Monogenic Causes in Familial Stroke Across Intracerebral Hemorrhage and Ischemic Stroke Subtypes Identified by Whole-Exome Sequencing.

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification. Among 161 familial stroke probands, 33 (20.5%) had been identified pathogenic or likely pathogenic monogenic variants related to stroke. The positive hit rate among all subtypes was high in intracerebral hemorrhage (ICH) and ischemic small vessel disease (SVD). Notably, two previously unreported variants, KRIT1 p.E379* in a familial cerebral cavernous malformation and F2 p.F382L in familial cerebral venous sinus thrombosis, were disclosed. CVT cerebral venous thrombosis; HTN Hypertensive subtype; LAA large artery atherosclerosis; SV structural vasculopathy; U Undetermined.

The 2020 Taiwan Stroke Society guidelines for blood pressure control at the acute stage of ischemic stroke.

The 2020 Taiwan Stroke Society (TSS) guidelines for blood pressure (BP) control related to ischemic stroke update the 2015 TSS BP guidelines. The early management of acute ischemic stroke has evolved rapidly in the previous two decades. Since the publication of the previous version of the TSS BP guidelines, many studies have addressed BP management in ischemic stroke. Particularly, several successful endovascular thrombectomy (EVT) trials published in 2015 led to a new era of acute treatment for ischemic stroke. With the ever-increasing use of EVT, evidence-based guidelines for ideal BP management during and after EVT are urgently needed. Consequently, the 2020 guidelines are updating and providing recommendations on BP control for the treatment and prevention of ischemic stroke based on new evidence. The present study encompasses the most important chapter of the 2020 Taiwan BP guidelines: BP control at the acute stage of ischemic stroke. We incorporated the most updated evidence regarding BP control at the acute stage of ischemic stroke in patients receiving or not receiving acute reperfusion therapy and provided specific recommendations for different treatment subgroups accordingly.

Association between impaired dynamic cerebral autoregulation and BBB disruption in reversible cerebral vasoconstriction syndrome.

BACKGROUND: Half of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption. METHODS: A cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption. RESULTS: Forty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index. CONCLUSIONS: Dysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure.

Untargeted metabolomics predicts the functional outcome of ischemic stroke.

BACKGROUND/PURPOSE: Metabolites in blood have been found associated with the occurrence of vascular diseases, but its role in the functional recovery of stroke is unclear. The aim of this study is to investigate whether the untargeted metabolomics at the acute stage of ischemic stroke is able to predict functional recovery. METHODS: One hundred and fifty patients with acute ischemic stroke were recruited and followed up for 3 months. Fasting blood samples within 7 days of stroke were obtained, liquid chromatography and mass spectrometry were applied to identify outcome-associated metabolites. The patients' clinical characteristics and identified metabolites were included for constructing the outcome prediction model using machine learning approaches. RESULTS: By using multivariate analysis, 220 differentially expressed metabolites (DEMs) were discovered between patients with favorable outcomes (modified Rankin Scale, mRS ≤ 2 at 3 months, n = 77) and unfavorable outcomes (mRS ≥ 3 at 3 months, n = 73). After feature selection, 63 DEMs were chosen for constructing the outcome prediction model. The predictive accuracy was below 0.65 when including patients' clinical characteristics, and could reach 0.80 when including patients' clinical characteristics and 63 selected DEMs. The functional enrichment analysis identified platelet activating factor (PAF) as the strongest outcome-associated metabolite, which involved in proinflammatory mediators release, arachidonic acid metabolism, eosinophil degranulation, and production of reactive oxygen species. CONCLUSION: Metabolomics is a potential method to explore the blood biomarkers of acute ischemic stroke. The patients with unfavorable outcomes had a lower PAF level compared to those with favorable outcomes.

Protective effects of ischemic preconditioning against neuronal apoptosis and dendritic injury in the hippocampus are age-dependent.

Ischemic preconditioning with non-lethal ischemia can be protective against lethal forebrain ischemia. We hypothesized that aging may aggravate ischemic susceptibility and reduce brain plasticity against preconditioning. Magnetic resonance diffusion tensor imaging (DTI) is a sensitive tool to detect brain integrity and white matter architecture. This study used DTI and histopathology to investigate the effect of aging on ischemic preconditioning. In this study, adult and middle-aged male Mongolian gerbils were subjected to non-lethal 5-min forebrain ischemia (ischemic preconditioning) or sham-operation, followed by 3 days of reperfusion, and then lethal 15-min forebrain ischemia. A 9.4-Tesla MR imaging system was used to study DTI indices, namely fractional anisotropy (FA), mean diffusivity (MD), and intervoxel coherence (IC) in the hippocampal CA1 and dentate gyrus (DG) areas. In situ expressions of microtubule-associated protein 2 (MAP2, dendritic marker protein) and apoptosis were also examined. The 5-min ischemia did not cause dendritic and neuronal injury and any significant change in DTI indices and MAP2 in adult and middle-aged gerbils. The 15-min ischemia-induced significant delayed neuronal apoptosis and early dendritic injury evidenced by DTI and MAP2 studies in both CA1 and DG areas with more severe injury in middle-aged gerbils than adult gerbils. Ischemic preconditioning could improve neuronal apoptosis in CA1 area and dendritic integrity in both CA1 and DG areas with better improvement in adult gerbils than middle-aged gerbils. This study thus suggests an age-dependent protective effect of ischemic preconditioning against both neuronal apoptosis and dendritic injury in hippocampus after forebrain ischemia.

Systematic Review and Meta-Analysis of Home-Based Rehabilitation on Improving Physical Function Among Home-Dwelling Patients With a Stroke.

OBJECTIVE: To evaluate the effects of home-based rehabilitation on improving physical function in home-dwelling patients after a stroke. DATA SOURCES: Various electronic databases, including PubMed, Cumulative Index to Nursing and Allied Health, Embase, the Cochrane Central Register of Controlled Trials, and 2 Chinese data sets (ie, Chinese Electronic Periodical Services and China Knowledge Resource Integrated) were searched for studies published before March 20, 2019. STUDY SELECTION: Randomized controlled trials conducted to examine the effect of home-based rehabilitation on improving physical function in home-dwelling patients with a stroke and published in English or Chinese were included. In total, 49 articles in English (n=23) and Chinese (n=26) met the inclusion criteria. DATA EXTRACTION: Data related to patient characteristics, study characteristics, intervention details, and outcomes were extracted by 2 independent reviewers. DATA SYNTHESIS: A random-effects model with a sensitivity analysis showed that home-based rehabilitation exerted moderate improvements on physical function in home-dwelling patients with a stroke (g=0.58; 95% CI, 0.45∼0.70). Moderator analyses revealed that those patients with stroke of a younger age, of male sex, with a first-ever stroke episode, in the acute stage, and receiving rehabilitation training from their caregiver showed greater improvements in physical function. CONCLUSIONS: Home rehabilitation can improve functional outcome in survivors of stroke and should be considered appropriate during discharge planning if continuation care is required.

Percutaneous coronary intervention in patients hospitalized for non-ST-elevation myocardial infarction and the risk of postdischarge ischemic stroke at 6-month, 1-year, and 3-year follow-ups.

Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation myocardial infarction (NSTEMI) to reduce adverse cardiovascular events. However, the short- and long-term effects of PCI on the risk of postdischarge ischemic stroke (IS) in patients hospitalized for NSTEMI remain unclear. This study investigated the association of PCI on the risk of postdischarge IS in patients hospitalized for NSTEMI at different period follow-ups. A population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Propensity score matching (PSM) was used to select 6079 pairs of the patients with NSTEMI treated invasively by PCI (received PCI during hospitalization) and initial conservative strategy (did not receive PCI during hospitalization) with similar baseline characteristics for evaluation. After adjustment for patients' clinical variables and the duration of dual antiplatelet therapy, PCI was associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups [adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.26-0.67, p < 0.001; aHR = 0.61, 95% CI 0.43-0.86, p = 0.004; and aHR = 0.69, 95% CI 0.54-0.89, p = 0.005respectively]. In the patients who had a CHA2DS2-VASc score of ≥2, PCI was also associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups (aHR = 0.54, 95% CI 0.36-0.83, p = 0.005; aHR = 0.72, 95% CI 0.52-1.00, p = 0.048; and aHR =0.73, 95% CI 0.58-0.91, p = 0.005, respectively). These findings suggested that PCI might reduce the risk of postdischarge IS in patients hospitalized for NSTEMI.

Dynamic Cerebral Autoregulation Is an Independent Functional Outcome Predictor of Mild Acute Ischemic Stroke.

Background and Purpose- Cerebral autoregulation is impaired in patients with acute ischemic stroke. The purpose of this study was to investigate whether dynamic cerebral autoregulation (dCA) indices constitute an independent functional outcome predictor of acute ischemic stroke. Methods- In this study, 86 patients at days 3 to 7 after acute ischemic stroke and 40 age- and sex-matched controls were enrolled for assessing their dCA indices under spontaneous hemodynamic fluctuations. The dCA indices of patients with favorable outcomes (modified Rankin Scale score ≤1 at 3 months, n=65), patients with unfavorable outcomes (modified Rankin Scale score ≥2 at 3 months, n=21), and controls were compared. Results- The dCA indices, namely the phase shift at very low frequency band (phase_VLF), in the patients with unfavorable outcomes were significantly worse than those in the patients with favorable outcomes. However, the phase_VLF in the patients with favorable outcomes did not differ from those in the controls. Impaired dCA was associated with elevated mean arterial pressure and large infarction volume but was also present in patients with normal mean arterial pressure or small infarction volume. Phase_VLF was a predictor of outcomes in the receiver operating characteristic analysis (area under the curve: 0.722; P<0.001). Multivariate analysis revealed that a phase_VLF value of <61° was independently associated with unfavorable outcomes (odds ratio=4.90; P=0.024). Conclusions- Phase_VLF is an independent functional outcome predictor of acute ischemic stroke.

Health Care Costs and Utilization of Dabigatran Compared With Warfarin for Secondary Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation: A Retrospective Population Study.

BACKGROUND: It remains unclear whether the use of new oral anticoagulants, compared with warfarin, is economically beneficial in Asian countries. OBJECTIVE: The objective of this study is to compare the health care costs and utilization between dabigatran and warfarin in a real-world nonvalvular atrial fibrillation (NVAF) population. RESEARCH DESIGN: Data were obtained from the Taiwan National Health Insurance Database, and patients with an NVAF diagnosis between June 1, 2012, and May 31, 2014, were identified using the International Classification of Diseases, Ninth Revision code of 427.31. The patients in the dabigatran cohort were matched 1:2 to those in the warfarin cohort by sex, age, residential region, and a propensity score that incorporated a major bleeding history, CHADS2 score, and Charlson Comorbidity Index. The all-cause health care utilization and associated costs of the 2 treatment groups were compared at 3 and 12 months. RESULTS: A total of 1149 patients taking dabigatran were identified and matched with 2298 warfarin users. During the 3-month observation period, the likelihood of having at least 1 hospitalization among dabigatran users was significantly lower than that of warfarin users (odds ratio=0.78; P=0.001). Patients in the dabigatran group incurred lower mean emergency department costs ($2383.1 vs. $3033.6), mean ischemic stroke-related hospitalization costs ($8869.5 vs. $13,990.5), and mean all-cause hospitalization costs ($32,402.2 vs. $50,669.9) at 3 months. However, both the mean and median outpatient costs of warfarin users were consistently lower than those of dabigatran users ($17,161.2 vs. $24,931.4 and $10,509.0 vs. $20,671.5, respectively). Similar trends were observed at 12 months, except that the 2 groups had comparable total health care costs. CONCLUSIONS: The use of dabigatran is associated with lower emergency department and all-cause hospitalization costs but greater outpatient costs in a real-world, NVAF patient population compared with warfarin.

Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke.

BACKGROUND: Estrogen plays an important role as an anti-inflammatory and neuroprotective agent in ischemic stroke. In this study, we analyzed the effect of a polygenic risk score (PRS) constructed using inflammatory genes and estradiol levels on the risk of ischemic stroke. METHODS: This case-control study was conducted with 624 ischemic stroke patients and 624 age- and gender-matched controls. The PRS estimated the polygenic contribution of inflammatory genes from ischemic stroke susceptibility loci. Estradiol levels were measured using a radioimmunoassay. High and low estradiol levels were defined according to the log-transformed median estradiol levels in female and male controls. RESULTS: Subjects in the fourth quartile of the PRS had a significant 1.57-fold risk of ischemic stroke (95% confidence interval [CI], 1.12 ~ 2.19), after adjusting for covariates compared to individuals in the lowest quartile. Compared to individuals with high estradiol levels and a low PRS as the reference group, those exposed to low estradiol levels and a high PRS had an increased risk of ischemic stroke (odds ratio, 3.35; 95% CI, 1.79 ~ 6.28). Similar results were also observed in males when the analysis was stratified by gender. CONCLUSIONS: Our data suggest that the PRS can be useful in evaluating a high risk of ischemic stroke among patients, especially those exposed to low estradiol levels.

On- versus Off-Hour Patient Cohorts at a Primary Stroke Center: Onset-to-Treatment Duration and Clinical Outcomes after IV Thrombolysis.

BACKGROUND: The symptom onset-to-treatment (OTT) duration predicts symptomatic intracerebral hemorrhage (sICH) and adverse outcomes after ischemic stroke. Previous studies found disparities in OTT durations and clinical outcomes between stroke patients with symptom onset during on-hours versus off-hours, which led to the initiation of nationwide efforts to provide consistent 24-hour stroke care. GOAL: Our objective is to compare OTT durations and clinical outcomes in ischemic stroke patients whose symptoms originated during on- versus off-hours at a primary stroke center. METHODS: We analyzed clinical data from 210 consecutive patients receiving intravenous recombinant tissue plasminogen activator therapy between January 2009 and December 2013 at Yale-New Haven Stroke Center, a primary stroke center. Stroke severity was assessed by baseline National Institutes of Health Stroke Scale (NIHSS) scores. Clinical outcomes were assessed by presence of sICH and by stroke-related fatalities. OTT durations and clinical outcomes were compared using Mann-Whitney tests, 2-sample tests of proportions, and 2-sample t-tests after testing for equal variance. FINDINGS: We found no significant differences in OTT durations between on-hour and off-hour patient cohorts (137 minutes versus 145 minutes, P = .53). There were also no differences in stroke severity (mean NIHSS score 12.4 versus 11.3, P = .27), sICH rates (4.6% versus 6.5%, P = .56), or stroke fatality rates (9.2% versus 9.8%, P = .89) between the 2 cohorts. CONCLUSIONS: Our results represent progress in emergency response and acute stroke care, and reinforce ongoing nationwide efforts to increase stroke awareness and provide consistent quality care for patients with acute stroke.

Comparison of 8 scores for predicting symptomatic intracerebral hemorrhage after IV thrombolysis.

BACKGROUND: Intracerebral hemorrhage is a feared complication of IV thrombolytic (rt-PA) therapy. In recent years, at least 8 clinical scores have been proposed to predict either adverse outcome or symptomatic intracerebral hemorrhage (sICH) in patients undergoing rt-PA therapy. The purpose of this study was to evaluate the ability of these 8 scores to predict sICH in an independent clinical dataset. METHODS: Clinical data was analyzed from consecutive patients (n = 210) receiving IV rt-PA therapy from January 2009 to December 2013 at Yale-New Haven Hospital. Eight scores were calculated for each patient: Stroke-TPI, DRAGON, SPAN-100, ASTRAL, PRS, HAT, SEDAN, and SITS-ICH. sICH was defined according to the NINDS study criteria. Univariate logistic regression was performed using each score as an independent variable and sICH as the dependent variable. Goodness of fit was tested by Receiver operating characteristic (ROC) analysis and by Hosmer-Lemeshow statistics. RESULTS: sICH occurred in 12 patients (5.71 %) after IV rt-PA treatment. Only 4 scores predicted sICH with good accuracy (ROC area >0.7): DRAGON 0.76 (0.63, 0.89); Stroke-TPI 0.74 (0.61, 0.87); ASTRAL 0.72 (0.59, 0.86); and HAT 0.70 (0.55, 0.85), with odds ratios as follows: Stroke-TPI, 1.91 (1.26, 2.90); HAT, 1.67 (1.06, 2.62); DRAGON, 1.66 (1.21, 2.30); and ASTRAL, 1.10 (1.03, 1.16). CONCLUSIONS: Three scores showed good agreement with sICH: DRAGON, Stroke-TPI, and HAT with odds ratios substantially greater than 1. Stroke-TPI and HAT additionally benefited from low computational complexity and therefore performed best overall. Our results demonstrate the utility of clinical scores as predictors of sICH in acute ischemic stroke patients undergoing IV thrombolytic therapy.

TURN: A Simple Predictor of Symptomatic Intracerebral Hemorrhage After IV Thrombolysis.

BACKGROUND: IV Thrombolysis (rt-PA) for ischemic stroke treatment carries a substantial risk for symptomatic intracerebral hemorrhage (sICH). Our purpose was to develop a computationally simple and accurate sICH predictor METHODS : Our derivation dataset consisted of 210 ischemic stroke patients receiving IV rt-PA from January 2009 until July 2013 at Yale-New Haven Hospital. Our validation dataset included 303 patients who received IV rt-PA during the NINDS rt-PA trial. Independent sICH predictors were identified by logistic regression and combined to form the TURN score. Predictive ability and goodness of fit were quantified by odds ratios (OR) and areas under the receiver operating characteristic curve (AUROC). RESULTS: 3 out of 17 clinical parameters were identified as independent predictors of sICH: prestroke mRS score (OR 1.54, P = 0.02), baseline NIHSS score (OR 1.13, P = 0.002), and platelet count (OR 0.99, P = 0.04). We combined these three parameters to form the TURNP score. For added simplicity, prestroke mRS score and baseline NIHSS score alone were also combined to form the TURN score, and predicted sICH without a significant drop in OR or AUROC. CONCLUSIONS: We developed a new score for predicting sICH after IV thrombolysis. Our score is simple and with acceptable accuracy, making it ideal for use in the hyperacute stroke setting.

Cohort-Based Identification of Predictors of Symptomatic Intracerebral Hemorrhage After IV Thrombolysis.

INTRODUCTION: Symptomatic intracranial hemorrhage (sICH) is a serious complication of IV rt-PA therapy after acute ischemic stroke. Independent sICH predictors have been previously derived using case-control studies. Here we utilized a novel cohort-based comparison to identify additional independent predictors of sICH. METHODS: We included 210 patients receiving IV rt-PA therapy from January 2009 through December 2013 at the Yale-New Haven Stroke Center. Clinical parameters were compared using Mann-Whitney tests, two-sample tests of proportions and two-sample t tests. Logistic regression was performed using sICH as the dependent variable. Predictive ability was assessed using areas under the receiver operating characteristic (ROC) curve. RESULTS: sICH rates were lowest from 2010 to 2012 and comprised the low sICH cohort (2.0 % sICH), compared to the high sICH cohort from 2009 to 2013 (9.2 % sICH, P = 0.025). Patients in the low sICH cohort had significantly more visual field deficits (38.6 vs. 24.8 %, P = 0.03) and decreased levels of consciousness (62.4 vs. 39.4 %, P < 0.001), but fewer hyperdense MCA signs (5 vs. 13.8 %, P = 0.03) and early CT hypodensities (14.9 vs. 29.4 %, P = 0.01). These four parameters together predicted sICH modestly (area under ROC curve 0.66, odds ratio 2.72, P = 0.03) CONCLUSIONS: Using a novel cohort-based approach, we identified two new independent predictors of sICH after IV rt-PA therapy: the presence of the hyperdense MCA sign and early CT hypodensities. Novel methods are needed to reduce the risk of sICH for patients receiving antithrombolytic therapy for ischemic stroke.

Modest association between the discharge modified Rankin Scale score and symptomatic intracerebral hemorrhage after intravenous thrombolysis.

BACKGROUND: Thirty- and 90-day modified Rankin Scale (mRS) scores are used to monitor adverse outcome or symptomatic intracerebral hemorrhage (sICH) in ischemic stroke patients after intravenous (IV) thrombolytic therapy. Discharge mRS scores are more readily available and could serve as a proxy for 30- or 90-day mRS data. Our goal was to evaluate agreement between the discharge mRS score and sICH. Additionally, we tested for correlations between the discharge mRS score and 8 clinical scores developed to predict sICH or adverse outcomes based on 90-day mRS data. METHODS: Clinical data were analyzed from 210 patients receiving IV thrombolysis from January 2009 till December 2013 at the Yale New Haven Hospital. Agreement between sICH and the discharge mRS score was assessed using linear kappa. Eight clinical scores were calculated for each patient and compared with the discharge mRS score by univariate logistic regression. Goodness of fit was tested by receiver operating characteristic (ROC) analysis and by Hosmer-Lemeshow statistics. RESULTS: We found only modest agreement between sICH and unfavorable discharge mRS scores (mRS ≥ 5), with kappa .22, P = .0001. All 8 clinical scores tested showed good agreement with discharge mRS score of 5 or more (ROC area >.7). CONCLUSIONS: The discharge mRS score shows only modest agreement with sICH and therefore cannot be recommended as a proxy for 30- or 90-day mRS data. However, the discharge mRS score correlates strongly with clinical scores predicting long-term adverse outcome; therefore, assessment of discharge mRS scores may be of some clinical benefit.

The effect of osteoarthritis on 1-year risk of ischemic heart disease following total knee arthroplasty.

To evaluate the long-term risk of ischemic heart disease (IHD) following total knee arthroplasty (TKA), we conducted a retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. We evaluated 3599 primary TKA patients and 14,396 matched control patients. We further classified all patients into those with and without osteoarthritis (OA). The incidence rate of IHD was significantly higher among the TKA patients than among the matched control patients (1.13 vs 0.69 per 1000 person-months, P<.05). However, after controlling for OA, this difference was non-significant (HR=1.18, 95% confidence interval (CI): 0.63-2.20, P>.05). Our study results indicate that underlying OA conditions are predominantly responsible for increased long-term risk of IHD in TKA patients.

The mediating effect of psychological distress on functional dependence in stroke patients.

AIMS AND OBJECTIVES: To explore varied forms of psychological distress and to determine the mediating influence of psychological distress on functional outcomes in stroke patients. BACKGROUND: Previous studies attest to the influence of depression on poststroke functional recovery. While there is evidence for neuropathological deficits that occur after stroke to be associated with psychological distress, few studies have explored the effect of various types of psychological distress on functional recovery. DESIGN: A cross-sectional study was used. METHODS: Data were collected from 178 first-time stroke patients. Study variables included demographic and disease characteristics (stroke location and stroke syndrome classification), psychological distress (the Chinese language version of the Emotional and Social Dysfunction Questionnaire) and functional outcome (Barthel index). Regression and mediation models were used to evaluate the effect of psychological distress on functional outcome. RESULTS: Results revealed that stroke patients experience various forms of mild psychological distress, including anger, helplessness, emotional dyscontrol, indifference, inertia and euphoria, after stroke. Regression and mediation analyses further confirmed that various forms of psychological distress significantly mediated the effect of severe stroke syndromes on functional dependence. CONCLUSION: The various forms of psychological distress after stroke might play a mediating role in functional recovery and explain how stroke severity affects functional dependence. RELEVANCE TO CLINICAL PRACTICE: By understanding the nature of various forms of psychological distress, healthcare professionals should adopt appropriate assessment instruments and design effective interventions to help improve mental and physical function of stroke patients.

Intravenous Odatroltide for Acute Ischemic Stroke Within 24 Hours of Onset: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

Purpose: Odatroltide (LT3001), a novel small synthetic peptide molecule designed to recanalize occluded blood vessels and reduce reperfusion injury, is safe and efficacious in multiple embolic stroke animal models. This study aimed to investigate the safety and tolerability of intravenous administration of odatroltide in patients with acute ischemic stroke within 24 hours of onset. Patients and Methods: Patients with National Institutes of Health Stroke Scale (NIHSS 4-30) who were untreated with intravenous thrombolysis or endovascular thrombectomy were randomized (2:1) to receive a single dose of odatroltide (0.025 mg/kg) or placebo within 24 hours of stroke symptom onset. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) occurrence within 36 hours. Results: Twenty-four patients were enrolled and randomized; of these 16 and 8 received intravenous odatroltide infusion and placebo, respectively. sICH did not occur in both groups, and other safety measures were comparable between the groups. The rate of excellent functional outcome (modified Rankin Scale score, 0-1, at 90 days) was 21% and 14% in the odatroltide and placebo groups, respectively. Furthermore, 47% and 14% of patients in the odatroltide and placebo groups, respectively, showed major neurological improvement (NIHSS improvement ≥4 points from baseline to 30 days). Among the 9 odatroltide-treated patients with baseline NIHSS ≥6, 78% showed major neurological improvement. Conclusion: Compared with placebo, treatment with intravenous odatroltide within 24 hours following onset of ischemic stroke appears to be safe and may be associated with better neurological and functional outcomes. However, the efficacy and safety of odatroltide requires further confirmation in the next phase of clinical trials. Clinical Trial Registration: Clinicaltrials.gov identifier: NCT04091945.

Association between cerebral lesions and emotional changes in acute ischemic stroke patients.

Controversies and interest are present in the associations between specific brain locations and depression or anxiety. This study investigated the association between stroke location and emotional changes in stroke patients. This prospective observational study analyzed the neuroimages and neuropsychiatric conditions of 26 patients with acute middle cerebral artery infarction. Each patient's neurological and psychiatric condition was evaluated 1 week as well as 1 month after the stroke. We found that the right superior and middle temporal gyrus was associated with anxiety at 1 month after stroke. Moreover, better mentality is associated with deterioration of anxiety within 1 month after stroke, and larger lesion volume is associated with deterioration of depression within 1 month after stroke.