Recombinant Tissue Plasminogen Activator Treatment Research Articles

Therapeutic Effect of Thrombolytic Therapy on Motor Function Loss After Ischaemic Stroke: A Case Study

Stroke is a serious cerebrovascular disease that can cause disability and death if not treated with appropriate treatment methods at the right time. In ischaemic stroke, recombinant tissue plasminogen activator (rt-PA) treatment is effective in motor deficit recovery, especially in the first 4.5 hours. In this case study, rt-PA thrombolytic treatment of patients with motor deficit after acute ischaemic stroke aged 58 and 79 years was found to improve the loss of motor function.

Predictive value of neutrophil to apolipoprotein A1 ratio in patients with acute ischaemic stroke.

The neutrophil to apolipoprotein A1 ratio has emerged as a possible prognostic biomarker in different medical conditions. Nonetheless, the predictive potential of neutrophil to apolipoprotein A1 ratio in determining the 3-month prognosis of acute ischaemic stroke patients who undergo intravenous thrombolysis has yet to be fully acknowledged. In this study, 196 acute ischaemic stroke patients with recombinant tissue plasminogen activator and 133 healthy controls were included. Meanwhile, we incorporated a total of 386 non-thrombolytic acute ischaemic stroke patients. The acute ischaemic stroke patients with recombinant tissue plasminogen activator were divided into four groups based on quartiles of neutrophil to apolipoprotein A1 ratio. The association between neutrophil to apolipoprotein A1 ratio and the 3-month prognosis was evaluated through univariate and multivariate regression analyses. Additionally, subgroup analyses were conducted to investigate the predictive value of neutrophil to apolipoprotein A1 ratio in different patient populations. Adverse outcomes were defined as a modified Rankin Scale score of 3-6. The study findings revealed a significant association between elevated neutrophil to apolipoprotein A1 ratio levels and poor prognosis in acute ischaemic stroke patients. In the highest quartile of neutrophil to apolipoprotein A1 ratio levels (Q4), after controlling for age, gender, admission National Institutes of Health Stroke Scale score, blood urea nitrogen and stroke subtypes, the odds ratio for adverse outcomes at 3 months was 13.314 (95% confidence interval: 2.878-61.596, P = 0.001). An elevated neutrophil to apolipoprotein A1 ratio value was found to be associated with a poor prognosis in acute ischaemic stroke patients, regardless of whether they received recombinant tissue plasminogen activator treatment or not. The new model, which incorporating neutrophil to apolipoprotein A1 ratio into the conventional model, demonstrated a statistically significant improvement in discriminatory power and risk reclassification for 3-month poor outcomes in acute ischaemic stroke patients treated with recombinant tissue plasminogen activator. The new model exhibited a categorical net reclassification index (P = 0.035) of 12.9% and an integrated discrimination improvement (P = 0.013) of 5.2%. Subgroup analyses indicated that the predictive value of neutrophil to apolipoprotein A1 ratio differed across stroke subtypes. Neutrophil to apolipoprotein A1 ratio is a potential biomarker for predicting the prognosis of acute ischaemic stroke patients. The clinical implications of our findings are significant, as early identification and intervention in high-risk patients can improve their outcomes. However, further studies are required to validate our results and elucidate the underlying mechanisms of the association between neutrophil to apolipoprotein A1 ratio and poor prognosis in acute ischaemic stroke patients.

Factors predicting functional outcome after rtPA for patients with acute ischemic stroke

BackgroundAccurate outcome prediction for patients with acute ischemic stroke after intravenous recombinant tissue plasminogen activator (rtPA) treatment is essential for optimizing patients’ management. We aimed to identify factors associated with unfavorable outcomes following intravenous rtPA treatment. This study was carried out on 162 patients who presented with acute ischemic stroke within 4.5 h from onset of neurological symptoms and were eligible for intravenous rtPA. After exclusion of 48 patients, 114 patients were finally eligible for follow-up. After complete medical and neurological history, complete medical and neurological examination and brain image (CT and or MRI brain) were collected from the patients. patients eligible were included in the study. NIHS scale was assessed for all patients at time of admission, after 24 h, and follow-up for 3 months.ResultsAfter a 90-day follow-up period for 114 patients with acute ischemic stroke after rtPA, 35.8% had good outcome (MRS; 0–2), 18.5% had partial outcome (MRS; 3–4) and 12.5% had poor outcome (MRS; 5–6). Atrial fibrillation (AF), PH of stroke, stroke severity, and severity of symptom (NIHSS) score were significantly (P: 0.004, 0.001, 0.007 and 0.001) correlated with poor outcome after rtPA. Similarly, old age, high blood pressure at time of presentation, hypertension, and dyslipidemia were showed to carry poor outcome.ConclusionsAF, high NIHSS score, PH of stroke, previous stroke, hypertension, dyslipidemia, and high blood pressure on presentation were significantly correlated with poor functional outcome.

Performance comparison of stress hyperglycemia ratio for predicting fatal outcomes in patients with thrombolyzed acute ischemic stroke.

The stress hyperglycemia ratio (SHR), a newly developed metric, is used to assess adverse outcomes in patients with acute ischemic stroke (AIS). However, the relationship between SHR and fatal outcomes (in-hospital mortality [IHM], malignant cerebral edema [MCE], symptomatic intracerebral hemorrhage [sICH], 3-month mortality, and poor functional outcome) in AIS patients receiving recombinant tissue plasminogen activator (rt-PA) treatment is unclear, and determining the optimal threshold remains incomplete. We retrospectively enrolled a total of 345 AIS patients treated with rt-PA during 2015-2022 and collected data on various glucose metrics, including different types of SHR, glycemic gap (GG), random plasma glucose (RPG), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). SHR and GG were calculated using these equations: SHR1, [FPG]/[HbA1c]; SHR2, [admission RPG]/[HbA1c]; SHR3, FPG/[(1.59 × HbA1c)-2.59]; SHR4, [admission RPG]/[(1.59 × HbA1c)-2.59]; GG, admission RPG - [(1.59 × HbA1c)-2.59]. We used multivariable logistic regression analysis (MVLR) to identify the association between different glucose metrics and outcomes while comparing their predictive values. SHR1 had the greatest predictive power and a more significant correlation with fatal outcomes than other continuous glucose metrics. The area under the curve of the SHR1 for IHM, MCE, and sICH, 3-month mortality, and poor functional outcome were 0.75, 0.77, 0.77, 0.76, and 0.73, respectively. SHR1 (per 1-point increases) was independently associated with IHM (Odds ratios [ORs] = 5.80; 95% CI [1.96, 17.17]; p = 0.001), MCE (ORs = 4.73; 95% CI [1.71, 13.04]; p = 0.003), sICH (ORs = 4.68, 95% CI [1.48-14.82]; p = 0.009), 3-month mortality (ORs = 10.87; 95% CI [3.56, 33.21]; p<0.001), and 3-month poor functional outcome (ORs = 8.05; 95% CI [2.77, 23.39]; p<0.001) after adjustment in MVLR. In subgroup analysis, elevated SHR1 was associated with fatal outcomes in patients with non-diabetes, SBP≥ 180 mmHg, and NIHSS <16. SHR1 demonstrates an independent association with fatal outcomes in AIS patients treated with rt-PA, exhibiting superior predictive ability over other glucose metrics.

Effect of rt-PA on Shear Wave Mechanical Assessment and Quantitative Ultrasound Properties of Blood Clot Kinetics In Vitro.

The consequences associated with blood clots are numerous and are responsible for many deaths worldwide. The assessment of treatment efficacy is necessary for patient follow-up and to detect treatment-resistant patients. The aim of this study was to characterize the effect of treatment on blood clots in vitro using quantitative ultrasound parameters. Blood from 10 pigs was collected to form three clots per pig in gelatin phantoms. Clots were subjected to 1) no treatment, 2) rt-PA (recombinant tissue plasminogen activator) treatment after 20 minutes of clotting, and 3) rt-PA treatment after 60 minutes of clotting. Clots were weighted before and after the experiment to assess the treatment effect by the mass loss. The clot kinetics was studied over 100 minutes using elastography (Young's modulus, shear wave dispersion, and shear wave attenuation). Homodyne K-distribution (HKD) parameters derived from speckle statistics were also studied during clot formation and dissolving (diffuse-to-total signal power ratio and intensity parameters). Treated clots loosed significantly more mass than non-treated ones (P < .005). A significant increase in Young's modulus was observed over time (P < .001), and significant reductions were seen for treated clots at 20 or 60 minutes compared with untreated ones (P < .001). The shear wave dispersion differed for treated clots at 60 minutes versus no treatments (P < .001). The shear wave attenuation decreased over time (P < .001), and was different for clots treated at 20 minutes versus no treatments (P < .031). The HKD intensity parameter varied over time (P < .032), and was lower for clots treated at 20 and 60 minutes than those untreated (P < .001 and P < .02). The effect of rt-PA treatment could be confirmed by a decrease in Young's modulus and HKD intensity parameter. The shear wave dispersion and shear wave attenuation were sensitive to late and early treatments, respectively. The Young's modulus, shear wave attenuation, and HKD intensity parameter varied over time despite treatment.

A weakly supervised deep learning model integrating noncontrasted computed tomography images and clinical factors facilitates haemorrhagic transformation prediction after intravenous thrombolysis in acute ischaemic stroke patients

BackgroundHaemorrhage transformation (HT) is a serious complication of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS). Accurate and timely prediction of the risk of HT before IVT may change the treatment decision and improve clinical prognosis. We aimed to develop a deep learning method for predicting HT after IVT for AIS using noncontrast computed tomography (NCCT) images.MethodsWe retrospectively collected data from 828 AIS patients undergoing recombinant tissue plasminogen activator (rt-PA) treatment within a 4.5-h time window (n = 665) or of undergoing urokinase treatment within a 6-h time window (n = 163) and divided them into the HT group (n = 69) and non-HT group (n = 759). HT was defined based on the criteria of the European Cooperative Acute Stroke Study-II trial. To address the problems of indiscernible features and imbalanced data, a weakly supervised deep learning (WSDL) model for HT prediction was constructed based on multiple instance learning and active learning using admission NCCT images and clinical information in addition to conventional deep learning models. Threefold cross-validation and transfer learning were performed to confirm the robustness of the network. Of note, the predictive value of the commonly used scales in clinics associated with NCCT images (i.e., the HAT and SEDAN score) was also analysed and compared to measure the feasibility of our proposed DL algorithms.ResultsCompared to the conventional DL and ML models, the WSDL model had the highest AUC of 0.799 (95% CI 0.712–0.883). Significant differences were observed between the WSDL model and five ML models (P < 0.05). The prediction performance of the WSDL model outperforms the HAT and SEDAN scores at the optimal operating point (threshold = 1.5). Further subgroup analysis showed that the WSDL model performed better for symptomatic intracranial haemorrhage (AUC = 0.833, F1 score = 0.909).ConclusionsOur WSDL model based on NCCT images had relatively good performance for predicting HT in AIS and may be suitable for assisting in clinical treatment decision-making.

A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

BackgroundThrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient’s prognosis. ObjectivesTo investigate the association between genetically determined natural hemostatic factors’ levels and increased risk of HT after r-tPA treatment. MethodsUsing data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT. ResultsLocal correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10−11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10−10; rs1421067 (CHD9), P = 1.81 × 10−14; and rs34780449, near ROBO1 gene, P = 1.64 × 10−8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10−14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [−0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05). ConclusionWe identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.

Leukoaraiosis and stroke severity scores in post-rtPA intracerebral haemorrhage

IntroductionPost thrombolytic symptomatic intracerebral haemorrhage (sICH) is a major concern in patients who had acute ischaemic stroke. Leukoaraiosis (LA) is reported to be related with sICH after intravenous thrombolytic treatment....

Low-dose intravenous recombinant tissue plasminogen activator in acute ischemic stroke without large vessel occlusion screened by 3T MRI.

Globally, there are more than six million deaths due to cerebrovascular disease, which is the second leading cause of death. Although the imaging findings of magnetic resonance imaging (MRI) are more accurate than computed tomography for acute ischemic stroke (AIS), it is uncommon in recombinant tissue plasminogen activator (rTPA) treatment. Alteplase is not only strongly recommended treatment for acute ischemic stroke within 4.5 hours, but also decreases the disability and mortality rate. Besides, low-dose rTPA was associated with significant reductions in symptomatic intracerebral hemorrhage (sICH), compared with standard one. However, the benefits of low-dose rTPA for the treatment of AIS without large vessel occlusion (LVO) have not been fully demonstrated. We evaluated whether the low-dose rTPA in AIS without LVO could improve prognosis in patients three months post-treatment. This was a cross-sectional study on patients with AIS treated within 4.5 hours of symptom onset admitted to Can Tho S.I.S General Hospital between February 2019 and July 2021. The eligibility criteria were patients aged > 18 years treated with low-dose rTPA (0.6 mg/kg) and screened by 3T MRI. Patients with a pre-hospital modified Rankin score (mRS) ≥ 2 points, intracranial hemorrhage, LVO, or ≥ 3 microbleeds on brain MRI were excluded. The primary outcomes were the favorable outcome rate at three months and safety, which were evaluated by the rates of intracranial hemorrhage and mortality at three months. This study enrolled 92 eligible patients between February 2019 and July 2021. Their National Institute of Health Stroke Scale (NIHSS) scores were 7.5 ± 3.7 at admission, 3.3 ± 3.5 at discharge or seven days after discharge, and 2.2 ± 2.8 at three months. Their mRS were 2.9 ± 0.8 at admission, 1.4 ± 1.3 at discharge or seven days after discharge, and 1.1 ± 1.1 at three months. Elevated cardiac enzymes, age ≥ 75 years, and body mass index ≥ 25 were associated with increased poor outcomes at three months. While AIS was more common in men than women, a similar number of men (33.3%) and women had poor mRS. Three patients had complications associated with low-dose rTPA treatment: one (1.1%) had intracranial hemorrhage, one (1.1%) had new infarcts, and one (1.1%) had gastrointestinal bleeding. No deaths occurred within three months. Our study indicates the efficacy and safety of low-dose rTPA treatment for AIS without LVO within 4.5 hours. Patient selection for rTPA by 3T MRI decreased complications and mortality.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke

DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. ClinicalTrials.gov Identifier: NCT03539445.

Recurrence stroke of ischemic stroke patients in Thailand: a nationwide study

Stroke is a global health problem and a leading cause of mortality and disability. Patients who survived an initial stroke are at risk for a recurrence stroke of the same type or another. However, few studies have documented at a national level. This research aimed to investigate the magnitude of recurrence stroke among ischemic stroke patients. This descriptive study used the data from neurology database collected between 2006 to 2020 in hospitals under the National Health Security System (NHSO) of Thailand. Among 511,322 ischemic stroke patients, recurrence of all types of strokes occurred in 85,968 patients or 16.81% (95% CI: 16.71-16.92). The prevalence was highest among patients with hypertension and diabetes mellitus at 18.89% (95% CI: 18.54-19.26), atrial fibrillation at 18.79% (95% CI: 18.42-19.15), and ischemic heart disease at 18.59% (95% CI: 18.05- 19.15). Furthermore, patients who received recombinant tissue plasminogen activator (rt-PA) treatment (12.15% %, 95%CI: 11.75-12.55) and rehabilitation (14.39%, 95% CI: 14.25-14.54) had a lower prevalence. Co- morbidities were an important factor had a high recurrence and treatment factors that patients receive had a low recurrence. Therefore, policymakers and health institutions could use these findings to implement treatment and monitoring policies for recurrence stroke.

Specificity and sensitivity of the SeLECT score in predicting late seizures in patients undergoing intravenous thrombolytic treatment and the effect of diabetes mellitus and leukoaraiosis

Seizures after stroke can negatively affect the prognosis of ischemic stroke and cause a decrease in quality of life. The efficacy of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke has been demonstrated in many studies, and IV rt-PA treatment has been increasingly used around the world. The SeLECT score is a useful score for the prediction of late seizures after stroke and includes the severity of stroke (Se), large artery atherosclerosis (L), early seizure (E), cortical involvement (C), and the territory of the middle cerebral artery (T). However, the specificity and sensitivity of the SeLECT score have not been studied in acute ischemic stroke patients that received IV rt-PA treatment. In the present study, we aimed to validate and develop the SeLECT score in acute ischemic stroke patients receiving IV rt-PA treatment. The present study included 157 patients who received IV thrombolytic treatment in our third-stage hospital. The 1-year seizure rates of the patients were detected. SeLECT scores were calculated. In our study, we found that the SeLECT score had low sensitivity but high specificity for predicting the likelihood of late seizure after stroke in patients administered IV rt-PA therapy. In addition to the SeLECT score, we found that the specificity and sensitivity were higher when we evaluated diabetes mellitus (DM) and leukoaraiosis. We found that DM was an independent risk factor for late seizures after stroke in a patient group receiving thrombolytic therapy, and late seizures after stroke were less frequent in patients with leukoaraiosis.

Abstract 90: Butylphthalide Improves Functional Outcome In Patients With Acute Ischemic Stroke Receiving Intravenous Thrombolysis And/or Endovascular Treatment In Comparison To Placebo

Introduction: Butylphthalide is a cerebro-protection drug that was originally extracted from seeds of Apium graveolens. Pre-clinical experiments have shown the cerebro-protective effect of Butylphthalide in animal models of ischemia-reperfusion. This study evaluated whether Butylphthalide can improve the functional outcome in acute ischemic stroke patients who receive intravenous recombinant tissue plasminogen activator (rt-PA) and/or endovascular treatment (EVT) compared to placebo. Methods: In the randomized, double-blinded, placebo-controlled trial, we enrolled patients with acute ischemic stroke who received intravenous rt-PA and/or EVT in 59 centers. Patients were randomized in a 1:1 ratio to receive either Butylphthalide or placebo daily for 90 days, including 14 days of intravenous injections and 76 days of oral capsules. All trial personnel and patients were masked to treatment allocation. The primary outcome was an adjusted favorable outcome at 90 days after randomization, defined as a score of 0 on the modified Rankin Scale (mRS) in patients with a baseline score of 4-7 on the National Institutes of Health Stroke Scale (NIHSS); an mRS score of 0-1 in patients with a baseline NIHSS score of 8-14; and an mRS score of 0-2 in patients with a baseline NIHSS score of 15-25. Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke and mortality. The analysis was done in the intention-to-treat population and in subgroups of age, sex, baseline NIHSS score, hypertension, and reperfusion treatment methods. This trial is registered with ClinicalTrials.gov, NCT03539445. Results: Between July 1, 2018 and 19 February, 2022, 1216 patients were enrolled, with 607 assigned to the butylphthalide group and 609 to the placebo group. The primary outcome of a favorable outcome on day 90 occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (OR, 1.70; 95% CI, 1.35 to 2.14; P &lt;0.001). Secondary outcomes were similar between groups. There was no evidence of treatment modification effect in the subgroups. Conclusions: In conclusion, Butylphthalide improved favorable clinical outcome compared with placebo in patients with acute ischemic stroke receiving intravenous rt-PA and/or EVT.

Prognostic factors for acute large vessel occlusion with NIHSS 5 or lower.

Intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular treatment have been performed for severe large vessel occlusion (LVO) and the results have been reported at high levels of evidence. However, acute treatment for LVO with mild symptom remains controversial. We retrospectively examined prognostic factors for LVO with mild symptoms. We studied retrospectively the patients within 24 h of onset with large vessel occlusion with NIHSS score ??5. Outcomes were evaluated by modified Rankin Scale (mRS) at 90 days, with 0?2 defined as a good outcome and 3?6 as a poor outcome. Clinical characteristics of each case were examined. Participants comprised 76 patients. Of the 76 patients. ICA occlusion showed good outcome in 17?/?19 cases (90%), whereas MCA occlusion showed good outcome in 36?/?54 cases (67%). Among the 14 cases showing positive results for distal intraarterial signal (d-IAS), outcomes were good in 6 cases (43%). On the other hand, the 32 d-IAS-negative cases showed good outcome in 28 cases (88%). Outcomes were thus significantly poorer for d-IAS-positive cases. MCA occlusion is associated with poor prognosis, even with NIHSS score ??5, and d-IAS may provide a predictor. J. Med. Invest. 70 : 22-27, February, 2023.

Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated with increased blood–brain barrier (BBB) disruption and hemorrhagic transformation. Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects against acute ischemic stroke. However, whether and how RIC regulates rtPA-associated BBB disruption remains unclear. Here, a rodent model of thromboembolic stroke followed by rtPA thrombolysis at different time points was performed with or without RIC. Brain infarction, neurological outcomes, BBB permeability, and intracerebral hemorrhage were assessed. The platelet-derived growth factor CC (PDGF-CC)/PDGFRα pathway in the brain tissue, PDGF-CC levels in the skeletal muscle and peripheral blood were also measured. Furthermore, impact of RIC on serum PDGF-CC levels were measured in healthy subjects and AIS patients. Our results showed that RIC substantially reduced BBB injury, intracerebral hemorrhage, cerebral infarction, and neurological deficits after stroke, even when rtPA was administrated in a delayed therapeutic time window. Mechanistically, RIC significantly decreased PDGFRα activation in ischemic brain tissue and reduced blood PDGF-CC levels, which partially resulted from PDGF-CC reduction in the skeletal muscle of RIC-applied hindlimbs and platelets. Intravenous or intraventricular recombinant PDGF-CC supplementation abolished RIC protective effects on BBB integrity. Moreover, similar changes of PDGF-CC in serum by RIC were also observed in healthy humans and acute ischemic stroke patients. Together, our study demonstrates that RIC can attenuate rtPA-aggravated BBB disruption after ischemic stroke via reducing the PDGF-CC/PDGFRα pathway and thus supports RIC as a potential approach for BBB disruption prevention or treatment following thrombolysis.

Platelet-to-lymphocyte ratio at 24h after thrombolysis is a prognostic marker in acute ischemic stroke patients.

BackgroundThe changes in the platelet-to-lymphocyte ratio (PLR) before and after recombinant tissue plasminogen activator (rtPA) treatment and the time point at which the PLR is a potentially valuable prognostic predictor in patients wit ischemic stroke remain largely unknown. Therefore, the purpose of this study was to explore the characteristics of the PLR and evaluate their effects on clinical outcomes before and 24 h after rtPA treatment.MethodsThis study included 741 consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis with rtPA. We collected data on demographics, vascular risk factors, medication history, and other clinical information pertaining to all patients. Specifically, blood samples for PLR measurement were collected on admission and 24 h after stroke. The outcome was assessed by using the Modified Rankin Scale (mRS) at 3 months and whether death occurred within 3 months or not. Univariate and multivariate logistic regression analysis was used to assess the association of the PLR with the risks of poor outcome (mRS>2) and death. An individualized prediction model was established to predict poor outcome.ResultsOf the 741 patients, 255 (34.4%) had poor outcome, and 43 (5.8%) died. The PLR significantly increased 24 h after rtPA in patients with poor outcome and death. Logistic analysis revealed that higher PLR 24 h after rtPA was independently associated with increased risks of poor outcome and death. However, the PLR on admission was not associated with the risks of poor outcome and death. The individualized prediction model for poor outcome based on the 24-h PLR exhibited favorable discrimination (areas under the curves of the training and validation groups: 0.743 and 0.729, respectively), calibration (P > 0.05), and clinical usefulness.ConclusionsWe found the PLR to be a variable that potentially predicts the risks of poor outcome and death in patients with acute ischemic stroke 24 h after rtPA; however, it cannot make the same prediction on admission.

Identification of magnetic resonance imaging features for the prediction of unrecognized atrial fibrillation in acute ischemic stroke.

Background and purposeThe early identification of cardioembolic stroke is critical for the early initiation of anticoagulant treatment. However, it can be challenging to identify the major cardiac source, particularly since the predominant source, paroxysmal atrial fibrillation (AF), may not be present at the time of stroke. In this study, we aimed to evaluate imaging predictors for unrecognized AF in patients with acute ischemic stroke.MethodsWe performed a cross-sectional analysis of data and magnetic resonance imaging (MRI) scans from two prospective cohorts of patients who underwent serial 12-lead electrocardiography and 24-h Holter monitoring to detect unrecognized AF. The imaging patterns in diffusion-weighted imaging and imaging characteristics were assessed and classified. A logistic regression model was used to identify predictive factors for newly detected AF in patients with acute ischemic stroke.ResultsA total of 734 patients were recruited for analysis, with a median age of 72 (interquartile range: 65–79) years and a median National Institutes of Health Stroke Scale score of 4 (interquartile range: 2–6). Of these patients, 64 (8.7%) had newly detected AF during the follow-up period. Stepwise multivariate logistic regression revealed that age ≥75 years [adjusted odds ratio (aOR) 5.66, 95% confidence interval (CI) 2.98–10.75], receiving recombinant tissue plasminogen activator treatment (aOR 4.36, 95% CI 1.65–11.54), congestive heart failure (aOR 6.73, 95% CI 1.85–24.48), early hemorrhage in MRI (aOR 3.62, 95% CI 1.52–8.61), single cortical infarct (aOR 6.49, 95% CI 2.35–17.92), and territorial infarcts (aOR 3.54, 95% CI 1.06–11.75) were associated with newly detected AF. The C-statistic of the prediction model for newly detected AF was 0.764.ConclusionInitial MRI at the time of stroke may be useful to predict which patients have cardioembolic stroke caused by unrecognized AF. Further studies are warranted to verify these findings and their application to high-risk patients.

Outcomes of asymptomatic recombinant tissue plasminogen activator associated intracranial hemorrhage.

Intracranial hemorrhage (ICH) is the most devastating complication of recombinant tissue plasminogen activator (rtPA) treatment in acute ischemic stroke patients. Data on rtPA-associated asymptomatic ICH (aICH) are limited. To determine the incidence, risk factors, characteristics, management, and clinical outcome of rtPA-associated aICH. The data were retrieved from the Chiang Mai University Hospital Stroke Registry between 1995 and 2019. Consecutive ischemic stroke patients were included if they were 18 or older and received rtPA. Study outcomes were the incidence and characteristics of aICH, management, 90-day modified Rankin scale (mRS), National Institute of Health Stroke Scale (NIHSS), Barthel index, and all-cause mortality. Of 725 rtPA treated patients, 166 (16.0%, 95% confidence interval [CI] 13.4-18.9) had aICH, 50 (6.9%, 95% CI 5.2-9.0) had symptomatic ICH (sICH). Patients with aICH had more hemorrhagic infarctions (HI) compared to sICH (81.9% vs 2.0%, P-value < 0.001). Fresh Frozen Plasma and cryoprecipitate were the most common blood products used to reverse the anticoagulant effect in sICH. Craniotomy was performed in 1% and 60% of patients who had aICH and sICH. At 90 days, patients who had aICH had poorer clinical outcomes (mRS, NIHSS and Barthel index) as compared to those without ICH. Compared to non-ICH patients, aICH patients were associated with increased risk of 90-day mortality, the hazard ratio (HR), 3.7, 95% CI 1.6-8.9. The rtPA-associated aICH increased the risk of morbidity and mortality outcomes. Further treatment consensus, guideline generation, or clinical trials focusing on the treatment of rtPA-associated aICH may be required.

The Sky's the Limit: Expanding Nursing's Contribution to Acute Stroke Science.

Stroke is the number one cause of preventable disability in adults in the United States. Significant advances have occurred in medications and technology supporting rapid stroke diagnosis and treatment during the past 30 years, along with blurring of the lines of what traditionally constituted nursing or medical research. Ischemic stroke is a disease of vascular insufficiency that mirrors myocardial infarction more than any other neurologic diagnosis. My primary program of research is focused on exploration of methods to improve intracranial blood flow in patients with hyperacute ischemic stroke who have viable, yet vulnerable, brain tissue to prevent worsening or enable improvement of stroke symptoms. I am also examining augmentation of recombinant tissue plasminogen activator treatment and stimulation of both arteriogenesis and angiogenesis with external counter-pulsation in patients with intracranial atherosclerosis. My secondary program of research focuses on methods to improve stroke systems of care, including improvement of advance practice providers' contributions to acute stroke care, use of innovative mobile stroke units, and improvement of quality core measure processes. Lessons learned along the way are highlighted, along with the value of interdisciplinary "team science" to build knowledge and enhance the care of highly vulnerable patients with acute stroke.

The Sky’s the Limit: Expanding Nursing’s Contribution to Acute Stroke Science

Stroke is the number one cause of preventable disability in adults in the United States. Significant advances have occurred in medications and technology supporting rapid stroke diagnosis and treatment during the past 30 years, along with blurring of the lines of what traditionally constituted nursing or medical research. Ischemic stroke is a disease of vascular insufficiency that mirrors myocardial infarction more than any other neurologic diagnosis. My primary program of research is focused on exploration of methods to improve intracranial blood flow in patients with hyperacute ischemic stroke who have viable, yet vulnerable, brain tissue to prevent worsening or enable improvement of stroke symptoms. I am also examining augmentation of recombinant tissue plasminogen activator treatment and stimulation of both arteriogenesis and angiogenesis with external counterpulsation in patients with intracranial atherosclerosis. My secondary program of research focuses on methods to improve stroke systems of care, including improvement of advance practice providers’ contributions to acute stroke care, use of innovative mobile stroke units, and improvement of quality core measure processes. Lessons learned along the way are highlighted, along with the value of interdisciplinary “team science” to build knowledge and enhance the care of highly vulnerable patients with acute stroke.