Plasma brain-derived tau correlates with cerebral infarct volume.

Background: A blood-based biomarker that accurately reflects neuronal injury in acute ischemic stroke could be an easily accessible and cost-effective complement to clinical and radiological evaluation. Here, we investigate whether plasma levels of the novel biomarker brain-derived tau (BD-tau) reflect cerebral infarct volumes and whether BD-tau can improve clinical outcome prediction.

Methods: The present study included 713 consecutive cases from two different hospital-based cohorts, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) and SAHLSIS phase 2 (SAHLSIS2).

Interleukin-6, C-Reactive Protein, and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data.

Background: Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials.

The genetic landscape of neuro-related proteins in human plasma.

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL.

Circulating levels of neurofilament light chain as a biomarker of infarct and white matter hyperintensity volumes after ischemic stroke.

Serum neurofilament light chain protein (sNfL) shows promise as a biomarker for infarct size in acute ischemic stroke and for monitoring cerebral small vessel disease (cSVD). However, distinguishing the cSVD contribution after stroke may not be possible due to post-stroke sNfL increase. Additionally, it remains unclear if etiologic subtype differences exist.

A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome.

Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies.

Introduction: Inflammation is an emerging target for secondary prevention after stroke and randomised trials of anti-inflammatory therapies are ongoing. Fibrinogen, a putative pro-inflammatory marker, is associated with first stroke, but its association with major adverse cardiovascular events (MACE) after stroke is unclear.

Materials And Methods: We did a systematic review investigating the association between fibrinogen and post-stroke vascular recurrence.

Association of Plasma Brain-Derived Tau With Functional Outcome After Ischemic Stroke.

Objectives: To investigate whether circulating acute-phase brain-derived tau (BD-tau) is associated with functional outcome after ischemic stroke.

Methods: Plasma tau was measured by a novel assay that selectively quantifies BD-tau in the (), which includes adult cases with ischemic stroke and controls younger than 70 years, and in an independent cohort of adult cases of all ages (). Associations with unfavorable 3-month functional outcome (modified Rankin scale score >2) were analyzed by logistic regression.

Scaling behaviours of deep learning and linear algorithms for the prediction of stroke severity.

Deep learning has allowed for remarkable progress in many medical scenarios. Deep learning prediction models often require 10-10 examples. It is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis.

Background And Objectives: Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention.

Methods: Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack.

Proteomic profiling identifies novel inflammation-related plasma proteins associated with ischemic stroke outcome.

Background: The inflammatory response to cerebral ischemia is complex; however, most clinical studies of stroke outcome focus on a few selected proteins. We, therefore, aimed to profile a broad range of inflammation-related proteins to: identify proteins associated with ischemic stroke outcome that are independent of established clinical predictors; identify proteins subsets for outcome prediction; and perform sex and etiological subtype stratified analyses.

Methods: Acute-phase plasma levels of 65 inflammation-related proteins were measured in 534 ischemic stroke cases.

Mosaic Loss of Chromosome Y Is Associated With Functional Outcome After Ischemic Stroke.

Background: Mosaic loss of chromosome Y (LOY) is associated with cardiovascular and neurodegenerative diseases in men, and genetic predisposition to LOY is associated with poor poststroke outcome. We, therefore, tested the hypothesis that LOY itself is associated with functional outcome after ischemic stroke.

Methods: The study comprised male patients with ischemic stroke from the cohort studies SAHLSIS2 (Sahlgrenska Academy Study on Ischemic Stroke Phase 2; n=588) and LSR (Lund Stroke Register; n=735).

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke-A Prospective Observational Study.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome.

FIND Stroke Recovery Study (FIND): rationale and protocol for a longitudinal observational cohort study of trajectories of recovery and biomarkers poststroke.

Introduction: Comprehensive studies mapping domain-specific trajectories of recovery after stroke and biomarkers reflecting these processes are scarce. We, therefore, initiated an exploratory prospective observational study of stroke cases with repeated evaluation, the . We aim to capture trajectories of recovery from different impairments, including cognition, in combination with broad profiling of blood and imaging biomarkers of the recovery.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis.

Background: Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines.

Methods: We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies.

Genetic mechanisms of 184 neuro-related proteins in human plasma.

Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-reiated proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL.

The relevance of rich club regions for functional outcome post-stroke is enhanced in women.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions.

Investigation of 91 proteins implicated in neurobiological processes identifies multiple candidate plasma biomarkers of stroke outcome.

The inter-individual variation in stroke outcomes is large and protein studies could point to potential underlying biological mechanisms. We measured plasma levels of 91 neurobiological proteins in 209 cases included in the Sahlgrenska Academy Study on Ischemic Stroke using a Proximity Extension Assay, and blood was sampled in the acute phase and at 3-month and 7-year follow-ups. Levels were also determined once in 209 controls.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.

Deep profiling of multiple ischemic lesions in a large, multi-center cohort: Frequency, spatial distribution, and associations to clinical characteristics.

Background Purpose: A substantial number of patients with acute ischemic stroke (AIS) experience multiple acute lesions (MAL). We here aimed to scrutinize MAL in a large radiologically deep-phenotyped cohort.

Materials And Methods: Analyses relied upon imaging and clinical data from the international MRI-GENIE study.