Non-stroke Controls Research Articles

Injurious Falls Before, During, and After Stroke Diagnosis: A Population-based Study.

We aimed to examine changes in the incidence of injurious falls before, during, and after stroke, and to identify risk factors of injurious falls before and after stroke diagnosis. Prospective cohort study. Within the Swedish Twin Registry, 4431 participants (aged 66.5 ± 10.3years) with incident stroke and 4431 stroke-free controls (aged 66.5 ± 10.3years) were identified and matched with cases according to birth year and sex. Cases and controls were retrospectively and prospectively followed for a total of 21years. Information on the onset of stroke and injurious falls was ascertained from medical records in the National Patient Registry. Data were analyzed using conditional Poisson regression and generalized estimating equation models. During the 4- to 10-year pre-stroke period, the standardized incidence rates of injurious falls were 4.29-7.53 per 1000 person-years in stroke and 3.97-7.47 per 1000 person-years in control groups. The incidence of injurious falls among participants with stroke was significantly higher compared with non-stroke controls beginning 3years before stroke (incidence rate ratio [IRR], 1.27; 95% confidence interval [CI], 1.02-1.59), peaked during the year of stroke diagnosis (IRR, 2.55; 95% CI, 2.17-3.01), and declined 4years after stroke (IRR, 1.42; 95% CI, 1.14-1.77) until reaching a similar level as the controls (IRRs around 1.11-1.56). Former/current smoking, heavy drinking, and overweight were associated with increased falls during the pre-stroke period, and being single and heart disease with falls during the post-stroke period. Among people with stroke, incidence of injurious falls is significantly elevated already 3years before stroke diagnosis and lasting until 4years post-stroke. Risk factors for falls differ pre-stroke and post-stroke. Taking preventive measures may be beneficial in managing both stroke and fall-related risks.

Mendelian randomization analysis reveals causal effects of migraine and its subtypes on early-onset ischemic stroke risk

Previous observational studies have suggested at a potential link between migraine, particularly migraine with aura, and the susceptibility to early-onset ischemic stroke. We aimed to investigate the causal effects of genetically determined migraine and its subtypes on the risk of early-onset ischemic stroke using the two-sample Mendelian randomization method. Genetic instrumental variables associated with migraine and its subtypes were acquired from two sources with the largest sample sizes available. Summary data for early-onset ischemic stroke was acquired from a study encompassing individuals aged 18–59 years, comprising 16,730 cases and 599,237 non-stroke controls. The random-effects inverse variance weighted method was used as the primary analysis approach. Additionally, linkage disequilibrium score regression analysis was used to evaluate the genetic correlation. The Mendelian randomization analysis revealed no association between overall migraine and migraine without aura with the risk of early-onset ischemic stroke. However, migraine with aura showed a suggestive association with an elevated risk of early-onset ischemic stroke, with odds ratios of 1.114 (95% confidence interval = 1.005 to 1.236, p-value = 0.040) and 1.062 (95% confidence interval = 1.002 to 1.126, p-value = 0.042) based on instruments from two independent sources. The odds ratio was 1.074 (95% confidence interval = 1.022 to 1.130, p-value = 0.005) based on instruments from both two sources. No evidence of heterogeneity or horizontal pleiotropy was found. By contrast, migraine with aura was not related to ischemic stroke in all adults. Furthermore, a significant positive genetic correlation was found between migraine with aura and early-onset ischemic stroke (genetic correlation = 0.208, 95% confidence interval = 0.038 to 0.377, p-value = 0.016). This study provides evidence of a causal relationship between migraine with aura and the risk of early-onset ischemic stroke, as well as a positive genetic correlation between them.

Can lung function be used as a predictor of cerebral stroke?

Background and objectivesLimited research has looked into the precise connection between lung function, arterial blood gases, and cerebral stroke. This study was focused on examining the correlation between pulmonary function and carotid intima-media thickness (CIMT) in patients with and without cerebral stroke who do not have chronic pulmonary disease.MethodsA case–control study included 125 cerebral stroke patients and 125 non-stroke controls selected from the outpatient clinics of the Neurology and Rheumatology & Rehabilitation departments at Zagazig University Hospital, Sharkia Governorate, Egypt. The assessment of lung function passed through measuring forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) ratio, and maximum voluntary ventilation (MVV). Arterial blood gases were measured, and CIMT was evaluated using high-resolution ultrasonography by the radiology author.ResultsThe research findings suggested that patients exhibiting elevated carotid intima-media thickness (CIMT) faced a heightened risk of suffering from a cerebral stroke in comparison to those with normal CIMT levels. Additionally, the study revealed a negative relationship between lung function, as measured by FEV1, FVC, the ratio (FEV1/FVC), and MVV, and arterial blood gases, as indicated by the partial pressure of oxygen (PaO2), in relation to CIMT. Reduced FEV1, FVC, FEV1/FVC, MVV, and PaO2 were found to be associated with elevated CIMT. The stepwise multivariable regression model further showed that CIMT was positively correlated with age, while it displayed negative correlations with FEV1, FVC, FEV1/FVC, MVV, and PaO2.ConclusionPatients who have an elevated carotid intima-media thickness (CIMT) are at a greater risk of experiencing a cerebral stroke. In addition, reduced forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, maximal voluntary ventilation (MVV), and arterial partial pressure of oxygen (PaO2) are all linked with increased CIMT levels. Patients with elevated CIMT have a higher risk of cerebral stroke. These findings suggest that lung function tests in individuals without respiratory conditions could be beneficial for identifying those who may be at a heightened risk for experiencing a cerebrovascular stroke.

Climate Change Projections for Stroke Incidence in Taiwan: Impact of 2°C and 4°C Global Warming Level.

This study aimed to establish the exposure-lag-response effect between daily maximum temperature and stroke-related emergency department visits and to project heat-induced stroke impacts under global warming levels (GWL) of 2°C and 4°C. Stroke-related emergency department visits in Taiwan from 2001 to 2020 were identified using the National Health Insurance Research Database (NHIRD). The study population consisted of 1,100,074 initial stroke cases matched with 2,200,148 non-stroke controls. We employed Distributed Lag Nonlinear Models (DLNM) in a case-crossover study to investigate the association between temperature and stroke. Generalized Estimating Equations (GEE) models with a Poisson function were used to correlate high-temperature exposure with annual stroke incidence rates. Projections were made under two global warming scenarios, GWL 2.0°C and 4.0°C, using Coupled General Circulation Model (GCMs). Baseline data from 1995 to 2014 were transformed for spatial distribution at the township level. Geographic Information System (GIS) spatial analysis was performed using Quantum GIS 3.2.0 software. DLNM exposure-lag-response effect revealed that daily maximum temperature exceeding 34°C significantly increased the risk of stroke-related emergency department visits, particularly for ischemic stroke. Under the 2°C GWL scenario, the frequency of days with temperatures surpassing 34°C is projected to rise substantially by the median year of 2042, with a further increase to 92.6 ± 18.0 days/year by 2065 under the 4°C GWL scenario. Ischemic stroke showed the highest increase in temperature-related incidence rates, notably rising from 7.80% under the GWL 2°C to 36.06% under the GWL 4°C. Specifically, the annual temperature-related incidence rate for ischemic stroke is expected to increase significantly by 2065. Regions such as Taichung, Hsinchu, Yilan, and Taitung demonstrated pronounced changes in heat-related ischemic stroke incidence under the GWL 4°C. The findings emphasize the importance of addressing temperature-related stroke risks, particularly in regions projected to experience significant temperature increases. Effective mitigation strategies are crucial to reduce the impact of rising temperatures on stroke incidence and safeguard public health.

The association between TLR2/4 and clinical outcome in intracerebral hemorrhage

Background and purposeToll-like receptors (TLRs) are involved in innate immunity and inflammatory responses in various diseases. Our study aimed to investigate the association between the levels of soluble TLR4 (sTLR4) and soluble TLR2 (sTLR2) and clinical outcomes following intracerebral hemorrhage (ICH). MethodsPatients admitted to department of Neurology with acute ICH were included. Plasma levels of sTLR4 and sTLR2 after ICH were measured by enzyme-linked immunosorbent assay. Poor clinical outcome was defined as a modified Rankin score (mRS) of 3–6 at 3-month and 12-month after onset. ResultsAll 207 patients with ICH and 100 non-stroke controls were included in our analysis. The mean sTLR4 level was 4.53±1.51 ng/ml and mean sTLR2 level was 3.65±0.72 ng/ml. There was significant trend towards worse clinical outcomes with increasing sTLR4 and sTLR2 terciles at 3 and 12 months. According to receiver operating curve (ROC), the sTLR4 was reliable predictor for poor clinical outcome at 3 months (ROC=0.75) and 12 months (ROC=0.74). The sTLR2 was less reliable predictor for poor clinical outcome at 3 months (ROC=0.64) and 12 months (ROC=0.65). The level of sTLR4 was an independent predictor of poor clinical outcome at 12-month (OR 1.24, 95 % CI 1.16–1.80; P=0.019). ConclusionsThe sTLR4 quantification may provide accurate prognostic information after ICH.

Retinal Ischemic Perivascular Lesion Reflects Cerebral Small Vessel Disease Burden in Single Subcortical Infarction.

Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. In this case-control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept-source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept-source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365-1.662], P<0.001). Eyes with RIPLs showed lower deep vascular complex density (P=0.035) compared with eyes without RIPLs in patients with SSI. After adjusting for vascular risk factors, the presence of RIPLs in patients with SSI was associated with an increased periventricular white matter hyperintensity burden (β=0.414 [95% CI, 0.181-0.647], P<0.001) and perivascular spaces-basal ganglia (β=0.296 [95% CI, 0.079-0.512], P=0.008). RIPLs are associated with SSI independent of underlying risk factors. The relationship between the presence of RIPLs and small vessel disease markers provides evidence that RIPLs might be an additional indicator of cerebral ischemic changes.

Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4-6. Logistic regression was employed toexamine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03-1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01-1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06-2.50, p = 0.025; aOR 1.63, 95% CI 1.07-2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05-1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04-3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13-3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population.

A retrospective examination of pain in acute stroke at hospital discharge

ObjectivesPain is an overlooked sequela of stroke. Persistent pain after stroke is an underrecognized experience and significantly impacts survivors’ function, ability to participate in rehabilitation, and quality of life. The aim of this retrospective, observational study is to examine the incidence of pain at the acute hospitalization period immediately after stroke, to identify the characteristics of those reporting pain at discharge, and to compare pain reporting between stroke and non-stroke hospital controls. Materials and methodsUsing discharge diagnosis, this retrospective review examined self- reports of pain during acute hospitalization for stroke compared to those with COPD (control group) admitted during the same time in the same facilities. Variables of interest included age, gender, body mass index (BMI), length of stay, pain assessment score (numeric rating scale [NRS], behavior pain scale [BPS], and medication administration record pain score total [MAR]), smoking history, prevalence of hypertension and race. 821 subjects were included from a total of three campuses from one large hospital system. 772 subjects were included in the comparative analysis with COPD patients from the same facilities during the same time. Results43% of patients diagnosed with stroke reported pain at discharge. For stroke survivors reporting pain at discharge, the average BMI was higher (p=0.009), average arrival NIHSS was higher (p=0.044), and mean hospital length of stay was longer (p<0.001). ConclusionsThe evidence demonstrated in this study highlights the critical need for the implementation of targeted objective pain assessment and effective pain interventions for stroke survivors beginning at initial hospitalization.

Protein Z and Protein Z-dependent protease inhibitor in patients with acute ischemic stroke: A prospective mechanistic study

ObjectivesProtein Z (PZ) /Protein Z-dependent protease inhibitor (ZPI) (PZ/ZPI) system is a new anticoagulant system discovered in recent years, which plays an important role in many diseases. We aimed to compare the plasma PZ/ZPI levels of acute ischemic stroke (AIS) patients and non-stroke control participants and the role of PZ/ZPI in the development of stroke was preliminarily analyzed. Materials and methodsEnzyme linked immunosorbent assay (ELISA) was used to detect and compare plasma PZ levels of 86 patients with acute AIS and 85 non-stroke control patients. Multivariable Logistic regression was used to analyze whether PZ was an independent risk factor for AIS. ResultsIn the present study, plasma PZ is closely related to inflammatory response, coagulation process and platelet activation, and may participate in the development of AIS by inducing inflammatory responses and interfering with the coagulation process. ConclusionsOur results suggested that plasma PZ level is one of the independent risk factors of AIS, and plasma ZPI was closely related to coagulation and platelet parameter and may play a role in the coagulation process during AIS.

Herpes zoster associated with stroke incidence in people living with human immunodeficiency virus: a nested case–control study

BackgroundThe incidence of stroke is increasing among younger people with human immunodeficiency virus (HIV). The burden of stroke has shifted toward the young people living with HIV, particularly in low- and middle-income countries. People infected with herpes zoster (HZ) were more likely to suffer stroke than the general population. However, the association of HZ infection with the incidence of stroke among patients with HIV remains unclear.MethodsA nested case–control study was conducted with patients with HIV registered in the Taiwan National Health Insurance Research Database in 2000–2017. A total of 509 stroke cases were 1:10 matched to 5090 non-stroke controls on age, sex, and date of first stroke diagnosis. Logistic regression models were used to estimate the odds ratio and 95% confidence intervals (CI) of stroke incidence.ResultsThe odds ratio of stroke was significantly higher in the HIV-infected population with HZ (adjusted odds ratio [AOR]: 1.85, 95% CI: 1.42–2.41). A significantly increased AOR of stroke was associated with hypertension (AOR: 3.53, 95% CI: 2.86–4.34), heart disease (AOR: 2.32, 95% CI: 1.54–3.48), chronic kidney disease (AOR: 1.82, 95% CI: 1.16–2.85), hepatitis C virus infection (AOR: 1.49, 95% CI: 1.22–1.83), hyperlipidemia (OR: 1.41, 95% CI: 1.12–1.78), and treatment with protease inhibitors (AOR: 1.33, 95% CI: 1.05–1.69).ConclusionsOur findings suggest that HZ concurrent with HIV may increase the risk of stroke. The incidence rates of stroke were independent of common risk factors, suggesting strategies for early prevention of HZ infection among people living with HIV.

Depression and anxiety in acute ischemic stroke involving the anterior but not paramedian or inferolateral thalamus.

Emotional and cognitive deficits are prevalent in strokes involving the thalamus. In contrast to cognitive deficits, emotional deficits have not been studied prospectively in isolated thalamic stroke. In 37 ischemic thalamic stroke patients (57.0 [50.0; 69.5] years [median (Q1; Q3)], 21 males, 5 anterior, 12 paramedian, 20 inferolateral vascular territory), and 37 non-stroke control patients matched for age and sex, we prospectively examined depression, anxiety, activities of daily living, and quality of life at 1, 6, 12, and 24 months post-stroke using the Hospital-Anxiety-and-Depression Scale (HADS), Nürnberger-Alters-Alltagsaktivitäten scale (NAA), and Short Form-36 (SF36) questionnaire. Voxel-based lesion-symptom mapping (VLSM) and lesion-subtraction analyzes were performed to determine associations between questionnaire scores and thalamic stroke topography. At 1 month post-stroke, anterior thalamic stroke patients had higher depression scores [8.0 (7.5; 10.5)] than paramedian [4.5 (1.0; 5.8)] and inferolateral [4.0 (1.0; 7.0)] thalamic stroke patients. Furthermore, anterior thalamic stroke patients had higher anxiety scores [11.0 (8.0; 14.5)] than their matched controls [2.5 (2.0; 2.5)], paramedian [4.5 (1.0; 5.8)] and inferior [4.0 (1.0; 7.0)] thalamic stroke patients. Depression and anxiety scores in anterior thalamic stroke patients remained high across the follow-up [depression: 9.0 (3.5; 13,8); anxiety:10.05 (2.8, 14.5)].Physical health assessed by SF36 was intact in anterior [1 month post-stroke: T-score = 55.9 (37.0; 57.6)] but reduced in inferolateral [44.5(32.4; 53.1)] thalamic stroke, whereas mental health was reduced in anterior thalamic stroke [32.0 (29.8; 47.3)].VLSM confirmed that voxels in the anterior thalamus around Montreal Neurological Institute (MNI) coordinates X = -8, Y = -12, Z = 2 were more often affected by the stroke in depressed (HADS-score ≥ 8) than non-depressed (HADS-score < 8) patients and voxels around coordinates X = -10, Y = -12, Z = 2 were more often affected in anxious (HADS-score ≥ 8) than non-anxious (HADS-score < 8) patients. Anterior, but not paramedian or inferolateral thalamic stroke was associated with depression and anxiety. Even though our results are mostly significant in the left thalamus, this observation on stroke laterality might be confounded by the fact that the right hemisphere was underrepresented in our study.

Migraine and the risk of cervical artery dissection: A systematic review and meta-analysis.

Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have suggested an elevated risk of cervical artery dissection (CeAD) in patients with a history of migraine. We aimed to investigate this potential association using systematic review and meta-analytic methods. We utilized a pre-defined search protocol to identify and screen studies related to migraine and CeAD in PubMed, Embase, and the Web of Science Core Collection. We assessed the risk of bias and performed a meta-analysis of selected studies to assess the association between migraine and CeAD. We also performed subgroup analyses by migraine subtype, biological sex, and the use of stroke versus non-stroke controls. We identified 11 studies (N = 9857 patients) for inclusion in the meta-analysis. Meta-analysis showed an association between migraine and CeAD with an odds ratio of 1.74 (95%CI 1.38-2.19). There was high heterogeneity among the included studies (I2 = 61%). Publication bias was present but the Trim-Fill imputation suggested that the impact on results was likely minimal. Subgroup analyses revealed an association between migraine without aura and CeAD (OR 1.86, 95%CI 1.55-2.24) but not migraine with aura and CeAD (OR 1.15, 95%CI 0.71-1.88). There was no difference in the association between migraine and CeAD in men compared to women. A history of migraine is associated with an increased risk of CeAD. Further studies are needed to elucidate the potential pathophysiologic mechanisms underlying this association.

Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment.

Dyskinesia caused by transient ischemic attack (TIA) and mild ischemic stroke (MIS) is mild and short-lived; however, cognitive impairment (CI) can occur in the acute phase and be easily overlooked. DNA methylation is an epigenetic phenomenon that can affect gene expression through gene silencing. Blood levels of matrix metalloproteinase (MMP) 9 are elevated in ischemic stroke patients and is associated with the destruction of the blood-brain barrier and the occurrence of CI. No studies have investigated the relationship between MMP9 gene methylation and TIA/MIS with early cognitive impairment (ECI). As such, the purpose of the present study was to investigate the correlation between MMP9 gene methylation and TIA/MIS with ECI. Data from 112 subjects were collected, including 84 with TIA/MIS (National Institutes of Health Stroke Scale <5 points) and 28 non-stroke control subjects. Patients were evaluated within 7 days of TIA/MIS onset according to four single-domain cognitive scales. Whole blood DNA methylation was detected using MethylTarget sequencing technology. Comparison of MMP9 gene methylation levels among subgroups was performed using statistical methods. The site S33-79 in the TIA/MIS group was hypomethylated compared with the control group, and sites S33-25 and S33-30 in TIA/MIS with ECI was hypomethylated compared with TIA/MIS without ECI. Compared with the small artery occlusion group, MMP9 gene, S33-25, 30, 39, 53, 58, 73, 79, 113 and 131 sites in the large artery atherosclerosis group were hypomethylated. MMP9 gene hypomethylation sites were associated with TIA/MIS and TIA/MIS with ECI, and there was a strong correlation between MMP9 gene hypomethylation and atherosclerotic TIA/MIS. MMP9 gene methylation can reflect the severity of TIA/MIS. MMP9 gene hypomethylation sites may be used as potential biomarkers and therapeutic targets for TIA/MIS and TIA/MIS with ECI.

Differential Effect of Stroke Types on Cerebral White Matter Disease Progression (S45.001)

<h3>Objective:</h3> To determine the annual rate of WMD progression and cognition by stroke types in a cohort of real-world patients hospitalized for cerebrovascular diseases. <h3>Background:</h3> White matter disease (WMD) of presumed vascular origin is a type of cerebral small vessel disease associated with cognitive impairment. Studies have suggested that stroke may accelerate the progression of WMD, yet little is known on the potential differential effect of stroke types on WMD progression and cognition. <h3>Design/Methods:</h3> Consecutive patients with two brain MRI scans at least one year apart from a single-center cerebrovascular registry were included. Stroke types were categorized as ischemic stroke, non-traumatic intracranial hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). Non-stroke served as control. SPM-lesion predictive algorithm was used to quantify WMD volume with primary outcome measured as annual change in WMD volume (cm³/year). Rate of WMD progression were compared across stroke types. <h3>Results:</h3> Of the 207 patients, mean age was 60±16 years, 54.6% were women, and median time between MRI brain scans was 4.3 (1.3–11.8) years. Of the stroke types, 65.8% had AIS, 11.1% had ICH, 3.4% had aSAH and 19.8% were non-stroke control. The rate of WMD progression was fastest in patients with ICH (1.63 cc/yr, IQR 0.0–4.14 cc/yr), followed by ischemic stroke (1.43 cc/yr, IQR 0.24–3.51 cc/yr), aSAH (0.53 cc/yr, IQR 0.13–0.79 cc/yr) and non-stroke control (0.32 cc/yr, IQR −0.01–1.35 cc/yr). In terms of cognition, median MMSE was lowest in ICH (22.5), followed by aSAH (23.2), ischemic stroke (24.8) and non-stroke control (28.7) (trend-p=0.002). <h3>Conclusions:</h3> Our study showed differential effects of stroke types on the rate of WMD progression and post-stroke cognition. Patients with ICH had greater risk for WMD progression and cognitive impairment compared to other stroke types. Larger longitudinal study is needed to better test this observation. <b>Disclosure:</b> Dr. Elkhair has nothing to disclose. Mr. Youssef has nothing to disclose. Dr. Anisetti has nothing to disclose. Mr. Salem has nothing to disclose. Mr. Mateti has nothing to disclose. Dr. Lin has nothing to disclose.

Naïve-memory regulatory T cells ratio is a prognostic biomarker for patients with acute ischemic stroke.

Regulatory T cells (Treg) have been identified as a key modulator of neuroinflammation in stroke. However, little is known about the association of Treg subpopulations with clinical outcome in patients with acute ischemic stroke (AIS). Patients within 1 week from stroke onset were prospectively enrolled in this study. Healthy controls were sex-and age-matched 1:1 to AIS patients. The frequencies of Treg and Treg subsets were analyzed by flow cytometry and compared with nonstroke control. Univariate and multivariate logistic regression analysis was performed to investigate the prognostic value of Treg subsets in stroke outcomes. A total of 328 patients and 328 controls were included in the study. Compared with controls, patients with AIS had higher levels of Treg frequency and memory Treg (mTreg) frequency, but lower levels of naïve Treg (nTreg) frequency and nTreg/mTreg ratio. One hundred twenty-six (38.4%) patients experienced unfavorable outcome (modified Rankin score 2-6). Multivariate regression analysis showed that nTreg/mTreg ratio was negatively associated with unfavorable 90-day outcome (the highest tertile versus the lowest tertile: odds ratio 0.13, 95% confidential interval [CI] 0.05-0.35). The risk estimation of unfavorable 90 day outcome can be significantly improved by adding nTreg/mTreg ratio to the conventional clinical parameters (continuous net reclassification improvement 91.26, 95% CI 69.04-113.5%, p < 0.001; integrated discrimination improvement 22.38, 95% CI 17.16-27.59%, p < 0.001). This study showed that patients with AIS had elevated Treg frequency and mTreg frequency, but reduced nTreg frequency and nTreg/mTreg ratio. Admission nTreg/mTreg ratio was an independent predictor of unfavorable 90 day outcome in AIS. However, large sample-size cohort studies are needed to confirm our findings.

Phenylacetyl glutamine: a novel biomarker for stroke recurrence warning

BackgroundStroke is the second leading cause of disease-related death and the third leading cause of disability worldwide. However, how to accurately warn of stroke onset remains extremely challenging. Recently, phenylacetyl glutamine (PAGln) has been implicated in the onset of stroke, but evidences from cohort studies of onset are lacking, especially in patients with first-onset or recurrent. It is necessary to deeply demonstrate the effectiveness of PAGln level on warning stroke onset.MethodsOne hundred fifteen first onset stroke patients, 33 recurrent stroke patients, and 135 non-stroke controls were included in the analysis. Risk factors associated with stroke attacking were evaluated, and plasma PAGln levels were detected via HPLC-MS based method. LASSO regression, Pearson correlation analysis, and univariate analysis were carried out to demonstrate the associations between PAGln levels and risk factors of stroke. Random forest machine learning algorithm was used to build classification models to achieve the distinction of first-onset stroke patients, recurrent stroke patients, and non-stroke controls, and further demonstrate the contribution of PAGln levels in the distinction of stroke onset.ResultsThe median level of PAGln in the first-onset stroke group, recurrent stroke group, and non-stroke group was 933 ng/mL, 1014 ng/mL, and 556 ng/mL, respectively. No statistical correlation was found between PAGln level and subject’s living habits, eating preferences, and concomitant diseases (hypertension, hyperlipidemia, and diabetes). Stroke severity indicators, mainly age and NIHSS score, were found associate with the PAGln levels. Machine learning classification models confirmed that PAGln levels, as the main contributing variable, could be used to distinguish recurrent stroke patients (but not first-onset stroke patients) from non-stroke controls.ConclusionPAGln may be an effective indicator to monitor the recurrence in stroke patients.

Derivation and Validation of an Algorithm to Detect Stroke Using Arm Accelerometry Data.

Background Early diagnosis is essential for effective stroke therapy. Strokes in hospitalized patients are associated with worse outcomes compared with strokes in the community. We derived and validated an algorithm to identify strokes by monitoring upper limb movements in hospitalized patients. Methods and Results A prospective case-control study in hospitalized patients evaluated bilateral arm accelerometry from patients with acute stroke with lateralized weakness and controls without stroke. We derived a stroke classifier algorithm from 123 controls and 77 acute stroke cases and then validated the performance in a separate cohort of 167 controls and 33 acute strokes, measuring false alarm rates in nonstroke controls and time to detection in stroke cases. Faster detection time was associated with more false alarms. With a median false alarm rate among nonstroke controls of 3.6 (interquartile range [IQR], 2.1-5.0) alarms per patient per day, the median time to detection was 15.0 (IQR, 8.0-73.5) minutes. A median false alarm rate of 1.1 (IQR. 0-2.2) per patient per day was associated with a median time to stroke detection of 29.0 (IQR, 11.0-58.0) minutes. There were no differences in algorithm performance for subgroups dichotomized by age, sex, race, handedness, nondominant hemisphere involvement, intensive care unit versus ward, or daytime versus nighttime. Conclusions Arm movement data can be used to detect asymmetry indicative of stroke in hospitalized patients with a low false alarm rate. Additional studies are needed to demonstrate clinical usefulness.

Fuerza de asociación de factores de riesgo vascular clásicos en pacientes jóvenes con ictus isquémico: un estudio de casos y controles

IntroductionRecent studies have reported an increasing incidence of ischaemic stroke among young adults. However, the strength of the association between traditional vascular risk factors has not been fully established. MethodsWe compared 120 patients with a first ischaemic stroke before the age of 55 years admitted to the stroke unit of our centre with 600 healthy non-stroke controls from a population-based cohort study (HERMEX), matched for sex. Risk factors assessed included: hypertension, obesity, auricular fibrillation, current smoking, estimated glomerular filtration rate (eGFR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C) and diabetes mellitus. We used logistic regression analysis and calculated population attributable risk. We performed an overall analysis, by sex and aetiological subgroup. ResultsUsing logistic regression analysis we found that overall the significant risk factors were: hypertension (OR: 1.58; 95%CI: 1.01-2.50), auricular fibrillation (OR: 4.77; 95%CI: 1.20-19.00), low eGFR (OR: 4.74; 95%CI: 1.3-21.94) and low HDL-C (OR: 5.20; 95%CI: 3.29-8.21), as well as smoking for males (OR: 1.86; 95%CI: 1.14-3.03). LDLc showed an inverse association with stroke. The population attributable risk for HDL-C was 37.8% and for hypertension 21.1%. In terms of aetiological subgroups, only low HDL-C was associated with stroke of undetermined aetiology. ConclusionsHypertension, auricular fibrillation, low eGFR and low HDL-C, plus tobacco use in men, are the main risk factors among patients under 55 years of age with a first ischaemic stroke. We believe that it would be of particular interest to further explore the management of low HDL-C levels as part of preventive strategies in young stroke patients.

Strength of association of classical vascular risk factors in young patients with ischaemic stroke: a case-control study

IntroductionRecent studies have reported an increasing incidence of ischaemic stroke among young adults. However, the strength of the association between traditional vascular risk factors has not been fully established. MethodsWe compared 120 patients with a first ischaemic stroke before the age of 55 years admitted to the stroke unit of our centre with 600 healthy non-stroke controls from a population-based cohort study (HERMEX), matched for sex. Risk factors assessed included: hypertension, obesity, auricular fibrillation, current smoking, estimated glomerular filtration rate (eGFR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C) and diabetes mellitus. We used logistic regression analysis and calculated population attributable risk. We performed an overall analysis, by sex and aetiological subgroup. ResultsUsing logistic regression analysis, we found that overall, the significant risk factors were: hypertension (OR: 1.58; 95%CI: 1.01-2.50), atrial fibrillation (OR: 4.77; 95%CI: 1.20-19.00), low eGFR (OR: 4.74; 95%CI: 1.3-21.94) and low HDL-C (OR: 5.20; 95%CI: 3.29-8.21), as well as smoking for males (OR: 1.86; 95%CI: 1.14-3.03). LDL-C showed an inverse association with stroke. The population attributable risk for HDL-C was 37.8% and for hypertension 21.1%. In terms of aetiological subgroups, only low HDL-C was associated with stroke of undetermined aetiology. ConclusionsHypertension, auricular fibrillation, low eGFR, and low HDL-C, plus tobacco use in men, are the main risk factors among patients under 55 years of age with a first ischaemic stroke. We believe that it would be of particular interest to further explore the management of low HDL-C levels as part of preventive strategies in young stroke patients.

Schizophrenia, but not depression or bipolar affective disorder, adds additional risk of aspiration pneumonia among stroke survivors: A national cohort study in Taiwan

ObjectiveFew studies have assessed the sex-specific and age-specific risk of aspiration pneumonia (AP) in patients with stroke and evaluated whether mental disorders may increase this risk. In this population-based cohort study, we investigated the sex-specific and age-specific risk of AP in association with stroke and the joint effects of stroke and mental disorders on the risk of AP. MethodsWe included 23,288 patients with incident stroke admitted between 2005 and 2017 and 68,675 matched nonstroke controls. Information on mental disorders was obtained from medical claims data within the 3 years before the stroke incidence. Cox proportional hazards models considering death as a competing risk event were constructed to estimate the hazard ratio of AP incidence by the end of 2018 associated with stroke and selected mental disorders. ResultsAfter ≤14 years of follow-up, AP incidence was higher in the patients with stroke than in the controls (11.30/1000 vs. 1.51/1000 person-years), representing a covariate-adjusted subdistribution hazard ratio (sHR) of 3.64, with no significant sex difference. The sHR significantly decreased with increasing age in both sexes. Stratified analyses indicated schizophrenia but not depression or bipolar affective disorder increased the risk of AP in the patients with stroke. ConclusionCompared with their corresponding counterparts, the patients with schizophrenia only, stroke only, and both stroke and schizophrenia had a significantly higher sHR of 4.01, 5.16, and 8.01, respectively. The risk of AP was higher in younger stroke patients than those older than 60 years. Moreover, schizophrenia was found to increase the risk of AP in patients with stroke.