Search

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself.

Background and Purpose: Mechanical thrombectomy (MT) in ischemic stroke patients with poor prestroke conditions remains controversial. We aimed to analyze the frequency of previously disabled patients treated with MT in clinical practice, the safety and clinical response to MT of patients with preexisting disability, and the disabled patient characteristics associated with a better response to MT. Methods: We studied all consecutive patients with anterior circulation occlusion treated with MT from January 2017 to December 2019 included in the Codi Ictus Catalunya registry—a government-mandated, prospective, hospital-based data set. Prestroke disability was defined as modified Rankin Scale score 2 or 3. Functional outcome at 90 days was centrally assessed by a blinded evaluator of the Catalan Stroke Program. Favorable outcome (to return at least to prestroke modified Rankin Scale at 90 days) and safety and secondary outcomes were compared with patients without previous disability. Logistic regression analysis was used to assess the association between prestroke disability and outcomes and to identify a disabled patient profile with favorable outcome after MT. Results: Of 2487 patients included in the study, 409 (17.1%) had prestroke disability (313 modified Rankin Scale score 2 and 96 modified Rankin Scale score 3). After adjustment for covariates, prestroke disability was not associated with a lower chance of achieving favorable outcome at 90 days (24% versus 30%; odds ratio, 0.79 [0.57–1.08]), whereas it was independently associated with a higher risk of symptomatic intracranial hemorrhage (5% versus 3%; odds ratio, 2.04 [1.11–3.72]) and long-term mortality (31% versus 18%; odds ratio, 1.74 [1.27–2.39]) compared with patients without disability. Prestroke disabled patients without diabetes, Alberta Stroke Program Early CT Score >8 and National Institutes of Health Stroke Scale score Conclusions: Despite a higher mortality and risk of symptomatic intracranial hemorrhage, prestroke-disabled patients return as often as independent patients to their prestroke level of function, especially those nondiabetic patients with favorable early ischemic signs profile. These data support a potential benefit of MT in patients with previous mild or moderate disability after large anterior vessel occlusion stroke.

Objective: To assess whether the effect of intravenous thrombolysis in patients with large-vessel occlusion differed between patients directly admitted to thrombectomy-capable centers and patients transferred from local stroke centers without thrombectomy capabilities. Methods: We included 3206 patients with an acute ischemic large-vessel stroke with first imaging within 7 hours after onset that were directly admitted to thrombectomy-capable centers and treated with thrombectomy, or transferred from local stroke centers for thrombectomy evaluation, between 2017 and 2021 in Catalonia, Spain. Primary outcome was the degree of disability at 90 days, as evaluated by the shift analysis on the mRs score. Secondary outcomes included mortality at 90 days and the rate of parenchymal hemorrhage and successful reperfusion. Inverse-probability weighting clustered at the type of stroke center was used to estimate the effects. Results: The analysis included 2268 patients (975[49%] treated with thrombolysis) directly admitted to thrombectomy-capable centers and 938 patients (580[66%] treated with thrombolysis and 616[67%] treated with thrombectomy) transferred from local stroke centers (mean age 72±13 years, median NIHSS score 17[IQR 12-21], 1363 female[48%]). Patients treated with intravenous thrombolysis were younger, had shorter time from onset to first image acquisition, and higher rates of wake-up stroke, atrial fibrillation and anticoagulation intake. The effect of intravenous thrombolysis on the primary outcome was similar in patients directly admitted to thrombectomy-capable centers (acOR 1.50, 95% CI 1.24-1.81) and patients transferred from local stroke centers (acOR 1.44, 95% CI 1.04 to 2.01)(p interaction =0.68). Patients treated with intravenous thrombolysis had lower mortality rate, higher rate of parenchymal hematoma and similar rate of successful reperfusion, with no difference according to type of center (p interaction >0.1). Conclusion: Administration of intravenous thrombolysis in patients with a large-vessel stroke with intention to thrombectomy was associated with higher odds of good functional outcome and higher rates of parenchymal hematoma, independently of the type of stroke center were it was administered.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body’s first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Atherosclerosis is responsible for 20% of ischemic strokes, and severe carotid stenosis is associated with a higher incidence of first-ever and recurrent strokes. The release of pro-inflammatory mediators into the blood in severe atherosclerosis may aggravate endothelial dysfunction after stroke contributing to impair disease outcomes. We hypothesize that environments of severe carotid atherosclerotic disease worsen endothelial dysfunction in stroke linked to enhanced risk of further cerebrovascular events. We mounted nonischemic common carotid arteries from 2- to 4-month-old male Oncins France 1 mice in tissue baths for isometric contraction force measurements and exposed them to serum from men with a recent ischemic stroke and different degrees of carotid stenosis: low- or moderate-grade stenosis (LMGS

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Background and Purpose: The minor stroke concept has not been analyzed in intracerebral hemorrhage (ICH) patients. Our purpose was to determine the optimal cut point on the NIH Stroke Scale (NIHSS) for defining a minor ICH (mICH) in patients with primary ICH. Methods: An ICH was considered minor if associated with a favorable 3-month outcome (modified Rankin Scale score ≤2). For supratentorial ICH, the discovery cohort consisted of 478 patients prospectively admitted at University Hospital del Mar. Association between NIHSS at admission and 3-month outcome was evaluated with area under the curve-receiver operating characteristics (AUC-ROC) and Youden’s index to identify the optimal NIHSS cutoff point to define mICH. External validation was performed in a cohort of 242 supratentorial ICH patients from University Hospital Sant Pau. For infratentorial location, patients from both hospitals ( n = 85) were analyzed together. Results: The best ­NIHSS cutoff point defining supratentorial-mICH was 6 (AUC-ROC = 0.815 [0.774–0.857] in the discovery cohort and AUC-ROC = 0.819 [0.756–0.882] in the external validation cohort). For infratentorial ICH, the best cutoff point was 4 (AUC-ROC = 0.771 [0.664–0.877]). Using these cutoff points, 40.5% of all primary ICH cases were mICH. Of these, 70.2% were living independently at 3-month follow-up (72% for supratentorial ICH and 56.1% for infratentorial ICH) and 6.5% had died (5.3% for supratentorial ICH, and 14.6% for infratentorial ICH). For patients identified as non-mICH, good 3-month outcome was observed in 11.3% of cases; mortality was 51%. Conclusions: The definition of mICH using the NIHSS cutoff point of 6 for supratentorial ICH and 4 for infratentorial ICH is useful to identify good outcome in ICH patients.

Background and Purpose: Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source. Methods: Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily. Results: During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7–4.3]), East Asia region (HR, 2.5 [95% CI, 1.6–3.9]), systolic blood pressure ≥160 mm Hg (HR, 2.2 [95% CI, 1.2–3.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL/min per 1.73 m 2 decrease, [95% CI, 1.0–1.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2–18.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin. Conclusions: Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.

Background: Speed of administration conditions the effectiveness of intravenous fibrinolysis in treating acute ischaemic stroke. To reduce the risk of haemorrhagic complications, the intervention is contraindicated in certain cases, such as where the International Normalised Ratio (INR) is ≥1.7. This study aimed to determine the reliability of point-of-care INR readings (POC-INR) taken using the CoaguChek® XS portable coagulometer compared to laboratory results (L-INR). Methods: We conducted a retrospective observational study of consecutive patients admitted to our centre with acute ischaemic stroke and who were treated with intravenous fibrinolysis, over a period of 4 years. Patients’ INR was measured with a portable coagulometer and in the laboratory. Results were compared using the paired-sample t test; using L-INR results as a reference value, ROC analysis was performed to determine POC-INR with greater predictive value. Results: The study included 210 patients with a mean age of 74.3 ± 11.5 years old; 18 (8.6%) were taking vitamin K antagonist oral anticoagulants (OAC). There were no significant differences between the 2 INR measurements in the population as a whole (POC-INR–L-INR difference: 0.001 ± 0.085; P = .82). In subgroup analysis, the results coincided for patients taking OACs (0.001 ± 0.081; P = .42) and those with L-INR ≤ 1.2 (0.008 ± 0.081; P = .16). For L-INR > 1.2, however, the portable coagulometer underestimated INR (0.058 ± 0.095; P = .01). Through ROC analysis, POC-INR 1,2, CPINR infraestimó la INR (diferencia LINR-CPINR 0,058 ± 0,095; p = 0,01). Mediante análisis ROC una CPINR < 1,6 fue el punto de corte más sensible y específico para seleccionar pacientes tratables con fibrinólisis intravenosa (LINR < 1,7). Conclusiones: El CP en el código ictus tiene una buena concordancia con el laboratorio. Este estudio indica que en nuestro centro una CPINR < 1,6 es el mejor umbral para predecir una LINR< 1,7. La validación de la CPINR en cada centro es recomendable para su uso protocolizado.

Resumen: Introducción: La eficacia de la fibrinólisis intravenosa como tratamiento en el ictus isquémico agudo depende de la rapidez en su administración. Para reducir el riesgo de complicaciones hemorrágicas existen contraindicaciones, como una INR ≥ 1,7. Nuestro objetivo fue determinar la fiabilidad del valor de INR obtenido mediante el coagulómetro portátil (CP) CoaguChek XS® (CPINR) frente al resultado del laboratorio (LINR). Métodos: Estudio retrospectivo observacional de pacientes consecutivos con ictus isquémico tratados con fibrinólisis intravenosa en nuestro centro durante 4 años. La INR fue medida con CP y en el laboratorio. Se compararon ambos valores mediante t de Student para datos apareados y, tomando como referencia la LINR, se realizó análisis ROC para determinar la CPINR con mayor valor predictivo. Resultados: Analizamos a 210 pacientes, con edad media 74,3 ± 11,5 años, y 18 (8,6%) tomaban anticoagulantes orales antivitamina K. Se compararon LINR y CPINR sin evidenciarse diferencias significativas (diferencia LINR-CPINR –0,001 ± 0,085; p = 0,82). En el análisis por subgrupos: para pacientes con anticoagulantes orales (diferencia LINR-CPINR 0,001 ± 0,081; p = 0,42) y para LINR ≤ 1,2 (diferencia LINR-CPINR –0,008 ± 0,081; p = 0,16) ambas técnicas fueron concordantes, mientras que para LINR > 1,2, CPINR infraestimó la INR (diferencia LINR-CPINR 0,058 ± 0,095; p = 0,01). Mediante análisis ROC una CPINR < 1,6 fue el punto de corte más sensible y específico para seleccionar pacientes tratables con fibrinólisis intravenosa (LINR < 1,7). Conclusiones: El CP en el código ictus tiene una buena concordancia con el laboratorio. Este estudio indica que en nuestro centro una CPINR < 1,6 es el mejor umbral para predecir una LINR< 1,7. La validación de la CPINR en cada centro es recomendable para su uso protocolizado. Abstract: Background: Speed of administration conditions the effectiveness of intravenous fibrinolysis in treating acute ischaemic stroke. To reduce the risk of haemorrhagic complications, the intervention is contraindicated in certain cases, such as where the International Normalised Ratio (INR) is ≥ 1.7. This study aimed to determine the reliability of point-of-care INR readings (POC-INR) taken using the CoaguChek® XS portable coagulometer compared to laboratory results (L-INR). Methods: We conducted a retrospective observational study of consecutive patients admitted to our centre with acute ischaemic stroke and who were treated with intravenous fibrinolysis, over a period of 4 years. Patients’ INR was measured with a portable coagulometer and in the laboratory. Results were compared using the paired-sample t test; using L-INR results as a reference value, ROC analysis was performed to determine POC-INR with greater predictive value. Results: The study included 210 patients with a mean age of 74.3 ± 11.5 years old; 18 (8.6%) were taking vitamin K antagonist oral anticoagulants (OAC). There were no significant differences between the 2 INR measurements in the population as a whole (POC-INR–L-INR difference: 0.001 ± 0.085; P=.82). In subgroup analysis, the results coincided for patients taking OACs (0.001 ± 0.081; P=.42) and those with L-INR ≤ 1.2 (0.008 ± 0.081; P=.16). For L-INR > 1.2, however, the portable coagulometer underestimated INR (0.058 ± 0.095; P=.01). Through ROC analysis, POC-INR < 1.6 was found to be the cut-off point with greatest sensitivity (100%) and specificity (98.97%) for identifying patients eligible for intravenous fibrinolysis (L-INR < 1.7). Conclusions: POC-INR shows a good correlation with L-INR. Our results suggest that the best threshold to predict an L-INR < 1.7 is POC-INR < 1.6. Internal validation studies for POC-INR should be considered in all treatment centres. Palabras clave: Ictus isquémico, Urgencias, International Normalized Ratio, Anticoagulantes orales, Coagulómetro, Fibrinólisis, Keywords: Ischaemic stroke, Emergency department, International Normalized Ratio, Oral anticoagulants, Coagulometer, Fibrinolysis

BACKGROUND AND PURPOSE Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. METHODS Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. RESULTS Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. CONCLUSIONS Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909).

Background and purpose Plaque neovascularization is a hallmark of carotid plaque vulnerability. With contrast-enhanced ultrasound (CEUS) it is possible to visualize plaque neovessels in vivo. Our aim was to determine if CEUS-detected neovessels were associated with stroke recurrences in patients with a recent stroke and carotid atherosclerosis. Methods We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the internal carotid artery on the side consistent with symptoms. All of our patients underwent a carotid ultrasound examination including a CEUS study. Neovascularization was graded into three categories according to the extent of neovessels. During the follow-up, we recorded stroke recurrences. A multivariable Cox regression analysis was performed to evaluate predictors of recurrence. Results We included 78 patients whose mean age was 74.3 +/- 10.4 years. There were 29 (37.2%) patients with a low-grade stenosis (= 70%) stenosis. CEUS was not interpretable in 35.9% of the patients, mainly due to calcium shadows. We detected neovascularization in 80% of the plaques. After a median follow-up of 14.1 (interquartile range, 9.5-19.6) months, there were 15 (19.2%) stroke recurrences. In the Cox regression analysis, CEUS-detected neovascularization was independently associated with the risk of stroke recurrence, even after adjusting for the degree of stenosis (hazard ratio, 6.57; 95% confidence interval, 1.66-26.01). Conclusion In patients with an anterior circulation ischaemic stroke and carotid atherosclerosis, plaque neovascularization detected with CEUS was an independent predictor of stroke recurrence.

Resumen: Introducción: El uso de anticoagulantes orales es controvertido en pacientes con antecedentes de fibrilación auricular (FA) y hemorragia intracraneal (HIC), por riesgo de recurrencia de ictus hemorrágico. Presentamos la experiencia de nuestro centro en relación con la seguridad y la eficacia del cierre percutáneo de orejuela (CPO), una alternativa a la anticoagulación en dicho contexto. Métodos: Estudio observacional, retrospectivo y unicéntrico. El CPO se realizó en pacientes con antecedentes de HIC y FA no valvular. El riesgo de eventos isquémicos y hemorrágicos se estimó usando las escalas CHA2DS2Vasc y HAS-BLED. Se registraron: complicaciones periprocedimiento, recurrencia de HIC, embolismo cerebral/sistémico, mortalidad tras el cierre y al seguimiento y uso de antitrombóticos tras el procedimiento. Resultados: El CPO se realizó en 9 pacientes (7 hombres, 2 mujeres). Se utilizó en 7 casos el dispositivo Amplatzer Amulet y en 2 el Amplatzer Cardiac Plug. La media de edad fue 72,7 ± 8,2 años. El tiempo entre la HIC y el CPO fue menor de un mes en 5 pacientes y mayor en 4. La mediana y el rango intercuartil para la escala CHA2DS2Vasc fueron de 4 y 2,5, respectivamente, siendo de 3 y 0 para la escala HAS-BLED. No hubo complicaciones periprocedimiento. Todos recibieron antiagregación simple tras el procedimiento (5 clopidogrel y 4 aspirina); en 5 se mantuvo 6 meses, en 4 indefinidamente. Durante el seguimiento (15 meses de promedio) no se registraron eventos isquémicos ni hemorrágicos. Conclusiones: En nuestra serie, el CPO supone una alternativa segura y eficaz en pacientes que han presentado HIC y que precisan ser anticoagulados por FA. Abstract: Introduction: The use of oral anticoagulants in patients with a history of atrial fibrillation (AF) and intracranial haemorrhage (ICH) is controversial on account of the risk of haemorrhagic stroke recurrence. This study presents our experience regarding the safety and efficacy of percutaneous left atrial appendage closure (LAAC), an alternative to anticoagulation in these patients. Methods: We conducted a retrospective, single-centre, observational study. LAAC was performed in patients with a history of ICH and non-valvular AF. Risk of ischaemic and haemorrhagic events was estimated using the CHA2DS2-VASc and HAS-BLED scales. We recorded periprocedural complications, IHC recurrence, cerebral/systemic embolism, mortality and use of antithrombotic drugs following the procedure. Results: LAAC was performed in 9 patients (7 men, 2 women) using the AMPLATZER Amulet device in 7 cases and the AMPLATZER Cardiac Plug device in 2. Mean age was 72.7 ± 8.2 years. Time between ICH and LAAC was less than one month in 5 patients and more than one month in 4 patients. Median CHA2DS2-VASc score was 4 (interquartile range of 2.5). Median HAS-BLED score was 3 (interquartile range of 0). No periprocedural complications were recorded. All patients received single anti-platelet therapy (clopidogrel in 5 patients, aspirin in 4) after the procedure; 5 patients received this treatment for 6 months and 4 received it indefinitely. No ischaemic or haemorrhagic events were recorded during follow-up (mean duration of 15 months). Conclusions: In our series, LAAC was found to be safe and effective in patients with a history of ICH who required anticoagulation due to AF. Palabras clave: Cierre percutáneo de orejuela, Fibrilación auricular, Hemorragia intracraneal, Anticoagulación oral, Keywords: Left atrial appendage closure, Atrial fibrillation, Intracranial haemorrhage, Oral anticoagulation

Contains fulltext : 220280.pdf (Publisher’s version ) (Closed access)

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); 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, This work was supported by EPIGENESIS (Epigenetic and Genetic Study Combined With Integromics and Functional Analysis to Find Genes Associated With Neurological Deterioration After Ischemic Stroke) project (Carlos III Institute (PI17/02089,); Marató TV3; MAESTRO project (Carlos III Institute, PI18/01338); SEDMAN study (Dabigatran Study in the Early Phase of Stroke, New Neuroimaging Markers and Biomarkers; Boehringer Ingelheim); BasicMar Register projects from the Carlos III Health Institute, and Ibiostroke (Eranet Neuron). Dr Fernandez-Cadenas is a recipient of a research contract from Miguel Servet Program; Dr Gallego-Fabrega is supported by a Sara Borrell contract (CD20/00043), Dr Muiño is supported by a Río Hortega Contract (CM18/00198) and M. Lledós is supported by a PFIS (Contratos Predoctorales de Formación en Investigación en Salud) Contract, by Carlos III Health Institute (CPII17/00021). J. Cárcel-Márquez is supported by AGAUR Contract (agència de gestió d’ajuts universitaris i de recerca; FI_DGR 2019, grant number 2019_FI_B 00853) co-financed with Fons Social Europeu (FSE).

The spectrum of distribution of white matter hyperintensities (WMH) may reflect different functional, histopathological, and etiological features. We examined the relationships between cerebrovascular risk factors (CVRF) and different patterns of WMH in MRI using a qualitative visual scale in ischemic stroke (IS) patients. We assembled clinical data and imaging findings from patients of two independent cohorts with recent IS. MRI scans were evaluated using a modified visual scale from Fazekas, Wahlund, and Van Swieten. WMH distributions were analyzed separately in periventricular (PV-WMH) and deep (D-WMH) white matter, basal ganglia (BG-WMH), and brainstem (B-WMH). Presence of confluence of PV-WMH and D-WMH and anterior-versus-posterior WMH predominance were also evaluated. Statistical analysis was performed with SPSS software. We included 618 patients, with a mean age of 72 years (standard deviation [SD] 11 years). The most frequent WMH pattern was D-WMH (73%). In a multivariable analysis, hypertension was associated with PV-WMH (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.29–2.50, p = 0.001) and BG-WMH (OR 2.13, 95% CI 1.19–3.83, p = 0.012). Diabetes mellitus was significantly related to PV-WMH (OR 1.69, 95% CI 1.24–2.30, p = 0.001), D-WMH (OR 1.46, 95% CI 1.07–1.49, p = 0.017), and confluence patterns of D-WMH and PV-WMH (OR 1.62, 95% CI 1.07–2.47, p = 0.024). Hyperlipidemia was found to be independently related to brainstem distribution (OR 1.70, 95% CI 1.08–2.69, p = 0.022). Different CVRF profiles were significantly related to specific WMH spatial distribution patterns in a large IS cohort. • An observational study of WMH in a large IS cohort was assessed by a modified visual evaluation. • Different CVRF profiles were significantly related to specific WMH spatial distribution patterns. • Distinct WMH anatomical patterns could be related to different pathophysiological mechanisms.

18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) identifies carotid plaque inflammation and predicts stroke recurrence in patients with atherothrombotic stroke. The aim of the study was to identify plasma inflammatory biomarkers associated with plaque inflammation according to 18F-FDG uptake. We conducted a prospective study of consecutive adult patients with a recent (18F-FDG PET, and a blood sample was obtained at days 7 ± 1 from the stroke. The plasma concentration of 16 inflammation-related molecules was analyzed in a Luminex using xMAP technology. Multivariable linear regression was used to assess the association between plasma biomarkers and the standardized uptake value (SUV) of 18F-FDG uptake. Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and fractalkine (FKN) were independently associated with plaque inflammation (β = 0.121, 95% CI 0.061–0.181, p β = 0.144, 95% CI 0.012–0.276, p = 0.033; β = 0.136, 95% CI 0.037–0.235, p = 0.008). In a multivariable logistic regression analysis, sICAM-1 was associated with SUVmax ≥ 2.85 (OR = 1.02, 95% CI 1.00–1.03, p = 0.020). Multivariable Cox regression was used to assess the association between biomarkers and stroke recurrence. sICAM-1 was associated with stroke recurrence (HR = 1.03, 95% CI 1.00–1.05, p = 0.002). In summary, elevated concentrations of sICAM-1 were associated with carotid plaque inflammation and an increased risk of stroke recurrence in patients with recent ischemic stroke and carotid atherosclerosis.

IMPORTANCE: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. OBJECTIVE: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. INTERVENTIONS: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. RESULTS: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%). CONCLUSIONS AND RELEVANCE: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40

Background and ObjectivesIn pooled analyses of endarterectomy trials for symptomatic carotid stenosis, several subgroups experienced no net benefit from revascularization. The validated symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score includes stenosis severity and inflammation measured by PET and improves the identification of patients with recurrent stroke compared with lumen-stenosis alone. We investigated whether the SCAIL score improves the identification of recurrent stroke in subgroups with uncertain benefit from revascularization in endarterectomy trials.MethodsWe did an individual-participant data pooled analysis of 3 prospective cohort studies (Dublin Carotid Atherosclerosis Study [DUCASS], 2008–2011; Biomarkers and Imaging of Vulnerable Atherosclerosis in Symptomatic Carotid Artery Disease [BIOVASC], 2014–2018; Barcelona Plaque Study, 2015–2018). Eligible patients had a recent nonsevere (modified Rankin Scale score ≤3) anterior circulation ischemic stroke/TIA and ipsilateral mild carotid stenosis (14 days to revascularization; or monocular loss of vision. Patients underwent coregistered carotid 18F-fluorodeoxyglucosePET/CT angiography (≤7 days from inclusion). The primary outcome was 90-day ipsilateral ischemic stroke. Multivariable Cox regression modeling was performed.ResultsWe included 135 patients. All patients started optimal modern-era medical treatment at admission, and 62 (45.9%) underwent carotid revascularization (36 within the first 14 days and 26 beyond). At 90 days, 18 (13.3%) patients had experienced at least 1 stroke recurrence. The risk of recurrence increased progressively according to the SCAIL score (0.0% in patients scoring 0–1, 15.1% scoring 2–3, and 26.7% scoring 4–5; p = 0.04). The adjusted (age, smoking, hypertension, diabetes, carotid revascularization, antiplatelets and statins) hazard ratio for ipsilateral recurrent stroke per 1-point SCAIL increase was 2.16 (95% CI 1.32–3.53; p = 0.002). A score ≥2 had a sensitivity of 100% for recurrence.DiscussionThe SCAIL score improved the identification of early recurrent stroke in subgroups who did not experience benefit in endarterectomy trials. Randomized trials are needed to test whether a combined stenosis-inflammation strategy will improve selection for carotid revascularization when benefit is currently uncertain.Classification of EvidenceThis study provides Class II evidence that, in patients with recent anterior circulation ischemic stroke who do not benefit from carotid revascularization, the SCAIL score accurately distinguishes those at risk for recurrent ipsilateral ischemic stroke.

Background: In drip-and-ship protocols, non-invasive vascular imaging (NIVI) at Referral Centers (RC), although recommended, is not consistently performed and its value is uncertain. We evaluated the role of NIVI at RC, comparing patients with (VI+) and without (VI-) vascular imaging in several outcomes. Methods: Observational, multicenter study from a prospective government-mandated population-based registry of code stroke patients. We selected acute ischemic stroke patients, initially assessed at RC from January-2016 to June-2020. We compared and analyzed the rates of patients transferred to a Comprehensive Stroke Center (CSC) for Endovascular Treatment (EVT), rates of EVT and workflow times between VI+ and VI-patients. Results: From 5128 ischemic code stroke patients admitted at RC; 3067 (59.8%) were VI+, 1822 (35.5%) were secondarily transferred to a CSC and 600 (11.7%) received EVT. Among all patients with severe stroke (NIHSS >16) at RC, a multivariate analysis showed that lower age, thrombolytic treatment, and VI+ (OR:1.479, CI95%: 1.117-1.960, p=0.006) were independent factors associated to EVT. The rate of secondary transfer to a CSC was lower in VI+ group (24.6% vs. 51.6%, p

Transient ischemic attacks (TIAs) before an acute ischemic stroke (AIS) could induce ischemic tolerance (IT) phenomena. with an endogenous neuroprotective role (Ischemic preconditioning. IPC). A consecutive prospective cohort of patients with AIS were recruited from 8 different hospitals. Participants were classified by those with non-previous recent TIA vs. previous TIA (within seven days. TIA ≤7d). A total of 541 AIS patients were recruited. 40 (7.4%). of them had previous TIA ≤7d. In line with IPC. patients with TIA ≤7d showed: 1) a significantly less severe stroke at admission by NIHSS score. 2) a better outcome at 7–90 days follow-up and reduced infarct volumes. 3) a specific upregulated metabolomics/lipidomic profile composed of diverse lipid categories. Effectively. IPC activates an additional adaptive response on increasing circulation levels of structural and bioactive lipids to facilitate functional recovery after AIS which may support biochemical machinery for neuronal survival. Furthermore. previous TIA before AIS seems to facilitate the production of anti-inflammatory mediators that contribute to a better immune response. Thus. the IT phenomena contributes to a better adaptation of further ischemia. Our study provides first-time evidence of a metabolomics/lipidomic signature related to the development of stroke tolerance in AIS patients induced by recent TIA.

Background and PurposeThe genetic architecture of cardioembolic stroke (CES) is still poorly understood. Atrial fibrillation (AF) is the main cause of CES, with which it shares heritability. We aimed to discover novel loci associated with CES by performing a Multitrait Analysis of the GWAS (MTAG) with atrial fibrillation genetic data.MethodsFor the MTAG analysis we used the MEGASTROKE cohort, which comprises European patients with CES and controls (n=362,661) and an AF cohort composed of 1,030,836 subjects. Regional genetic pleiotropy of the significant results was explored using an alternative Bayesian approach with GWAS-pairwise method. A replication was performed in an independent European cohort comprising 9,105 subjects using a Genome Wide Association Study (GWAS).ResultsMTAG-CES analysis revealed 40 novel and significant loci (p-value−8) associated with CES, four of which had not previously been associated with AF. A significant replication was assessed for eight novel loci: CAV1, IGF1R, KIAA1755, NEURL1, PRRX1, SYNE2, TEX41 and WIPF1, showing a p-valueKIAA1755, a locus not previously described associated with AF. Interestingly, 51 AF risk loci were not associated with CES according to GWAS-pairwise analysis. Gene Ontology (GO) analysis revealed that these exclusive AF genes from the 51 loci participate in processes related mainly to cardiac development, whereas genes associated with AF and CES participate mainly in muscle contraction and the conduction of electrical impulses.ConclusionsWe found eight new loci associated with CES. In addition, this study provides novel insights into the pathogenesis of CES, highlighting multiple candidate genes for future functional experiments.

Background and Purpose: Mechanical thrombectomy (MT) is effective for acute ischemic stroke (AIS) in selected patients with large intracranial vessel occlusion. A minority of patients with AIS receive MT. We aimed to describe the reasons for excluding patients with AIS for MT. Methods: We evaluated patients with AIS in a prospective population-based multicenter registry (Codi Ictus Catalunya registry) that includes all stroke code activations from January to June 2018 in Catalonia, Spain. We analyzed the major reasons for not treating with MT. Results: Stroke code was activated in 3060 patients. Excluding 355 intracranial hemorrhages and 502 stroke mimics, resulted in 2203 patients with AIS (mean age 72.8±13.8 years; 44.6% were women). Of the patients with AIS, 405 (18.4%) were treated with MT. We analyzed the reasons for not treating with MT. The following reasons were considered not modifiable: absence of large intracranial vessel occlusion (922, 41.9%), transient ischemic attack (206, 9.4%), and more than one cause (124, 5.6%). The potentially modifiable reasons for not performing MT by changing selection criteria were as follows: an intracranial artery occlusion that was considered inaccessible or not indicated (48, 2.2%); clinical presentation that was considered too mild to be treated (222, 10.1%); neuroimaging criteria (129, 5.9%), age/prior modified Rankin Scale score/medical comorbidities (129, 5.9%), and therapeutic time window >8 hours (16, 0.7%). Conclusions: In our area, considering all potentially modifiable causes for not performing MT, the percentage of patients with AIS eligible for MT could increase from 18.4% to a maximum of 43.1%. The clinical benefit of this increase is still uncertain and should be confirmed in future trials. Criteria for stroke code activation must be considered for the generalizability of these results.

Producción Científica, Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 × 10−8) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 × 10−8) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer’s disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases., Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - ( Projects PI 11/0176 and PI18/01338), Instituto de Salud Carlos III - (Project CM18/00198), Agencia de Gestión de Ayudas Universitarias y de Investigación (AGAUR) y Fondo Social Europeo - (Grant 2020FI_B1 00157), Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) - (Project CD20/00043), Instituto de Salud Carlos III - (Projects FI19/00309, CP12/03298, CPII17/00027, CPII19/00020)

The brain regions responsible for hallucinations remain unclear. We studied 89 brain lesions causing hallucinations using a recently validated technique termed lesion network mapping. We found that hallucinations occurred following lesions to a variety of different brain regions, but these lesion locations fell within a single functionally connected brain network. This network was defined by connectivity to the cerebellar vermis, inferior cerebellum (bilateral lobule X), and the right superior temporal sulcus. Within this single hallucination network, additional connections with the lesion location dictated the sensory modality of the hallucination: lesions causing visual hallucinations were connected to the lateral geniculate nucleus in the thalamus while lesions causing auditory hallucinations were connected to the dentate nucleus in the cerebellum. Our results suggest that lesions causing hallucinations localize to a single common brain network, but additional connections within this network dictate the sensory modality, lending insight into the causal neuroanatomical substrate of hallucinations.

ObjectiveTo analyze the clinical differences between patients with primary intracerebral hemorrhage (ICH) with and without atrial fibrillation (AF) and assess whether the effect of the antithrombotic pretreatment on outcome is modified by the presence of AF.MethodsIn this prospective observational study, researchers from 2 university hospitals included 1,106 consecutive patients with ICH. Clinical characteristics were described and stratified by presence of AF. In-hospital and 3-month mortality and 3-month disability were analyzed, considering antithrombotic pretreatment (none, antiplatelets, or oral anticoagulants) and AF (yes/no).ResultsAF was present in 21.9% of primary ICH cases. Patients with AF-ICH were older, with more vascular risk factors, more antithrombotic pretreatment, higher clinical severity, higher hematoma volume, and higher in-hospital and 3-month mortality. Do-not-resuscitate orders were applied more frequently in AF-ICH cases. After 2 different adjustment models, mortality remained significantly higher in patients with AF-ICH. However, after introducing previous antithrombotic treatment in the model, the adjusted odds ratio for 3-month mortality was 1.45 (95% confidence interval 0.74–2.85, p = 0.284) for patients with AF-ICH compared with non-AF cases. AF modified the effect of antithrombotic pretreatment on in-hospital (pint = 0.077) and 3-month mortality (pint = 0.008). Among patients without AF, antithrombotic pretreatment increased mortality; no effect was observed in patients with AF-ICH.ConclusionsPatients with AF and ICH had increased mortality; however, AF had no independent effect on mortality after adjustment for antithrombotic pretreatment. Conversely, antithrombotic pretreatment had a deleterious effect on outcome in patients with ICH without AF, but no detectable effect in patients with AF with ICH.

Background and Purpose— Plaque inflammation contributes to stroke and coronary events. 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid 18 F-FDG uptake and early recurrent stroke. Methods— We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid 18 F-FDG PET/computed tomography angiography, 18 F-FDG uptake was expressed as maximum standardized uptake value (SUV max ) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUV max with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only. Results— In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUV max was 2.2 (CI, 1.1–4.5; P =0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1–4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98–5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUV max was higher in patients with all recurrence ( P P =0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41–3.39; P P =0.008). Recurrent stroke risk increased across SUV max quartiles (log-rank P =0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59–0.78) and for post-PET recurrence was 0.80 (CI, 0.64–0.96). Conclusions— Plaque inflammation-related 18 F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed, 18 F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.

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.

Background: In-hospital stroke death rate is an important sanitary issue. Despite advances in the acute phase management of stroke patients, mortality and disability rates remain high. In aging populations and with different mortality between the sexes in general, the study of sex- and age-related differences becomes increasingly relevant for optimization of post-acute clinical care of stroke patients. Methods: We designed a cohort follow-up study with 13,932 consecutive ischemic stroke (IS) patients from 19 Spanish hospitals. Data was obtained from the Spanish Stroke Registry; transient ischemic attacks and ages Results: The median (percentiles 2.5 and 97.5%) age was 78 (41–92) years old for women and 71 (41–92) for men. IS women were more likely to be older, to exhibit cardio-embolic aetiology, and less likely to have been admitted to a stroke unit or to have had a stroke code activated. Both pre-stroke modified Rankin Scale and National Institute of Health Stroke Scale (NIHSS) scores at admission increased significantly with age and were higher in women than those in men. Differences in distributions of common risk factors for IS and of in-hospital outcomes between women and men actually changed with patient’s age. It is to be noted here that although there were no statistically significant differences (p > 0.05) between the sexes within any age group, in-hospital mortality appeared significantly higher in women than that in men when analysed overall, due to confounding. Death was more closely related to stroke in women than in men and occurred earlier. Although there were some age-specific sex differences between the predictors for in-hospital mortality, stroke severity measured by NIHSS was the main predictor of in-hospital mortality for both sexes. Topographic classifications – partial anterior circulatory infarct and total anterior circulatory infarct – were significant prognostic factors for men aged Conclusion: Although most of our findings were consistent with previous studies, it is important to take into account and highlight differences in in-hospital mortality between the sex and age group. Not to account for age-related differences between the sexes can give false results that may mislead management decisions. As most deaths in women were related to stroke, it is important to improve their early management, stroke code activation, access to stroke units and/or revascularisation therapies, especially in the older age groups.