Post-stroke Functional Outcome Research Articles

The burden of executive dysfunction after ischemic stroke (Bulgaria, 2019-2021)

Abstract Background Executive dysfunctions have great impact on behavior and quality of life in elderly. They also play important role for post-stroke functional outcome. The aim of our study was to examine the frequency, severity and types of executive dysfunctions at the third month after the ischemic stroke. Methods We examined 108 patients 3 months after ischemic stroke (66.67±9.03 years old, 66 males and 42 females) via 128-Wisconsin Card Sorting Test (WCST). WCST is a standardized instrument for detecting various executive dysfunctions. It is applicable for patients after stroke, because the test doesn’t require preserved arm motor functions. It measures global executive functioning (GEF), inhibitory control system (ICS), executive attention (EA), cognitive flexibility (CF) and working memory (WM). Our patients’ results were compared to the normal population test results. SPSS 24 was used for statistical analysis. Results Impaired GEF were found in 46% of our patients, most of them had mild or moderate impairment. One fourth of them showed impaired ICS, although the impairment in most of the cases was mild. EA deficits were found in 43% of our cases (17% had mild, 15% mild to moderate, 7% moderate and 4% severe impairment). WM dysfunction was found in 1/3 of them (the average result was about 27 percentiles; 29% had mild and 5% had mild to moderate deficits) and about ¼ of our patients had borderline results. CF was impaired in 68% of our patients (11% had mild, 28% mild to moderate, 16% moderate and 13% severe impairment). Conclusions GEF impairment is frequent after stroke. Patients had problems in ICS, EA, CF and WM. However, in most of the cases the dysfunction is mild or moderate and can be found only if it is actively searched and accessed. The most impaired functions were CF and EA. Patients with executive dysfunction require cognitive rehabilitation and specific social support. Key messages • Executive dysfunctions are frequent after ischemic stroke. The impairment is mild or moderate, but however it impacts the quality of life, behavior, prognosis and outcome of post-stroke survivors. • Patients with executive dysfunctions require specific cognitive rehabilitation and social support.

Predictors of functional outcome after stroke: Sex differences in older individuals.

Sex differences in stroke are well documented, with females being older at onset, with more severe strokes and worse outcomes than males. Females receive less comprehensive stroke unit treatment. Similarly, older individuals receive poorer quality care than younger ones. There is limited research on sex differences in factors that impact 3-month poststroke functional outcome in people older than 80 years. This register-based and cross-sectional study analyzed data from two stroke quality registers in Sweden from 2014 through 2019. The study included patients aged ≥80 with a diagnosis of ischemic or hemorrhagic stroke. Sociodemographic features, prestroke condition, stroke severity on admission (National Institutes of Health Stroke Scale [NIHSS]), stroke unit care, rehabilitation plans, and 3-month poststroke functional outcome measured with the modified Rankin Scale were analyzed. Ordinal regression analyses stratified by sex were conducted to assess sex differences in factors that impact poststroke functional outcome 3 months after the stroke. A total of 2245 patients were studied with the majority (59.2%) being females. Females experienced more severe strokes (NIHSS median 4 vs. 3, p = 0.01) and were older at stroke onset than males (87.0 vs. 85.4, p < 0.001). Females were also less independent prestroke (69.9% vs. 77.4%, p < 0.001) and a higher proportion of females lived alone (78.2% vs. 44.2%, p < 0.001). Males received intravenous thrombolysis more often than females (16.3% vs. 12.0%, p = 0.005). Regarding 3-month functional outcome, males benefited more from thrombolysis (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.30-0.83), whereas females benefited more from thrombectomy (OR 0.40, 95% CI 0.20-0.71). Stroke care should be adapted to sex disparities in older individuals, while clinicians should be aware of these sex disparities. Further research could clarify the mechanisms behind these disparities and lead to a more personalized approach to stroke care of the older population.

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. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Causal effects of immune cell surface antigens and functional outcome after ischemic stroke: a Mendelian randomization study.

While observational studies link immune cells with post-stroke functional outcome, the underlying immune mechanisms are not well understood. Immune cell surface antigens are actively involved in the biological behavior of immune cells, investigating immune cell surface antigens could deepen our comprehension of their role and biological processes in stroke recovery. Therefore, we aimed to investigate the immunological basis of stroke outcome by exploring the causal relationship between immune cell surface antigens and functional outcome after ischemic stroke in a Mendelian randomization study. Genetic variants related to immune cell surface antigens and post-stroke functional outcome were selected for two-sample Mendelian randomization (MR) analysis. 389 fluorescence intensities (MFIs) with surface antigens were included. Inverse variance weighted (IVW) modeling was used as the primary MR method to estimate the causal effect of exposure on the outcome, followed by several alternative methods and sensitivity analyses. Additional analysis of the association between immune cell surface antigens and risk of ischemic stroke for assessment of collider bias. We found that suggestive associations between CD20 on switched memory B cell (OR = 1.16, 95% CI: 1.01-1.34, p = 0.036) and PDL-1 on monocyte (OR = 1.32, 95% CI: 1.04-1.66, p = 0.022) and poor post-stroke functional outcome, whereas CD25 on CD39+ resting Treg (OR = 0.77, 95% CI: 0.62-0.96, p = 0.017) was suggestively associated with good post-stroke functional outcome. The elevated CD20 on switched memory B cell, PDL-1 on monocyte, and CD25 on CD39+ resting Treg may be novel biomarkers and potential causal factors influencing post-stroke functional outcome.

Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study.

Most previous studies suggested obesity deteriorates the functional outcome after ischemic stroke. But there are researches claiming that obesity is associated with lower mortality, recurrence, and readmission rates, which is known as the obesity paradox. Our current research aimed to investigate the correlation between genetically obesity and the post-stroke outcome with the Mendelian randomization (MR) method. The UK Biobank and the GIANT consortium provided instrumental variables for body mass index (BMI, 806,834 individuals) and waist-to-hip ratio (WHR, 697,734 individuals). Data of functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network (6012 individuals). Inverse-variance weighted approach was utilized as the primary analyses. Sensitivity analyses involved the utilization of different MR methods. The heterogeneity among genetic variants was assessed by I2 and Q value statistics. In univariable analysis, there was a significant connection between genetic susceptibility to WHR and worse functional outcome (modified Rankin Scale 3) after ischemic stroke (OR [95%CI] = 1.47 [1.07, 2.02], P = 0.016). Genetic liability to BMI and was not associated with post-stroke functional outcome (all P > 0.05). The overall patterns between genetic liability to WHR and functional outcome post-ischemic outcome no longer existed in the multivariable MR analysis after adjusting for BMI (OR [95%CI] = 1.26[0.76,1.67], P = 0.56). The current MR study provided evidence that WHR was correlated to unfavorable outcome post-ischemic stroke. Exploring interventions against obesity may potentially improve recovery after ischemic stroke.

Abstract WP273: The Association of Social Determinants of Health on Functional Outcome After Intracerebral Hemorrhage

Background: It remains unknown which social determinants of health (SDOH) are impactful or when disparities begin to emerge in intracerebral hemorrhage (ICH). This study aimed to investigate the association between pre-stroke SDOH and post-stroke functional outcome. Methods: Data from the Massachusetts General Hospital (MGH) ICH cohort was used and included age, sex, ICH severity, history of hypertension, tobacco use, diabetes, coronary artery disease, atrial fibrillation, liver disease, history of dementia, and history of prior ICH. SDOH exposures included income bracket, educational attainment, marital status, race, and religion. The primary outcome was the modified Rankin Score (mRS) measured at 12 months. Baseline characteristics, past medical history, and SDOH among those with mild stroke versus severe stroke were compared using the Wilcoxon Rank Sum test and chi-square tests. Factors from the univariate analysis which were associated with stroke severity (p&lt;0.05) were included in a logistic regression model. Results: Of the 315 patients with available 12-month mRS, 180 (57%) had mRS scores &lt;3 or relatively good functional outcomes, and 135 (43%) had mRS scores &gt;=3 or relatively poor functional outcomes. The median age of those with low mRS was 69 compared to 76 for those with high mRS. Those with high mRS were more likely to have high school-only education or a diagnosis of dementia on admission compared to those with low mRS. Those with high school-only education were 2.94 times more likely than college diplomates to have high mRS (OR 2.94, 95% CI 1.57-5.53). Similarly, those with a diagnosis of dementia on admission, were 6.22 times more likely than those without a diagnosis of dementia to have high mRS (OR 6.22, 95% CI 1.70-22.75). Discussion: In addition to clinical determinants of age, ICH severity, and underlying dementia, educational attainment was an independent predictor of poor functional outcome after ICH. We recognize the impact of survival bias in our study design; however, we found differences in recovery despite this bias. Our findings suggest that disparities in outcomes exist even in relatively homogenous patient populations and that SDOH prior to an ICH still have associations with functional outcomes after stroke.

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

BackgroundThe 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.MethodsAcute-phase plasma levels of 65 inflammation-related proteins were measured in 534 ischemic stroke cases. Logistic regression was used to estimate associations to unfavorable 3-month functional outcome (modified Rankin Scale score > 2) and LASSO regressions to identify proteins with independent effects.ResultsTwenty proteins were associated with outcome in univariable models after correction for multiple testing (FDR < 0.05), and for 5 the association was independent of clinical variables, including stroke severity (TNFSF14 [LIGHT], OSM, SIRT2, STAMBP, and 4E-BP1). LASSO identified 9 proteins that could best separate favorable and unfavorable outcome with a predicted diagnostic accuracy (AUC) of 0.81; three associated with favorable (CCL25, TRAIL [TNFSF10], and Flt3L) and 6 with unfavorable outcome (CSF-1, EN-RAGE [S100A12], HGF, IL-6, OSM, and TNFSF14). Finally, we identified sex- and etiologic subtype-specific associations with the best discriminative ability achieved for cardioembolic, followed by cryptogenic stroke.ConclusionsWe identified candidate blood-based protein biomarkers for post-stroke functional outcome involved in, e.g., NLRP3 inflammasome regulation and signaling pathways, such as TNF, JAK/STAT, MAPK, and NF-κB. These proteins warrant further study for stroke outcome prediction as well as investigations into the putative causal role for stroke outcome.

Development and validation of a nomogram model for predicting unfavorable functional outcomes in ischemic stroke patients after acute phase.

Prediction of post-stroke functional outcome is important for personalized rehabilitation treatment, we aimed to develop an effective nomogram for predicting long-term unfavorable functional outcomes in ischemic stroke patients after acute phase. We retrospectively analyzed clinical data, rehabilitation data, and longitudinal follow-up data from ischemic stroke patients who underwent early rehabilitation at multiple centers in China. An unfavorable functional outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 90 days after onset. Patients were randomly allocated to either a training or test cohort in a ratio of 4:1. Univariate and multivariate logistic regression analyses were used to identify the predictors for the development of a predictive nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive ability in both the training and test cohorts. A total of 856 patients (training cohort: n = 684; test cohort: n = 172) were included in this study. Among them, 518 patients experienced unfavorable outcomes 90 days after ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment classification (p = 0.024), antihypertensive agents use [odds ratio (OR) = 1.86; p = 0.041], 15-day Barthel Index score (OR = 0.930; p < 0.001) and 15-day mRS score (OR = 13.494; p < 0.001) were selected as predictors for the unfavorable outcome nomogram. The nomogram model showed good predictive performance in both the training (AUC = 0.950) and test cohorts (AUC = 0.942). The constructed nomogram model could be a practical tool for predicting unfavorable functional outcomes in ischemic stroke patients underwent early rehabilitation after acute phase.

Prognostic significance of serum NLRC4 in patients with acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study.

Caspase activation and recruitment domain-containing protein 4 (NLRC4) is implicated in neuroinflammation. The aim of the study was to discern the potential ability of serum NLRC4 in assessment of prognosis after intracerebral hemorrhage (ICH). In this prospective, observational study, serum NLRC4 levels were quantified in 148 acute supratentorial ICH patients and 148 controls. Severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume, and poststroke 6-month functional outcome was estimated according to the modified Rankin Scale (mRS). Early neurologic deterioration (END) and 6-month poor outcome (mRS 3-6) were deemed as the two prognostic parameters. Multivariate models were established for investigating associations, and receiver operating characteristic (ROC) curves were configured to indicate predictive capability. Patients had substantially higher serum NLRC4 levels than controls (median, 363.2 pg/ml vs. 74.7 pg/ml). Serum NLRC4 levels had independent correlation with NIHSS scores [β, 0.308; 95% confidence interval (CI), 0.088-0.520], hematoma volume (β, 0.527; 95% CI, 0.385-0.675), serum C-reactive protein levels (β, 0.288; 95% CI, 0.109-0.341) and 6-month mRS scores (β, 0.239; 95% CI, 0.100-0.474). Serum NLRC4 levels above 363.2 pg/ml were independently predictive of END (odds ratio, 3.148; 95% CI, 1.278-7.752) and 6-month poor outcome (odds ratio, 2.468; 95% CI, 1.036-5.878). Serum NLRC4 levels significantly distinguished END risk [area under ROC curve (AUC), 0.765; 95% CI, 0.685-0.846] and 6-month poor outcome (AUC, 0.795; 95% CI, 0.721-0.870). In terms of predictive ability for 6-month poor outcome, serum NLRC4 levels combined with NIHSS scores and hematoma volume was superior to NIHSS scores combined with hematoma volume, NIHSS scores and hematoma volume (AUC, 0.913 vs. 0.870, 0.864 and 0.835; all P < 0.05). Nomograms were built to reflect prognosis and END risk of combination models, where serum NLRC4, NIHSS scores and hematoma volume were enforced. Calibration curves confirmed stability of combination models. Markedly raised serum NLRC4 levels following ICH, in close relation to illness severity, are independently associated with poor prognosis. Such results are indicative of the notion that determination of serum NLRC4 may aid in severity assessment and prediction of functional outcome of ICH patients.

Depressive Symptoms and Risk of Acute Stroke: INTERSTROKE Case-Control Study.

Depression has been reported to be a risk factor of acute stroke, based largely on studies in high-income countries. In the INTERSTROKE study, we explored the contribution of depressive symptoms to acute stroke risk and 1-month outcome across regions of the world, within subpopulations and by stroke type. The INTERSTROKE is an international case-control study of risk factors of first acute stroke, conducted in 32 countries. Cases were patients with CT- or MRI-confirmed incident acute hospitalized stroke, and controls were matched for age, sex, and within sites. Standardized questions asked about self-reported depressive symptoms during the previous 12 months and the use of prescribed antidepressant medications were recorded. Multivariable conditional logistic regression was used to determine the association of prestroke depressive symptoms with acute stroke risk. Adjusted ordinal logistic regression was used to explore the association of prestroke depressive symptoms with poststroke functional outcome, measured with the modified Rankin scale at 1 month after stroke. Of 26,877 participants, 40.4% were women, and the mean age was 61.7 ± 13.4 years. The prevalence of depressive symptoms within the last 12 months was higher in cases compared with that in controls (18.3% vs 14.1%, p < 0.001) and differed by region (p interaction <0.001), with lowest prevalence in China (6.9% in controls) and highest in South America (32.2% of controls). In multivariable analyses, prestroke depressive symptoms were associated with greater odds of acute stroke (odds ratio [OR] 1.46, 95% CI 1.34-1.58), which was significant for both intracerebral hemorrhage (OR 1.56, 95% CI 1.28-1.91) and ischemic stroke (OR 1.44, 95% CI 1.31-1.58). A larger magnitude of association with stroke was seen in patients with a greater burden of depressive symptoms. While preadmission depressive symptoms were not associated with a greater odds of worse baseline stroke severity (OR 1.02, 95% CI 0.94-1.10), they were associated with a greater odds of poor functional outcome at 1 month after acute stroke (OR 1.09, 95% CI 1.01-1.19). In this global study, we recorded that depressive symptoms are an important risk factor of acute stroke, including both ischemic and hemorrhagic stroke. Preadmission depressive symptoms were associated with poorer functional outcome, but not baseline stroke severity, suggesting an adverse role of depressive symptoms in poststroke recovery.

Predictive value of fibrinogen levels for 90-day functional outcomes after intravenous thrombolysis in patients with acute ischaemic stroke

PurposeWe aimed to investigate the correlation between fibrinogen levels and functional outcomes at 90 days after intravenous thrombolysis therapy (IVT) in patients with acute ischaemic stroke (AIS). MethodsWe identified patients with AIS who received IVT (alteplase 0.6 or 0.9 mg/kg) between 1 January 2019 and 31 March 2022 in Yancheng 1st People's Hospital. Fibrinogen levels were measured before IVT, and the 90-day post-stroke functional outcome was evaluated using the modified Rankin Scale (mRS). An mRS score of 0–2 indicated functional independence, whereas an mRS score of 3–6 indicated functional dependence. Potential outcome predictors were evaluated using univariate and multivariate analyses, and receiver operating characteristic (ROC) curve analysis was performed to assess the performance of fibrinogen levels in predicting the 90-day outcome. ResultsA total of 276 patients with AIS who received IVT within 4.5 h of stroke onset were enrolled, of whom 165 and 111 were categorised into the functional independence and functional dependence groups, respectively. Univariate analysis showed that the fibrinogen, homocysteine, high-density lipoprotein cholesterol, and D-dimer levels; age; National Institutes of Health Stroke Scale (NIHSS) score on admission; NIHSS score 24 h after IVT; and incidence of cardioembolism were higher in the functional dependence group than in the functional independence group (P < 0.05). Meanwhile, the thrombin time and the incidence of small-vessel occlusion in the functional dependence group were smaller than those in the functional independence group (P < 0.05). Multivariate logistic regression analysis showed that fibrinogen and homocysteine levels were both independent risk factors for 90-day functional dependence in patients with AIS (odds ratio [OR] 2.822, 95% confidence interval [95% CI]: 1.214–6.558, P = 0.016 for fibrinogen; OR 1.048, 95 %CI: 1.002–1.096, P = 0.041 for homocysteine). The area under the ROC curve of fibrinogen levels before IVT for predicting poor functional outcomes was 0.664, with a sensitivity, specificity, positive predictive value, and negative predictive value of 40.9%, 80.8%, 68.9%, and 64.3%, respectively. ConclusionIn patients with AIS, fibrinogen levels have a certain predictive value for short-term functional outcomes after IVT.

Genetically Predicted Sleep Traits and Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study.

Sleep traits can have implications for ischemic stroke recovery in observational studies. The purpose of our present study was to explore the relationship between genetically predicted sleep traits and poststroke functional outcomes with Mendelian randomization (MR) method. Instrumental variables for insomnia and sleep duration were adopted from genome-wide association studies data of European ancestry individuals. Summary data for functional outcome after ischemic stroke were retrieved from the Genetics of Ischemic Stroke Functional Outcome network. Inverse-variance weighted approach was adopted as the main analyses. Alternative MR approaches were used in sensitivity analyses. I2 and Q value statistics were used to appraise the heterogeneity among genetic variants. In univariable analysis, genetic liability to insomnia was significantly associated with worse functional outcome (modified Rankin Scale ≥3) after ischemic stroke (odds ratio [OR] = 1.30; 95% CI: 1.10-1.54, p = 0.002). Genetic liability to short sleep, long sleep, and continuous sleep duration were not associated with poststroke functional outcome (all p > 0.05). Sensitivity analyses without adjustment for stroke severity also supported that insomnia was causally associated with poor functional outcome (OR = 1.25; 95% CI: 1.08-1.44, p = 0.003). In the multivariable MR analysis adjusting for potentially confounding traits including body mass index, depression, type 2 diabetes, smoking, and alcohol consumption, the overall patterns between genetic liability to insomnia and poststroke outcome remained (all p < 0.05). This MR study supports potential adverse effects of liability to insomnia on functional outcome after ischemic stroke. Interventions that address insomnia may offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context.

Systematic review to identify proxy measures to assess post-stroke functional outcomes

• Home-time was the most frequently evaluated proxy of post-stroke functional outcome • Discharge to a location other than home was strongly predictive of poor outcome • Discharge destination and home-time are reasonable proxies of functional outcome : To perform a systematic review of studies evaluating prognostic factors (proxy measures) to predict patients’ post-stroke functional outcome status recommended by clinical guidelines. : MEDLINE and Embase databases were searched from January 1, 2000, through January 8, 2021. Studies that evaluated stroke survivors and assessed a proxy measure's ability to predict functional outcome status as measured by the modified Rankin Scale (mRS), Barthel Index (BI), Glasgow Outcomes Scale, and/or Functional Independence Measure between 30 and 365 days post-stroke were included. : Nine studies met inclusion criteria (median N per study=1,699; range: 530-6,809). Seven studies evaluated ischemic stroke ± transient ischemic attack (TIA), 1 evaluated subarachnoid hemorrhage, and 1 evaluated both ischemic and hemorrhagic stroke and TIA (each reported separately). All studies utilized mRS score to assess post-stroke functional outcome, while 3 utilized the BI. Home-time was the most frequently evaluated proxy (7/9, 77.8%) and had moderate-to-strong correlation/discriminative ability with 3- to 12-month post-stroke functional outcome measurement. Home-time was less able to discriminate between neighboring mRS score values >3 and was only weakly-to-moderately correlated with mRS in TIA patients. Discharge to a location other than home or a relative's home was assessed in 2 of 9 studies (22.2%) and was found to be a moderate-to-strong correlate/predictor of unfavorable mRS score. In a single study, index hospital length of stay weakly correlated with post-stroke function status. : This systematic review provides evidence supporting the use of home-time and discharge destination as proxy measures for predicting post-stroke functional outcome.

Association of cognitive reserve with stroke outcome: a protocol for a systematic review

IntroductionThe concept of cognitive reserve (CR) was introduced to account for individual differences in the clinical manifestation of neurodegenerative diseases. Though several mechanisms and risk factors are shared between neurodegeneration...

Association between Early Cognitive Impairment and Short-Term Functional Outcome in Acute Ischemic Stroke

Background: Little is known about the association between poststroke cognitive impairment (PSCI) and functional outcome in the acute care phase of ischemic stroke and the influence of the clinical condition of acute stroke on this association. We examined this issue, taking into account stroke-related factors, in a hospital-based prospective study of patients with acute ischemic stroke. The same analysis was also performed after subsequent rehabilitation to investigate whether the association observed in the acute care phase persisted after that. For comparison, the same analysis was performed for pre-stroke dementia (PreSD). Methods: We included in the study a total of 923 patients with acute ischemic stroke who were admitted to a hospital from 2012 to 2020 in Japan. Cognitive function was assessed using the Mini-Mental State Examination and Raven’s Colored Progressive Matrices test at an average of 6.3 days after stroke onset. The subjects were divided into three groups with normal cognition, PSCI, and PreSD. Study outcome was a poor functional outcome, defined as a modified Rankin Scale score of ≥3 at the end of acute care (median 21 days after admission). Among total subjects, 460 were also assessed for poor functional outcome after rehabilitation (median 77 days after admission). A logistic regression model was applied in this study. Results: Patients with PSCI and PreSD had higher median National Institute of Health Stroke Scale scores than those with normal cognition (median [IQR]: 3 [2–6], 4 [2–12], and 2 [1–4], respectively). The age- and sex-adjusted cumulative incidence of poor functional outcome was significantly higher in patients with PSCI and PreSD than in those with normal cognition in the acute care and rehabilitation phases. In the acute care phase, these associations remained significant after adjustment for stroke-related factors and other confounders (multivariable-adjusted odds ratio [95% CI] for PSCI vs. normal cognition: 3.28 [2.07–5.20]; for PreSD: 2.39 [1.40–4.08]). Similar results were observed in the rehabilitation phase (for PSCI: 2.48 [1.31–4.70]; for PreSD: 3.92 [1.94–7.92]). Conclusions: Our findings suggest that PSCI, as well as PreSD, is possibly associated with the development of poor functional outcome in the acute care phase of ischemic stroke, and this association continues thereafter.

Endothelial Progenitor Cells Count after Acute Ischemic Stroke Predicts Functional Outcome in Patients with Carotid Atherosclerosis

ObjectivesCirculating Endothelial Progenitor Cells (EPCs) predict cardiovascular outcomes in patients with coronary disease. However, the predictive value of EPCs after ischemic stroke is not well established. We aimed to study the prognostic role of EPCs in patients with acute ischemic stroke and carotid atherosclerosis, focusing on post-stroke functional outcome and stroke recurrences. Materials and MethodsWe studied consecutive adult patients with an acute (<7 days) anterior circulation ischemic stroke and carotid atherosclerosis. Cardioembolic strokes were excluded. We measured circulating EPCs by flow cytometry (CD34+/CD133+/KDR+) at inclusion (7±1 days after stroke) and at one year of follow-up. At three months and at one year we registered the modified Rankin Scale score, stroke recurrences and coronary syndromes during the follow-up. ResultsWe studied 80 patients with a mean age of 74.3±10.4 years. We divided the population in tertiles according to the EPCs count. At three months we observed a favorable outcome in 25/36 (69.4%) patients in the lowest, 19/22 (86.4%) in the medium and 21/22 (95.5%) in the highest tercile (p=0.037). In the multivariable analysis a higher EPCs count was associated with favorable functional outcome after adjusting for age and baseline NIHSS score (OR=3.61, 95%CI 1.34-9.76; p=0.011). This association persisted at one year of follow-up. We did not find association between counts of EPCs and stroke recurrence. ConclusionsIn patients with acute ischemic stroke and carotid atherosclerosis, a higher count of EPCs was associated with favorable functional outcome in the mid and long-term follow-up. Counts of EPCs did not predict stroke recurrences.

The Comparison and Interpretation of Machine-Learning Models in Post-Stroke Functional Outcome Prediction.

Prediction of post-stroke functional outcomes is crucial for allocating medical resources. In this study, a total of 577 patients were enrolled in the Post-Acute Care-Cerebrovascular Disease (PAC-CVD) program, and 77 predictors were collected at admission. The outcome was whether a patient could achieve a Barthel Index (BI) score of >60 upon discharge. Eight machine-learning (ML) methods were applied, and their results were integrated by stacking method. The area under the curve (AUC) of the eight ML models ranged from 0.83 to 0.887, with random forest, stacking, logistic regression, and support vector machine demonstrating superior performance. The feature importance analysis indicated that the initial Berg Balance Test (BBS-I), initial BI (BI-I), and initial Concise Chinese Aphasia Test (CCAT-I) were the top three predictors of BI scores at discharge. The partial dependence plot (PDP) and individual conditional expectation (ICE) plot indicated that the predictors’ ability to predict outcomes was the most pronounced within a specific value range (e.g., BBS-I < 40 and BI-I < 60). BI at discharge could be predicted by information collected at admission with the aid of various ML models, and the PDP and ICE plots indicated that the predictors could predict outcomes at a certain value range.

Multiple Chronic Conditions Explain Ethnic Differences in Functional Outcome Among Patients With Ischemic Stroke.

Mexican Americans (MAs) have worse stroke outcomes and a different profile of multiple chronic conditions (MCC) compared with non-Hispanic White people. MCC has implications for stroke treatment, complications, and poststroke care, which impact poststroke functional outcome (FO). We sought to assess the contribution of MCC to the ethnic difference in FO at 90 days between MAs and non-Hispanic White people. In a prospective cohort of ischemic stroke patients (2008-2016) from Nueces County, Texas, data were collected from patient interviews, medical records, and hospital discharge data. MCC was assessed using a stroke-specific and function-relevant index (range, 0-35; higher scores greater MCC burden). Poststroke FO was measured by an average score of 22 activities of daily living (ADLs) and instrumental ADLs at 90 days (range, 1-4; higher scores worse FO). The contribution of MCC to the ethnic difference in FO was assessed using Tobit regression. Effect modification by ethnicity was examined. Among the 896 patients, 70% were MA and 51% were women. Mean age was 68±12.2 years; 33% of patients were dependent in ADL/instrumental ADLs (FO score >3, representing a lot of difficulty with ADL/instrumental ADLs) at 90 days. MAs had significantly higher age-adjusted MCC burden compared with non-Hispanic White people. Patients with high MCC score (at the 75th percentile) on average scored 0.70 points higher in the FO score (indicating worse FO) compared with those with low MCC score (at the 25th percentile) after adjusting for age, initial National Institutes of Health Stroke Scale, and sociodemographic factors. MCC explained 19% of the ethnic difference in FO, while effect modification by ethnicity was not statistically significant. MAs had a higher age-adjusted MCC burden, which partially explained the ethnic difference in FO. The prevention and treatment of MCC could potentially mitigate poststroke functional impairment and lessen ethnic disparities in stroke outcomes.

3D-Printed Endoport vs. Open Surgery for Evacuation of Deep Intracerebral Hemorrhage.

Large-sized clinical trials have failed to show an overall benefit of surgery over medical treatment in managing spontaneous intracerebral hemorrhages (ICH); less invasive techniques have shown to decrease brain injury caused by surgical manipulation in the standard open approach improving the clinical outcomes of patients. Thereby, we propose a low-cost 3D-printed endoport for a less invasive ICH evacuation. In this study, the authors compare the clinical outcomes of early surgical evacuation using a 3D-printed endoport vs. a standard open surgery (OS). A retrospective analysis was conducted comparing patients who underwent early evacuation of a deep hypertensive ICH through an endoport vs. OS at a single center from August 2017 to March 2019. Demographic, clinical, and radiologic data were reviewed. The primary outcomes were the 90-day post-stroke functional outcome and mortality. A total of 36 patients were included. The two cohorts (18 endoport; 18 OS) showed no statistically significant differences in demographic, clinical, and radiologic characteristics, including median admission hemorrhage volume, Glasgow Coma Scale, and ICH scores. At 90-day post-stroke, 44% of patients in the endoport group and 17% in the OS group had a favorable functional outcome (mRS 0-3) (p = 0.039); moreover, the endoport group showed lower mortality (33% vs. 72%, p = 0.019). This study suggests that an endoport-assisted ICH evacuation may have better functional outcomes and lower mortality than OS. The proposed device could provide a safe, low-cost alternative for ICH's surgical treatment. More rigorous research is hence needed to assess the potential benefits of this technique.

Circulating granulocyte colony-stimulating factor and functional outcome after ischemic stroke: an observational study

ABSTRACT Objectives: While granulocyte colony-stimulating factor (G-CSF) has shown beneficial effects in experimental ischemic stroke (IS), these effects have not been reproduced clinically. Small-to-medium-sized observational studies have reported varying associations for G-CSF with stroke severity and post-stroke functional outcome, prompting their investigation in a larger study. Methods: Endogenous serum G-CSF (S-GCSF) was measured in the acute phase and after 3 months in patients with IS (N = 435; 36% females; mean age, 57 years) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was scored according to the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) assessed functional outcomes at 3-month and 2-year post-stroke. Correlation and logistic regression analyses with confounder adjustments assessed the relationships. Results: The acute S-GCSF level was 23% higher than at 3-month post-stroke (p < 0.001). Acute G-CSF correlated weakly with stroke severity quintiles (r = 0.12, p = 0.013) and with high-sensitivity C-reactive protein (r = 0.29, p < 0.001). The association between S-GCSF (as quintiles, q) and poor functional outcome at 3 months (mRS 3–6; S-GCSF-q5 vs. S-GCSF-q1, age- and sex-adjusted odds ratio: 4.27, 95% confidence interval: 1.82–9.99; p = 0.001) withstood adjustment for cardiovascular risk factors and stroke subtype, but not additional correction for stroke severity. Post-stroke changes in S-GSCF and absolute 3-month S-GCSF were not associated with 3-month or 2-year functional outcomes. Discussion: Early post-stroke S-GCSF is increased in severe IS and associated with 3-month poor functional outcomes. The change in S-GCSF and the 3-month S-GCSF appear to be less-important, and S-GCSF likely reflects inflammation in large infarctions.