Lipidomic signature of stroke recurrence after transient ischemic attack.

While TIA patients have transient symptoms, they should not be underestimated, as they could have an underlying pathology that may lead to a subsequent stroke: stroke recurrence (SR). Previously, it has been described the involvement of lipids in different vascular diseases. The aim of the current study was to perform a lipidomic analysis to identify differences in the lipidomic profile between patients with SR and patients without. Untargeted lipidomic analysis was performed in plasma samples of 460 consecutive TIA patients recruited < 24 h after the onset of symptoms. 37 (8%) patients suffered SR at 90 days. Lipidomic profiling disclosed 7 lipid species differentially expressed between groups: 5 triacylglycerides (TG), 1 diacylglyceride (DG), and 1 alkenyl-PE (plasmalogen) [specifically, TG(56:1), TG(63:0), TG(58:2), TG(50:5), TG(53:7, DG(38:5)) and PE(P-18:0/18:2)]. 6 of these 7 lipid species belonged to the glycerolipid family and a plasmalogen, pointing to bioenergetics pathways, as well as oxidative stress response. In this context, it was proposed the PE(P-18:0/18:2) as potential biomarker of SR condition.The observed changes in lipid patterns suggest pathophysiological mechanisms associated with lipid droplets metabolism and antioxidant protection that is translated to plasma level as consequence of a more intensive or high-risk ischemic condition related to SR.

La influencia de la gestión organizativa en el tiempo puerta-aguja del tratamiento fibrinolítico / The influence of organisational management on door-to-needle times for fibrinolytic treatment

Introducción: El tiempo puerta-aguja (TPA) es el principal indicador del proceso del código ictus (CI). Según la guía de 2018 de la American Heart Association/American Stroke Associa-tion, el objetivo TPA debe ser inferior a 45 minutos. Para conseguirlo son necesarios protocolos eficaces y revisados de actuación extrahospitalaria e intrahospitalaria. Método: Analizamos la influencia de cambios organizativos entre 2011 y 2019 en el TPA y en la evolución clínica de los pacientes tratados con fibrinólisis. Utilizamos los datos de nuestro centro monitorizados y custodiados por el Pla Director en l’àmbit de la Malaltia Vascular Cerebral dela Generalitat de Catalunya. Entre otras medidas se han analizado las diferencias entre los a ̃nos y las derivadas de la implantación del modelo Helsinki. Resultados: Se estudiaron 447 pacientes, existiendo diferencias estadísticamente significativas en el TPA entre los diferentes a ̃nos. La activación del CI de forma extrahospitalaria en 315(70,5%) pacientes redujo el TPA una mediana de 14 minutos. Sin embargo, el modelo de regresión lineal sólo evidenció una relación inversamente proporcional entre la adopción del modelo deCI Helsinki (MH) y el TPA (coeficiente beta −0,42; p < 0,001). La eliminación de la figura delneurólogo vascular tras la adopción del MH empeoró el TPA y la mortalidad a los 90 días.Conclusión: El modelo organizativo influye en el TPA, siendo en nuestra muestra la aplicacióndel MH, la existencia de la figura del neurólogo vascular referente y la prenotificación del CIfactores claves para la reducción del TPA y la mejora clínica del paciente.(AU)

Introduction: Door-to-needle time (DNT) has been established as the main indicator in codestroke protocols. According to the 2018 guidelines of the American Heart Association/AmericanStroke Association, DNT should be less than 45 minutes; therefore, effective and revised pre-admission and in-hospital protocols are required. Method: We analysed organisational changes made between 2011 and 2019 and their influenceon DNT and the clinical progression of patients treated with fibrinolysis. We collected datafrom our centre, stored and monitored under the Master Plan for Cerebrovascular Disease ofthe regional government of Catalonia. Among other measures, we analysed the differencesbetween years and differences derived from the implementation of the Helsinki model.Results: The study included 447 patients, and we observed significant differences in DNTbetween different years. Pre-hospital code stroke activation, recorded in 315 cases (70.5%),reduced DNT by a median of 14 minutes. However, the linear regression model only showed aninversely proportional relationship between the adoption of the Helsinki code stroke model andDNT (beta coefficient, —0.42; P < .001). The removal of vascular neurologists after the adoptionof the Helsinki model increased DNT and the 90-day mortality rate. Conclusion: DNT is influenced by the organisational model. In our sample, the application ofthe Helsinki model, the role of the lead vascular neurologist, and notification of code strokeby pre-hospital emergency services are key factors for the reduction of DNT and the clinicalimprovement of the patient.(AU)

The influence of organisational management on door-to-needle times for fibrinolytic treatment.

INTRODUCTION: Door-to-needle time (DNT) has been established as the main indicator in code stroke protocols. According to the 2018 guidelines of the American Heart Association/American Stroke Association, DNT should be less than 45minuts; therefore, effective and revised pre-admission and in-hospital protocols are required. METHOD: We analysed organisational changes made between 2011 and 2019 and their influence on DNT and the clinical progression of patients treated with fibrinolysis. We collected data from our centre, stored and monitored under the Master Plan for Cerebrovascular Disease of the regional government of Catalonia. Among other measures, we analysed the differences between years and differences derived from the implementation of the Helsinki model. RESULTS: The study included 447 patients, and we observed significant differences in DNT between different years. Pre-hospital code stroke activation, recorded in 315 cases (70.5%), reduced DNT by a median of 14minutes. However, the linear regression model only showed an inversely proportional relationship between the adoption of the Helsinki code stroke model and DNT (beta coefficient, -0.42; P<.001). The removal of vascular neurologists after the adoption of the Helsinki model increased DNT and the 90-day mortality rate. CONCLUSION: DNT is influenced by the organisational model. In our sample, the application of the Helsinki model, the role of the lead vascular neurologist, and notification of code stroke by pre-hospital emergency services are key factors for the reduction of DNT and the clinical improvement of the patient.

The influence of organisational management on door-to-needle times for fibrinolytic treatment. / La influencia de la gestión organizativa en el tiempo puerta-aguja del tratamiento fibrinolítico.

INTRODUCTION: Door-to-needle time (DNT) has been established as the main indicator in code stroke protocols. According to the 2018 guidelines of the American Heart Association/American Stroke Association, DNT should be less than 45minutes; therefore, effective and revised pre-admission and in-hospital protocols are required. METHOD: We analysed organisational changes made between 2011 and 2019 and their influence on DNT and the clinical progression of patients treated with fibrinolysis. We collected data from our centre, stored and monitored under the Master Plan for Cerebrovascular Disease of the regional government of Catalonia. Among other measures, we analysed the differences between years and differences derived from the implementation of the Helsinki model. RESULTS: The study included 447 patients, and we observed significant differences in DNT between different years. Pre-hospital code stroke activation, recorded in 315 cases (70.5%), reduced DNT by a median of 14minutes. However, the linear regression model only showed an inversely proportional relationship between the adoption of the Helsinki code stroke model and DNT (beta coefficient, -0.42; P<.001). The removal of vascular neurologists after the adoption of the Helsinki model increased DNT and the 90-day mortality rate. CONCLUSION: DNT is influenced by the organisational model. In our sample, the application of the Helsinki model, the role of the lead vascular neurologist, and notification of code stroke by pre-hospital emergency services are key factors for the reduction of DNT and the clinical improvement of the patient.

The determination of copeptin levels helps management decisions among transient ischaemic attack patients.

BACKGROUND: Most approaches to transient ischaemic attack (TIA) triage use clinical scores and vascular imaging; however, some biomarkers have been suggested to improve the prognosis of TIA patients. METHODS: Serum levels of copeptin, adiponectin, neopterin, neuron-specific enolase, high-sensitivity C-reactive protein, IL-6, N-terminal pro-B-type natriuretic peptide, S100ß, tumour necrosis factor-alpha and IL-1α as well as clinical characteristics were assessed on consecutive TIA patients during the first 24 h of the onset of symptoms. RESULTS: Among 237 consecutive TIA patients, 12 patients (5%) had a stroke within 7 days and 15 (6%) within 90 days. Among all candidate biomarkers analysed, only copeptin was significantly increased in patients with stroke recurrence (SR) within 7 days (P = 0.026) but not within 90 days. A cut-off point of 13.8 pmol/l was established with a great predictive negative value (97.4%). Large artery atherosclerosis (LAA) [hazard ratio (HR) 12.7, 95% CI 3.2-50.1, P < 0.001] and copeptin levels ≥13.8 pmol/l (HR 3.9, 95% CI 1.01-14.4, P = 0.039) were independent predictors of SR at the 7-day follow-up. LAA was the only predictor of 90-day SR (HR 7.4, 95% CI 2.5-21.6, P < 0.001). ABCD3I was associated with 7- and 90-day SRs (P = 0.025 and P = 0.034, respectively). The association between copeptin levels and LAA had a diagnostic accuracy of 90.3%. CONCLUSIONS: Serum copeptin could be an important prognostic biomarker to guide management decisions among TIA patients. Therefore, TIA patients with copeptin levels below 13.8 pmol/l and without LAA have an insignificant risk of 7-day SR and could be managed on an outpatient basis.

Prediction of myocardial infarction in patients with transient ischaemic attack.

BACKGROUND: Determinants of risk of myocardial infarction (MI) after transient ischaemic attack (TIA) are not well defined. The aim of our study was to determine the risk and risk factors for MI after TIA. METHODS: We prospectively recruited patients within 24 h of transient ischaemic cerebrovascular events between October 2006 and January 2013. A total of 628 TIA patients were followed for six months or more. MI and stroke recurrence (SR) were recorded. The duration and typology of clinical symptoms, vascular risk factors and aetiological work-ups were prospectively recorded and established prognostic scores (ABCD2, ABCD2I, ABCD3I, Essen Stroke Risk Score, California Risk Score and Stroke Prognosis Instrument) were calculated. RESULTS: Twenty-eight (4.5%) MI and 68 (11.0%) recurrent strokes occurred during a median follow-up period of 31.2 months (16.1-44.9). In Cox proportional hazards multivariate analyses, we identify previous coronary heart disease (CHD) (hazard ratio [HR] 5.65, 95% confidence interval [CI] 2.45-13.04, P < 0.001) and sex male (HR 2.72, 95% CI 1.02-7.30, P = 0.046) as independent predictors of MI. Discrimination for the prognostic scores only ranged from 0.60 to 0.71. The incidence of MI did not vary among the different aetiological subtypes. Positive diffusion weighted imaging (DWI) (7.5% vs 2.5%, P = 0.007), and ECG abnormalities (Q wave or ST-T wave changes) (13.6% vs 3.6%, P = 0.001) were associated to MI. CONCLUSION: According to our results, discrimination was poor for all previous risk prediction models evaluated. Variables such as previous CHD, male sex, DWI and ECG abnormalities should be considered in new prediction models.

N-terminal pro-brain natriuretic peptide level determined at different times identifies transient ischaemic attack patients with atrial fibrillation.

BACKGROUND AND PURPOSE: The etiological classification of patients with transient ischaemic attack (TIA) is a difficult endeavor and the use of serum biomarkers could improve the diagnostic accuracy. The aim of this study was to correlate atrial fibrillation, the main cardioembolic etiology (CE), with different serum biomarkers measured in consecutive TIA patients. METHODS: The concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha, neuron-specific enolase, high-sensitivity C-reactive protein, IL-1-α and the N-terminal pro-B type natriuretic peptide (NT-proBNP) were quantified in the serum of 140 patients with TIA and 44 non-stroke subjects. Measurements were performed at different times throughout evolution: within 24 h of symptoms onset and at days 7 and 90. RESULTS: With the exception of IL-6, all biomarkers were higher in TIA patients than in controls. NT-proBNP was significantly related to the presence or new diagnosis of AF at all time points analyzed. Furthermore, the baseline NT-proBNP level was significantly higher than values at the 7-day and 90-day follow-up. For this reason, different cut-off values were obtained at different times: 313 pg/ml at baseline [odds ratio (OR) = 18.99, P < 0.001], 181 pg/ml at 7 days (OR = 11.4, P = 0.001) and 174 pg/ml (OR = 8.46, P < 0.001) at 90 days. CONCLUSION: High levels of NT-proBNP determined during the first 3 months after a TIA were associated with AF. Consequently, this biomarker may be useful to reclassify undetermined TIA patients as having disease of CE.

Predictive value of brain and vascular imaging including intracranial vessels in transient ischaemic attack patients: external validation of the ABCD3-I score.

BACKGROUND AND PURPOSE: Recently, brain and vascular imaging have been added to clinical variables to identify patients with transient ischaemic attack (TIA) with a high risk of stroke recurrence. The aim of our study was to externally validate the ABCD3-I score and the same score taking into account intracranial circulation. METHODS: We analyzed data from 1137 patients with TIA from the PROMAPA study who underwent diffusion-weighted magnetic resonance imaging (DWI) within 7 days of symptom onset. Clinical variables and diagnostic work-up were recorded prospectively. The end-points were subsequent stroke at 7 and 90 days follow-up. RESULTS: A total of 463 (40.7%) subjects fulfilled all inclusion criteria. During follow-up, eight patients (1.7%) had a stroke within 7 days, and 14 (3.1%) had a stroke within 3 months. In the Cox proportional hazard multivariate analyses, the combination of large-artery atherosclerosis and positive DWI remained as independent predictors of stroke recurrence at 7- and 90-day follow-up [HR 8.23, 95% confidence interval (CI) 2.89-23.46, P < 0.001]. The ABCD3-I score was a powerful predictor of subsequent stroke. The area under the receiver operating characteristic curve was 0.83 (95% CI 0.72-0.93) at 7 days and 0.69 (95% CI 0.53-0.85) at 90 days. When we include intracranial vessel disease in the score, the area under the curve increases but the difference observed was non-significant. CONCLUSION: The inclusion of vascular and neuroimaging information to clinical scales (ABCD3-I score) provides important prognostic information and also helps management decisions, although it cannot give a complete distinction between high-risk and low-risk groups.

[Neurological disorders associated with gluten sensitivity]. / Neurogluten: patologia neurologica por intolerancia al gluten.

Gluten sensitivity is a systemic autoimmune disease that occurs in genetically susceptible individuals on ingesting gluten. It can appear at any age, then becoming a permanent condition. It is more frequent in women, as happens with other autoimmune diseases. Celiac disease is the intestinal form and the most important manifestation among a set of gluten-induced autoimmune pathologies that affect different systems. Neurological manifestations of gluten sensitivity, with or without enteropathy, are also frequent, their pathogenesis including an immunological attack on the central and peripheral nervous tissue accompanied by neurodegenerative changes. The clinical manifestations are varied, but the most common syndromes are cerebellar ataxia and peripheral neuropathy. Finally, gluten sensitivity is associated to a varying degree, with other complex diseases and could influence their evolution. The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.