Ischemic Stroke Attack Research Articles

Acute headache attributed to ischemic stroke: assessment of its characteristics and associated factors

It is estimated that headache attributed to ischemic stroke occurs in 7.4% to 34% of the cases. Despite its frequency, this headache has been little studied in terms of its risk factors and characteristics. To assess the frequency and clinical characteristics of headache attributed to ischemic stroke and the factors associated with its occurrence. The present was a cross-sectional study which included patients consecutively admitted within 72 hours of the onset of ischemic stroke. A semi-structured questionnaire was used. The patients underwent magnetic resonance imaging. A total of 221 patients were included, 68.2% of whom were male, and the mean age was of 68.2 ± 13.8 years. The frequency of headache attributed to ischemic stroke was of 24.9% (95% confidence interval [95%CI]: 19.6-31.1%). The headache had a median duration of 21 hours and most frequently began at the same time as the focal deficit (45.3%), with a gradual onset (83%). It was of moderate intensity, pulsatile (45.3%), bilateral (54.6%), and presented a similar pattern to that of tension-type headache (53.6%). Headache attributed to stroke was significantly associated with previous tension-type headache, and previous migraine with and without aura (logistic regression). Headache attributed to stroke is common, with a pattern similar to that of tension-type headache, and it is associated with a history of tension-type and migraine headaches.

Abstract P598: Highly Purified Eicosapentaenoic Acid Use Can Reduce Neurological Severity at the Onset of Ischemic Stroke in Patients With Hyperlipidemia

Introduction: Functional outcomes after acute ischemic stroke (AIS) are related to initial neurological severity (NS). Therefore, neuroprotective drugs against ischemic injury are promising. Not only statins but also eicosapentaenoic acid (EPA) have neuroprotective effects. Hypothesis: Highly purified EPA (hp-EPA) pre-stroke may reduce NS at the onset of AIS. Methods: We retrospectively included patients with AIS and hyperlipidemia admitted to our institution between July 2012 and March 2019 from the prospectively and consecutively enrolled institutional stroke registry database. Hyperlipidemia was defined as serum values of low-density lipoprotein cholesterol (LDL-C) at arrival ≥140 mg/dl or triglycerides ≥150 mg/dl. We excluded patients: (1) admitted to our institution 24 h after AIS onset, (2) who did not stay in the hospital, and (3) in whom dyslipidemia drugs pre-stroke except the hp-EPA were administered. We collected data on age; sex; pre-stroke statin use, antiplatelets, anticoagulants, antihypertensives, and antidiabetic drugs; serum albumin, glucose, glycated hemoglobin (HbA1c), cholesterol, triglycerides, and c-reactive protein levels; pre-stroke modified Rankin scale and the National Institutes of Health Stroke Scale (NIHSS) scores; stroke subtypes at admission; hospitalizations; and home discharge. We performed a multivariable linear regression analysis to identify significant variables of NIHSS scores at arrival. Results: Of the 2,199 patients with AIS and hyperlipidemia during the study period, 691 met our inclusion and exclusion criteria, their median age was 75 years, and 18 (2.6%) received pre-stroke hp-EPA. In patients with and without pre-stroke EPA use, the median NIHSS scores were one and three, respectively. Multivariable regression analysis showed that the glucose, mRS, age, LDL-C, and anticoagulants increased the NIHSS score, albumin, HbA1c, high-density lipoprotein cholesterol, antihypertensives, antidiabetic drugs, and hp-EPA use decreased the NIHSS score. Conclusion Pre-stroke hp-EPA use reduced NS at the AIS onset in patients with hyperlipidemia and without other dyslipidemia drugs.

Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Older Patients with Acute Ischemic Stroke.

The prognostic value of the neutrophil-to-lymphocyte ratio (NLR), an inflammatory indicator, for 90-day outcomes has not been determined for patients with acute ischemic stroke aged ≥ 80 years. Therefore, this study examined the predictive significance of the NLR for estimating the 90-day outcomes of older patients with acute ischemic stroke. Data from patients aged ≥ 80 years were recorded within 7 days of ischemic stroke onset during the period from January 2019 to June 2021. A Kaplan-Meier curve was drawn based on the incidence of adverse outcomes to compare the survival probability of each group at different time periods. Cox multivariate regression was used to explore adverse events affecting patient prognosis. A total of 560 patients were initially recruited; of these, 476 were eligible for inclusion. The log-rank test showed that the survival rates of the groups differed. The 90-day survival rate was significantly lower in the group with the highest NLR than in the group with the lowest NLR. Multivariate Cox regression analysis showed that after adjusting for risk factors, a high NLR and a high National Institutes of Health Stroke Scale score were independent risk factors for 90-day mortality. According to the receiver operating characteristic analysis, the area under the curve for predicting mortality at 90 days was 0.74. This study confirmed that a high NLR is an independent risk factor for acute ischemic stroke and has predictive value for 90-day prognosis in patients aged ≥ 80 years.

MEASUREMENT OF WALKING IMPAIRMENT RECOVERY AFTER STROKE

Introduction: One of the most important goals in rehabilitating patients affected by stroke is re-establishing independent movement by activating as many motor patterns as possible and changing existing preexisting abnormal motor patterns Objective: To determine recovery level with the accent on motor functions recovery in a patient affected by an ischemic stroke for the first time. The study included patients with anterior circulation syndrome, posterior circulation syndrome, and lacunar syndrome in the acute and post-acute phases of physical therapy and rehabilitation.Material and methods: We conducted a prospective study, which included a total of 90 patients with the first onset of ischemic stroke. The first group consisted of 30 patients with the anterior circulation syndrome of; the second group of 30 patients with the posterior circulation syndrome and the third group of 30 patients with the lacunar syndrome. At the beginning of their early rehabilitation treatment at the Clinic of Physical Medicine and Rehabilitation, the Bamford Scale was used in the initial assessment of the clinical classification of stroke. After the rehabilitation treatment and six months after the stroke, an assessment of motor functions and improvement in overall functionality was performed using a six-minute walk test.Results: The six-minute walk test in all the studied groups showed significant improvement six months after the stroke compared to testing done immediately after their rehabilitation treatment (p = 0.01 anterior circulation, p = 0.05 posterior circulation, p = 0.01 lacunar syndrome). The six-minute walk test was statistically significantly better in patients with lacunar syndrome compared to patients with posterior circulation syndrome after the rehabilitation treatment (p = 0.005) and six months after stroke; p = 0.02.Conclusion: The importance of rehabilitation in the acute and post-acute phases of patients with first ischemic stroke is evident. The six-minute walk test in all studied groups showed statistically significant improvement after six months post-stroke period compared to post-rehabilitation testing. The results were statistically significantly better in patients with lacunar syndrome compared to patients with posterior circulation syndrome after the physical treatment and the time period of six months after the stroke.

Hurdles of intravenous thrombolysis in acute ischemic stroke at Balochistan

Background and objective:
 Intravenous thrombolysis (IVT) with alteplase tPA (tissue plasminogen Activator) is the FDA approved treatment for acute ischemic stroke. The objective of this study was to determine the hurdles of intravenous thrombolysis in acute ischemic stroke in Balochistan.
 Methods:
 A prospective cross-sectional observational study was carried out from June 2021 to December 2021 at Neurology department of Bolan Medical Complex Hospital Quetta on 272 patients of acute ischemic stroke who fulfilled the criteria. Proforma was filled by relative or patient after informed consent. Proforma included sex, age, diagnosis, time of presentation after stroke and reason of delay. Data was collected, tabulated, and statistically analyzed using an IBM Statistical Package for the Social Sciences (SPSS), version 20.
 Results:
 Out of 272 patients, 156 patients were male and 116 patients were female. Only two patients presented within 4.5 hours of onset of acute ischemic stroke, 27 patients within 13- 24 hours,44 patients within 25-72 hours and 171 patients beyond three days. Two-hundred patients first took advice from faith healer (peer), 50 patients from general practitioner and 22 patients preferred neurologist.
 Conclusion:
 Very few patients presented within Alteplase window. Major reason of delay was contacting faith healer first. There is necessity of awareness campaigns to overcome this hurdle and to minimize barriers for improving access to thrombolysis and specialized stroke care in Balochistan.

Genetic variants in the promoters of let-7 are associated with the risk and age at onset of ischemic stroke: A case control study

PurposeLet-7 family members serve as crucial regulatory molecules in the pathogenesis of ischemic stroke. We predicted that genetic variations in the let-7 family's promoters may be linked to the risk of ischemic stroke. The connection of rs10877887 and rs13293512 in the let-7 family promoters with liability to ischemic stroke was explored in this study. Patients and methodsClinical data and peripheral blood samples were collected from 914 ischemic stroke patients and 836 controls in this case–control study. All statistical analyses were carried out using SPSS. ResultsOur analysis results reveal that the rs10877887 TC+CC genotype in the dominant model is associated with a lower risk of ischemic stroke than the TT genotype. Individuals with heterozygous TC or homozygous CC genotypes in the male population showed higher odds of ischemic stroke than those with the wild TT genotype in rs13293512 analysis. Furthermore, there existed a multiplicative interaction between the rs10877887 C allele and the rs13293512 T allele. In the presence of the rs13293512 T allele, the effect of the rs10877887 C allele on ischemic stroke risk was increased. Similarly, in the presence of the rs10877887 C allele, the outcome of the rs13293512 T allele on ischemic stroke risk was elevated. In addition, the rs13293512 CC genotype seemed to lead to an earlier onset of ischemic stroke. ConclusionOur findings indicated that these two SNPs might have a joint role in IS and could potentially act as risk markers. Detecting let-7 promoter polymorphisms could raise awareness of the risk of IS, which directed individuals with risk alleles to have regular checks at an appropriate frequency to avoid developing the disease.

Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer.

Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer. We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen. The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival. S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

Friends or foes: The mononuclear phagocyte system in ischemic stroke.

Ischemic stroke (IS) is a major cause of disability and death in adults, and the immune response plays an indispensable role in its pathological process. After the onset of IS, an inflammatory storm, with the infiltration and mobilization of the mononuclear phagocyte system (MPS), is triggered in the brain. Microglia are rapidly activated in situ, followed by waves of circulating monocytes into the ischemic area. Activated microglia and monocytes/macrophages are mainly distributed in the peri-infarct area. These cells have similar morphology and functions, such as secreting cytokines and phagocytosis. Previously, the presence of the MPS was considered a marker of an exacerbated inflammatory response that contributes to brain damage. However, recent studies have suggested a rather complicated role of the MPS in IS. Here, we reviewed articles focusing on various functions of the MPS among different phases of IS, including recruitment, polarization, phagocytosis, angiogenesis, and interaction with other types of cells. Moreover, due to the characteristics of the MPS, we also noted clinical research addressing alterations in the MPS as potential biomarkers for IS patients for the purposes of predicting prognosis and developing novel therapeutic strategies.

Nomogram including indirect bilirubin for the prediction of post-stroke depression at 3 months after mild acute ischemic stroke onset.

Post-stroke depression (PSD) has been proven to be associated with stroke severity. Thus, we hypothesized that the prevalence of PSD would be lower in patients with mild stroke. We aim to explore predictors of depression at 3 months after mild acute ischemic stroke (MAIS) onset and to develop a practical and convenient prediction model for the early identification of patients at high risk. A total of 519 patients with MAIS were consecutively recruited from three hospitals in Wuhan city, Hubei province. MAIS was defined as a National Institute of Health Stroke Scale (NIHSS) score of ≤5 at admission. Meeting the DSM-V diagnostic criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) score of >7 at their 3-month follow-up were considered the primary outcomes. A multivariable logistic regression model was used to determine the factors adjusted for potential confounders, and all independent predictors were brought into the construction of a nomogram to predict PSD. The prevalence of PSD is up to 32% at 3 months after MAIS onset. After adjusting for potential confounders, indirect bilirubin (p = 0.029), physical activity (p = 0.001), smoking (p = 0.025), hospitalization days (p = 0.014), neuroticism (p < 0.001), and MMSE (p < 0.001) remained independently and significantly related with PSD. The concordance index (C-index) of the nomogram jointly constructed by the aforementioned six factors was 0.723 (95% CI: 0.678-0.768). The prevalence of PSD seems equally high even if the ischemic stroke is mild, which calls for great concern from clinicians. In addition, our study found that a higher level of indirect bilirubin can lower the risk of PSD. This finding may provide a potential new approach to PSD treatment. Furthermore, the nomogram including bilirubin is convenient and practical to predict PSD after MAIS onset.

Abstract WMP106: Sex-stratified Transethnic GWAS Meta-analysis Identifies Novel Candidates For Early Onset Ischemic Stroke

Background: Early onset ischemic stroke (IS) affects males and females unequally, but the etiologic background of the sex differences remains inadequately understood. We hypothesize that stratifying GWAS by sex provides an opportunity to 1) identify loci that shed light on mechanisms and pathways relevant to sex specific effects in IS and 2) discover novel IS loci. Methods: We performed a sex-stratified transethnic GWAS meta-analysis in 6,879 female IS cases and 11,264 male cases &lt; 60 years-old and &gt; 700,000 sex-matched controls from the Early Onset Stroke Genetics Consortium. We tested for difference (p-diff) between the men- and women-specific beta-estimates with corresponding standard errors using the t statistics. Results: We found genome-wide significant evidence for association (p &lt; 5 х 10 -8 ) at a locus near NYAP2 for females (chr2:225661726:C:CT, p = 2.11 х 10 -8 , OR = 1.38, p-diff = 1.69 х 10 -4 ) and in PIAS4 for males (chr19:4013652:C:CA, p = 6.29 х 10 -9 , OR = 0.85, p-diff = 0.02) in transethnic analysis. NYAP2 has previously shown suggestive evidence for association with early onset menopause. PIAS4 , a candidate gene for migraine, has shown sex-specific expression levels in migraine patients compared to controls. Additional loci with suggestive evidence (p &lt; 1 х 10 -6 ) for association in a sex-dependent manner included MMP1-MMP3 - MMP12 , a previously known stroke locus, for males (chr11:102822455:A:G, p = 3.99 х 10 -7 , OR = 1.17, p-diff = 0.02), and a novel stroke locus near TMX1 , a transmembrane platelet protein, for females (chr14:51193174:G:C, p = 4.15 х 10 -7 , OR = 1.76, p-diff = 4.08 х 10 -3 ). The known early onset IS locus ABO did not show evidence for sex-specific association despite suggestive association in the male stratified analysis (chr9:133274295:A:T, p = 3.15 х 10 -7 , OR = 1.17, p-diff = 0.81). Conclusions: We identified potential novel stroke loci and evidence for sex differences at other biologically relevant loci by stratifying GWAS by sex. To our knowledge, our cohort represents the largest early onset IS GWAS cohort to date. However, our findings require verification in large sample sizes and also evaluation in older onset IS. Sex-specific association analysis is a potentially useful tool for characterizing the genetic basis of early onset IS.

Abstract TP92: Early Hyperacute Ion Dysregulation Following A Temporary Large Vessel Occlusion Stroke

Introduction: Ion dysregulation is a hallmark of energy failure after onset of ischemic stroke. To better understand the nature of the ion concentration changes in the early hyperacute phase after stroke onset we have quantitatively imaged the trace element distribution in the stroke lesion territory after a 30-minute temporary large vessel occlusion stroke. Methods: A temporary large vessel occlusion stroke was generated with the middle cerebral artery occlusion (MCAO) mouse model (insertion of an occluding filament via the ECA) with reperfusion after 30 minutes (occluding filament withdrawn). C57BL/6 mice (5 per time point) were euthanized at 5-, 30-, 60-, 90-, and 120-minutes post reperfusion. Shams included all surgical procedures, however the occluding filament was withdrawn immediately after insertion. Heads were immediately frozen post mortem and sectioned for trace element mapping. Quantitative X-ray fluorescence microscopy was performed at the Stanford Synchrotron Radiation Lightsource. Results: Loss of potassium is observed throughout the affected tissue at all post-reperfusion time points, with most of the initial loss occurring in the 30-minutes prior to reperfusion. Loss of essential zinc began to be observed 1-hour post reperfusion. No significant elevations in chlorine or calcium were observed during the early hyperacute phase. At subsequent post reperfusion time points the lesion (as defined by diminished potassium) grew steadily for 90-minutes. After 90-minutes post reperfusion some lesions demonstrated a distinct pattern consistent with a central infarct core surrounded by an ischemic penumbra. Conclusions: At all early hyperacute time points the stroke lesion demonstrated on-going potassium dysregulation, despite reperfusion. The loss of potassium was a bulk phenomenon in the tissue. Potassium is essential for maintenance of neuronal membrane potential and therefore function. Restoration of normal blood flow is insufficient to protect the brain from the enduring reduction in vital potassium levels or expansion of the region of ion dysregulation. The lack of available potassium within the affected tissue may hinder recovering neuronal cells from restoring action potentials, even after tissue perfusion is restored.

Abstract WP201: Outcomes Of Ischemic And Hemorrhagic Stroke Patients With Cancer: Japan Stroke Data Bank

Purpose: We aim to clarify the association between history of cancer with clinical outcomes after ischemic stroke (IS) or hemorrhagic stroke (HS). Methods: Study participants were adult patients within seven days after onset of IS or HS from the register of the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between 2000 and 2021, whose modified Rankin Scale score at discharge was available. Participants were divided into three groups [active cancer (AC) group, inactive cancer (iAC) group, and without cancer group]. Outcomes including good functional outcome, representing modified Rankin Scale score 0-2 at discharge, and in-hospital death was compared between the groups using multivariate analysis by forward-backward stepwise selection method for stroke subtype. AC was defined as cancer diagnosed within six months, requiring chemotherapy or surgical treatment, metastatic, or inoperable. Results: Of 171292 stroke patients, including 128145 with IS and 43147 with HS, 1074 patients had AC (women 42.5%; median age, 77 years; median (interquartile range) baseline National Institutes of Health Stroke Scale 5 [2–15]; IS 84.3%), 6337 patients had iAC (37.9%; 73 years; 4 [2–13]; 79.5%), and 163881 patients did not have cancer (42.4%; 73years; 4 [2–12]; 74.6%). Good functional outcome after IS was less common in cancer patients [AC; 39.4%, adjusted odds ratio (OR) 0.78, 95% confidence interval (CI) 0.71-0.86: iAC; 49.1%, adjusted OR 0.92, 95% CI 0.85-0.99] than those without cancer (56.3%), and mortality in cancer patients was higher (AC; 10.6%, adjusted OR 1.77, 95% CI 1.56-2.01: iAC; 5.6%, adjusted OR 1.26, 95% CI 1.09-1.47) than those without cancer (4.4%). Good functional outcome after HS was less common in cancer patients [AC; 22.0%, adjusted OR 0.81, 95% CI 0.61-1.07: iAC; 24.6%, adjusted OR 0.78, 95% CI 0.64-0.94] than those without cancer (35.3%), and mortality after HS was higher in AC patients (29.8%) than those without cancer (15.9%, adjusted OR 1.61, 95% CI 1.26-2.07) Conclusions: IS patients with AC and those with iAC significantly had less achievement of good functional outcomes and more in-hospital death, and HS patients with AC led to more in-hospital death than patients without cancer.

Abstract TP43: Circadian Variation In Stroke Onset On Weekdays Compared With Weekends/Holidays

Background: Ischemic and hemorrhagic stroke onset exhibit is known to exhibit diurnal variation throughout the 24-hour cycle. But whether this variation differs on weekdays compared with weekends/holidays has not been well delineated. Methods: We evaluated consecutive patients with acute cerebral ischemia [(ACI), including ischemic stroke (IS) and transient ischemic attack (TIA)] and intraparenchymal hemorrhage (IPH) enrolled during ambulance transport to 60 receiving stroke centers in the NIH FAST-MAG trial. Enrollment required onset within the prior 2 hours, excluding confounding by wake-up and unwitnessed onset strokes. The patterns of time of onset were analyzed: 1) hourly, 2) in 4-hour increments, and 3) daytime (08:00-19:59) vs. night-time (20:00-07:59). Diurnal variation in presenting demographic/clinical features were assessed using ANOVA, Kruskal-Wallis, t-tests, and Wilcoxon Rank-Sum. Results: Among 1615 patients (1202 enrolled on weekdays and 442 on weekends/holidays), 64% had IS, 12.5% TIA, and 23.5% IPH. ACI patients had different patterns of onset time (Figure). During weekdays, a broad plateau of highest rates of onset occurred 09:00-22:00. Conversely, during weekends/holidays, a unimodal peak was observed between 14:00-16:00. In contrast, patterns of onset time in IPH patients were broadly similar, with bimodal peaks on both weekdays and weekends/holidays. However, the first peak occurred earlier on weekdays (09:00-12:00 vs. 11:00-13:00), with the second peak occurring within 17:00-20:00 in both groups. Conclusion: Acute cerebral ischemia shows marked, and intraparenchymal hemorrhage minor, pattern differences in onset times on weekdays vs. weekends/holidays, likely related to variations in times of greater physical activity and stress. These findings can inform EMS resource allocation to stroke, aligned with weekday vs. weekend/holiday onset patterns.

Independent Predictive Value of Elevated YKL-40 in Ischemic Stroke Prognosis: Findings from a Nationwide Stroke Registry

Introduction: Elevated circulatory concentrations of YKL-40 have been reported in patients with ischemic stroke. This study further investigated the association of plasma YKL-40 concentrations at admission and short, long-term prognosis after ischemic stroke. Methods: Based on a prospective, nationwide multicenter registry focusing consecutive patients of ischemic stroke and transient ischemic attack, plasma YKL-40 levels were detected by enzyme-linked immunosorbent assay at admission, and patients were stratified into percentile according to the plasma YKL-40 concentrations. The multivariate Cox or logistic regression model was used to investigate the association of YKL-40 concentration with death and functional outcomes at 3 months, 6 months, and 12 months after ischemic stroke, with potential confounders adjusted. Results: A total of 8,006 first-ever ischemic stroke patients, with the age of 61.7 ± 11.5, were included in this study. The mortality of 0–33%, 34–66%, 67–90%, and 91–100% groups at 12 months follow-up was 0.9%, 2.2%, 4.4%, and 9.4%, respectively (p < 0.0001), and the modified Rankin Scale 3–6 ratio was 6.8%, 10.5%, 15.7%, and 24.0%, respectively (p < 0.0001). In the multivariate regression, after adjusting for potential confounders, 91–100% group had higher risk of death (hazard ratio 2.99, 95% confidence interval 1.75–5.11)and modified Rankin Scale 3–6 (odds ratio 1.42, 95% confidence interval 1.08–1.88) at 12 months since onset of ischemic stroke compared to the 0–33% group. Conclusions: The elevated YKL-40 at admission can potentially help predict death, functional prognosis after ischemic stroke, which may help further studies to explore the potential physiological and pathological mechanism including the effects of vulnerable plaque and collateral circulation.

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24hours) hyperacute stroke groups. Cross-sectional cohort. A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. Patients were divided into hyperacute (0-24hours), acute (24hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F=14.321) and creatine (F= 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r=-0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r=-0.472; lactate: r=0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC]=0.90). High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. 1. Stage 2.

Neutrophil-to-Lymphocyte Ratio as a Predictor of Short-Term Functional Outcomes in Acute Ischemic Stroke Patients.

Neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory biomarker, has been associated with poorer outcomes in acute ischemic stroke patients. The present study was designed to expand these findings by investigating the association between NLR and short-term functional outcomes in acute ischemic stroke patients. This retrospective study evaluated patients within 7 days after the onset of acute ischemic stroke. Stroke severity on admission was measured using the National Institutes of Health Stroke Scale (NIHSS). The functional outcomes were assessed using the Berg Balance Scale (BBS), Manual Function Test (MFT), the Korean version of the modified Barthel Index (K-MBI), and the Korean Mini-Mental State Examination (K-MMSE) within 2 weeks of stroke onset. The modified Rankin Scale (mRS) was evaluated at discharge. This study included 201 patients, who were grouped into three NLR tertiles (&lt;1.84, 1.84-2.71, and &gt;2.71) on admission. A multivariate analysis showed that the top tertile group (NLR &gt; 2.71) had significantly higher risks of unfavorable outcomes on the K-MBI (p = 0.010) and K-MMSE (p = 0.029) than the bottom tertile group (NLR &lt; 1.84). Based on the optimal cut-off values from a receiver operating characteristic curve analysis, a higher NLR was significantly associated with higher NIHSS scores (p = 0.011) and unfavorable outcomes on the K-MBI (p = 0.002) and K-MMSE (p = 0.001). A higher NLR is associated with poorer short-term functional outcomes in acute ischemic stroke patients.

The influence of COVID-19 on the treatment of patients with acute ischemic stroke: aretrospective observational study.

Since December 2019, coronavirus 2019 (COVID-19) has rapidly spread to become a global pandemic, exerting a great pressure on medical staff worldwide. This study aimed to observe whether COVID-19 influenced the diagnosis and treatment of ischemic stroke (IS). This study retrospectively analysed the clinical data (number of emergencies, time from onset to treatment, and door-to-needle time [DNT]) of patients with acute IS (AIS) treated in our hospital within six months of the first case of COVID-19 reported in the city; the derived data were then compared with the situation of patients during the same period in 2019. The results showed that the number of medical visits during the period of COVID-19 decreased by 44.3%, and the median time from the onset of IS to emergency treatment was 35 min longer than that during the same period in 2019. The median time from entering the emergency department to the completion of cranial computerized tomography was 8 min shorter than during the same period in 2019, and the median time of DNT was relatively shorter than that during the same period in 2019. The pandemic situation of COVID-19 significantly reduced the number of patients with AIS and prolonged the travel time to the hospital whereas most of the stroke treatment services were maintained.

A deep learning analysis of stroke onset time prediction and comparison to DWI-FLAIR mismatch

IntroductionWhen time since stroke onset is unknown, DWI-FLAIR mismatch rating is an established technique for patient stratification. A visible DWI lesion without corresponding parenchymal hyperintensity on FLAIR suggests time since onset of under 4.5 h and thus a potential benefit from intravenous thrombolysis. To improve accuracy and availability of the mismatch concept, deep learning might be able to augment human rating and support decision-making in these cases. MethodsWe used unprocessed DWI and coregistered FLAIR imaging data to train a deep learning model to predict dichotomized time since ischemic stroke onset. We analyzed the performance of Group Convolutional Neural Networks compared to other deep learning methods. Unlabeled imaging data was used for pre-training. Prediction performance of the best deep learning model was compared to the performance of four independent junior and senior raters. Additionally, in cases deemed indeterminable by human raters, model ratings were used to augment human performance. Post-hoc gradient-based explanations were analyzed to gain insights into model predictions. ResultsOur best predictive model performed comparably to human raters. Using model ratings in cases deemed indeterminable by human raters improved rating accuracy and interrater agreement for junior and senior ratings. Post-hoc explainability analyses showed that the model localized stroke lesions to derive predictions. DiscussionOur analysis shows that deep learning based clinical decision support has the potential to improve the accessibility of the DWI-FLAIR mismatch concept by supporting patient stratification.

Exosome-transported lncRNA H19 regulates insulin-like growth factor-1 via the H19/let-7a/insulin-like growth factor-1 receptor axis in ischemic stroke.

LncRNA (long non-coding RNA) H19 is a transcript of the H19 gene that is expressed during embryogenesis. We previously discovered a role for circular lncRNA H19 in the onset and prognosis of cerebral ischemic stroke. In this study, we used serum from patients with ischemic stroke, and mouse and cell culture models to elucidate the roles of plasma and neuronal exosomes in the regulatory effect of lncRNA H19 on insulin-like growth factor-1 and its mechanism in ischemic stroke, using western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assays. Plasma exosomal lncRNA H19 was negatively associated with blood levels of insulin-like growth factor-1 in samples from patients with cerebral ischemic stroke. In a mouse model, levels of exosomal lncRNA H19 were positively correlated with plasma and cerebral lncRNA H19. In a cell co-culture model, we confirmed that lncRNA H19 was transported from neurons to astrocytes by exosomes to induce downregulation of insulin-like growth factor-1 through the H19/let-7a/insulin-like growth factor-1 receptor axis. This study provides the first evidence for the transportation of lncRNA H19 by exosomes and the relationship between lncRNA H19 and insulin-like growth factor-1.

In-Hospital Emergency Treatment Delay Among Chinese Patients with Acute Ischaemic Stroke: Relation to Hospital Arrivals and Implications for Triage Pathways.

Timely access to emergency treatment during in-hospital care phase is critical for managing the onset of acute ischaemic stroke (AIS), particularly in developing countries. We aimed to explore in-hospital emergency treatment delay and the relation of door-to-needle (DTN) time to ambulance arrivals vs walk-in arrivals. Data were collected from 1276 Chinese AIS patients admitted to a general, tertiary-level hospital for intravenous thrombolysis. Information on patients' characteristics and time taken during in-hospital emergency treatment was retrieved from the hospital registry data and medical records. Ambulance arrival was defined as being transported by emergency ambulance services, while walk-in arrival was defined as arriving at hospital by regular vehicle. In-hospital emergency treatment delay occurred when the DTN time exceeded 60 minutes. We performed multivariable logistic regression analysis to explore the association between hospital arrivals (by ambulance vs by walk-in) and treatment delay after adjustment for age, sex, education, marital status, residence, medical insurance, number of symptoms, clinical severity and survival outcome. Over half (53.76%) of patients aged over 60 years. Around one-fifth (20.61%) of patients admitted to hospital through emergency ambulance services, while their counterparts arrived by regular vehicle. Overall, the median time taken from the hospital door to treatment initiation was 86.0 minutes. Patients arrived by ambulance (adjusted odds ratio [aOR] = 1.744, 95% confidence interval [CI] = 1.185-2.566, p = 0.005), had higher socio-economic status (aOR = 1.821, 95% CI = 1.251-2.650; p = 0.002), or paid out-of-pocket (aOR = 2.323, 95% CI = 1.764-3.060; p < 0.001) had an increased likelihood of in-hospital emergency treatment delays. In-hospital emergency treatment delay is common in China, and occurs throughout the entire emergency treatment journey. Having a triage pathway involving hospital arrival by ambulance seems to be more likely to experience in-hospital emergency treatment delay. Further efforts to improve triage pathways may require qualitative evidence on provider- and institutional-level factors associated with in-hospital emergency treatment delay.