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Background: Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking., Methods: A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls). IS subtypes using Trial of ORG 10172 in Acute Stroke Treatment criteria were explored in a sex-stratified approach. Replication efforts involved the MEGASTROKE, GIGASTROKE, and the UK Biobank international cohorts. Post-genome-wide association study analysis included: in silico proteomic analysis, gene-based analysis, quantitative trait loci annotation, transcriptome-wide association analysis, and bioinformatic analysis using chromatin accessibility data., Results: Identified as associated with IS and its subtypes were 4 significant and independent loci. Replication confirmed 5p15.2 as a new locus associated with small-vessel occlusion stroke, with rs59970332-T as the lead variant (beta [SE], 0.13 [0.02]; P =4.34×10 -8 ). Functional analyses revealed CTNND2 given proximity and its implication in pathways involved in vascular integrity and angiogenesis. Integration of Hi-C data identified additional potentially modulated genes, and in silico proteomic analysis suggested a distinctive blood proteome profile associated with the lead variant. Gene-set enrichment analyses highlighted pathways consistent with small-vessel disease pathogenesis. Gene-based associations with known stroke-related genes such as F2 and FGG were also observed, reinforcing the relevance of our findings., Conclusions: We found CTNND2 as a potential key molecule in small-vessel occlusion stroke risk, and predominantly in males. This study sheds light on the genetic architecture of IS in the Spanish population, providing novel insights into sex-specific associations and potential molecular mechanisms. Further research, including replication in larger cohorts, is essential for a comprehensive understanding of these findings and for their translation to clinical practice., Competing Interests: Dr Arenillas reports compensation from Medtronic, Daiichi Sankyo, Boehringer Ingelheim, and Pfizer for consultant services; grants from AstraZeneca, Instituto de Salud Carlos III, European Commission and Gerencia de Salud Castilla y León; compensation from Philips for data and safety monitoring services; travel support from Daiichi Sankyo Company. Dr Ribo reports stock holdings in Methinks, Nora, and Ancaonda Biomed; compensation from Cerenovus, Vesalio, Stryker Corporation, Philips, Rapid Pulse, AptaTargets, and Medtronic MiniMed Inc for consultant services; compensation from Sensome for data and safety monitoring services. Dr Heitsch reports employment by Washington University School of Medicine in St. Louis; reports funding from National Institutes of Health and American Heart Association. Dr Dhar reports grants from National Institute of Neurological Disorders and Stroke. The other authors report no conflicts.

Purpose: Surgery close to or in contact with the ventricular system is challenging due to the complications. We sought to evaluate the effectiveness and safety of TachoSil® as a ventricular sealant in preventing complications after cranial surgery with an open ventricular system (OVS)., Methods: This is a single-center and prospective cohort study We included patients who underwent elective surgery for supratentorial craniotomy and periventricular pathology between December 2020 and November 2023. We registered surgical complications arising from CSF dynamics (such as percutaneous cerebrospinal fluid (CSF) leakage, hydrocephalus, pseudomeningocele), infections, and other complications (postsurgical hematoma) adverse drug reactions (ADRs), reintervention or hospital readmission up to 90 days after surgery., Results: Forty interventions were performed on 39 patients, whose median age was 56 years. Eleven patients (28.2%) had antecedents of previous surgery in the same location, 5 (12.8%) had previously received radiotherapy and chemotherapy, and 11 (28.2%) were smokers. Twenty-four patients (60%) underwent surgery for high-grade glioma, 8 (20%) for low-grade gliomas, 6 (15%) for metastasis and 2 (5%) for meningioma. Throughout the study and up to 90 days after surgery, none of the patients presented an ADR. Only 2 patients (5%) presented with a surgery complications derived from ventricular opening (one patient with a percutaneous CSF leakage and one patients with external hydrocephalus). Both patients resolved with a ventriculoperitoneal shunt., Conclusions: TachoSil® is a dural sealant that can be used safely and effectively intraparenchymally in patients whose surgery involves a ventricular opening. Only 5% of treated patients presented complications arising from CSF hydrodynamics. No patients had pseudomeningocele, infections or complications related to the use of this sealant. To confirm these positive results, randomized and comparative clinical trials assessing the efficacy of TachoSil® in patients after cranial surgery with an OVS are essential., Trial Registration Number and Date of Registration: This study was registered in the Clinical Trials.gov (NCT05717335). Date May 1 st , 2022., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis., Objectives: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment., Methods: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT., Results: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10 -11 . Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10 -10 ; rs1421067 (CHD9), P = 1.81 × 10 -14 ; and rs34780449, near ROBO1 gene, P = 1.64 × 10 -8 . Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10 -14 . Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05)., Conclusion: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade., Methods: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models., Results: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 ( ρ =0.667; P <0.01 and ρ =0.614; P <0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively., Conclusions: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.

Background: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification., Methods: Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort ( n = 362,661) and AF cohort ( n = 1,030,836). We considered significant variants and replicated those variants with MTAG p -value < 5 × 10 -8 influencing both traits (GWAS-pairwise) with a p -value < 0.05 in the original GWAS and in an independent cohort ( n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort., Results: We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1 , and ZEB2 . KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension., Conclusion: The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cárcel-Márquez, Muiño, Gallego-Fabrega, Cullell, Lledós, Llucià-Carol, Sobrino, Campos, Castillo, Freijo, Arenillas, Obach, Álvarez-Sabín, Molina, Ribó, Jiménez-Conde, Roquer, Muñoz-Narbona, Lopez-Cancio, Millán, Diaz-Navarro, Vives-Bauza, Serrano-Heras, Segura, Ibañez, Heitsch, Delgado, Dhar, Krupinski, Delgado-Mederos, Prats-Sánchez, Camps-Renom, Blay, Sumoy, de Cid, Montaner, Cruchaga, Lee, Martí-Fàbregas and Férnandez-Cadenas.)

Background: Chronic shunt-dependent hydrocephalus is a well-known complication of subarachnoid hemorrhage. Although the risk factors have been extensively investigated, most fail to predict permanent shunt dependency. It is unknown whether the volume of cerebrospinal fluid (CSF) from external ventricular drainage and the daily volume of drainage during the acute hydrocephalus phase (first 72 hours) can predict shunt dependency. We aimed to determine whether CSF output during the acute hydrocephalus phase is a risk factor for shunt dependency., Methods: Patients with aneurysmal subarachnoid hemorrhage and hydrocephalus treated with external ventricular drainage were prospectively registered in our database between January 2017 and March 2020. Factors evaluated for predicting shunt dependency included age; sex; Hunt and Hess grade; World Federation of Neurological Surgeons grade; acute hydrocephalus; modified Fisher grade; aneurysm treatment modality; hospital length of stay; modified Rankin score; average daily overall CSF production; average CSF output for the first 24, 48, and 72 hours; external ventricular drainage days; the number of wean/clamp failures; and ventriculoperitoneal shunting., Results: Univariate analysis identified Hunt and Hess grade; acute hydrocephalus at onset; external ventricular drainage; overall CSF output; average CSF output for the first 24, 48, and 72 hours; and CSF output until the first clamp as significant risk factors for shunt dependency (P < 0.001). In a multivariate logistic regression analysis, overall CSF output and average CSF output for the first 72 hours were significant risk factors for shunt dependency., Conclusions: Overall CSF output, especially during the acute hydrocephalus phase (first 72 hours), predicts the development of chronic hydrocephalus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Haemorrhagic transformation is a complication of recombinant tissue-plasminogen activator treatment. The most severe form, parenchymal haematoma, can result in neurological deterioration, disability, and death. Our objective was to identify single nucleotide variations associated with a risk of parenchymal haematoma following thrombolytic therapy in patients with acute ischaemic stroke. A fixed-effect genome-wide meta-analysis was performed combining two-stage genome-wide association studies (n = 1904). The discovery stage (three cohorts) comprised 1324 ischaemic stroke individuals, 5.4% of whom had a parenchymal haematoma. Genetic variants yielding a P-value < 0.05 1 × 10-5 were analysed in the validation stage (six cohorts), formed by 580 ischaemic stroke patients with 12.1% haemorrhagic events. All participants received recombinant tissue-plasminogen activator; cases were parenchymal haematoma type 1 or 2 as defined by the European Cooperative Acute Stroke Study (ECASS) criteria. Genome-wide significant findings (P < 5 × 10-8) were characterized by in silico functional annotation, gene expression, and DNA regulatory elements. We analysed 7 989 272 single nucleotide polymorphisms and identified a genome-wide association locus on chromosome 20 in the discovery cohort; functional annotation indicated that the ZBTB46 gene was driving the association for chromosome 20. The top single nucleotide polymorphism was rs76484331 in the ZBTB46 gene [P = 2.49 × 10-8; odds ratio (OR): 11.21; 95% confidence interval (CI): 4.82-26.55]. In the replication cohort (n = 580), the rs76484331 polymorphism was associated with parenchymal haematoma (P = 0.01), and the overall association after meta-analysis increased (P = 1.61 × 10-8; OR: 5.84; 95% CI: 3.16-10.76). ZBTB46 codes the zinc finger and BTB domain-containing protein 46 that acts as a transcription factor. In silico studies indicated that ZBTB46 is expressed in brain tissue by neurons and endothelial cells. Moreover, rs76484331 interacts with the promoter sites located at 20q13. In conclusion, we identified single nucleotide variants in the ZBTB46 gene associated with a higher risk of parenchymal haematoma following recombinant tissue-plasminogen activator treatment., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSS baseline - NIHSS 24hours = ΔNIHSS 6-24h ), to examine its relevance to AIS mechanisms and long-term outcomes., Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS 6 -24h . In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS 6-24h was examined. Finally, the association of ΔNIHSS 6 -24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA)., Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median ΔNIHSS 6 -24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS 6 -24h (R 2 =0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R 2 =0.27), but much of the variance remained unexplained. ΔNIHSS 6 -24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS 3 -24h was similarly associated with 90-day outcomes., Conclusions: The dynamic phenotype, ΔNIHSS 6-24h , captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS 6 -24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

New reperfusion therapies have improved the clinical recovery rates of acute ischemic stroke patients (AISP), but it is not known whether other factors, such as the ability to cope, might also have an effect. The aim of this study was to evaluate the effect of endovascular treatment (EVT) on coping strategies, quality of life, and neurological and functional outcomes in AISP at 3 months and 1 year post-stroke. A multicenter, prospective, longitudinal, and comparative study of a sub-study of the participants in the Endovascular Revascularization with Solitaire Device versus Best Medical Therapy in Anterior Circulation Stroke within 8 Hours (REVASCAT) clinical trial was conducted after recruiting from two stroke centers in Catalonia, Spain. The cohort consisted of 82 ischemic stroke patients ( n = 42 undergoing EVT and n = 40 undergoing standard best medical treatment (BMT) as a control group), enrolled between 2013-2015. We assessed the coping strategies using the Brief Coping Questionnaire (Brief-COPE-28), the health-related quality of life (HRQoL) with the EQ-5D questionnaire, and the neurological and functional status using the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), and Stroke Impact Scale-16 (SIS-16). Bivariate analyses and multivariate linear regression models were used. EVT patients were the ones that showed better neurological and functional outcomes, and more patients presented reporting no pain/discomfort at 3 months; paradoxically, problem-focused coping strategies were found to be significantly higher in patients treated with BMT at 1 year.

Public hospitals in Catalonia, Spain, have recommended assessing pain in non-communicative inpatients by means of the Spanish version of the Pain Assessment in Advanced Dementia scale (PAINAD-Sp) since 2010; a modification for patients with neurologic disorders and cancer, PAINAD-Sp&#95;Hosp, has also been validated. However, nurses are not routinely trained in the use of the scales. The aim of this study was to assess knowledge on pain assessment in nurses following an online training course. We surveyed participants prior to the course to determine baseline knowledge of pain and pain assessment. Course material included conceptual content on pain and practical videos demonstrating the scoring system for the PAINAD-Sp&#95;Hosp scale. After completing the course, participants took a multiple choice quiz to test understanding of course content and a satisfaction survey to determine acceptability. Of the 836 nurses invited, 401 participated in the training course; 37.7% reported having no previous specific training on pain, and just 32.2% used the PAINAD-Sp scale regularly. Following the course, virtually all (99%) of the participants passed the quiz. Overall satisfaction among nurses with regard to the training received was 8.6/10. Thus, the e-learning course was effective and acceptable for training nurses on pain assessment using validated tools., Competing Interests: Declaration of competing interest The authors report no current or potential conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Purpose- Stroke Risk Analysis (SRA) comprises an algorithm for automated analysis of ECG monitoring, enabling the detection of paroxysmal atrial fibrillation (pxAF) and identifying patterns indicating a high risk of atrial fibrillation (R&#95;AF). We compared Holter-enabled continuous ECG monitoring in combination with SRA (hSRA) with standard continuous ECG monitoring for pxAF detection in patients with acute ischemic stroke. Also, we sought to identify whether the detection of R&#95;AF patterns during the first cycle (first 2 hours) of hSRA recording was associated with the detection of pxAF during the Stroke Unit stay. Methods- We enrolled 524 consecutive patients admitted in the Stroke Unit with acute ischemic stroke or transient ischemic attack with neither history of AF nor AF at admission into a prospective multicentric observational analytic clinical study with intrapatient comparison, who received both continuous ECG monitoring as well as hSRA up to 7 days. Investigators were blinded to hSRA results unless pxAF was detected on SRA. Results- Of the 524 consecutive acute stroke patients (median age, 70.0 years; 60% male; acute ischemic stroke 93%, transient ischemic attack 7%), 462 were eligible and included in the study. Among 462 patients with hSRA available for 66 hours, AF was documented by hSRA in 79 patients (17.1%). From this group, 45 AF cases (9.7%) were confirmed after review by an independent and blinded cardiologist. continuous ECG monitoring detected 21 AF cases (4.3%; P <0.0001). hSRA detected R&#95;AF patterns in 92 patients. 35 out of the 92 R&#95;AF patients showed an episode of AF during the Stroke Unit stay. Predictive values of R&#95;AF patterns within the first cycle of hSRA were: sensitivity 71%, specificity 86%, positive predictive value 38%, and negative predictive value 96%. Conclusions- Automated analysis using SRA technology strongly improves pxAF detection in acute ischemic stroke patients compared with continuous ECG monitoring. The predictive value of a R&#95;AF pattern, as detected by hSRA during the first few hours after admission, deserves further investigation.

Background and Purpose- Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke. Methods- Ischemic stroke patients with leukocyte counts data during the first 24h were included. Genome-wide association study and gene expression studies were performed. Results- Our genome-wide association study, which included 2064 (Discovery) and 407 (Replication) patients, revealed a new locus (14q24.3) associated with leukocyte counts. After Joint analysis (n=2471) 5 more polymorphisms reached genome-wide significance ( P <5×10 -8 ). The 14q24.3 locus was associated with acute stroke outcome (rs112809786, P =0.036) and with ACOT1 and PTGR2 gene expression. Previous polymorphisms associated with leukocyte counts in general-population did not show any significance in our study. Conclusions- We have found the first locus associated with leukocyte counts in ischemic stroke, also associated with acute outcome. Genetic analysis of acute endophenotypes could be useful to find the genetic factors associated with stroke outcome. Our findings suggested a different modulation of immune cells in stroke compared with healthy conditions.

Background: Public hospitals in Catalonia (Spain) recommend using the Spanish version of the Pain Assessment in Advanced Dementia (PAINAD-Sp) scale for assessing pain in adult patients unable to self-report. However, since its inclusion in Catalonian nursing care plans in 2010, there have been no training programs for nurses, contributing to its current underuse., Aims: The aim of this study was to assess the impact of a nurse training intervention on the PAINAD-Sp scale in noncommunicative inpatients unable to self-report., Design: Before-after study., Settings: Two public hospitals in Catalonia (Spain)., Participants/subjects: Four hundred and one nurses participated in the training course and 219 patients received PAINAD-Sp assessments., Methods: We used a before-after study design, evaluating the use of the PAINAD-Sp scale over two 6-month periods before and after an online training intervention for nurses in February 2017, in two public hospitals. Data were collected from patient records in each center. The primary outcome was the number of patients receiving PAINAD-Sp assessments during admission. Secondary outcomes were the number of assessments undertaken per patient during admission, the total (0-10) and item-specific (0-2) PAINAD-Sp score, and pharmacologic treatment administered., Results: There were 401 nurses who took part in the training program. Over the study period, 219 patients received PAINAD-Sp assessments: 29 in the preintervention period and 190 in the postintervention period (p < .001). Administration of analgesics and antipyretics decreased (p < .001) after the intervention, whereas use of hypnotic drugs and sedatives increased., Conclusions: Theoretical and practical training may be an effective way to improve nurses' approach to identifying, assessing, and managing pain in patients unable to self-report., (Copyright © 2019 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

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.

Introduction: Physical activity (PhA) prior to stroke has been associated with good outcomes after the ischemic insult, but there is scarce data on the involved molecular mechanisms., Methods: We studied consecutive acute ischemic stroke patients admitted to a single tertiary stroke center. Prestroke PhA was evaluated with the International Physical Activity Questionnaire (metabolic equivalent of minutes/week). We studied several circulating angiogenic and neurogenic factors at different time points: vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and brain-derived neurotrophic factor (BDNF) at admission, day 7, and at 3 months. We considered good functional outcome at 3 months (modified Rankin scale  ≤ 2) as primary end point, and final infarct volume as secondary outcome., Results: We studied 83 patients with at least 2 time point serum determinations (mean age 69.6 years, median National Institutes of Health Stroke Scale 17 at admission). Patients more physically active before stroke had a significantly higher increment of serum VEGF on the seventh day when compared to less active patients. This increment was an independent predictor of good functional outcome at 3 months and was associated with smaller infarct volume in multivariate analyses adjusted for relevant covariates. We did not find independent associations of G-CSF or BDNF levels neither with level of prestroke PhA nor with stroke outcomes., Conclusions: Although there are probably more molecular mechanisms by which PhA exerts its beneficial effects in stroke outcomes, our observation regarding the potential role of VEGF is plausible and in line with previous experimental studies. Further research in this field is needed., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: To compare the prognostic value of pulse amplitude on intracranial pressure (ICP) monitoring and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on magnetic resonance imaging (MRI) for predicting surgical benefit after shunt placement in idiopathic normal pressure hydrocephalus (iNPH)., Method: Patients with suspected iNPH were prospectively recruited from a single centre. All patients received preoperative MRI and ICP monitoring. Patients were classified as shunt responders if they had an improvement of one point or more on the NPH score at 1 year post-surgery. The sensitivity, specificity, Youden index, and positive and negative predictive values of the two diagnostic methods were calculated., Results: Sixty-four of 89 patients clinically improved at 1 year post-surgery and were classed as shunt responders. Positive DESH findings had a sensitivity of 79.4 % and specificity of 80.8 % for predicting shunt responders. Fifty-five of 89 patients had positive DESH findings: 50 of these responded to VP shunt, giving a positive and negative predictive value of 90.9 % and 61.8 %, respectively. Fifty-seven of 89 patients had high ICP pulse amplitude. High ICP pulse amplitude had a sensitivity of 84.4 %, specificity of 88 %, positive predictive value of 94.7 % and negative predictive value of 61.8 % for predicting shunt responders., Conclusions: Both positive DESH findings and high ICP pulse amplitude support the diagnosis of iNPH and provide additional diagnostic value for predicting shunt-responsive patients; however, high ICP amplitude was more accurate than positive DESH findings, although it is an invasive test.