First-ever Acute Ischemic Stroke Patients Research Articles

Predicting asymptomatic coronary artery disease in first-ever acute ischemic stroke patients: a cross-sectional study.

It is frequently observed that patients with first-ever acute ischemic stroke (AIS) have a common occurrence of asymptomatic coronary artery disease (CAD). This condition is associated with a poor prognosis. Early detection and recognition of asymptomatic CAD in first-ever AIS patients may optimize the clinical management and ultimately lead to improved outcomes. The aim of this study was to investigate the role of aortic arch plaque (AAP) detected through combined computed tomography angiography (CTA) as an early predictor of asymptomatic CAD in patients with first-ever AIS without prior diagnosis of CAD. A cross-sectional study was conducted at Xuanwu Hospital, Capital Medical University from January 2019 to December 2021, involving patients with first-ever AIS caused by large arterial atherosclerosis. Patients with a history of recognized cardiovascular disease, nonatherosclerotic arterial stenosis, atrial fibrillation related to cardioembolism, and complete carotid occlusions were excluded. The study utilized a combined coronary and cervicocephalic CTA to evaluate atherosclerosis in the cervicocephalic, aortic, and coronary arteries simultaneously. First-ever AIS patients without prior diagnosis of CAD were divided into 2 groups: 1 with asymptomatic CAD detected through CTA and the other without. Multivariate logistic regression was used to identify independent risk factors associated with the presence of asymptomatic CAD, including aortic arch, cervical and intracranial atherosclerotic characteristics (e.g., vascular stenosis, plaque thickness, extent, and complexity). Among 182 AIS patients, 84 (46.2%) had asymptomatic CAD. Increased aortic arch plaque (AAP) thickness per millimeter [adjusted odds ratio (aOR): 1.26; 95% confidence interval (CI): 1.08-1.47], presence of severe AAP (aOR: 4.24; 95% CI: 1.59-12.03), mixed AAP (aOR: 2.65; 95% CI: 1.09-6.62), and ulcerative AAP (aOR: 11.76; 95% CI: 2.05-222.84) raised the risk of asymptomatic CAD in stroke patients, independent of other factors. The combination of ulcerative AAP, diabetes mellitus, and smoking could predict asymptomatic CAD with an area under the receiver operating characteristic curve (AUC) of 0.71 (95% CI: 0.64-0.79; P<0.001). Ulcerative AAP was found to be more valuable than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in first-ever AIS patients. The presence of ulcerative AAP was associated with asymptomatic CAD in first-ever AIS patients. As an early systemic atherosclerosis feature, ulcerative AAP is probably a more valuable indicator than cervicocephalic atherosclerotic characteristics for predicting asymptomatic CAD in AIS patients.

Association between high-resolution magnetic resonance vessel wall imaging characteristics and recurrent stroke in patients with intracranial atherosclerotic steno-occlusive disease: A prospective multicenter study.

High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) is a promising technique for identifying intracranial vulnerable plaques beyond lumen narrowing. However, the association between HRMR-VWI characteristics and recurrent stroke remains uncertain. This study aimed to investigate the association between HRMR-VWI characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS). This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (>50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multiparametric magnetic resonance imaging (MRI) including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HRMR-VWI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HRMR-VWI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis. Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12 month ipsilateral recurrence incidence was 4.1% (95% confidence interval (CI): 1.6-6.6%). Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs 6.5%) and eccentric plaque (90.0% vs 48.2%), and lower occurrence of occlusive thrombus (10.0% vs 23.7%). Plaque length (5.69 ± 2.21 mm vs 6.67 ± 4.16 mm), plaque burden (78.40 ± 7.37% vs 78.22 ± 8.32%), degree of stenosis (60.25 ± 18.95% vs 67.50% ± 22.09%) and remodeling index (1.07 ± 0.27 vs 1.03 ± 0.35) on HRMR-VWI did not differ between patients with and without recurrent ipsilateral stroke. In the multivariable Cox regression analysis, IPH (hazard ratio: 6.64, 95% CI: 1.23-35.8, p = 0.028) was significantly associated with recurrent ipsilateral stroke after adjustment.Conclusions:Our results suggest intraplaque hemorrhage (IPH) is significantly associated with recurrent ipsilateral stroke and has potential value in the selection of patients for aggressive treatment strategies. Data from this study are available and can be accessed upon request.

Abstract 36: Association Between High-Resolution Magnetic Resonance Imaging Characteristics and Recurrent Stroke in Patients With Symptomatic Intracranial Atherosclerotic Steno-Occlusive Disease: A Prospective Multicenter Study

Background and Objectives: This study aimed to investigate the association between high-resolution magnetic resonance imaging (HR-MRI) characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS). Methods: This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (&gt;50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multi-parametric MRI including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HR-MRI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HR-MRI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis. Results: Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12-month ipsilateral recurrence incidence was 4.1% (95% confidence interval [CI]: 1.6-6.6%). The plaque length (5.69±2.21 mm vs. 6.67±4.16 mm), plaque burden (78.40±7.37% vs. 78.22±8.32%), degree of stenosis (60.25±18.95% vs. 67.50±22.09%) and remodeling index (1.07±0.27 vs. 1.03±0.35) on HR-MRI did not exhibit discernible difference between patients with and without recurrent ipsilateral stroke. Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs. 6.5%) and eccentric plaque (90.0% vs. 48.2%), and lower occurrence of occlusive thrombus (10.0% vs. 23.7%). In the multivariable Cox regression analysis, IPH (hazard ratio: 7.05, 95% CI: 1.53-32.41, p=0.012) was significantly associated with recurrent ipsilateral stroke after adjustment. Discussion: We found IPH is significantly associated with recurrent ipsilateral stroke. Our results suggest IPH has potential value in the selection of patients for aggressive treatment strategies.

Cerebellar antibodies in post-stroke sera of acute ischemic stroke patients

<p>Although serum anti-neuronal antibodies are found in acute ischemic stroke (AIS) patients, it is not completely clear whether they are already present before the cerebrovascular event or emerge thereafter.&nbsp;</p>. <p>Sera of 21 consecutive first-ever AIS patients were collected within the first day of AIS (baseline), as well as 1 and 6 months after AIS. Well-characterized and novel anti-neuronal antibodies were investigated by cell-based assays, immunoblotting and indirect immunohistochemistry.</p>. <p>None of the AIS sera collected at different time points showed well-characterized antibodies. In 7 patients, 1- and 6-month sera (but not baseline sera) showed IgG mostly reacting with soma and dendrites of cerebellar Purkinje cells. Antibody-positive patients did not differ in terms of clinical and etiological features.</p>. <p>Our results provide evidence for the antibody-triggering action of AIS. Although anti-cerebellar antibodies are not associated with the severity of stroke, they may potentially contribute to chronic post-stroke complications and disability.</p>.

Structural disconnection-based prediction of poststroke depression

Poststroke depression (PSD) is a common complication of stroke. Brain network disruptions caused by stroke are potential biological determinants of PSD but their conclusive roles are unavailable. Our study aimed to identify the strategic structural disconnection (SDC) pattern for PSD at three months poststroke and assess the predictive value of SDC information. Our prospective cohort of 697 first-ever acute ischemic stroke patients were recruited from three hospitals in central China. Sociodemographic, clinical, psychological and neuroimaging data were collected at baseline and depression status was assessed at three months poststroke. Voxel-based disconnection-symptom mapping found that SDCs involving bilateral temporal white matter and posterior corpus callosum, as well as white matter next to bilateral prefrontal cortex and posterior parietal cortex, were associated with PSD. This PSD-specific SDC pattern was used to derive SDC scores for all participants. SDC score was an independent predictor of PSD after adjusting for all imaging and clinical-sociodemographic-psychological covariates (odds ratio, 1.25; 95% confidence interval, 1.07, 1.48; P = 0.006). Split-half replication showed the stability and generalizability of above results. When added to the clinical-sociodemographic-psychological prediction model, SDC score significantly improved the model performance and ranked the highest in terms of predictor importance. In conclusion, a strategic SDC pattern involving multiple lobes bilaterally is identified for PSD at 3 months poststroke. The SDC score is an independent predictor of PSD and may improve the predictive performance of the clinical-sociodemographic-psychological prediction model, providing new evidence for the brain-behavior mechanism and biopsychosocial theory of PSD.

Frequency of Stress Hyperglycemia in Acute Ischemic Stroke with Immediate Mortality

Introduction: Stroke is a leading cause of morbidity, death, and a significant socioeconomic burden. This is especially true in poor nations like Bangladesh, where the health-care system, including rehabilitation, is out of reach for the average citizen. This life-threatening ailment impacts not only the patients but also their families. The goal of this hospital-based study was to determine stroke-related in-hospital mortality. For various reasons, the findings of our study are important to stroke care in our setting. Attention to modifiable variables that have a negative influence on stroke outcome (e.g. hyperglycemia and comorbidities) may help to reduce stroke mortality, which is particularly high in poor countries. The aim of the study was to evaluate the frequency of stress hyperglycemia in acute ischemic stroke cases, and observe the difference in mortality and morbidity among patients with hyperglycemia and normoglycemia. Methods: This observational cross-sectional study was conducted at the Department of Medicine, Sir Salimullah Medical College &amp; Mitford Hospital, Dhaka, Bangladesh. The study duration was 6 months, from April 2017 to October 2017. The purposive sampling technique was used to select a total of 100 consecutively attending first-ever acute ischemic stroke patients attending the study hospital within 72 hours of stroke onset. Result: Among the participants, the majority (54%) were between the age range of 41-55 years, with a mean age of 58.37 (±6.23) years. The male: female ratio was 1.7:1. Over half the participants were from urban areas, and 29% were housewives while 25% were businessmen. Unilateral weakness, speech disturbance, and headache were the most common clinical presentations. During admission, the majority were conscious, while 7% were unconscious. Stress hyperglycemia was observed in 29% of the cases. Recovery rates were higher among normoglycemic patients. Conclusion: Present study showed that stress hyperglycemia is .............

Application of hyperglycemia/diabetes-derived polygenic risk scores on the risk of poor outcomes after an ischemic stroke.

Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application. A hospital-based cohort study was conducted including 1320 first-ever acute ischemic stroke (AIS) patients and 1210 patients who completed the follow-up at 3 months. PRSs were calculated for hyperglycemia/diabetes mellitus using results from genome-wide association studies in Asians. An unfavorable functional outcome was defined as a modified Rankin Scale score of ≥3 at 3, 6, and 12 months of follow-up. The prediction of a poor prognosis was evaluated using measures of model discrimination, calibration, and net reclassification improvement (NRI). The second to fourth PRS quartiles (≥Q2) were significantly associated with higher risks of unfavorable outcomes at 3 months compared with the first quartile as the reference group after adjusting for age, baseline stroke severity, hypertension, diabetes, dyslipidemia, smoking, heart disease, and ischemic stroke subtype (p for trend <0.0001). The addition of the PRS to traditional risk predictors of poor outcomes after an AIS significantly improved the model fit (likelihood ratio test p < 0.0001) and enhanced measures of reclassification (NRI, 0.245; 95% confidence interval [CI], 0.195-0.596). The corrected C-index for the PRS combining traditional risk factors at 3 months after a stroke was 0.899 (95% CI, 0.878-0.980). Among hyperglycemic AIS patients, those who did not take an antidiabetic drug and whose PRS was ≥Q2 had higher risks of an unfavorable outcome at 3 months compared with patients who took the medicine. The hyperglycemia/diabetes-derived PRS was associated with poor outcomes after an AIS, but further studies are needed to validate its use for clinical applications.

Correlation of Serum Albumin Level with Short Term Outcome of Acute Ischemic Stroke Patients

Abstract Objectives We aimed to Detect if there is association between serum albumin level in acute ischemic stroke patients and its short term neurological and functional outcome in a tertiary care hospital in Cairo. Methods The study was carried out as descriptive (cross-sectional) study conducted on 50 cases first-ever acute ischemic stroke patients were enrolled between June 2018 to December 2018 with follow up after 30 days of discharge from hospital. Inclusion and exclusion criteria were strictly exercised. National Institute of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) score was noted. Serum albumin (SA) was estimated from blood Clinical, functional, and radiological evaluation was done for the patients. Statistical SPSS 20.0 software and Microsoft excel were used for statistical analysis (P ≤ 0.05).Relationship between serum albumin and stroke outcome was determined. Results A total of 50 stroke cases were thus included in the study comprising 34 males and 16 females. The mean age of patients was 40-65 [59.26±6.25] years, we found the most prevalent risk factors in the present study results were hypertension 36 (72.0%). The mean serum level of albumin were (3.73±0.63) on day o of onset and (3.72±0.63) after 30 days of discharge from hospital. Bivariate analysis shows serum albumin was inversely associated with NIHS score and mRS on day o of onset and after 30 days of discharge from hospital which were NIHSS(r= -0.264, P = 0.044) (r= -0.645, P = &amp;lt;0.001) and mrs (r= -0.321, P = 0.031) (r= -0.587, P = &amp;lt;0.001) respectively. Conclusion Hypoalbuminemia had influence to degree of stroke severity, degree of disability and functional outcome. Serum albumin levels had a negatively correlation with NIHSS score and modified Rankin scale. Low serum albumin levels associated with poor prognosis in acute ischemic stroke patients.

A pilot study of the ticagrelor role in ischemic stroke secondary prevention

Introduction: Ticagrelor is one of the most recent antiplatelet drugs used to treat ischemic heart disease. Its efficacy may equal or exceed aspirin in improving clinical outcomes in patients with acute ischemic stroke who are ineligible for rt-PA. Aim of the Work: We aimed at evaluating the safety (as a primary endpoint) and efficacy (as a secondary endpoint) of a 180 mg loading dose of ticagrelor given within 9 h from the onset of first-ever ischemic stroke. Methods: We conducted an open-label, randomized prospective controlled clinical trial between May 2019 and September 2020 on patients who presented with their first-ever ischemic stroke and were recruited from the emergency department, of Kafr el-sheik University Hospitals, Egypt. Eligible patients randomly received aspirin or ticagrelor loading and maintenance doses. Treatment began within 9 h of stroke onset. Results: Aspirin was given to 84 patients; ticagrelor was given to 85. There was no significant difference between the 2 groups regarding the hemorrhagic and nonhemorrhagic complications. Patients who received ticagrelor had a better outcome regarding NIHSS improvement at 2 days and 1 week or discharge and a favorable mRS score after 1 week or discharge and at 90-day follow-up. Conclusion: Ticagrelor was noninferior to aspirin regarding safety profile. Compared with aspirin, ticagrelor had a better clinical outcome based on NIHSS and mRS in first-ever acute ischemic stroke patients who received it within 9 h from symptom onset, leading to a shorter hospital stay.

Serum Interleukin-37 Increases in Patients after Ischemic Stroke and Is Associated with Stroke Recurrence.

Background This study seeks to assess interleukin-37 (IL-37) serum level in acute ischemic stroke and the value of predicting 3-month stroke recurrence and functional outcome in acute ischemic stroke. Methods From January 1, 2018, to June 30, 2019, all consecutive first-ever acute ischemic stroke patients from our hospital, China, were included. Serum samples, clinical information, and stroke severity (defined by the National Institute of Health stroke scale (NIHSS) score) were collected at baseline. Serum IL-37 level was measured by the enzyme-linked immunosorbent assay (ELISA) method. Functional impairment (defined by the modified Rankin scale (mRS)) and recurrent stroke were assessed 3 months after admission. The relation of IL-37 with either clinical severity at baseline, unfavorable functional outcome, or stroke recurrence at follow-up was evaluated by logistic regression analysis, and the results were presented as odds ratios (OR) with 95% confidence intervals (CI). Results Three hundred and ten stroke patients were included. The median IL-37 serum level in those patients was 344.1 pg/ml (interquartile range (IQR), 284.4-405.3 vs. control cases: 122.3 pg/ml (IQR, 104.4-1444.0); P < 0.001). At 3 months, a total of 36 (11.6%) patients had a stroke recurrence. IL-37 serum levels in those patients were higher than in those patients without stroke recurrence (417.0 pg/ml (IQR, 359.3-436.1) vs. 333.3 pg/ml (279.0-391.0)). In a logistic model adjusted for other factors, IL-37 in the highest quartile (>405.3 pg/ml) was still associated with recurrent stroke (OR = 3.32; 95%CI = 2.03–6.13; P < 0.001). IL-37 could promote the NIHSS score (area under the curve (AUC) of the IL-37/NIHSS, 0.75; 95% CI, 0.67–0.83; P < 0.001), corresponding to a difference of 0.085 (0.005). Serum IL-37 increases in patients with poor outcome, and an IL-37 in the highest quartile is related to poor outcome (OR = 4.85; 95%CI = 3.11 − 8.22; P < 0.001). Conclusion Serum IL-37 increased in patients after ischemic stroke and was associated with stroke recurrence events and poor stroke outcomes. Large randomized controlled trials should be carried out to confirm whether IL-37 lowering treatment improves stroke prognosis.

Reminiscence therapy serves as an optional nursing care strategy in attenuating cognitive impairment, anxiety, and depression in acute ischemic stroke patients.

Reminiscence therapy is revealed to improve cognitive function and attenuate psychological disorders in neurological diseases such as Alzheimer's disease patients, while its application in acute ischemic stroke (AIS) is seldom reported. So, the current study aimed to explore the effect of reminiscence therapy on cognitive impairment, anxiety, depression, and disease recurrence in AIS patients. A total of 216 first-ever AIS patients were enrolled and randomized into reminiscence therapy group or control group in 1:1 ratio. MMSE, HADS, and Zung SAS/SDS scales were evaluated at the discharge from hospital (M0), 3months (M3), 6months (M6), 9months (M9), and 12months (M12), respectively. Besides, patients were further followed up to 36months for recurrence-free survival (RFS) calculation. Reminiscence therapy group showed higher MMSE score at M9 and M12, lower cognitive impairment rate by MMSE at M12 compared to control group. As to anxiety, HADS-anxiety score and anxiety rate by HADS were of no difference at each time point, while SAS score and anxiety rate by SAS were lower at M12 in reminiscence therapy group compared with control group. Regarding depression, HADS-depression score and depression rate by HADS at M12, SDS score at M9 and M12, and depression rate by SDS at M12 were all lower in reminiscence therapy group compared with control group. In terms of RFS, it was similar between reminiscence therapy group and control group. Reminiscence therapy cripples cognitive impairment, anxiety, and depression, but does not affect RFS in AIS patients, indicating its potential for post-stroke management.

Early diagnostic value of serum procalcitonin levels for catheter-related blood stream infection in first-ever acute ischemic stroke patients

ObjectiveThe traditional approaches for diagnosing catheter-related bloodstream infection(CRBSI) is time consuming, which could not meet the clinical requirement. Our aim was to investigate the value of serum procalcitonin(PCT) in predicting CRBSI in first-ever acute ischemic stroke patients with central venous catheters (CVCs).MethodsThis was a retrospective study. First-ever acute ischemic stroke patients hospitalized in neurological intensive care unit(NICU) of Aerospace Center Hospital and NICU of Beijing Chaoyang Hospital during January 2010 and December 2017 with clinically suspected CRBSI were enrolled. Peripheral blood white blood cell (WBC) count, neutrophils percentage(NE%), the levels of serum PCT, dwell time of catheterization and outcome of the patients were collected. According to the diagnosis of CRBSI or not, they were divided into CRBSI group and no CRBSI group. We used receiver operating characteristic curve (ROC) to evaluate the value of serum PCT levels in predicting CRBSI in patients with clinically suspected CRBSI.ResultsForty-five patients with suspected CRBSI were included in this study, and 13 patients were diagnosed with CRBSI. Comparing to those in no CRBSI group, the maximum body temperature (Tmax) (p = 0.036) and the PCT levels (P = 0.013) in CRBSI group were both significantly higher. The area under ROC of the serum PCT levels and the Tmax to predict the CRBSI were 0.803 (0.95CI,0.660–0.946) and 0.680 (0.95CI,0.529–0.832) respectively. The PCT cut-off value was 0.780 ng/ml, with the sensitivity 69.23%, specificity 87.50%, positive predictive values 69.23% and negative predictive values 87.50%.ConclusionIt could be helpful to adopt PCT as a rapid diagnostic biomarker for first-ever acute stroke patients with suspected CRBSI.

Design of stroke imaging package study of intracranial atherosclerosis: a multicenter, prospective, cohort study.

Intracranial atherosclerosis (ICAS) is a major cause of stroke worldwide. However, much remains unknown regarding its underlying pathophysiology. High-resolution magnetic resonance imaging (HR-MRI) can clearly display intracranial vessel wall lesions in vivo. The aim of stroke imaging package study of ICAS (SIPS-ICAS) study is to explore the stroke mechanisms of symptomatic ICAS, the dynamic changes under aggressive medical treatment and their associations with clinical events using conventional MRI sequences plus HR-MRI. This is a multicenter, prospective, cohort study recruiting first-ever acute ischemic stroke patients attributed to intracranial large artery stenosis (>50% or occlusion). Subjects undergo a pre-designed stroke imaging packages at baseline and are recommended to receive aggressive medical treatments. Participants will be followed up for functional outcome, stroke recurrence, and death events at 3, 6 and 12 months and retake HR-MRI imaging at 6 months. Enrollment began in November 2018 and 96 patients have been enrolled as of September 2019. The SIPS-ICAS study will provide insights into the pathophysiology of ICAS and identify specific imaging markers for risk stratification and prognosis prediction. At the same time, the feasibility and validity of the new stroke imaging package including HR-MRI will be assessed, which is promising for clinical routine use.

Research of Clinical Features about first-ever ischemic stroke in small-artery occlusion patients

Objective Small-Vessel Occlusion is a common etiology of ischemic stroke. In this study, we investigate the Clinical Features of first-ever ischemic stroke in small-artery occlusion patients. Methods All the information were provided by the database of patients with acute ischemic stroke admitted to the Department of Neurology, Shanghai Yueyang Hospital, Shanghai, China, from January 2011 to January 2016. According to the TOAST criteria, 172 first-ever acute ischemic stroke patients were divided into SAO group (small-artery occlusion) and Non-SAO group. We compared the differences of two groups in risk factors, clinical manifestations and laboratory data. Results In SAO group, family history of stroke (14.2% vs 4.5%， P = 0.045) and diabetes (33.0% vs 18.2%， P = 0.034) were more common， and the proportion of patients with atrial fibrillation (7.6% vs 16.7%, P = 0.009) was less common when compared to those in Non-SAO group. Paralysis (49.4% vs 77.8%，P = 0.002), speech disorder (55.4% vs 80%， P = 0.006)and pulmonary infection (13.2% vs 33.3%, P = 0.002)were less common， and the severity of the disease is mild according to MIHSS, BI and MRS in the SAO group (P = 0.000； P = 0.000； P = 0.009). And the contents of WBC、GOT、LDL、CRP、D-Di was significantly lower in SAO group than those in Non-SAO group. Conclusion There was significantly difference in risk factors, clinical manifestations and laboratory data between SAO group and Non-SAO group.

Serotonergic Regulation and Cognition after Stroke: The Role of Antidepressant Treatment and Genetic Variation

Introduction: Serotonin affects several brain functions including cognition. The serotonin transporter (SERT) regulates brain serotonin levels through reuptake into neurons. The gene encoding this transporter, the SERT gene, has several functional polymorphisms affecting the number of transporters and thereby the serotonin levels. SERT gene expression may be important for cognition and selective serotonin reuptake inhibitors (SSRI) may improve cognition post stroke. We therefore examined the association between SERT genotypes, cognitive function and early treatment with the SSRI citalopram among non-depressed Caucasian stroke patients. Patients and Methods: SERT gene polymorphisms in 270 non-depressed first-ever acute ischemic stroke patients randomized to citalopram, n = 130, or placebo, n = 140, were investigated. Patients were genotyped for a length polymorphism (L = long and S = short allele) and a single nucleotide polymorphism (A/G substitution) dividing the L-allele into L_A and L_G. According to these genotypes, patients were further grouped according to low (S/S, L_G/S and L_G/L_G), medium (S/L_A and L_G/L_A), or high functional gene expression (L_AL_A). Cognition was measured by the Symbol Digit Modalities Test (SDMT) at 1 and 6 months. Mean SDMT scores according to genotype and randomization groups were compared using multiple logistic regression adjusting for age, stroke severity, premorbid functional status, and vascular risk factors including smoking, hypertension, and diabetes. Results: Stratified by genotype groups, there were no statistically significant differences in SDMT scores between randomization groups. Placebo-treated patients with low SERT expression genotypes, however, tended to have lower mean SDMT scores (at 1 month: 30.2, SD 10.8) compared to citalopram-treated patients (33.6, SD 13.7). Within the placebo group, the low genotype expression patients had significantly lower adjusted mean SDMT scores at 1 month compared to the high genotype expression patients (adjusted mean difference of –6 points, CI –12.0 to –0.05). We found similar results at 6 months, although not statistically significant. The genotype expression was not associated with SDMT scores among citalopram-treated patients. Conclusion: There was no difference in cognition between citalopram and placebo-treated patients according to the genotype group. Our results indicate, however, that low expression SERT genotype may contribute to reduced cognitive function post stroke as placebo-treated patients with low SERT expression tended to score lower on the SDMT. The significant difference in SDMT scores between low and high expression patients was present only in the placebo-treated group, thereby warranting further exploration of the potential effect of early citalopram treatment on cognitive functioning. Our results are preliminary and need replication in larger-scale studies.

The Prognostic Value of Serum Cytokines in Patients with Acute Ischemic Stroke.

The inflammatory response is an unavoidable process and contributes to the destruction of cerebral tissue during the acute ischemic stroke (AIS) phase and has not been addressed fully to date. Insightful understanding of correlation of inflammatory mediators and stroke outcome may provide new biomarkers or therapeutic approaches for ischemic stroke. Here, we prospectively recruited 180 first-ever AIS patients within 72 hrs after stroke onset. We used the National Institutes of Health Stroke Scale (NIHSS) to quantify stroke severity and modified Rankin scale (mRS) to assess the 3-month outcome for AIS patients. Initially, we screened 35 cytokines, chemokines, and growth factors in sera from 75 AIS patients and control subjects. Cytokines that were of interest were further investigated in the 180 AIS patients and 14 heathy controls. We found that IL-1RA, IL-1β, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-13, IL-15, EGF, G-CSF, Flt-3L, GM-CSF and Fractalkine levels were significantly decreased in severe stroke patients. In particular, IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-15, G-CSF and GM-CSF were significantly reduced in AIS patients with poor outcome, compared to those with good prognosis. IL-6 was notably higher in the poor outcome group. Only IL-9 level decreased in the large infarct volume group. After adjusting for confounders, we found that IL-5 was an independent protective factor for prognosis in AIS patients with an adjusted OR of 0.042 (P = 0.007), whereas IL-6 was an independent risk predictor for AIS patients with an adjusted OR of 1.293 (P = 0.003). Our study suggests the levels of serum cytokines are related to stroke severity, short-term prognosis and cerebral infarct volume in AIS patients.

Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke.

Irisin was discovered as a PGC-1a-activated messenger of myocytes that links sedentary lifestyle, obesity, and diabetes. In this study, we investigated the short-term prognostic value of early measurement of irisin concentration in 1530 Han Chinese patients with acute ischemic stroke (AIS) from three stroke centers. The subjects were the first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Clinical information and stroke severity were collected at admission. Neurological evaluations were conducted at the 6-month follow-up. Serum levels of irisin, National Institutes of Health Stroke Scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 6months. Multivariate analyses were performed using logistic regression models. During follow-up, a poor functional outcome was found in 588 patients (38.4%; 95% confidence interval (CI), 36.0-40.9%), and 325 patients died (21.2%; 95% CI, 19.2-23.3%). The stroke patients included in the study were divided into four groups according to irisin quartiles (first is the lowest level). Poor outcome across the irisin quartiles ranged from 54.5% (first quartile) to 21.7% (fourth quartile), and mortality rate ranged from 39.3% (first quartile) to 6.3% (fourth quartile). In a multivariate model using the first quartile (Q1) of irisin vs. Q2-Q4 together with the clinical variables, the marker displayed prognostic information and increased odds ratios of poor outcome by 58% (OR for Q1, 1.58 [95% CI, 1.12-2.43]) and mortality by 185% (OR for Q1, 2.85 [95% CI, 1.79-4.02]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability to predict poor outcome (the area under the curve (AUC) with an increase from 0.73 to 0.75 [95% CI, 0.70-0.81]) and mortality (the AUC increased from 0.80 to 0.83 [95% CI, 0.78-0.87]). Irisin is a novel, independent prognostic marker improving currently used risk stratification of stroke patients. Further studies are needed to confirm this association, which may pave the way to new therapeutic options. Trial registration: ChiCTR-OPC- 17013501.

Serum 25-hydroxyvitamin D deficiency predicts poor outcome among acute ischemic stroke patients without hypertension

25-Hydroxyvitamin D (25(OH)D) deficiency is a frequent condition in patients who suffer acute ischemic stroke (AIS), and several studies suggested that it may be associated with a poorer prognosis. Whether this association is affected by hypertension is unclear. Our aim was to investigate the association between 25(OH)D levels and both clinical severity and outcome after 3 months in AIS patients stratified by the history of hypertension. Consecutive first-ever AIS patients admitted to the Third Affiliated Hospital of Sun Yat-sen University, China were identified. Clinical information was collected. Serum 25(OH)D levels were measured at baseline. Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS) score. Functional outcome was evaluated after 3 months of onset using the modified Rankin Scale (mRS). Multivariate analyses were performed using logistic regression models. During the study period, 377 patients were diagnosed as AIS and were included in the analysis. 25(OH)D deficiency was not associated with the risk of NIHSS at admission and 3 months mRS both in total patients and the hypertension subgroup. Among AIS without hypertension, 25(OH)D deficiency subjects had a significantly higher of NIHSS at admission and 3 months mRS compared with those with 25(OH)D ≥ 50 nmol/L. The odds ratios (95% confidence interval) were 5.51(1.83–16.60) and 4.63(1.53–14.05) in the multivariable adjusted model (P for linear trend < 0.05). Serum lower 25(OH)D levels can be seen as an independent prognostic factor of functional outcome in AIS without hypertension. Additional studies about improving prognosis of AIS by vitamin D supplementation could be first applied to these patients.

Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population

BackgroundDepression is a frequent mood disorder in stroke patient. Our aim was to determine irisin levels in serum and investigate their associations with post-stroke depression (PSD) in a 6-month follow-up study in Chinese patients with first-ever acute ischemic stroke (AIS).MethodsThe subjects were first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Neurological and neuropsychological evaluations were conducted at the 6-month follow-up. Serum irisin concentrations were measured by enzyme-linked immunosorbent assay (ELISA).ResultsDuring the study period, 1205 patients were included in the analysis. There were 370 patients (30.7%) classified as depression. The depression distribution across the irisin quartiles ranged between 49.8% (first quartile) and 9.9% (fourth quartile). In the patients with depression, serum irisin levels were lower compared with those in patients without depression (P < 0.001). In a multivariate model using the first (Q1) quartile of irisin vs. Q2–4 together with the clinical variables, the marker displayed predictive information and increased risk of PSD by 75% (odds ratio [OR] for Q1, 1.75 [95% confidence interval [CI], 1.15–2.65]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability; the area under the curve (AUC) increased from 0.77 to 0.81 (95% CI, 0.76–0.86).ConclusionsThe data suggested that reduced serum levels of irisin were powerful biological markers of risk of developing PSD even after adjustment by variables. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options.Trial registrationChiCTR-OPC-17013501. Retrospectively registered 23 September 2017

Elevated plasma macrophage migration inhibitor factor as a risk factor for the development of post-stroke depression in ischemic stroke

BackgroundMacrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory responses, has been reported to link to the pathophysiology of cardiovascular disease and depression. The aim of this study was to test the possible association between plasma MIF and the development of post-stroke depression (PSD) in Chinese patients with acute ischemic stroke (AIS). MethodsThe first-ever AIS patients who were hospitalized at Affiliated Hospital of Weifang Medical College during the period from November 2015 to September 2017 were included. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up. Plasma concentrations of MIF were tested by Quantikine Human MIF Immunoassay. Plasma levels of homocysteine (HCY), C-reactive protein (CRP) and Interleukin 6 (IL-6) were also tested. Results were expressed as percentages for categorical variables and as medians (Interquartile range-IQR) for the continuous variables. ResultsFinally, 333 stroke patients were included, and 95 out of those patients (28.5%) were classified as major depression. In the patients with major depression, plasma levels of MIF were higher compared with those in patients free-depression [27.3(IQR, 23.5–34.9) ng/ml vs. 20.9(IQR, 17.0–24.8) ng/ml; Z = 8.369, P < 0.001]. For each 1unit increase of MIF, the unadjusted and adjusted risk of PSD increased by 18% (odds ratios [OR]: 1.18; 95% confidence interval [CI], 1.13–1.23, P < 0.001) and 11% (1.11; 1.02–1.16, P = 0.001), respectively. In a multivariate model using the elevated levels of MIF (≥median) vs. normal (<median) together with the other significant clinical variables, the marker displayed prognostic information (PSD: OR for fourth quartile, 3.05 [95% CI, 1.65–6.11; P < 0.001]). When MIF was added to the model containing established significant risk factors, Area Under the Receiver Operating Characteristic curve (AUROC; standard error) was increased from 0.81(0.025) to 0.86(0.019). A significant difference in the AUROC between the established risk factors alone and the addition of MIF was observed (difference, 0.05[0.006]; P = 0.004). ConclusionThe present study demonstrated that elevated plasma levels of MIF at admission were associated with increased risk of PSD in the next three months and might be useful in identifying stroke at risk for PSD for early prevention strategies.