muy variados mecanismos etiopatogénicos, las dificultades que comporta el estudio de su componente genético y las soluciones que se han aportado. Se subraya en especial el valor de las colaboraciones entre distintos centros, ya sea de manera puntual o sobre todo a través de la creación de consorcios estables. Esta estrategia actualmente se hace imprescindible a la hora de realizar estudios de alta calidad científica que permitan seguir avanzando en el conocimiento de las bases genéticas del ictus tanto en etiología, como en tratamiento y prevención

This article provides an overview of stroke genetics studies ranging from the candidate gene approach to more recent studies by the genome wide association. It highlights the complexity of stroke owing to its different aetiopathogenic mechanisms, the difficulties in studying its genetic component, and the solutions provided to date. The study emphasises the importance of cooperation between the different centres, whether this takes places occasionally or through the creation of lasting consortiums. This strategy is currently essential to the completion of high-quality scientific studies that allow researchers to gain a better knowledge of the genetic component of stroke as it relates to aetiology, treatment, and prevention

Exploring the genetic basis of stroke. Spanish stroke genetics consortium.

This article provides an overview of stroke genetics studies ranging from the candidate gene approach to more recent studies by the genome wide association. It highlights the complexity of stroke owing to its different aetiopathogenic mechanisms, the difficulties in studying its genetic component, and the solutions provided to date. The study emphasises the importance of cooperation between the different centres, whether this takes places occasionally or through the creation of lasting consortiums. This strategy is currently essential to the completion of high-quality scientific studies that allow researchers to gain a better knowledge of the genetic component of stroke as it relates to aetiology, treatment, and prevention.

Comparison between CHADS2 and CHA2 DS2 -VASc score in a stroke cohort with atrial fibrillation.

BACKGROUND AND PURPOSE: In patients with atrial fibrillation (AF), stroke risk stratification schemes have been developed to optimize antithrombotic treatment. The CHADS(2) score is frequently used but has limitations. The CHA(2) DS(2) -VASc score improves risk prediction. Our objectives are to describe CHADS(2) and CHA(2) DS(2) -VASc score distribution in a cohort of patients with AF and first-ever ischaemic stroke (FIS) and to identify differences in embolic risk stratification. METHODS: Our cohort included 589 patients with FIS, previous modified Rankin score ≤ 3, and non-valvular AF. We recorded demographic data, vascular risk factors, and antithrombotic pre-treatment. The CHADS(2) and CHA(2) DS(2) -VASc scores were calculated according to clinical status before stroke onset. RESULTS: In 186 (31.6%) patients, AF was previously unknown. Of patients with known AF and CHADS(2) ≥ 2 (n=320), only 103 (32.2%) were taking anticoagulants; more than half of these patients had an INR <2. The CHADS(2) score placed 142 (24.1%) patients in the low-intermediate risk (score ≤ 1) category compared with 21 (3.6%) with CHA(2) DS(2) -VASc, P < 0.001. Applying CHA(2) DS(2) -VASc reclassified 121 (85.2%) subjects in the CHADS(2) low-intermediate risk category as high risk (≥ 2), an indication for anticoagulants. Of the 21 patients who suffered a stroke despite their low CHA(2) DS(2) -VASc score (≤ 1), seven (33.3%) reported alcohol overuse, and six (28.5%) had a concomitant stroke etiology. CONCLUSIONS: About 25% of FIS patients with AF had a CHADS(2) score ≤ 1. Despite the high CHADS(2) score of our population, few patients received the recommended antithrombotic treatment according to their thromboembolic risk. Using the CHA(2) DS(2) -VASc schema significantly increased the percentage of patients indicated for anticoagulation.