Therapy In Acute Ischemic Stroke Patients Research Articles

Prospective randomized controlled trial on the safety and neuroprotective efficacy of remote administration of hypothermia over spleen during acute ischemic stroke with mechanical thrombectomy: rationale, design, and protocol.

Brain inflammation plays a key role in ischemia/reperfusion (I/R) injury and is the main cause of "ineffective or futile recanalization" after successful mechanical thrombectomy (MT) in acute ischemic stroke (AIS). One of the primary sources of inflammatory cells after AIS are derived from the spleen. As an innovative and potential neuroprotective strategy after stroke, Remote Administration of Hypothermia (RAH) temporarily suppresses immune activities in the spleen, reduces the release of inflammatory cells and cytokines into blood, and thus reversibly diminishes inflammatory injury in the brain. This single-center, prospective, randomized controlled study (RCT) is proposed for AIS patients with anterior circulation large vessel occlusion (LVO). Subjects will be randomly assigned to either the control or intervention groups in a 1:1 ratio (n = 40). Participants allocated to the intervention group will receive RAH on the abdomen above the spleen prior to recanalization until 6 h after thrombectomy. All enrolled patients will receive standard stroke Guideline care. The main adverse events associated with RAH are focal cold intolerance and abdominal pain. The primary outcome will assess safety as it pertains to RAH application. The secondary outcomes include the efficacy of RAH on spleen, determined by spleen volumes, blood inflammatory factor (cells and cytokines), and on brain injury, determined by infarction volumes and poststroke functional outcomes. This study aims to examine the safety and preliminary effectiveness of RAH over the spleen during endovascular therapy in AIS patients. The results of this study are expected to facilitate larger randomized clinical trials and hopefully prove RAH administration confers adjuvant neuroprotective properties in AIS treated with MT. https://www.chictr.org.cn/. Identifier ChiCTR 2300077052.

Delipid extracorporeal lipoprotein filter from plasma system: a new intensive lipid lowering therapy for patients with acute ischemic stroke.

To investigate the safety and efficacy of the delipid extracorporeal lipoprotein filter from plasma (DELP) system, a new low-density lipoprotein cholesterol (LDL-C) adsorption system, in acute ischemic stroke (AIS) patients. In the present study, a total of 180 AIS patients were enrolled during March 2019 to February 2021. They were divided into DELP group (n1 = 90) and the control group (n2 = 90). The treatment protocol and vascular access of DELP treatment was established and evaluated. For the DELP group, clinical data and laboratory results including plasma lipid and safety parameters before and after the apheresis were collected and analyzed. For all participants, neurological scores were assessed and recorded. For the DELP group, 90 patients including 70 males and 20 females were included. The mean LDL-C was significantly decreased from 3.15 ± 0.80 mmol/L to 2.18 ± 0.63 mmol/L (30.79%, p < 0.001) during a single DELP treatment, and decreased from 3.42 ± 0.87 mmol/L to 1.87 ± 0.48 mmol/L (45.32%, p < 0.001) after two DELP treatments. No clinically relevant changes were observed in hematologic safety parameters and blood pressure levels except for hematocrit and total protein throughout the whole period of DELP treatment. The DELP group showed improvement relative to the control group in National Institute of Health stroke scale scores (NIHSS) on the 14th and 90th day after stroke. Moreover, the DELP group had a significantly higher ratio of mRS 0 to 1 on the 90th day after stroke. The new LDL-C adsorption system, the DELP system, may provide a new option for intensive lipid lowering therapy in AIS patients in view of its safety, efficacy, and operation feasibility.

Development and validation of outcome prediction model for reperfusion therapy in acute ischemic stroke using nomogram and machine learning.

To develop logistic regression nomogram and machine learning (ML)-based models to predict 3-month unfavorable functional outcome for acute ischemic stroke (AIS) patients undergoing reperfusion therapy. Patients undergoing reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) were prospectively recruited. Unfavorable outcome was defined as 3-month modified Rankin Scale (mRS) score 3-6. The independent risk factors associated with unfavorable outcome were obtained by regression analysis and included in the prediction model. The performance of nomogram was assessed by the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). ML models were compared with nomogram using AUC; the generalizability of all models was ascertained in an external cohort. A total of 505 patients were enrolled, with 256 in the model construction, and 249 in the external validation. Five variables were identified as prognostic factors: baseline NIHSS, D-dimer level, random blood glucose (RBG), blood urea nitrogen (BUN), and systolic blood pressure (SBP) before reperfusion. The AUC values of nomogram were 0.865, 0.818, and 0.779 in the training set, test set, and external validation, respectively. The calibration curve and DCA indicated appreciable reliability and good net benefits. The best three ML models were extra trees (ET), CatBoost, and random forest (RF) models; all of them showed favorable discrimination in the training cohort, and confirmed in the test and external sets. Baseline NIHSS, D-dimer, RBG, BUN, and SBP before reperfusion were independent predictors for 3-month unfavorable outcome after reperfusion therapy in AIS patients. Both nomogram and ML models showed good discrimination and generalizability.

A multicenter, prospective, randomized controlled trial of intracranial hemorrhage risk of intensive statin therapy in patients with acute ischemic stroke combined with cerebral microbleeds (CHRISTMAS): Study protocol.

Low serum levels of major lipid markers have been proved to be significantly associated with increased risks of hemorrhagic stroke (HS) and cerebral microbleeds (CMBs). However, there is no lipid modification guideline telling us how to maintain a balance between the prevention of ischemic stroke recurrence and the prevention of hemorrhagic events, especially in patients with acute ischemic stroke (AIS) and CMBs. The Intracranial Hemorrhage Risk of Intensive Statin Therapy in Patients with Acute Ischemic Stroke combined with Cerebral Microbleeds (CHRISTMAS) trial evaluates the risk of intracranial hemorrhage (i.e., HS and CMBs) of high-dose statin therapy in patients with AIS combined with CMBs. This is an investigator-initiated, multicenter, prospective, randomized controlled clinical trial design. Up to 344 eligible patients will be consecutively randomized to receive high-dose or low-dose atorvastatin in 1:1 ratio in 5 stroke centers in China. CHRISTMAS trial has co-primary outcomes, namely, hemorrhage risk: the incidence of HS and the changes in degree of CMBs until the end of 36-month follow-up. The primary hypothesis of this study is that an excessive reduction in serum lipid levels by an intensive statin therapy in AIS patients with CMBs can increase the risk of intracranial hemorrhage. This study will shed light on new clinical decisions regarding the long-term serum lipid management in these patients with dilemma in clinical practice. Clinicaltrials.gov, identifier: NCT05589454.

Treatment of acute ischemic stroke in patients with active malignancy: insight from a comprehensive stroke center.

Despite the high incidence of acute ischemic stroke (AIS) in cancer patients, there is still no consensus about the safety of recanalization therapies in this cohort. In this observational study, our aim was to investigate the bleeding risk after acute recanalization therapy in AIS patients with active malignancy. We retrospectively analyzed observational data of 1016 AIS patients who received intravenous thrombolysis with rtPA (IVT) and/or endovascular therapy (EVT) between January 2017 and December 2020 with a focus on patients with active malignancy. The primary safety endpoint was the occurrence of stroke treatment-related major bleeding events, that is, symptomatic intracranial hemorrhage (SICH) and/or relevant systemic bleeding. The primary efficacy endpoint was neurological improvement during hospital stay (NI). None of the 79 AIS patients with active malignancy suffered from stroke treatment-related systemic bleeding. The increased rate (7.6% versus 4.7%) of SICH after therapy compared to the control group was explained by confounding factors. A total of nine patients with cerebral tumor manifestation received acute stroke therapy, two of them suffered from stroke treatment-related intracranial hemorrhage remote from the tumor, both asymptomatic. The group of patients with active malignancy and the control group showed comparable rates of NI. Recanalization therapy in AIS patients with active malignancy was not associated with a higher risk for stroke treatment-related systemic or intracranial bleeding. IVT and/or EVT can be regarded as a safe therapy option for AIS patients with active malignancy.

A Novel Nomogram for Predicting Prognosis after Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

Mounting evidence has shown that mechanical thrombectomy (MT) improves clinical outcomes for large vessel occlusions (LVOs) in patients with acute ischemic stroke (AIS) of the anterior circulation. The present study aimed to provide a comprehensive analysis of risk factors associated with clinical outcomes in AIS patients receiving MT. A total of 212 consecutive patients who underwent MT for AIS were enrolled in the present study. Clinical characteristics were recorded at admission. Two endpoints were defined according to the 3-month modified Rankin scale (mRS) score after AIS (good outcome, mRS 0-2; and death, mRS 6). Additionally, we compared the clinical outcomes and safety of MT alone and bridging therapy in AIS patients. Of the 212 patients treated with MT, 114 (53.77%) patients had a good outcome and 31 (14.62%) died. The incidence of a worse outcome after MT was significantly elevated in males and patients with high WBC counts, high admission blood glucose levels, high baseline NIHSS scores and a long interval time from groin puncture to reperfusion in AIS patients treated with MT after adjustment for covariates (P<0.05); these risk factors were further confirmed by our constructed nomograms. In addition, we observed no significant benefit of bridging therapy compared to MT alone in AIS patients. Our constructed nomogram based on male sex, admission WBC, admission blood glucose, NIHSS, and the interval time from groin puncture to reperfusion predicts prognosis after mechanical thrombectomy in patients with acute ischemic stroke.

Prognostic value of neutrophil to lymphocyte ratio in acute ischemic stroke after reperfusion therapy

The purpose of this study was to investigate whether baseline neutrophil to lymphocyte ratio (NLR) was an independent predictor for early symptomatic intracranial hemorrhage (sICH), poor functional outcome and mortality at 3 months after reperfusion therapy in acute ischemic stroke (AIS) patients. Using PubMed and EMBASE, we searched for literature published before January 19th, 2019. Two reviewers independently confirmed each study’s eligibility, assessed risk of bias, and extracted data. One reviewer combined studies using random effects meta-analysis. 9 studies with 3651 patients were pooled in the meta-analysis. Overall, baseline NLR levels were greater in patients with poor outcome. The standardized mean difference (SMD) in the NLR levels between patients with poor functional outcome (mRS > 2) and good functional outcome (mRS ≤ 2) was 0.54 units (95% credible interval [CI] [0.38, 0.70]). Heterogeneity test showed that there were significant differences between individual studies (p = 0.02; I2 = 72.8%). The NLR levels were associated with sICH in four included studies (n = 2003, SMD = 0.78, 95% [CI] [0.18, 1.38], I2 = 73.9%). Higher NLR levels were positively correlated with 3-month mortality (n = 1389, ES = 1.71, 95% CI [1.01,2.42], p < 0.01, I2 = 0%) when data were used as categorical variables. Our meta-analysis suggests that increased NLR levels are positively associated with greater risk of sICH, 3-month poor functional outcome and 3-month mortality in AIS patients undergoing reperfusion treatments. Although there are some deficits in this study, it may be feasible to predict the prognosis of reperfusion therapy in AIS patients with NLR levels.

Remote Ischemic Conditioning as an Additional Treatment for Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is the leading cause of disability in adults worldwide and has the second highest mortality of all cardiovascular diseases[1]. The burden of stroke is likely to increase significantly during the next decades, primarily due to population growth and aging[2]. Given the detrimental impact of stroke on healthcare (costs) and patient well-being, it is imperative to explore opportunities for novel therapies to add to the current treatment to further minimize neurological injury. During an ischemic stroke, occlusion of a cerebral artery abrogates cerebral perfusion, causing brain tissue distal from the occlusion to become deprived of oxygen and nutrients, ultimately leading to ischemic injury. Surrounding the ischemic core an area called the penumbra contains potentially reversible injured brain tissue, which may remain viable for several hours. Whilst the time window to attenuate the detrimental impact of an ischemic stroke seems limited to six hours after onset of AIS[3, 4], recent research suggests that subgroups may benefit up to 24 hours[5, 6]. This time window of 6-24 hours offers perspective for hospital-based, additional therapies to reduce ischemic injury and minimize clinical deterioration in AIS patients. This review focuses on remote ischemic conditioning (RIC) as an additive therapy to improve clinical outcomes in AIS patients, both when applied as a single as well as repeated bouts. RIC refers to the application of several cycles of brief ischemia and reperfusion to a limb (using a blood pressure cuff). Pre-clinical work revealed this stimulus to reduce neural damage after reperfusion[7-11], validating the concept that RIC may have clinical potential in AIS. RIC therefore represents a simple, low cost therapeutic strategy that may salvage brain tissue in the penumbral area. In this review, we will summarize (pre)clinical evidence for the efficacy of RIC as an additional therapy in AIS patients.

Abstract TMP17: Safety of Thrombolysis for Acute Ischemic Stroke in Patients with Recent Stroke

Background: The safety of intravenous tissue plasminogen activator (IV-tPA) is uncertain in acute ischemic stroke patients (AIS) with recent stroke because these patients were generally excluded from randomized stroke trials evaluating IV-tPA. We aimed to determine whether history of stroke within the previous 3 months is associated with an increased risk of intracerebral hemorrhage (ICH) or death after thrombolysis for AIS. Methods: Using previously validated ICD-9-CM codes, we retrospectively analyzed all adult patients with AIS who received IV-tPA in nonfederal EDs or acute care hospitals in CA, FL, and NY from 2005-2013. The primary outcome was the development of ICH (ICD-9-CM code 431) during index hospitalization for AIS. The secondary outcome was inpatient death. Logistic regression was used to compare the rate of ICH and death in patients with previous ischemic stroke within 3 months of IV-tPA therapy for AIS to all other patients treated with IV-tPA for AIS. Results: We identified 34,461 AIS patients treated with IV-tPA, including 454 with prior ischemic stroke in the past 3 months. Patients with recent stroke were on average younger and had more vascular risk factors and Elixhauser comorbidities than patients without recent stroke. The ICH rate after IV-tPA was similar in patients with AIS within the previous 3 months (6.6%, 95% CI 6.3-6.8) compared to patients without recent AIS (6.8%, 95% CI 4.5–9.1), but the rate of death was higher in those with AIS within the previous 3 months (16.5%, 95% CI 13.1-19.9 vs. 11.1%, 95% CI 10.7-11.4, p&lt;0.001). After adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index, the risk of ICH following IV-rPA in patients with AIS in the previous 3 months was not different from those without recent AIS (OR=1.0, 95% CI 0.7-1.5, p=0.90), although the risk of death remained higher in patients with AIS in the previous 3 months (OR=1.6, 95% CI 1.2-2.1, p&lt;0.001). Our results were unchanged in sensitivity analyses excluding patients with other approved indications for thrombolysis (e.g., MI, PE, and hemodialysis). Conclusions: In a large, multistate cohort, prior stroke within 3 months of receiving IV-tPA for AIS was not associated with an increased risk of ICH but was associated with a higher risk of death.

The Role of Circulating Platelets Microparticles and Platelet Parameters in Acute Ischemic Stroke Patients

Platelet activation and aggregation are critical in the pathogenesis of acute ischemic stroke (AIS). Circulating platelet microparticles (PMPs) and platelet parameters are biologic markers of platelet function in AIS patients; however, their associations with stroke subtypes and infarct volume remain unknown. We recruited 112 AIS patients including large-artery atherosclerosis (LAA) and small-artery occlusion [SAO] subtypes and 35 controls in this study. Blood samples were collected at admission and after antiplatelet therapy. The levels of circulating PMPs and platelet parameters (mean platelet volume [MPV], platelet count, plateletocrit, and platelet distribution width) were determined by flow cytometry and hematology analysis, respectively. Infarct volume was examined at admission by magnetic resonance imaging. (1) The levels of circulating PMPs and MPV were significantly elevated in AIS patients compared with healthy controls; (2) the level of circulating PMPs, but not platelet parameters, was decreased after antiplatelet therapy in AIS patients; (3) the infarct volume in LAA subtype was larger than that in SAO subtype. Notably, circulating PMP level was positively correlated with the infarct volume in LAA subtype. No association with infarct volume in either AIS subtype was observed for platelet parameters; and (4) according to the regression analysis, circulating PMP was an independent risk factor for the infarct volume in pooled AIS patients after adjustments of other impact factors (hypertension and diabetes). Our results suggest that circulating PMP level is associated with cerebral injury of AIS, which offers a novel evaluation parameter for AIS patients.

Abstract T P56: The Safety of Clopidogrel Loading Therapy in Acute Ischemic Stroke Patients with Chronic Hemorrhage on Gradient Echo MRI

Objective: To determine if an acute loading dose of clopidogrel is safe in acute ischemic stroke (AIS) patients with chronic intracerebral hemorrhage (ICH). Background: Clopidogrel loading is a promising therapy for AIS patients not eligible for tissue plasminogen activator (tPA) who are at risk for progressive stroke. Previous ICH is a risk factor for developing a new ICH. However, the acute risk of these events in this population after loading with clopidogrel has not been studied. Methods: We examined 1,011 AIS patients presenting to our center from 06/07/07-07/31/13. Only those loaded with at least 300mg of clopidogrel (with or without aspirin) within 6 hours of admission were analyzed. We compared new onset hemorrhagic complications in patients with and without chronic ICH, defined as areas of parenchymal hypodensity on gradient recall echo (GRE) sequencing on MRI. Repeat CT or MRI during admission was evaluated by a vascular neurologist for evidence of new ICH, hemorrhagic infarct using ECASS II criteria, or new ischemic infarct. Results: Of 365 AIS patients loaded with clopidogrel, 67 had chronic ICH on GRE. Patients with chronic ICH were more likely to be African American (80.0% vs. 65.9%, p=0.028) and male (69.2% vs. 50.9%, p=0.008). These patients were more likely to have existing comorbidities: history of stroke (67.7% vs 37.5%, p&lt;0.001), hypertension (90.8% vs 78.2%, p=0.021), and hyperlipidemia (56.9% vs 42.5%, p=0.036). After logistic regression analysis adjusting for significant covariates, chronic ICH patients did not have significant differences in any new hemorrhagic changes (p=0.709), new infarct (p=0.429), neuroworsening (defined as an increase in NIHSS score by 2 points within 24 hours, p=0.297), poor functional outcome (defined as modifed Rankin Scale &gt; 2 on discharge, p=0.889), or unfavorable discharge disposition (defined as disposition other than home or inpatient rehabilitation, p=0.166). Conclusion: The presence of chronic ICH on GRE did not increase the risk of new ICH, hemorrhagic infarct, ischemic event, or neurologic deterioration after administration of an acute loading dose of clopidogrel for AIS.