Comparison of the impact of atrial fibrillation on the risk of early death after stroke in women versus men

BACKGROUND: Atrial fibrillation (AF) is considered a predictive factor of poor clinical outcome in patients with an ischemic stroke (IS). This study addressed whether the impact of AF on the in-hospital mortality after first ever IS is different according to the patient’s gender. METHODS: We prospectively studied 1678 patients with first ever IS consecutively admitted to two University Hospitals. We recorded demographic data, vascular risk factors, and the stroke severity (NIHSS) at admission analyzing their impact on the in-hospital mortality and on the combined mortality-dependency at discharge using a Cox proportional hazards model. Two variable interactions between those factors independently related to in-hospital mortality and combined mortality-dependency at discharge were tested. RESULTS: Overall in-hospital mortality was 11.3%. Cox proportional hazards model showed that NIHSS at admission (HR: 1.178 [95% CI 1.149–1.207]), age (HR: 1.044 [95% CI 1.026–1.061]), AF (HR: 1.416 [95% CI 1.048–1.913]), male gender (HR: 1.853 [95% CI 1.323–2.192) and ischemic heart disease (HR: 1.527 [95% CI 1.063–2.192]) were independent predictors of in-hospital mortality. A significant interaction between gender and AF was found (p = 0.017). Data were stratified by gender, showing that AF was an independent predictor of poor outcome just for woman (HR: 2.183 [95% CI 1.403–3.396]; p < 0.001). The independent predictors of combined mortality-disability at discharge were NIHSS at admission (HR: 1.052 [95% CI 1.041–1.063]), age (HR: 1.011 [95% CI 1.004–1.018]), AF (HR: 1.197 [95% CI 1.031–1.390]), ischemic heart disease (HR: 1.222 [95% CI 1.004–1.488]), and smoking (HR: 1.262 [95% CI 1.033–1.541]). CONCLUSIONS: The impact of AF is different in the twogenders and appears as a specific ischemic stroke predictor of in-hospital mortality just for women

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model

IMPORTANCE: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. OBJECTIVE: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. EXPOSURES: Type of acute symptomatic seizure. MAIN OUTCOMES AND MEASURES: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). RESULTS: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. CONCLUSIONS AND RELEVANCE: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up

PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis

RATIONALE: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. METHODS AND RESULTS: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P=1.70×10-9). CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Impacto social del ictus producido por fibrilación auricular

Resumen: La fibrilación auricular (FA) es la arritmia cardíaca más frecuente y responsable de un porcentaje importante de ictus isquémicos; como tal tiene su impacto en la gravedad del ictus y en la morbimortalidad de éste. Su importancia como factor etiológico del ictus aumenta con la edad, y además estamos asistiendo a un aumento de su detección en las últimas décadas. La presencia de FA condiciona una mayor intensidad del déficit neurológico inicial, una estancia hospitalaria más prolongada y una peor evolución funcional con mayor discapacidad y menor probabilidad de poder volver al domicilio habitual; además, es un factor de riesgo independiente de mortalidad, especialmente en mujeres y en población de edad avanzada. Todo esto conlleva que los pacientes con ictus con FA presenten un mayor impacto socioeconómico. Abstract: Atrial fibrillation (AF) is the most frequent heart arrhythmia and causes a substantial proportion of ischemic strokes. AF has a marked impact on stroke severity, as well as on morbidity and mortality in these patients. The importance of AF as an etiologic factor of stroke increases in the elderly and in the last few years its detection has increased. The presence of AF leads to more severe initial neurological involvement, longer hospitalization, greater disability and a lower probability of discharge to home. In addition, AF is an independent risk factor for mortality, especially in women and the elderly. All these factors lead to a higher social and economic impact among stroke patients with AF. Palabras clave: Ictus, Fibrilación auricular, Impacto, Keywords: Stroke, Atrial fibrillation, Impac

Descriptive analysis of neurological in-hospital consultations in a tertiary hospital

Introduction: In-hospital consultations (IHCs) are essential in clinical practice in tertiary hospitals. The aim of this study is to analyse the impact of neurological IHCs. Patients and method: One-year retrospective descriptive study of neurological IHCs conducted from May 2013 to April 2014 at our tertiary hospital. Results: A total of 472 patients were included (mean age, 62.1 years; male patients, 56.8%) and 24.4% had previously been evaluated by a neurologist. Patients were hospitalised a median of 18 days and 19.7% had been referred by another hospital. The departments requesting the most in-hospital consultations were intensive care (20.1%), internal medicine (14.4%), and cardiology (9.1%). Reasons for requesting an IHC were stroke (26.9%), epilepsy (20.6%), and confusional states (7.6%). An on-call neurologist evaluated 41.9% of the patients. The purpose of the IHC was to provide a diagnosis in 56.3% and treatment in 28.2% of the cases; 69.5% of the patients required additional tests. Treatment was adjusted in 18.9% of patients and additional drugs were administered to 27.3%. While 62.1% of cases required no additional IHCs, 11% required further assessment, and 4.9% were transferred to the neurology department. Of the patient total, 16.9% died during hospitalisation (in 37.5%, the purpose of the consultation was to certify brain death); 45.6% were referred to the neurology department at discharge and 6.1% visited the emergency department due to neurological impairment within 6 months of discharge. Conclusions: IHCs facilitate diagnosis and management of patients with neurological diseases, which may help reduce the number of visits to the emergency department. On-call neurologists are essential in tertiary hospitals, and they are frequently asked to diagnose brain death. Resumen: Introducción: Las consultas intrahospitalarias (IC) son fundamentales en la actividad asistencial dentro de un hospital de tercer nivel. El objetivo de este estudio es analizar y cuantificar el impacto de las mismas. Pacientes y método: Estudio descriptivo retrospectivo de las IC realizadas a Neurología durante un año (período: mayo del 2013-abril del 2014) en nuestro centro. Resultados: Se incluyó a 472 pacientes (edad media 62,1, varones 56,8%). Previamente, el 24,4% había sido valorado por un neurólogo. Mediana de 18 días de ingreso y el 19,7% de ellos fueron derivados desde otro hospital. Servicios más demandantes: Medicina Intensiva 20,1%, Medicina Interna 14,4% y Cardiología 9,1%. Motivos IC: ictus 26,9%, epilepsia 20,6% y cuadros confusionales 7,6%. El 41,9% fue valorado por un neurólogo de guardia. Objetivo IC: diagnóstico 56,3% y tratamiento 28,2%. En el 69,5% de los casos fueron necesarias pruebas complementarias. En el 18,9% se ajustó el tratamiento y se introdujo al menos un medicamento en 27,3%. El 62,1% de las IC se resolvieron con una valoración. El 11% precisó revaluación y un 4,9% fue trasladado a Neurología. El 16,9% delos pacientes fallecieron durante ingreso (de ellos, en el 37,5% el motivo fue el diagnóstico de muerte encefálica). El 45,6% fue derivado a Neurología al alta y consultó en Urgencias un 6,1% por motivos neurológicos en los 6 meses posteriores al alta. Conclusiones: Las IC facilitan el diagnóstico y el manejo de pacientes con enfermedades neurológicas, posiblemente disminuyendo las consultas de estos pacientes en Urgencias. En un hospital terciario, es destacable la labor del neurólogo de guardia y la importancia del diagnóstico de muerte encefálica. Keywords: Hospital Vall d’Hebron, In-hospital consultation, Brain death, On-call neurologist, Intensive Care Unit, Palabras clave: Hospital Vall d’Hebron, Interconsulta, Muerte encefálica, Neurólogo de guardia, Unidad de Cuidados Intensivo