Stroke Study Research Articles

Intravenous thrombolysis in young adults with ischemic stroke: A cohort study from the international TRISP collaboration.

Previous observational data indicate that young adults treated with intravenous thrombolysis (IVT) for acute ischemic stroke have more favorable outcomes and less complications when compared to older adults. Given the limited data on this topic, we aimed to provide more evidence on clinical outcomes and safety in such patients, using a large international thrombolysis registry. In this prospective multicenter study, we used data from the Thrombolysis in Ischemic Stroke Patients (TRISP) registry from 1998 to 2020. Patients who received endovascular treatment (EVT), as only treatment or in addition to IVT, were not included in this cohort. Using multivariable regression models, we compared thrombolysed young patients aged 18-49 years with those aged ⩾50 years with regards to the following outcomes: favorable outcome in stroke survivors (modified Rankin Scale ⩽2), symptomatic intracranial hemorrhage (sICH) according to European Cooperative Acute Stroke Study II (ECASS II) criteria, and three-months all-cause death. Of the 16,651 IVT treated patients, 1346 (8.1%) were 18-49 years. Young adults in TRISP were more often male (59.6% vs 54.0%), had a lower median NIHSS score on admission, 7 (4-13) versus 8 (5-15), and had less cardiovascular risk factors except for smoking (42.0% vs 19.0%) when compared to older patients. When compared to thrombolysed patients aged ⩾50 years, a favorable functional outcome was more likely in young adults: 81.9% versus 56.4%, aOR 2.30 (1.80-2.95), whilst sICH 1.6% versus 4.6%, aOR 0.45 (0.23-0.90) and death 2.3% versus 14.2%, aOR 0.21 (0.11-0.39) were less likely. Intravenous thrombolysis in young adults is independently associated with higher rates of favorable outcomes and lower rates of complications.

Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results From the ENCHANTED Study.

Hemorrhagic transformation may be a potentially devastating complication of IV thrombolysis (IVT) in acute ischemic stroke, but what degree of hemorrhage indicates the greatest negative effect is not known. We aimed to define the associations between hemorrhagic transformation patterns, classified according to clinical and imaging categories, and clinical outcomes after IVT. We conducted a post hoc analysis from the international Enhanced Control of Hypertension and Thrombolysis Stroke Study. Symptomatic intracerebral hemorrhage (sICH) was defined based on established criteria, such as the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. Asymptomatic intracerebral hemorrhage (aICH) was defined as any intracerebral hemorrhage that did not meet the criteria for sICH. Imaging subtypes of hemorrhagic transformation were assessed using the Heidelberg Bleeding Classification system. The primary outcome was death or major disability, defined by modified Rankin scale (mRS) scores 3-6 at 90 days. Secondary outcomes included death, death or disability (mRS 2-6), and poor health-related quality of life (HRQoL), defined as an overall heath utility score ≤0.7 (mean). Of the 4,370 participants, 779 (17.8%) developed any intracranial hemorrhage (ICH), with a median time from randomization to hemorrhage of 23.5 hours (interquartile range 18.92-26.07). According to the SITS-MOST criteria, 62 patients (1.4% of 4,370) were classified as sICH, and 717 patients (16.4% of 4,370) were classified as aICH. sICH per SITS-MOST criteria was associated with death or major disability (odds ratio [OR] 23.05, 95% CI 8.97-59.23), death (OR 20.14, 95% CI 11.32-35.84), death or disability (OR 61.36, 95% CI 8.40-448.01), and poor HRQoL (OR 17.87, 95% CI 7.47-42.71). Similarly, aICH per SITS-MOST criteria was also associated with death or major disability (OR 2.23, 95% CI 1.84-2.70), death (OR 1.82, 95% CI 1.39-2.38), death or disability (OR 2.29, 95% CI 1.87-2.80), and poor HRQoL (OR 1.81, 95% CI 1.50-2.18). Comparable associations were observed for sICH and aICH defined by other criteria, as well as for imaging subtypes based on Heidelberg Bleeding Classification system. All forms of post-IVT hemorrhagic transformation in acute ischemic stroke are associated with increased odds of poor clinical outcomes. Of note, aICH after IVT should not be considered clinically innocuous. ClinicalTrials.gov (NCT01422616).

Association of Cerebrovascular Reactivity With 1-Year Imaging and Clinical Outcomes in Small Vessel Disease: An Observational Cohort Study.

In patients with cerebral small vessel disease (SVD), impaired cerebrovascular reactivity (CVR) is related to worse concurrent SVD burden, but less is known about cerebrovascular reactivity and long-term SVD lesion progression and clinical outcomes. We investigated associations between cerebrovascular reactivity and 1-year progression of SVD features and clinical outcomes. Between 2018 and 2021, we recruited patients from the Edinburgh/Lothian stroke services presenting with minor ischemic stroke and SVD features as part of the Mild Stroke Study 3, a prospective observational cohort study (ISRCTN 12113543). We acquired 3T brain MRI at baseline and 1 year. At baseline, we measured cerebrovascular reactivity to 6% inhaled CO2 in subcortical gray matter, normal-appearing white matter, and white matter hyperintensities (WMH). At baseline and 1 year, we quantified SVD MRI features, incident infarcts, assessed stroke severity (NIH Stroke Scale), recurrent stroke, functional outcome (modified Rankin Scale), and cognition (Montreal Cognitive Assessment). We performed linear and logistic regressions adjusted for age, sex, and vascular risk factors, reporting the regression coefficients and odds ratios with 95% CIs. We recruited 208 patients of whom 163 (mean age and SD: 65.8 ± 11.2 years, 32% female) had adequate baseline CVR and completed the follow-up structural MRI. The median increase in WMH volume was 0.32 mL with (Q1, Q3) = (-0.48, 1.78) mL; 29% had a recurrent stroke or incident infarct on MRI. At 1 year, patients with lower baseline cerebrovascular reactivity in normal-appearing tissues had increased WMH (regression coefficient: B = -1.14 [-2.13, -0.14] log10 (%ICV) per %/mm Hg) and perivascular space volumes (B = -1.90 [-3.21, -0.60] log10 (%ROIV) per %/mm Hg), with a similar trend in WMH. CVR was not associated with clinical outcomes at 1 year. Lower baseline cerebrovascular reactivity predicted an increase in WMH and perivascular space volumes after 1 year. CVR should be considered in SVD future research and intervention studies.

Influence of renal function on blood pressure control and outcome in thrombolyzed patients after acute ischemic stroke: post-hoc analysis of the ENCHANTED trial

BackgroundThe effect of renal impairment in patients who receive intravenous thrombolysis for acute ischemic stroke (AIS) is unclear. We aimed to determine the associations of renal impairment and clinical outcomes and any modification of the effect of intensive versus guideline-recommended blood pressure (BP) control in the BP arm of the International Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).MethodsWe conducted a post-hoc analysis of the ENCHANTED BP arm, which involved 2,196 thrombolyzed AIS patients. Logistic regression models were used to define the association between eGFR and clinical outcomes of death, death or major disability [modified Rankin scale (mRS) scores 3–6], and major disability (mRS 3–5) at 90 days.ResultsOf the 2,151 patients with available baseline renal function data (mean age 66.9 years; 38% women), 993 (46.2%), 822 (38.2%), and 336 (15.6%) had normal (eGFR ≥ 90 mL/min/1.73 m2), mildly (60–89), and moderate-to-severely impaired (<60) renal function, respectively. Compared with patients with normal eGFR, mortality was higher in those with moderate-to-severe renal impairment (adjusted odds ratio 1.77, 95% confidence interval 1.05–2.99; p = 0.031 for trend). However, the difference in death or major disability (mRS 3–6) was not significant between groups. There was no heterogeneity in the effect of intensive versus guideline-recommended BP-lowering treatment on death by grades of renal function (p for interaction = 0.545).DiscussionThe presence of moderate-to-severe renal impairment is associated with increased mortality in thrombolyzed patients with AIS. Renal function does not modify the effect of early intensive BP-lowering treatment on death in this patient group.

Cost consequences analysis of early vocational rehabilitation compared with usual care for stroke survivors.

To compare costs and consequences of Early Stroke Specialist Vocational Rehabilitation (ESSVR) with usual care in working age, stroke survivors over 12 months. An economic evaluation nested within the pragmatic, multi-centre, randomised, controlled RETurn to work After stroKE (RETAKE) study. Twenty-one English and Welsh National Health Service (NHS) hospital-based stroke units. A UK NHS and Personal Social Services perspective was taken in the base-case and a wider perspective (participant, family, employer and other public services) in a secondary analysis. A total of 583 stroke survivors age ≥18 years (mean 54.0 years, 69% male). Participants were randomised to ESSVR, an early, individually tailored (in content, dose, intensity and duration) intervention, plus usual care or usual care alone. Disease-specific resource-use data and EQ-5D-5L (health-related quality of life) collected at baseline, 3, 6 and 12 months. Resource-use items were valued using unit costs in UK£ 2021/22. EQ-5D-5L was used to estimate Quality-adjusted life-years (QALYs). If ESSVR was found effective, an incremental cost-utility analysis was planned, otherwise a cost-consequence analysis. The clinical study found no evidence of a between-group difference in the proportion of participants returning to work at 12 months. This, and the level of missing data, means a cost-consequence analysis is reported. Using imputed data, ESSVR plus usual care is estimated to be more expensive with slightly higher QALYs compared with usual care. Early Stroke Specialist Vocational Rehabilitation is unlikely to be considered cost-effective over 12 months, which fits with the clinical finding of no between-group difference in return-to-work rates post-stroke. The ISRCTN registry: ISRCTN12464275 https://doi.org/10.1186/ISRCTN12464275.

Predicting high sensitivity C-reactive protein levels and their associations in a large population using decision tree and linear regression

High-sensitivity C-reactive protein (hs-CRP) is a biomarker of inflammation predicting the incidence of different health pathologies. In this study, we aimed to evaluate the association between hematological and demographic factors with hs-CRP levels using decision tree (DT) and linear regression (LR) modeling. This study was conducted on a population of 9704 males and females aged 35 to 65 years recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. We utilized a data mining approach to construct a predictive model of hs-CRP measurements, employing the DT methodology. DT model was used to predict hs-CRP level using biochemical factors and clinical features. A total of 9,704 individuals were included in the analysis, with 57% of them being female. Except for fasting blood glucose (FBG), hypertension (HTN), and Type 2 diabetes mellites (T2DM), all variables showed significant differences between the two groups. The results of the LR models showed that variables such as anxiety score, depression score, Systolic Blood Pressure, Cardiovascular disease, and HTN were significant in predicting hs-CRP levels. In the DT models, depression score, FBG, cholesterol, and anxiety score were identified as the most important factors in predicting hs-CRP levels. DT model was able to predict hs-CRP level with an accuracy of 72.1% in training and 71.4% in testing of both genders. The proposed DT model appears to be able to predict the hs-CRP levels based on anxiety score, depression scores, fasting blood glucose, systolic blood pressure, and history of cardiovascular diseases.

Depression and anxiety at 1- and 12-months post ischemic stroke: methods for examining individual change over time.

Background Depression is commonly studied post stroke, while anxiety is less studied. This study presents prevalence of depression and anxiety at 1- and 12-months post ischemic stroke alongside three methods for examining within-subjects change over time. Methods Participants were ischemic stroke patients of the Auckland Regional Community Stroke Study (ARCOS-V) with Hospital Anxiety and Depression Scale data at 1- (n =343) and 12-months (n =307). Change over time was examined using within-subjects repeated measures ANOVA, calculation of the Reliable Change Index, and a Sankey diagram of those meeting cut-off scores (>7) for caseness over time. Results Using repeated measures ANOVA, depression scores didn't change significantly over time, while anxiety symptoms decreased significantly. When reliable change was calculated, 4.2% of individuals had reliable decreases in anxiety symptoms, while 5.7% had reliable decreases in depression symptoms. Those who had a reliable decrease in one tended to have a reliable decrease in the other. In the Sankey, the proportion of those meeting the cut-off score for anxiety did not change over time (12.8 and 12.7% at 1- and 12-months), while those meeting the cut-off for depression increased slightly (3.7-4.5%) and those meeting cut-offs for both decreased from 10.4 to 8.1%. Conclusion The three methods produced very different findings. Use of cut-off scores is common but has limitations. Calculation of clinically reliable change is recommended. Further work is needed to ensure depression and anxiety are monitored over time post-stroke, and both should be the subject of intervention efforts in both acute and late stages post-stroke.

Transcriptomic Profiling Reveals Sex-Specific Epigenetic Dynamics Involving kdm6b and H3K27 Methylation in Cerebral Ischemia-Induced Neurogenesis and Recovery.

Cerebral ischemic stroke ranks among the leading causes of death and disability worldwide. A significant challenge, beyond the lack of effective therapies, is the frequent oversight of sex as a vital factor in stroke research. This study focuses on elucidating the sex-specific epigenetic mechanisms that contribute to neural damage and recovery in cerebral ischemia. In our previously reported study, we demonstrated that following ischemia-induced cerebral artery occlusion (ICAO), female striatal tissue exhibited an early reinstatement of H3K9me2 marks on the promoters of inflammatory genes compared to male striatal tissue. This restoration led to a reduction in the expression of inflammatory cytokines, ultimately contributing to accelerated recovery in females. Building upon these findings, the current study aimed to investigate the unidentified molecular pathways responsible for the accelerated recovery observed in females. To explore this, we performed illumina-RNA sequencing on striatal tissues 24-h post-ICAO. Interestingly, our analysis revealed differential regulation of H3K27me2 marks on the promoters of various neurogenic genes at an early stage, which facilitated early neurogenesis in the female striatum. This investigation identifies an epigenetic modulator, kdm6b/jmjd3, targeting H3K27, and delineates its sex-specific role in neural stem cell proliferation. The findings contribute to a comprehensive model linking gender-specific epigenetic regulation, neurogenesis, and post-ICAO recovery. In conclusion, the identified epigenetic modulators and their roles in neurogenesis offer potential targets for refined therapeutic interventions, emphasizing the importance of personalized and sex-specific considerations in stroke studies.

Multivariate linear regression to predict association of non-invasive arterial stiffness with cardiovascular events.

Arterial stiffness is a crucial factor in determining an increase in systolic blood pressure and pulse pressure and can also predict the development of cardiovascular disease (CVD). The purpose of this study was to examine the relationship between arterial stiffness and future CVD. Out of the original 9704 participants in the Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study, we randomly selected 363 healthy participants, 226 normal subjects (who reported symptoms of CVD but were not confirmed) and 292 individuals who had experienced a major cardiovascular event. The SphygmoCor XCEL System (AtCor Medical Incorporation) was utilized to measure pulse wave velocity (PWV), central augmentation index (CAI), cardio-ankle vascular index (CAVI) and central aortic pressure (CAP). A multivariate multiple regression model was used to analyse the factors associated with non-invasive arterial stiffness parameters (PWV, CAVI, CAP and CAI) after adjusting for potential confounders. All statistical analyses were conducted using SPSS 21 with a significance level of 0.05. The mean PWV was significantly higher in patients who had experienced a confirmed CVD event (P<0.001). The multivariate multiple regression model results, after adjusting for potential confounders, showed a significant association between PWV and the CVD group (normal vs. healthy and event vs. healthy), as well as between hypertension and obesity with PWV and diabetes with CAI (P<0.05). PWV was found to be associated with CVD and its related risk factors such as diabetes, obesity and hypertension. It may be more effective than other arterial stiffness parameters in predicting CVD in clinical settings.

MRI-Proven Incident Ischemia: A New Marker of Disease Progression in Small Vessel Diseases.

In ischemic cerebral small vessel diseases (cSVD), recurrent ischemic stroke is rare (2%-3% per year). Because acute ischemia may not always lead to stroke in cSVD due to the small size of lesions, acute stroke may not reliably reflect ischemic activity or the risk of further clinical worsening, as both incident lacunes and incidental diffusion-weighted imaging-positive lesions can occur without stroke symptoms. We aimed to evaluate the total ischemic activity by measuring the incidence of magnetic resonance imaging (MRI)-proven incident ischemia, independent of the presence of stroke symptoms in a large cohort of cSVD. DHU-LAC is an ongoing French multicenter cohort study of MRI-proven ischemic stroke presumably due to cSVD. We report data on patients recruited between June 2018 and October 2023. In DHU-LAC, patients are enrolled within 15 days of stroke onset and are cared for according to current guidelines. During the first 6 months, patients are systematically reassessed clinically and by brain MRI: (1) at any time if stroke symptoms occur and (2) at the end of the period. We defined MRI-proven incident ischemia as either recurrent ischemic stroke or at least 1 incident lacune or incidental diffusion-weighted imaging-positive lesion on brain MRI at 6 months. Two hundred forty-nine patients were included, of whom 172 had available data at both inclusion and after 6 months. They were aged 63±6 years, 28% were women, and 65% had hypertension. Six (3%) had a recurrent ischemic stroke, but 25 more (15%) had at least 1 incident lacune or incidental diffusion-weighted imaging-positive lesion on brain MRI. MRI-proven ischemia occurs about 5× more frequently than ischemic stroke in cSVD. As data confirming the detrimental clinical effect of both incident lacunes and incidental diffusion-weighted imaging-positive lesions accumulate, MRI-proven incident ischemia may become a plausible outcome for future clinical trials in cSVD. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552926.

A novel index for diagnosis of type 2 diabetes mellitus: Cholesterol, High density lipoprotein, and Glucose (CHG) index.

Gold standard methods of type 2 diabetes mellitus are expensive and therefore not practical for large scale studies in low-income countries. We have investigated the total cholesterol, high density lipoprotein (HDL), and glucose (CHG) index for diagnosis of type 2 diabetes mellitus index which is derived from fasting state. In this study we aimed to compare the accuracy of with CHG index and triglycerides (TG) and glucose levels (TyG) as surrogates of type 2 diabetes mellitus. A total of 9,704 individuals between 35 and 65 years of age were recruited as part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. They were categorized into two groups, those with and without type 2 diabetes mellitus. The cut-off in groups to detection of type 2 diabetes mellitus was fasting blood glucose ≥126 mg/dL in blood sample. Receiver operating characteristic (ROC) curve analysis was used to establish the cut-off of indices to evaluate the sensitivity and specificity of them. The best cut-off of CHG index for diagnosis of type 2 diabetes mellitus was 5.57 which was associated with a sensitivity of 70.38% and specificity of 89.82% values. This was in comparison to the TyG index. LR+ CHG index was 6.91 compared to 3.47 for the TyG index and the AUC of CHG index was 0.864 (0.857, 0.871) compared with 0.825 (0.818, 0.833) for the TyG index. This indicates that the CHG index has a higher efficiency value to diagnose of type 2 diabetes mellitus. The CHG index could be useful for the detection of type 2 diabetes mellitus.

Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype...

Abstract 4129036: Air pollution and Cardiovascular Disease Incidence in a Pooled Analysis of 6 U.S. Cohorts

Introduction/Background: Long term air pollution is associated with cardiovascular disease (CVD) incidence, however the effects at low levels in the US are unknown. Research Questions/Hypothesis: To assess the effect of long-term exposure to ambient air pollution CVD incidence (myocardial infarction [MI], stroke, and all CVD) in a pooled analysis of epidemiological cohorts. Materials and Methods: We harmonized data from six cohorts (Cardiovascular Health Study, Nurses’ Health Study II, Multi-Ethnic Study of Atherosclerosis, and Reasons for Geographic And Racial Differences in Stroke Study, Sister Study, and Women’s Health Initiative) with both CVD incidence data and extensive covariate information. We predicted time-varying two-year average concentrations of particulate matter &lt;2.5 microns (PM 2.5 ) and nitrogen dioxide (NO 2 ) from 1990-2019 at participant residential addresses using validated regionalized spatio-temporal models, combining spatio-temporal universal kriging and partial least squares regression with inputs from monitoring data from regulatory and researcher-deployed networks, satellite remote-sensing data and chemical transport modeling. Cox proportional hazards regression models adjusted for individual and area-level information, including smoking status, socio-economic factors, anthropometry, blood pressure, cholesterol, and other clinical variables. Results: Our analysis included over 300,000 participants and 10,229 incident CVD events. The median residential concentration of PM 2.5 was 10.1 µg/m 3 and NO 2 was 9.3 ppb. A 5 µg/m 3 increase in PM 2.5 was not significantly associated with a higher hazard ratio for all outcomes: 1.03 (95%CI: 0.96, 1.10) for CVD incidence, 1.03 (95%CI 0.93, 1.15) for MI, and 1.00 (95%CI 0.90, 1.10) for stroke. We found that a 10ppb increase in NO 2 was associated with a 1.06 (95%CI: 1.01, 1.11) higher hazard ratio for CVD, 1.07 (95%CI: 1.01, 1.11) for MI, and 1.02 (95%CI 0.96, 1.09) for stroke. Conclusions: In this analysis of a large, pooled cohort with excellent exposure, outcome, and covariate information, we found an association of NO 2 exposure—considered a surrogate for traffic-related air pollution—with CVD incidence and MI. Associations with particulate matter were not statistically significant, but could not exclude a small increased risk. We are extending this analysis to include 6 additional cohorts and an additional 700,000 participants to allow for generation of a highly resolved concentration-response function.

How Can Graph Theory Inform the Dual-stream Model of Speech Processing? A Resting-state Functional Magnetic Resonance Imaging Study of Stroke and Aphasia Symptomology.

The dual-stream model of speech processing describes a cortical network involved in speech processing. However, it is not yet known if the dual-stream model represents actual intrinsic functional brain networks. Furthermore, it is unclear how disruptions after a stroke to the functional connectivity of the dual-stream model's regions are related to speech production and comprehension impairments seen in aphasia. To address these questions, in the present study, we examined two independent resting-state fMRI data sets: (1) 28 neurotypical matched controls and (2) 28 chronic left-hemisphere stroke survivors collected at another site. We successfully identified an intrinsic functional network among the dual-stream model's regions in the control group using functional connectivity. We then used both standard functional connectivity analyses and graph theory approaches to determine how this connectivity may predict performance on clinical aphasia assessments. Our findings provide evidence that the dual-stream model of speech processing is an intrinsic network as measured via resting-state MRI and that functional connectivity of the hub nodes of the dual-stream network defined by graph theory methods, but not overall average network connectivity, is weaker in the stroke group than in the control participants. In addition, the functional connectivity of the hub nodes predicted linguistic impairments on clinical assessments. In particular, the relative strength of connectivity of the right hemisphere's homologues of the left dorsal stream hubs to the left dorsal hubs, versus to the right ventral stream hubs, is a particularly strong predictor of poststroke aphasia severity and symptomology.

Genome-wide association studies of ischemic stroke based on interpretable machine learning.

Despite the identification of several dozen genetic loci associated with ischemic stroke (IS), the genetic bases of this disease remain largely unexplored. In this research we present the results of genome-wide association studies (GWAS) based on classical statistical testing and machine learning algorithms (logistic regression, gradient boosting on decision trees, and tabular deep learning model TabNet). To build a consensus on the results obtained by different techniques, the Pareto-Optimal solution was proposed and applied. These methods were applied to real genotypic data of sick and healthy individuals of European ancestry obtained from the Database of Genotypes and Phenotypes (5,581 individuals, 883,749 single nucleotide polymorphisms). Finally, 131 genes were identified as candidates for association with the onset of IS. UBQLN1, TRPS1, and MUSK were previously described as associated with the course of IS in model animals. ACOT11 taking part in metabolism of fatty acids was shown for the first time to be associated with IS. The identified genes were compared with genes from the Illuminating Druggable Genome project. The product of GPR26 representing the G-coupled protein receptor can be considered as a therapeutic target for stroke prevention. The approaches presented in this research can be used to reprocess GWAS datasets from other diseases.

Automated Extraction of Stroke Severity From Unstructured Electronic Health Records Using Natural Language Processing.

Multicenter electronic health records can support quality improvement and comparative effectiveness research in stroke. However, limitations of electronic health record-based research include challenges in abstracting key clinical variables, including stroke severity, along with missing data. We developed a natural language processing model that reads electronic health record notes to directly extract the National Institutes of Health Stroke Scale score when documented and predict the score from clinical documentation when missing. The study included notes from patients with acute stroke (aged ≥18 years) admitted to Massachusetts General Hospital (2015-2022). The Massachusetts General Hospital data were divided into training/holdout test (70%/30%) sets. We developed a 2-stage model to predict the admission National Institutes of Health Stroke Scale, obtained from the GWTG (Get With The Guidelines) stroke registry. We trained a model with the least absolute shrinkage and selection operator. For test notes with documented National Institutes of Health Stroke Scale, scores were extracted using regular expressions (stage 1); when not documented, least absolute shrinkage and selection operator was used for prediction (stage 2). The 2-stage model was tested on the holdout test set and validated in the Medical Information Mart for Intensive Care (2001-2012) version 1.4, using root mean squared error and Spearman correlation. We included 4163 patients (Massachusetts General Hospital, 3876; Medical Information Mart for Intensive Care, 287); average age, 69 (SD, 15) years; 53% men, and 72% White individuals. The model achieved a root mean squared error of 2.89 (95% CI, 2.62-3.19) and Spearman correlation of 0.92 (95% CI, 0.91-0.93) in the Massachusetts General Hospital test set, and 2.20 (95% CI, 1.69-2.66) and 0.96 (95% CI, 0.94-0.97) in the MIMIC validation set, respectively. The automatic natural language processing-based model can enable large-scale stroke severity phenotyping from the electronic health record and support real-world quality improvement and comparative effectiveness studies in stroke.

Comparing the properties of traditional and novel approaches to the modified Rankin scale: Systematic review and meta-analysis.

The Modified Rankin Scale (mRS) is the most commonly used functional measure in stroke research but is limited by inter-rater reliability (IRR). Various interventions to improve mRS application have been described. We aimed to compare properties of differing approaches to mRS assessment. Multidisciplinary databases (MEDLINE, EMBASE, Health and Psychosocial Instruments [OVID], CINAHL, PsycINFO [EBSCO]) were searched for adult human stroke studies describing psychometric properties of mRS. Two researchers independently screened 20% titles and abstracts, reviewed all full studies, extracted data, and conducted risk of bias (ROB) analysis. Primary outcomes for random-effects meta-analysis were IRR measured by kappa (K) and weighted kappa (KW). Validity and inter-modality reliability measures (Spearman's rho, KW) were also summarised. From 897 titles, 46 studies were eligible, including twelve differing approaches to mRS, 8608 participants. There was high ROB in 14 (30.4%) studies. Overall, reliability was substantial (n = 29 studies, K = 0.65, 95% CI: 0.58-0.71) but IRR was higher for novel approaches to mRS, for example, the Rankin Focussed Assessment (n = 2 studies, K = 0.94, 95% CI: 0.90-0.98) than standard mRS (n = 13 studies, K = 0.55, 95%CI:0.46-0.64). Reliability improved following the introduction of mRS training (K = 0.56, 95% CI: 0.44-0.67; vs K = 0.69, 95% CI: 0.62-0.77). Validity ranged from poor to excellent, with an excellent overall concurrent validity of novel scales (n = 6 studies, KW = 0.86, 95% CI: 0.75-0.97). The agreement between face-to-face and telephone administration was substantial (n = 5 studies, KW = 0.80, 95% CI: 0.74-0.87). The mRS is a valid measure of function but IRR remains an issue. The present findings are limited by a high ROB and possible publication bias. Interventions to improve mRS reliability (training, structured interview, adjudication) seem to be beneficial, but single interventions do not completely remove reliability concerns.

Mild intracerebral bleeding does not adversely affect survival and neurological outcome of surgical therapy for left-sided infective endocarditis

Abstract Background Intracerebral bleeding (IB) is a serious condition that requires increased attention and has implications for treatment options. For patients with infective endocarditis (IE), current guidelines recommend postponing surgery if IB is present. IB can be classified into four relevant groups (following European Cooperative Acute Stroke Study and Heidelberger Bleeding classification): hemorrhagic transformation (HT) 1 and 2, and parenchymal hemorrhage (PH) 1 and 2. PH2 is the only IB with neurological deterioration. These classifications were originally introduced for stroke patients following thrombolysis but without IE. The hypothesis tested in our study is that IB may influence IE treatment and thus outcome. Method Patients were retrospectively identifyied who were operated for left-sided IE, neuroradiologists re-evaluated and classified preoperative cerebral imaging for any IB. Outcome was quantified using the modified Rankin score (mRS), and mRS were extracted from the patients’ hospital chart at admission and by follow-up telephone call (FU), also including mortality. To ensure that the influence of IB was comparable, patients with IB (IB+) were propensity matched (EuroScore 2, Charlson Comorbidity Index, C-reactive protein; nearest neighbor match) to patients without IB (IB-) who also received surgical IE therapy. All IB+ patients underwent a careful risk-benefit analysis before therapy. Results Of 286 consecutive patients (January 2015 - November 2022) operated for left-sided IE, 36 had IB (65±13 years, 26% female): 11 with HT1, 9 with HT2, 8 with PH1, and 8 with PH2. These patients were matched with 36 operated IB- patients. Survival analysis showed no overall effect of IB+ vs. IB- (p = 0.112, 95% CI of hazard ratio was 0.246-1.243 vs. 0.709-3.572). Although there was no effect of IB on survival in the mild IB subgroup (HT1/2, Figure A), there was a difference in patients with severe IB (PH1/2) with less survival in IB+ (Figure B). Neurological outcome (ΔmRS) showed an effect of IB grade in the two-way ANOVA analysis (p = 0.029). Intergroup comparison showed a significantly better outcome for IB- (vs. IB+) in the PH2 subgroup (p = 0.034), but not in other subgroups. For all groups, the mean ΔmRS for IB+ was 1.1±1.6 vs. 0.70±1.4 for IB- (p = 0.256). The mean FU time was 2.6±2.1 years. Conclusion In patients operated for left-sided IE, mild IB did not affect survival or neurological outcome. In the more severe forms of IB, i.e. PH1 and PH2, survival was less favorable compared to matched controls. Furthermore, we observed a difference in neurological outcome in patients with severe IB. Thus, surgical therapy of left-sided IE should be avoided in patients with severe IB, whereas we can add evidence to the safety of surgical therapy in mild IB. Therefore, we recommend regular assessment of the degree of IB in such patients.Figure

Association of Adherence to a MIND-Style Diet With the Risk of Cognitive Impairment and Decline in the REGARDS Cohort.

Diet may influence the development of cognitive impairment and affect cognitive decline, but whether this relationship varies between Black American and White American people is unclear. This study examined the association of Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) and incident cognitive impairment and cognitive trajectories in a biracial prospective cohort study. Using data derived from the Food Frequency Questionnaire in the REasons for Geographic and Racial Differences in Stroke study, we compared MIND diet adherence with incident cognitive impairment and cognitive trajectory in Black participants and White participants. Logistic regression was used to model MIND diet score (continuous variable and using tertiles) and incident cognitive impairment after adjusting for age, sex, race, region, education, income, total energy, hypertension history, dyslipidemia, diabetes, estimated glomerular filtration rate, ischemic heart conditions, atrial fibrillation, and lifestyle factors including sedentary, obesity, and smoking. Mixed-effects models were used to examine the association between cognitive trajectory and MIND diet adherence. Dietary data to calculate the MIND diet score and cognitive data were available on 14,145 participants with a mean age of 64 years (SD 9.0 years) that was 56.7% female. Greater MIND diet adherence was associated with a decreased incidence of cognitive impairment (odds ratio [OR] 0.96, 95% CI 0.93-0.99, p = 0.02) after adjusting for all covariates. In the fully adjusted model, greater MIND diet adherence was associated with decreased risk of cognitive impairment in female participants (OR 0.92, 95% CI 0.89-0.96, p < 0.001) but not in male participants (OR 1.01, 95% CI 0.97-1.06, p = 0.64). In all models, greater MIND diet adherence was associated with decreased risk of cognitive decline. MIND diet adherence was a better predictor of cognitive decline in Black participants (β = 0.04, SE = 0.007, p < 0.001) than in White participants (β = 0.03, SE = 0.004, p < 0.001). Greater MIND diet adherence was associated with decreased risk of cognitive impairment in female participants but not male participants, with no difference between Black participants and White participants. However, MIND diet adherence was a better predictor of cognitive trajectory in Black participants than in White participants.

Causal relationship between uric acid and stroke: a two-sample mendelian randomization study.

Many previous observational studies have disputed whether there is a link between uric acid and stroke. And the causal relationship between uric acid and stroke is unclear. To determine whether there is a causal relationship between uric acid and stroke by using mendelian randomization (MR). Uric acid dataset was obtained from Anna Kottgen et al, with a sample size of 110,347 people, including 2450,548 single nucleotide polymorphisms (SNPs). Stroke pooled data from Malik R et al, publicly available in MEGASTROKE genome-wide association study, included meta-analysis data from 40,585 stroke patients and 406,111 control patients, totaling 8211,693 SNPs. The summary data of genome-wide association study of uric acid and stroke were collected from publicly available online databases. Inverse variance weighting was used to determine the causal relationship between uric acid and stroke. MR-Egger and weighted median model were used for supplementary analysis. Results were then analyzed for heterogeneity, pleiotropy, and sensitivity to ensure no statistical pleiotropy and to reduce bias. A total of 27 SNPs were included in this study after the disequilibrium instrumental variables were excluded. Check the PhenoScanner database for SNPs associated with confounders. In the end, a total of 8 SNPs were excluded. Two SNPs were excluded because the correction direction was the same. Since the F statistic is >10, rs10761587 and rs1825043 are excluded. Finally, 15 SNPs were selected as uric acid instrumental variables. Inverse variance weighting-fixed effect model suggested that there was no causal relationship between uric acid and stroke (odds ratio = 1.004, 95% confidence interval = 0.940, 1.072). MR-Egger and weighted median model also showed the same result. In addition, the results of this study were robust without heterogeneity and pleiotropy. This MR study suggests no support of a causal relationship between uric acid and stroke.