Hemorrhagic Transformation Research Articles

Endovascular Therapy in Large Core Ischemic Strokes: Real-World Indian Experience.

Large core acute ischemic strokes have predominantly been excluded from endovascular therapy (EVT) studies due to perceived higher risks of hemorrhage and poorer functional outcomes. However, recent randomized controlled trials (RCTs) indicate that EVT for large vessel occlusion (LVO) strokes improves functional outcomes compared to medical management alone, despite higher hemorrhagic transformation rates, with no corresponding increase in symptomatic intracerebral hemorrhage (sICH) rates. The real-world outcomes of this intervention in Indian patients remain underexplored. To evaluate the real-world outcomes of EVT for large core acute ischemic strokes with LVO in an Indian population. We conducted a single-center, retrospective observational study using a 7 years prospective database of EVT in anterior circulation stroke patients. Patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 3-5 were included. Clinical and radiologic data were analyzed, with the primary endpoint being 90-day modified Rankin scale (mRS) scores. Safety outcomes included rates of sICH and mortality. Descriptive statistical analysis was done using Microsoft Excel. The study included 25 patients who met the inclusion criteria. Mean age of patients was 52.9 ± 14.3 years, and there were 13 (52%) males. Median ASPECTS was 5 (interquartile range 4-5). Successful recanalization, classified by modified Thrombolysis in Cerebral Infarction score, was 92%. Good functional recovery, that is, 90-day mRS 0-3, was achieved in nine (36%) patients. Safety outcomes: sICH was seen in four (16%) and mortality was reported in nine (36%) patients. Our results reaffirm findings from RCTs, provide updated real-world evidence, and suggest that EVT is a viable option to be considered in selected patients with large core ischemic infarcts.

Predicting haemorrhagic transformation through serum biochemical indices for patients after endovascular treatment: a retrospective study.

The aim of this study was to determine the serum biochemical markers that can predict the risk of haemorrhagic transformation (HT) before and after endovascular treatment (EVT). This study included patients with anterior circulation large vessel occlusion (ACLVO) who underwent EVT within six hours of symptom onset between September 2017 and September 2022. These patients were retrospectively categorised into two groups: an HT group and a No-HT group. A total of 180 patients were included in the study, of whom 55 (30.6%) had HT. The monocyte count before EVT (p = = 0.005, OR = 0.694, 95% CI 0.536-0.898), the activated partial thromboplastin time before EVT (p = 0.009, OR = 0.186, 95% CI 0.699-0.952), and the eosinophil count after EVT (p = 0.038, OR = 0.001, 95% CI 0.000-0.018) were all found to be independent predictors of HT, with warning values of 6.65%, 22.95 seconds, and 0.035*10^9/L, respectively. When compared to prediction using only demographic data [AUC = 0.662,95% CI (0.545, 0.780)], adding biochemical indices before EVT [AUC = 0.719,95% CI (0.617, 0.821)], adding biochemical indices after EVT [AUC = 0.670,95% CI (0.566, 0.773)], and adding both [AUC = 0.778,95% CI (0.686, 0.870)], the prediction efficiency of HT was improved among all three combinations, with no statistical significance. The levels of serum biochemical markers were found to show significant changes before and after EVT in ACLVO patients. A combination of demographic data and serum biochemical markers proved to be effective in predicting the occurrence of HT in patients with ACLVO who underwent EVT.

Case Report: Tongue deviation due to supranuclear injury with a rare semiological feature

Abstract* Hypoglossal nerve injuries are classified according to their anatomical localization in: Infranuclear, nuclear, and supranuclear. Supranuclear injuries can occur in cerebral cortex, corticobulbar tracts, internal capsule, cerebral peduncles, or in the pons, and most often caused by a stroke. These lesions usually do not generate a significant alteration of tongue motility due to the bilateral innervation of both nuclei from the cortex. We present a case of a 43-year-old male with dysarthria, left central facial paralysis, and an important tongue palsy and deviation to the same side. Brain CT revealed a right frontotemporal stroke with little hemorrhagic transformation, and an EKG that showed auricular fibrillation. He received treatment with amiodarone and rivaroxaban was initiated when a second brain CT scan showed no evidence of hemorrhage. This case is remarkable due the unusual presentation in a supranuclear lesion of the hypoglossal nerve. It is important to enrich the semiology and consider the possibility of cortical cerebrovascular events in patients with acute deviation of the tongue, even in the absence of involvement of other cranial nerves; or marked ipsilateral motor implication.

Endovascular thrombectomy for treatment of isolated posterior cerebral artery occlusion: a real-world analysis of hospitalizations in the United States.

Despite renewed interest and recently demonstrated efficacy for endovascular thrombectomy (EVT) for treatment of acute ischemic stroke (AIS) of the posterior circulation, to date, no randomized clinical trials have been conducted to evaluate EVT for isolated occlusions of the posterior cerebral artery (IPCA). Hospitalizations for adult patients with primary admission diagnoses of IPCA occlusion were identified in the National Inpatient Sample registry during the period of 2016-2020. The study exposure was treatment with EVT, and primary clinical endpoints included favorable functional outcome (defined as discharge disposition to home without services, previously shown to have high concordance with modified Rankin scale scores 0-2), in-hospital mortality, and any intracranial hemorrhage (ICH). Inverse probability of treatment weighting (IPTW) was performed to balance baseline clinical characteristics between those receiving EVT or medical management (MM). This analysis identified 34,880 IPCA occlusion hospitalizations, 730 (2.1%) of which documented treatment with EVT. Following IPTW adjustment, EVT was associated with favorable outcome in IPCA patients presenting with mild deficits (M-D) (NIHSS < 6) [adjusted odds ratio (aOR) 2.36, 95% confidence interval (CI) 2.27, 2.45; p < 0.001] and in those presenting with moderate-to-severe deficits (M-S-D) (NIHSS 6-42) (aOR 2.00, 95% CI 1.86, 2.15; p < 0.001). Mortality rates did not differ among those with M-S-D [EVT 4.8% vs. MM 4.7%, p = 0.742], while ICH rates were lower. Retrospective analysis of a large administrative registry in the Unites States demonstrates an association of EVT with favorable outcomes following IPCA occlusion, without concomitant risk of hemorrhagic transformation or mortality.

Alleviating Recombinant Tissue Plasminogen Activator-induced Hemorrhagic Transformation in Ischemic Stroke via Targeted Delivery of a Ferroptosis Inhibitor.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood-brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin-1 (Lip) is proposed to alleviate the side effects. A well-designed macrocyclic carrier, glucose-modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke.

The utility of serum glucose potassium ratio as a predictive factor for haemorrhagic transformation, stroke recurrence, and mortality among ischemic stroke patients

Background and ObjectiveGlucose-Potassium Ratio (GPR) has emerged as a biomarker in several pathophysiological conditions. However, the association between GPR and long-term outcomes in stroke patients has not been investigated. Our study evaluated the applicability of baseline GPR as a predictive prognostic tool for clinical outcomes in ischemic stroke patients. MethodsThe multicenter retrospective cohort study included acute-subacute adult ischemic stroke patients who had their baseline serum GPR levels measured. Eligible patients were categorized into two sub-cohorts based on the baseline GPR levels (<1.67 vs. ≥ 1.67). The primary outcome was the incidence of 30-day hemorrhagic transformation, while stroke recurrence, and all-cause mortality within twelve months, were considered secondary. ResultsAmong 4083 patients screened, 1047 were included in the current study. In comparison with GPR < 1.67 group, patients with ≥ 1.67 GPR had a significantly higher ratio of all-cause mortality within twelve months (aHR 2.07 [95 % CI 1.21–3.75] p = 0.01), and higher ratio of 30-day hemorrhagic transformation but failed to reach the statistical significance (aHR 1.60 [95 % CI 0.95–2.79], p = 0.08). ConclusionOverall, baseline GPR serum is an independent predictor of all-cause mortality within twelve months in patients with acute and subacute ischemic stroke. Further clinical studies are necessary to validate these findings.

Combined intravenous and intra-arterial thrombolysis in hyperacute cerebral ischemia without significant corresponding vascular occlusion/stenosis: A Preliminary investigation

ObjectiveIn this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction. MethodsPatients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days. ResultsNinety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar (P > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P < 0.05). Asymptomatic hemorrhage rates were 8.7 % for the experimental group and 12.5 % for the control group, with no hemorrhage detected in other locations. Post-treatment median NIHSS scores were lower in the experimental group than in the control group (7 vs 9, P < 0.05), but short-term NIHSS scores were similar (P > 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P < 0.05). ConclusionIn patients with acute ischemic stroke with an onset time of ≤6 h and no major intracranial vessel occlusion, combining rt-PA intravenous thrombolysis with intra-arterial thrombolysis via a microcatheter might yield superior functional outcomes.

Đặc điểm vi xuất huyết não và nguy cơ chuyển dạng xuất huyết ở bệnh nhân nhồi máu não cấp có điều trị tái thông

Objective: Evaluate the characteristics of cerebral microbleeds and factors related to hemorrhagic transformation in patients with acute cerebral infarction undergoing revascularization treatment at University Medical Center, Ho Chi Minh City. Subjects and methods: Cross-sectional descriptive study combined with medical record monitoring on 79 patients diagnosed with acute cerebral infarction who were admitted and treated at the Department of Neurology, University Medical Center, Ho Chi Minh City. Results: Patients with microhemorrhage (VXH) accounted for 37.97%. The number of 1-4 VXH accounted for the highest rate of 31.65%, only 01 case had more than 10 VXH, accounting for 1.27% %. The location of social lesions is mainly in the deep brain area, accounting for 21.52%. There is an association between VXH and dyslipidemia with p = 0.16 (OR 4.12, CL 1.14-18.47), white matter pathology according to Fazekas classification with p = 0.041. The main complications of hemorrhagic transformation after revascularization are HI, accounting for 26.58%, followed by PH, accounting for 6.33%, and ICH+, accounting for 3.8%. There is an association between Glasgow scale (OR = 1.66, CI 0.79 - 3.51) with symptomatic ICH and PH with p &lt; 0.05. Found an association between NIHSS Scale and ICH with p = 0.037 (OR = 5.46 CI 1.10 – 19.00). There is not enough evidence to conclude about the relationship between the number and location of microbleeds and complications of hemorrhagic transformation after revascularization. Conclusion: VXH is not a factor to delay recanalization interventions in acute myocardial infarction patients with indications for intervention. Patients at high risk of multiple VHs should have an MRI scan before intervention.

Acupuncture Extended the Thrombolysis Window by Suppressing Blood-Brain Barrier Disruption and Regulating Autophagy-Apoptosis Balance after Ischemic Stroke.

Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. The narrow therapeutic window (within 4.5 h) and severe hemorrhagic potential limits therapeutic efficacy of recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) acupuncture is an integral part of traditional Chinese medicine, specifically designed to address acute ischemic stroke by targeting key acupoints such as Shuigou (GV26) and Neiguan (PC6). In this study, we explored the therapeutic potential of XNKQ acupuncture in extending the time window for thrombolysis and interrogated the molecular mechanisms responsible for this effect. The effect of extending the thrombolysis window by acupuncture was evaluated via TTC staining, neuronal score evaluation, hemorrhagic transformation assay, and H&E staining. RNA sequencing (RNA-seq) technology was performed to identify the therapeutic targets and intervention mechanisms of acupuncture. Evans blue staining and transmission electron microscopy were used to assess blood-brain barrier (BBB) integrity. Immunofluorescence staining and co-immunoprecipitation were performed to evaluate the level of autophagy and apoptosis and validate their interactions with BBB endothelial cells. Acupuncture alleviated infarction and neurological deficits and extended the thrombolysis window to 6 h. The RNA-seq revealed 16 potential therapeutic predictors for acupuncture intervention, which related to suppressing inflammation and restoring the function of BBB and blood vessels. Furthermore, acupuncture suppressed BBB leakage and preserved tight junction protein expression. The protective effect was associated with regulation of the autophagy-apoptosis balance in BBB endothelial cells. Acupuncture intervention dissociated the Beclin1/Bcl-2 complex, thereby promoting autophagy and reducing apoptosis. XNKQ acupuncture could serve as an adjunctive therapy for rt-PA thrombolysis, aiming to extend the therapeutic time window and mitigate ischemia-reperfusion injury. Acupuncture suppressed BBB disruption by regulating the autophagy-apoptosis balance, which in turn extended the therapeutic window of rt-PA in IS. These findings provide a rationale for further exploration of acupuncture as a complementary candidate co-administered with rt-PA.

The use of thromboaspiration and combined treatment in patients with ischemic stroke in real-life clinical practice

The effectiveness of staged reperfusion therapy in real clinical practice requires clarification. Objective: to evaluate the efficacy and safety of mechanical thromboextraction and staged reperfusion therapy with alteplase in real clinical practice. Material and methods. The study included 106 patients who were retrospectively divided into two groups: Group I underwent staged reperfusion therapy (intravenous thrombolysis with alteplase followed by aspiration thromboextraction), Group II underwent thromboaspiration only. The clinical and functional results, incidence of hemorrhagic transformation and mortality rate were compared. Results. The groups did not differ in terms of demographic data, cardiovascular risk factors or stroke severity. Group II patients were characterized by a longer delay in reperfusion therapy (225 minutes versus 180 minutes) and a lower score on the Alberta Stroke Programme Early CT score (ASPECTS; 8.8 points versus 9.3 points). There were no differences in National Institutes of Health Stroke Scale (NIHSS) scores at day 28, dynamics of NIHSS scores, Rankin scores at day 28, rates of hemorrhagic transformation or mortality. In both groups, the deceased patients were older; in Group I they suffered more frequently from atrial fibrillation, in Group II – from diabetes mellitus type 2. In addition, mortality in Group II was associated with a higher severity of early signs of cerebral infarction.Conclusion. The results of the analysis of real-life clinical practice show the comparability of the efficacy and safety of staged reperfusion therapy and isolated thromboaspiration in a “natural” selection of patients.

The role of blood protein biomarkers in acute ischemic stroke prognosis

BackgroundStroke is one of the most frequent causes of mortality and disability, blood protein biomarkers are used to determine patients at high risk for a severe illness and to estimate the outcome. This study aimed to detect the relation between serum levels of C-reactive protein, matrix metalloproteinase 9, S100 calcium-binding protein B, brain natriuretic peptide, D-dimer and stroke severity and outcome in acute ischemic stroke patients.ResultsOne hundred eighty-six patients with acute ischemic stroke participated and were subjected to complete general, neurological examination, assessment of stroke severity clinically and radiologically using National Institute of Health Stroke Scale (NIHSS), and Alberta Stroke Program Early CT (ASPECT) score and assessment of functional outcome using (modified Rankin Scale). C-reactive protein, matrix metalloproteinase 9, S100 calcium-binding protein B, brain natriuretic peptide and D-dimer were assessed. Higher C-reactive protein was found in patients with ASPECT score ≤ 7 and in patients with cerebral edema, seizures and was positively correlated with stroke severity according to NIHSS and modified Rankin Scale. C-reactive protein serum level at onset was negatively correlated with NIHSS at onset and is a significant predictor for mortality. D-dimer was negatively correlated with NIHSS. S100 calcium-binding protein B was significantly elevated in patients who developed hemorrhagic transformation.ConclusionsSerum C-reactive protein level can be used as a predictor for mortality and higher S100 calcium-binding protein B was detected in patients with hemorrhagic transformation.

Automatic segmentation of hemorrhagic transformation on follow-up non-contrast CT after acute ischemic stroke.

Hemorrhagic transformation (HT) following reperfusion therapies is a serious complication for patients with acute ischemic stroke. Segmentation and quantification of hemorrhage provides critical insights into patients' condition and aids in prognosis. This study aims to automatically segment hemorrhagic regions on follow-up non-contrast head CT (NCCT) for stroke patients treated with endovascular thrombectomy (EVT). Patient data were collected from 10 stroke centers across two countries. We propose a semi-automated approach with adaptive thresholding methods, eliminating the need for extensive training data and reducing computational demands. We used Dice Similarity Coefficient (DSC) and Lin's Concordance Correlation Coefficient (Lin's CCC) to evaluate the performance of the algorithm. A total of 51 patients were included, with 28 Type 2 hemorrhagic infarction (HI2) cases and 23 parenchymal hematoma (PH) cases. The algorithm achieved a mean DSC of 0.66 ± 0.17. Notably, performance was superior for PH cases (mean DSC of 0.73 ± 0.14) compared to HI2 cases (mean DSC of 0.61 ± 0.18). Lin's CCC was 0.88 (95% CI 0.79-0.93), indicating a strong agreement between the algorithm's results and the ground truth. In addition, the algorithm demonstrated excellent processing time, with an average of 2.7 s for each patient case. To our knowledge, this is the first study to perform automated segmentation of post-treatment hemorrhage for acute stroke patients and evaluate the performance based on the radiological severity of HT. This rapid and effective tool has the potential to assist with predicting prognosis in stroke patients with HT after EVT.

Primary intradural Extraosseous Ewing’s sarcoma of the cauda equina: A case report and literature review

Intradural Extraosseous Ewing sarcoma (IEES) is an infrequent occurrence. We report a case of a 66-year-old male who presented with a 2-month history of low back pain and bilateral S1 sciatica, with acute sphincter dysfunction. Imaging studies revealed an intradural extramedullary lesion in the cauda equina spanning from level L4 to S1. The patient underwent partial removal of the intradural lesion. Histopathological examination showed the presence of small round cells, which were consistent with Ewing Sarcoma. The patient was then treated with targeted radiation therapy and chemotherapy.The rarity of IEES in this specific location underscores the significance of evaluating and managing patients with intradural spinal tumors with careful consideration of this diagnosis. To further investigate this condition, we conducted a thorough review of the literature on IEES involving the lumbar spine and cauda equina. Our analysis revealed that patients with this condition frequently exhibit rapidly progressive neurological symptoms likely attributed to hemorrhagic transformation. This characteristic may serve as a distinguishing factor from other lesion types, particularly benign ones. Our study provides a comprehensive summary that can offer direction for clinical management in comparable uncommon and novel cases.

Incidence, Risk Factors, and Clinical Implications of Subarachnoid Hyperdensities on Flat-Panel Detector CT following Mechanical Thrombectomy in Patients with Anterior Circulation Acute Ischemic Stroke.

Flat-panel detector CT immediately after mechanical thrombectomy can detect complications, including early hemorrhagic transformation and subarachnoid hyperdensities. The clinical significance of subarachnoid hyperdensities in patients undergoing mechanical thrombectomy remains unclear. We studied 223 patients who underwent mechanical thrombectomy for anterior circulation stroke who had flat-panel detector CT performed immediately after the procedure and had follow-up imaging within 24 hours. Subarachnoid hyperdensity severity was categorized into 5 grades (subarachnoid hyperdensities, 0: absent to subarachnoid hyperdensities, IV: extensive). Baseline and procedural characteristics as well as outcome measures were analyzed using group comparisons and multivariable logistic regression analyses. Overall, 100/223 (45%) patients showed subarachnoid hyperdensities on immediate postinterventional flat-panel detector CT. The factors associated with an increased subarachnoid hyperdensity risk were the following: medium-vessel occlusion or distal-vessel occlusion compared with a large-vessel occlusion, a more distal device position, a higher number of device passes, a larger volume of contrast applied, worse final reperfusion expanded TICI, and after receiving IV thrombolysis. The occurrence of subarachnoid hyperdensity grades II-IV was independently associated with worse functional outcomes (adjusted OR for mRS, 3-6: 2.2; 95% CI 1.1-4.3), whereas patients with subarachnoid hyperdensity grade I had outcomes similar to those in patients without subarachnoid hyperdensities. Our study identified risk factors for subarachnoid hyperdensities, most of which reflect increasingly challenging procedures or more peripheral recanalization attempts. The presence of subarachnoid hyperdensity grades II-IV was associated with poorer outcomes, suggesting the need for personalized strategies to reduce its incidence and severity or potentially improve recovery after subarachnoid hyperdensities.

Role of the gut microbiota in complications after ischemic stroke.

Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction and communication between the intestines and the brain. Recent studies have reported alterations in gut microbiota diversity post-IS, suggesting the involvement of gut microbiota in post-IS complications through various mechanisms such as bacterial translocation, immune regulation, and production of gut bacterial metabolites, thereby affecting disease prognosis. In this review, to provide insights into the prevention and treatment of post-IS complications and improvement of the long-term prognosis of IS, we summarize the interaction between the gut microbiota and IS, along with the effects of the gut microbiota on post-IS complications.

Low blood flow ratio is associated with hemorrhagic transformation secondary to mechanical thrombectomy in patients with acute ischemic stroke

Background and purposeA significant decrease of cerebral blood flow (CBF) is a risk factor for hemorrhagic transformation (HT) in acute ischemic stroke (AIS). This study aimed to ascertain whether the ratio of different CBF thresholds derived from computed tomography perfusion (CTP) is an independent risk factor for HT after mechanical thrombectomy (MT). MethodsA retrospective single center cohort study was conducted on patients with AIS undergoing MT at the First Affiliated Hospital of Wenzhou Medical University from August 2018 to December 2023. The perfusion parameters before thrombectomy were obtained according to CTP automatic processing software. The low blood flow ratio (LFR) was defined as the ratio of brain volume with relative CBF <20 % over volume with relative CBF <30 %. HT was evaluated on the follow-up CT images. Binary logistic regression was used to analyze the correlation between parameters that differ between the two groups with regards to HT occurrence. The predictive efficacy was assessed utilizing the receiver operating characteristic curve. ResultsIn total, 243 patients met the inclusion criteria. During the follow-up, 46.5 % of the patients (113/243) developed HT. Compared with the Non-HT group, the HT group had a higher LFR (0.47 (0.34–0.65) vs. 0.32 (0.07–0.56); P < 0.001). According to the binary logistic regression analysis, the LFR (aOR: 6.737; 95 % CI: 1.994–22.758; P = 0.002), Hypertension history (aOR: 2.231; 95 % CI: 1.201–4.142; P = 0.011), plasma FIB levels before MT (aOR: 0.641; 95 % CI: 0.456–0.902; P = 0.011), and the mismatch ratio (aOR: 0.990; 95 % CI: 0.980–0.999; P = 0.030) were independently associated with HT secondary to MT. The area under the curve of the regression model for predicting HT was 0.741. ConclusionLFR, a ratio quantified via CTP, demonstrates potential as an independent risk factor of HT secondary to MT.

MMP-9 release into collateral blood vessels before endovascular thrombectomy to assess the risk of major intracerebral haemorrhages and poor outcome for acute ischaemic stroke: a proof-of-concept study

Matrix metalloproteinases (MMPs) are implied in blood-brain barrier degradation and haemorrhagic transformation following ischaemic stroke, but their local relevance in the hyperacute disease phase is unknown. We aimed to examine ultra-early MMP-9 and MMP-2 release into collateral blood vessels, and to assess its prognostic value before therapeutic recanalisation by endovascular thrombectomy (EVT). We report a cross-sectional proof-of-concept study including patients undergoing EVT for large-vessel ischaemic stroke at the University Hospital Würzburg, Germany. We obtained liquid biopsies from the collateral circulation before recanalisation, and systemic control samples. Laboratory workup included quantification of MMP-9 and MMP-2 plasma concentrations by cytometric bead array, immunohistochemical analyses of cellular MMP-9 and MMP-2 expression, and detection of proteolytic activity by gelatine zymography. The clinical impact of MMP concentrations was assessed by stratification according to intracranial haemorrhagic lesions on postinterventional computed tomography (Heidelberg Bleeding Classification, HBC) and early functional outcome (modified Rankin Scale, mRS). We used multivariable logistic regression, receiver-operating-characteristic (ROC) curves, and fixed-level estimates of test accuracy measures to study the prognostic value of MMP-9 concentrations. Between August 3, 2018, and September 16, 2021, 264 matched samples from 132 patients (86 [65.2%] women, 46 [34.8%] men, aged 40-94 years) were obtained. Median (interquartile range, IQR) MMP-9 (279.7 [IQR 126.4-569.6] vs 441 [IQR 223.4-731.5] ng/ml, p<0.0001) but not MMP-2 concentrations were increased within collateral blood vessels. The median MMP-9 expression level of invading neutrophils was elevated (fluorescence intensity, arbitrary unit: 2276 [IQR 1007-5086] vs 3078 [IQR 1108-7963], p=0.0018). Gelatine zymography experiments indicated the locally confined proteolytic activity of MMP-9 but not of MMP-2. Pretherapeutic MMP-9 release into stroke-affected brain regions predicted the degree of intracerebral haemorrhages and clinical stroke severity after recanalisation, and independently increased the odds of space-occupying parenchymal haematomas (HBC1c-3a) by 1.54 times, and the odds of severe disability or death (mRS ≥5at hospital discharge) by 2.33 times per 1000ng/ml increase. Excessive concentrations of MMP-9 indicated impending parenchymal haematomas and severe disability or death with high specificity. Measurement of MMP-9 within collateral blood vessels is feasible and identifies patients with stroke at risk of major intracerebral haemorrhages and poor outcome before therapeutic recanalisation by EVT, thereby providing evidence of the concept validity of ultra-early local stroke biomarkers. This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the Interdisciplinary Centre for Clinical Research (IZKF) at the University of Würzburg.

Mechanism of microRNA regulating apoptosis after reperfusion in patients with mechanical thrombectomy.

Stroke is the second leading cause of death worldwide. Understanding of gene expression dynamics could bring new approaches in diagnostics and therapy of stroke. Small noncoding molecules termed 'microRNA' represent the most flexible network of gene expression regulators. To screen out miRNAs that are mainly regulated during reperfusion in mechanically embolized patients, and study their mechanisms of action in reperfusion injury after thrombectomy, in order to find new therapeutic targets for mechanically embolized patients. Serums from 30 patients with moderate to severe stroke after mechanical thrombectomy (MT) were collected to measure miRNA expressions. Clinical information of patients was analyze, and patients were divided into poor prognosis and good prognosis. Factors affecting prognosis was classified, and independent risk factors for poor prognosis were determined. Prognostic value of National Institutes of Health Stroke Scale (NIHSS) score on admission to patients with MT was assessed. ROC (receiver operating characteristic) curves were drawn, and Kaplan-Merier method determined whether different NIHSS scores at admission had any difference in the in-hospital survival rate of consistency index/random consistency index (CI/RI) patients treated with MT. An oxygen-glucose deprivation/reperfusion (OGD/R) cell model and an middle cerebral artery occlusion (MCAO)/reperfusion mouse model were established, in which miR-298 expression was tested. In OGD/R cells, proliferation, apoptosis, and autophagy were assessed after intervention with miR-298 and/or autophagy related gene 5 (ATG5). In MCAO mice, the infarct area was calculated, and neurological function was assessed. The relationship between miR-298 and ATG5 was explored and validated. Age, diabetes, hypertension, hemorrhage transformation, NIHSS score at admission, leukocyte, neutrophil count and neutrophil to lymphocyte ratio (NLR) level were associated with patient's prognosis. Diabetes, NIHSS score at admission, and hemorrhagic transformation were independent risk factors for predicting poor prognosis in patients treated with MT. NIHSS score on admission had a predictive value on patient's prognosis. miR-298 was upregulated in acute cerebral ischemia patients with MT (p<0.05), especially in those with poor prognosis. miR-298 was elevated in both cell and mouse models (p<0.05). Apoptosis and autophagy of cells were weakened after miR-298 knockdown, and infarction in the mouse brain tissues was reduced. ATG5 was a target of miR-298. Overexpressing ATG5 rescued miR-298-induced apoptosis and autophagy. In conclusion: regulation of miR-298 and ATG5 attenuates neuronal apoptosis and autophagy, providing a new strategy for brain injury after reperfusion in patients with MT.

391 Intraarterial Verapamil for Neuroprotection in Ischemic Stroke

INTRODUCTION: Verapamil is an FDA-approved calcium channel blocker administered for the standard-of-care treatment of vasospasm. Preclinical studies have shown that verapamil reduces inflammation and protects penumbra neurons from further damage and eventual death. METHODS: Patients were recruited based on inclusion and exclusion criteria in a clinical protocol reviewed and approved by two institutional review boards. The final cohort comprised 42 emergency care patients with an acute onset focal neurological deficit consistent with ischemic stroke and/or a computed tomographic scan consistent with acute cerebral ischemia. All patients were 18 years of age or older that presented within 24 hours of symptom onset and had a significant but not severe neurological deficit, measured by a National Institutes of Health Stroke Scale (NIHSS) score greater than four but less than 22. All patients received a mechanical thrombectomy intervention after identifying a large vessel occlusion (LVO). RESULTS: The Verapamil-treated group (N = 23) included 22 patients with middle cerebral artery (MCA) occlusions and 1 with a basilar posterior cerebral artery (PCA) occlusion. In these patients, investigators administered 10 mg of Verapamil intraarterially following mechanical thrombectomy. Patients exposed to control conditions (N = 19) were matched for age, biological sex, admission NIHSS score, occlusion location, administration of tPA, and achieved TICI score. Intraarterial Verapamil treatment did not significantly increase sICH, hemorrhagic transformation, or death compared to standard of care treatment, demonstrating safety in an acute ischemic stroke patient population. Verapamil treatment was associated with significantly greater changes in mRS score, improved recovery time, and shortened length of hospital stay compared to standard-of-care treatment. CONCLUSIONS: This study suggests that verapamil is a safe and effective neuroprotective drug in ischemic stroke clinical populations that require mechanical thrombectomy for treatment.

Hemorrhagic transformation after acute ischemic stroke thrombolysis treatment: navigating the landscape of hemostasis genetic risk factors

Hemorrhagic transformation after acute ischemic stroke thrombolysis treatment: navigating the landscape of hemostasis genetic risk factors