Hemorrhagic Transformation Research Articles

Analysis of predictors of hemorrhagic transformation after reperfusion therapy with recombinant tissue plasminogen activator in patients with acute ischemic stroke: a single-center experience

BackgroundHemorrhagic transformation (HT) is a serious complication of thrombolytic therapy for acute ischemic stroke, limiting its indications and affecting treatment plans and clinical prognosis. Identifying risk factors for HT could help improve the risk–benefit ratio of thrombolytic therapy. We aimed to analyze the predictors of HT after reperfusion therapy with recombinant tissue plasminogen activator (rTPA) in patients with acute ischemic stroke. This study included 115 patients who received rTPA. All patients underwent history taking, clinical examination, neurological examination including Glasgow Coma Scale and National Institutes of Health Stroke Scale scores (NIHSS), radiological investigation, and cardiac investigation. Patients were followed up strictly every 2 h for 1st 24 h then for two weeks clinically using the NIHSS and radiologically using CT or MRI to detect HT.ResultsPatients with HT represented 21.7% of all patients receiving rTPA, while symptomatic intracranial hemorrhage (sICH) represented 6.9%. Patients with HT had significantly higher blood pressure, respiratory rate, atrial fibrillation rate, NIHSS score, INR, prothrombin time, neutrophil-to-lymphocyte ratio (NLR), and lower platelet count, LDL level, higher Fazekas score, lower ASPECT score, and prolonged onset-to-needle time.ConclusionPredicting HT in acute ischemic stroke patients is crucial for optimizing management and potentially improving outcomes. In our study, six predictors were associated with HT: higher respiratory rate, higher atrial fibrillation rate, higher NLR, lower LDL level, higher Fazekas score, lower ASPECT score, and onset-to-needle time greater than 180 min.

Constructing machine learning models based on non-contrast CT radiomics to predict hemorrhagic transformation after stoke: a two-center study.

Machine learning (ML) models were constructed according to non-contrast computed tomography (NCCT) images as well as clinical and laboratory information to assess risk stratification for the occurrence of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. A retrospective cohort was constructed with 180 AIS patients who were diagnosed at two centers between January 2019 and October 2023 and were followed for HT outcomes. Patients were analyzed for clinical risk factors for developing HT, infarct texture features were extracted from NCCT images, and the radiomics score (Rad-score) was calculated. Then, five ML models were established and evaluated, and the optimal ML algorithm was used to construct the clinical, radiomics, and clinical-radiomics models. Receiver operating characteristic (ROC) curves were used to compare the performance of the three models in predicting HT. Based on the outcomes of the AIS patients, 104 developed HT, and the remaining 76 had no HT. The HT group consisted of 27 hemorrhagic infarction (HI) and 77 parenchymal-hemorrhage (PH). Patients with HT had a greater neutrophil-to-lymphocyte ratio (NLR), baseline National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and Rad-score and lower Alberta stroke program early CT score (ASPECTS) (all p < 0.01) than patients without HT. The best ML algorithm for building the model was logistic regression. In the training and validation cohorts, the AUC values for the clinical, radiomics, and clinical-radiomics models for predicting HT were 0.829 and 0.876, 0.813 and 0.898, and 0.876 and 0.957, respectively. In subgroup analyses with different treatment modalities, different infarct sizes, and different stroke time windows, the assessment accuracy of the clinical-radiomics model was not statistically meaningful (all p > 0.05), with an overall accuracy of 79.5%. Moreover, this model performed reliably in predicting the PH and HI subcategories, with accuracies of 82.9 and 92.9%, respectively. ML models based on clinical and NCCT radiomics characteristics can be used for early risk evaluation of HT development in AIS patients and show great potential for clinical precision in treatment and prognostic assessment.

Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio and Platelet-to-Lymphocyte Ratio as Predictors of Short- and Long-Term Outcomes in Ischemic Stroke Patients with Atrial Fibrillation.

Inflammatory response plays essential roles in the pathophysiology of both ischemic stroke and atrial fibrillation (AF). We aimed to investigate whether composite inflammatory markers, including neutrophil to lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR), can serve as early predictors of short- and long-term outcomes in ischemic stroke patients with AF. Ischemic stroke patients with AF were enrolled in this cohort study. The primary outcome was 1-year functional dependence or death (modified Rankin scale (mRS) score 3-6). Secondary outcomes included hemorrhagic transformation (HT) and early neurological deterioration (END, increase in the National Institutes of Health Stroke Scale (NIHSS) ≥4 within 7 days). Partial correlations were performed to assess the correlation between systemic inflammation markers and admission NIHSS scores. Univariate and multivariate logistic analyses were performed to investigate whether systemic inflammatory markers were independent predictors of adverse outcomes. A total of 408 patients were included. Partial correlation analysis revealed statistically significant but weak correlations between the NLR (r = 0.287; P < 0.001), PLR (r = 0.158; P = 0.001) and admission NIHSS score. Compared with patients without HT or END, patients who developed HT or END had higher NLR and PLR, and lower LMR. Patients in the functional dependence or death group had significantly higher NLR and PLR, and lower LMR than those in the functional independence group (all P < 0.001). Multivariate logistic analysis indicated that NLR, LMR and PLR were independent predictors of HT (OR = 1.069, 0.814 and 1.003, respectively), END (OR = 1.100, 0.768 and 1.006, respectively) and adverse 1-year functional outcome (OR = 1.139, 0.760 and 1.005, respectively). NLR, LMR and PLR were independent predictors for in-hospital HT, END and long-term functional outcome in ischemic stroke patients with AF. Close monitoring of these inflammatory markers may help guide risk stratification and clinical treatment strategies.

Characteristics and outcomes of atrial fibrillation detected before and after acute ischemic stroke.

Atrial fibrillation (AF) can be known before the stroke (KAF) or be newly detected after stroke (AFDAS). It is unknown whether the outcome of stroke differs between KAF and AFDAS. We performed a propensity-matched analysis to investigate the outcome of patients with AFDAS and their counterparts with KAF. We analysed a consecutive series of patients enrolled into the EIDASAF study, a single centre, retrospective study of ischemic stroke patients with a diagnosis of AF before or after the event who had been admitted to the Hyperacute Stroke Unit of Imperial College Healthcare NHS Trust between 2010 and 2017. Overall, our cohort included 959 patients with AF and acute ischemic stroke. After propensity score matching, 547 patients were matched (404 KAF group and 143 AFDAS group). The rates of in hospital death and of haemorrhagic transformation were significantly higher in KAF patients compared to AFDAS patients. Logistic regression analysis did not reveal a statistically significant influence of AF subtypes on the outcome of death. However, in logistic regression analysis KAF was associated with increased probability of haemorrhagic transformation (OR 9.64; CI 1.29-71.68, p = 0.022) after the index event. KAF is associated with an increased risk of haemorrhagic transformation but not of death when compared to AFDAS.

Apolipoprotein E deficiency exacerbates blood-brain barrier disruption and hyperglycemia-associated hemorrhagic transformation after ischemic stroke

BackgroundThe polymorphism of the apolipoprotein E (ApoE) gene has been implicated in both the susceptibility to neurodegenerative disease and the prognosis of traumatic brain injury (TBI). However, the influence of ApoE on the risk of hemorrhagic transformation (HT) after acute ischemic stroke remains inconclusive. The present study aimed to investigate the potential impact of ApoE deficiency on the risk of hyperglycemia-associated HT and to elucidate the underlying mechanisms. MethodsWild-type (WT) and ApoE knockout (ApoE−/−) mice were injected with 50 % glucose to induce hyperglycemia and subsequently subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO). The mortality, neurological function, HT incidence and HT grading-score were evaluated at 24 hours after reperfusion. To evaluate the integrity of blood-brain barrier (BBB), the immunoglobulin G (IgG) leakage and the protein expressions of tight junctions (TJs) were detected using immunofluorescent staining and western blotting. Finally, the levels of matrix metalloproteinases (MMP)-2/9, microglial activation and proinflammatory mediators were investigated using immunofluorescent staining and western blotting. ResultsApoE−/− mice exhibited increased mortality and exacerbated neurological impairment, concomitant with more severe hyperglycemia-associated HT 24 hours post-reperfusion. Meanwhile, ApoE deficiency exacerbated the disruption of BBB, characterized by increased leakage of IgG, aggravated degradation of TJs and microvascular basement membranes. Furthermore, ApoE deficiency further aggravated the upregulation of MMP-2/9 and microglia-triggered neuroinflammation. ConclusionsOur findings demonstrate that the absence of ApoE exacerbates neurological impairment and hyperglycemia-associated HT in ischemic stroke mice, which is closely associated with MMP-2/9 signaling and neuroinflammation-mediated disruption of BBB.

POST HERPETIC BASAL GANGLIA STROKE IN AN ADOLESCENT GIRL: BRIEF REVIEW OF LITERATURE AND A CASE REPORT

Herpes simplex encephalitis (HSE) is a leading cause of sporadic, non-epidemic viral encephalitis in children and adults. We report a very rare case of HSE complicated by multiple ischaemic infarcts involving both basal ganglia in a 15-year-old female adolescent admitted with complaints of headache and fever, irrational behavior and seizures. On clinical examination patient was unconscious with signs of raised intracranial pressure, right hemiparesis and meningeal irritation. She had elevated temperature (38.7°C), and anaemia (packed cell volume of 25.0%). Magnetic resonance imaging showed features of Multiple non-enhancing hypodensities in both basal ganglia with mild dilation of the 3rd and lateral ventricles. She was managed as a case of Post-encephalitis Basal ganglia stroke. The patient subsequently developed a repeat vascular event, with suspected haemorrhagic transformation after 4 weeks and succumbed to the illness.

Thrombolysis with tenecteplase in acute ischaemic stroke in a tertiary care setting in Sri Lanka: A retrospective study

Introduction: Alteplase (ALT) is the standard thrombolytic treatment in acute ischaemic stroke (AIS). Tenecteplase (TNK) is proven to be effective in acute coronary syndrome, is relatively cheap, widely available and can easily be given as a single intravenous (IV) bolus. Despite evidence for its use, there is equivocal guidance for the use of TNK in AIS. On the background of a global reduction in stroke admissions, treatment interventions and prolonged treatment time metrics due to the COVID-19 pandemic, this study highlights the experience with TNK in a tertiary care setting in Sri Lanka, during the pandemic.Objectives: To describe the outcomes at 48 hours among stroke patients who underwent thrombolysis with TNK at District General Hospital Hambantota, Sri Lanka over a period of one year.Methods: We retrospectively reviewed records of adults with AIS thrombolysed with 0.25 mg/kg TNK. The National Institutes of Health Stroke Scale (NIHSS) was assessed on admission and at 24-hours following treatment. Patients were observed for 48-hours for potential adverse events.Results: We thrombolysed 20 consecutive patients over one-year. The baseline mean NIHSS was 9.7 (standard deviation (SD)=4.4; range 4-22), and the 24h-post thrombolysis mean NIHSS was 6.0 (SD=7.3; range 0-28). Seventy percent (n=14) showed an improved NIHSS of at least 1-point after thrombolysis (mean difference=3.7; SD=6.46), and 55%(n=11) displayed a major clinical improvement (change in NIHSS ≥ 4). Ten percent (n=2) developed major adverse effects (one intra-cranial haemorrhage; one haemorrhagic transformation). There were no deaths.Conclusions: TNK 0.25mg/kg for the treatment of AIS appeared efficacious and safe in our case series. The limitation in this study was the low number of patients who underwent thrombolysis during the study period, as a probable effect of the COVID-19 pandemic. Thrombolysis with TNK could be a cost-effective alternative to alteplase in resource-limited South Asian settings.

Matrix Metalloproteinases as Biomarkers for Ischemic Stroke: A Systematic Review

Background: Ischemic stroke, a leading cause of mortality and disability worldwide, occurs due to the disruption of blood flow to the brain, resulting in neuronal damage and death. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, play a crucial role in the pathophysiology of ischemic stroke by degrading the extracellular matrix and contributing to blood-brain barrier disruption, inflammation, and neuronal cell death. This systematic review aims to comprehensively evaluate the current evidence regarding the potential of MMPs as biomarkers for ischemic stroke diagnosis, prognosis, and therapeutic monitoring. Methods: A systematic search of electronic databases (PubMed, Embase, and Cochrane Library) was conducted to identify relevant studies published between 2018 and 2024. Studies investigating the association between MMPs and ischemic stroke in human subjects were included. Data extraction and quality assessment were performed independently by two reviewers. Results: The search yielded 2,182 articles, of which 8 studies met the inclusion criteria. The included studies evaluated various MMPs, including MMP-2, MMP-3, MMP-9, and MMP-12, in different biological samples (serum, plasma, cerebrospinal fluid, and brain tissue) from ischemic stroke patients. The majority of studies reported elevated levels of MMPs in ischemic stroke patients compared to healthy controls, with MMP-9 being the most extensively studied. Furthermore, several studies demonstrated a correlation between MMP levels and stroke severity, functional outcome, and the risk of hemorrhagic transformation. Conclusion: The findings of this systematic review suggest that MMPs, particularly MMP-9, hold promise as potential biomarkers for ischemic stroke. However, further research is needed to validate their clinical utility and to explore their potential as therapeutic targets.

National trends and outcomes of hospital presentation mode for endovascular stroke treatment in the U.S.

BackgroundThe optimal triage strategy for patients suspected of acute ischemic stroke due to large vessel occlusion (LVO) remains debated. We explored trends in presentation mode and their outcomes for mechanical thrombectomy (MT) hospitalizations based on the National Inpatient Sample (NIS) database. MethodsWe retrospectively explored the NIS database from 2016 to 2020 for stroke hospitalizations with MT. We compared outcomes at discharge for MT hospitalizations with direct vs. transferred presentation. Outcomes comprised favorable discharge disposition (home without assistance), in-hospital mortality, and radiographic intracranial hemorrhage (ICH). ResultsThis study included 100,865 patients undergoing MT, of whom 32,685 patients (32.4 %) were transferred (median age 71[60–81] years, 16775(51.2 %) women). The utilization of MT in the U.S. nearly doubled during the study period, whereas the proportion of in-hospital transfers for MT remained unchanged (32.1–33.2 %). White race, higher presenting NIHSS, hospital size, status, and location were independent predictors of transferred status. Transferred status was significantly associated with a lower likelihood of achieving favorable outcome (OR:0.80,95 % CI: [0.72,0.89],P<0.001) and a higher likelihood of ICH (OR:1.18, 95 % CI:[1.07,1.31],P=0.001), whereas no association was observed between presentation mode and in-hospital mortality (OR:1.07,95 % CI:[0.93,1.23],P=0.33). ConclusionPatients with direct presentation for MT after a stroke had better discharge outcomes and a lower risk of hemorrhagic transformation compared to those who were transferred from another facility. Determining the optimal triage strategy for MT following LVO stroke is an insightful area for future clinical trials.

Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood–brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Association between metabolic syndrome and outcomes of large-artery atherosclerosis stroke treated with reperfusion therapy

AimWe aimed to investigate the impact of metabolic syndrome (MetS) on the outcomes of stroke patients with large-artery atherosclerosis who underwent reperfusion therapy. MethodsA retrospective analysis was carried out on patients receiving reperfusion therapy for atherothrombotic stroke between January 2019 and May 2021. MetS was diagnosed according to the AHA/NHLBI criteria. The primary outcome was the composite outcome of disability (modified Rankin Scale [mRS] score 3-5), death or stroke recurrence within 3 months of stroke onset. Secondary outcomes included disability and death within 3 months as well as hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 hours after reperfusion treatment. The independent association of MetS with the above outcomes and the highly correlated components of MetS was examined using binary logistic regression analysis. ResultsA total of 174 patients were enrolled. MetS patients had a higher proportion of the composite outcome (p = 0.012), disability (p = 0.029) and HT (p = 0.049) than those without MetS, except for death (p = 0.375) and sICH (p = 0.306). Following adjustments, MetS remained independently associated with the composite outcome (adjusted OR, 3.011 [95 %CI 1.372-6.604]; p = 0.006) and disability (adjusted OR, 2.727 [95 %CI 1.220-6.098]; p = 0.015), but not HT (adjusted OR, 1.872 [95 %CI 0.854-4.104]; p = 0.117). Hypertriglyceridemia was remarkedly associated with the composite outcome (adjusted OR, 9.746 [95 % CI 2.402-39.536]; p = 0.001) and disability (adjusted OR, 6.966 [95 % CI 1.889-25.692]; p = 0.004). ConclusionMetS is independently associated with an increased risk of composite outcome and disability in patients with large-artery atherosclerosis stroke receiving reperfusion therapy, and hypertriglyceridemia is the main component that drives the effect of MetS on outcomes.

Synergistic insights: the integrated role of CT/CTP and clinical parameters in hemorrhagic transformation prediction.

Acute ischemic stroke presents significant challenges in healthcare, notably due to the risk and poor prognosis associated with hemorrhagic transformation (HT). Currently, there is a notable gap in the early clinical stage for a valid and reliable predictive model for HT. This single-center retrospective study analyzed data from 224 patients with acute ischemic stroke due to large vessel occlusion. We collected comprehensive clinical data, CT, and CTP parameters. A predictive model for HT was developed, incorporating clinical indicators alongside imaging data, and its efficacy was evaluated using decision curve analysis and calibration curves. In addition, we have also built a free browser-based online calculator based on this model for HT prediction. The study identified atrial fibrillation and hypertension as significant risk factors for HT. Patients with HT showed more extensive initial ischemic damage and a smaller ischemic penumbra. Our novel predictive model, integrating clinical indicators with CT and CTP parameters, demonstrated superior predictive value compared to models based solely on clinical indicators. The research highlighted the intricate interplay of clinical and imaging parameters in HT post-thrombectomy. It established a multifaceted predictive model, enhancing the understanding and management of acute ischemic stroke. Future studies should focus on validating this model in broader cohorts, further investigating the causal relationships, and exploring the nuanced effects of these parameters on patient outcomes post-stroke.

Combinations of Clinical Factors, CT Signs, Radiomics for Differentiating High-density Areas After Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

Clinically, hemorrhagic transformation (HT) after mechanical thrombectomy (MT) is a common complication. This study is aim to investigate the value of clinical factors, CT signs, and radiomics in the differential diagnosis of high-density areas (HDAs) in the brain after MT in patients with acute ischemic stroke with large vessel occlusion (AIS-LVO). A total of 156 eligible patients with AIS-LVO in Center Ⅰ from December 2015 to June 2023 were retrospectively enrolled and randomly divided into training (n=109) and internal validation (n=47) sets at a ratio of 7:3. The data of 63 patients in Center Ⅱ were collected as an external validation set. According to the diagnostic criteria, the patients in the three datasets were divided into a HT group and a non-HT group. The clinical and imaging data from Centers Ⅰ and Ⅱ were used to construct a clinical factor and CT-sign model, a radiomic model and a combined model by logistic regression (LR). Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy of each model in the three datasets. Clinical blood glucose (Glu) and the maximum cross-sectional area (Areamax) on CT were associated with the nature of the HDA according to multivariate LR analyses (P < 0.05). Among the three models, the combined model had the highest diagnostic efficiency, with area under the curve (AUC) values of 0.895, 0.882, and 0.820 in the three datasets, which were significantly greater than the AUC values of the radiomic model (0.887, 0.898, 0.798) and clinical factor and CT sign model (0.831, 0.744, 0.684). The combined model based on radiomics had the best performance, indicating that radiomic features can be used as imaging biomarkers to aid in the clinical judgment of the nature of HDA after MT. HDA =high-density area; HT =hemorrhagic transformation; MT =mechanical thrombectomy; AIS-LVO =acute ischemic stroke with large vessel occlusion; LR =logistic regression; AUC =area under the curve; ICE =iodine contrast extravasation; DECT =dual energy CT; IOM =iodine overlay map; VNC =virtual noncontrast; Glu =glucose; LASSO =least absolute shrinkage and selection operator; ICC =intraclass correlation coefficient; ROC =receiver operating characteristic; DCA =decision curve analysis.

Oxidative Stress in Cerebral Ischemia/Reperfusion Injury

Oxidative stress in cerebral ischemia/reperfusion injury (CIRI) involves reactive oxygen and nitrogen species (ROS and RNS). Despite efficient antioxidant pathways in the brain, hypoxia triggers the production of oxygen free radicals and downregulates ATP, which leads to oxidative stress. Sources of free radicals during CIRI include Ca&lt;sup&gt;2+&lt;/sup&gt;-dependent enzymes, phospholipid degradation and mitochondrial enlargement. Upon reperfusion, the abrupt increase of oxygen triggers a massive radical production via enzymes like xantin oxidase (XO), phospholipase A2 (PLA2) and oxide synthases (OS). These enzymes play an essential role in neuronal damage by excitotoxicity, lipoperoxidation, nitrosylation, inflammation and programmed cell death (PCD). Endothelial nitric oxide synthase (eNOS) decreases as compared to neuronal nitric oxide synthase (nNOS). This is associated with neuronal damage, endothelial inflammation, apoptosis and oxidative stress. Strategies promoting activation of eNOS while inhibiting nNOS could offer neuroprotective benefits in CIRI. Understanding and targeting these pathways could mitigate brain damage in ischemia/reperfusion events. Clinically, tissue plasminogen activator (t-PA) has been shown to restore cerebral blood flow. However, serious side effects have been described, including hemorrhagic transformation. Different treatments are currently under investigation to avoid I/R injury. Baicalin has been reported as a potential agent that could improve t-PA adverse effects, which have to do with peroxynitrite synthesis and matrix metalloproteinase (MMP) expression. In this review, CIRI and interventions in oxidative stress are addressed. Special attention is paid to efficient antioxidant mechanisms in the brain and the production of free radicals, especially nNOS-derived nitric oxide (NO). The primary purpose is to describe accessible radical pathways with the activity of Ca&lt;sup&gt;2+&lt;/sup&gt;-dependent oxidative enzymes, leading to membrane phospholipids and mitochondrial breakdown. &lt;strong&gt;Key&lt;/strong&gt;&lt;strong&gt;w&lt;/strong&gt;&lt;strong&gt;ords&lt;/strong&gt;Oxidative stress; cerebral ischemia/reperfusion; nitric oxide; reactive oxygen species; nitric oxide synthase

External validation of different predictive scores for symptomatic intracranial hemorrhage after intravenous thrombolysis in Asian stroke patients

ObjectiveThis study aimed to externally validate different predictive scores for symptomatic intracranial hemorrhage (SICH) after intravenous thrombolysis (IVT), with a particular focus on their predictive abilities in Asian stroke patients. MethodsWe retrospectively enrolled stroke patients who received a standard dose of alteplase within 4.5 hours from symptom onset at the First Affiliated Hospital of Dalian Medical University from July 2010 to August 2023. SICH was defined as the hemorrhagic transformation detected on the head CT scan completed within 48 h post-IVT, accompanied by a clinical deterioration of at least a 4-point increase in NIHSS score. Predictive abilities of the HAT, MSS, SEDAN, SPAN-100, and GRASPS scores were tested. Discrimination and calibration were performed using the area under the receiver operating characteristic curve (ROC-AUC), DeLong test, and Hosmer-Lemeshow (H-L) goodness-of-fit test. ResultsThe study included 1007 stroke patients, of whom 31 (3.08 %) developed SICH. ROC-AUCs for predicting SICH were: 0.796 (95 %CI: 0.726–0.866) for the GRASPS score, 0.724 (95 %CI: 0.644–0.804) for the MSS score, 0.715 (95 %CI: 0.619–0.811) for the SEDAN score, 0.714 (95 %CI: 0.611–0.817) for the HAT score, and 0.605 (95 %CI: 0.491–0.720) for the SPAN-100 score (all P < 0.05). DeLong tests showed that the GRASPS score demonstrated significantly better discrimination than the MSS score (P = 0.010), the SEDAN score (P = 0.009), the HAT score (P = 0.049), and the SPAN-100 score (P = 0.000). H-L tests indicated good calibrations which were ranked HAT > SEDAN > MSS > SPAN-100 > GRASPS scores. ConclusionThe GRASPS score showed reasonable predictive ability for SICH, indicating its potential utility for Asian stroke patients receiving IVT.

Role of blood-brain barrier dysfunction in the development of poststroke epilepsy.

Stroke is a major contributor to mortality and morbidity worldwide and the most common cause of epilepsy in the elderly in high income nations. In recent years, it has become increasingly evident that both ischemic and hemorrhagic strokes induce dysfunction of the blood-brain barrier (BBB), and that this impairment can contribute to epileptogenesis. Nevertheless, studies directly comparing BBB dysfunction and poststroke epilepsy (PSE) are largely absent. Therefore, this review summarizes the role of BBB dysfunction in the development of PSE in animal models and clinical studies. There are multiple mechanisms whereby stroke induces BBB dysfunction, including increased transcytosis, tight junction dysfunction, spreading depolarizations, astrocyte and pericyte loss, reactive astrocytosis, angiogenesis, matrix metalloproteinase activation, neuroinflammation, adenosine triphosphate depletion, oxidative stress, and finally cell death. The degree to which these effects occur is dependent on the severity of the ischemia, whereby cell death is a more prominent mechanism of BBB disruption in regions of critical ischemia. BBB dysfunction can contribute to epileptogenesis by increasing the risk of hemorrhagic transformation, increasing stroke size and the amount of cerebral vasogenic edema, extravasation of excitatory compounds, and increasing neuroinflammation. Furthermore, albumin extravasation after BBB dysfunction contributes to epileptogenesis primarily via increased transforming growth factor β signaling. Finally, seizures themselves induce BBB dysfunction, thereby contributing to epileptogenesis in a cyclical manner. In repairing this BBB dysfunction, pericyte migration via platelet-derived growth factor β signaling is indispensable and required for reconstruction of the BBB, whereby astrocytes also play a role. Although animal stroke models have their limitations, they provide valuable insights into the development of potential therapeutics designed to restore the BBB after stroke, with the ultimate goal of improving outcomes and minimizing the occurrence of PSE. In pursuit of this goal, rapamycin, statins, losartan, semaglutide, and metformin show promise, whereby modulation of pericyte migration could also be beneficial.

Evaluating the interaction between hemorrhagic transformation and cerebral edema on functional outcome after ischemic stroke

BackgroundHemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation. Methods892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately. ResultsAmong the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001]. ConclusionsMost stroke patients with HT also have measurable CED. The co-occurrence of CED and HT occurs in larger and more severe strokes and is associated with worse functional outcome, although this is driven by greater severity of stroke-related edema in those with HT.

Effects of PCSK9 Inhibitors on Early Neurologic Deterioration in Patients with Acute Non-Cardioembolism without Hemorrhagic Transformation After Intravenous Thrombolysis.

END (Early Neurologic Deterioration) significantly elevates the risk of morbidity and mortality. While numerous studies have investigated END following hemorrhagic transformation post-thrombolysis in acute cerebral infarction research on END without hemorrhagic transformations in patients with acute cerebral infarction due to non-cardiogenic embolism remains scarce. This study aimed to elucidate the impact of PCSK9 inhibitors on early neurological deterioration (END) in patients with acute non-cardioembolism cerebral infarction without hemorrhagic transformation post-intravenous thrombolysis. Additionally it aimed to identify risk factors associated with END in patients suffering from this type of stroke. The objective of this study is to investigate the effect of PCSK9 inhibitors on early neurologic deterioration (END) in patients with acute non-cardiogenic cerebral infarction without hemorrhagic transformation after intravenous thrombolysis and identify associated risk factors for END in this patient population. In this retrospective case-control study the data of consecutive patients who underwent intravenous thrombolysis after AIS (acute ischemic stroke) without hemorrhagic transformation during hospitalization at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 to February 2023 were retrieved and assessed. An increase of >2 in the National Institutes of Health Stroke Scale (NIHSS) within 7 days after admission was defined as END. This study included 250 patients (56 males 22.4%) they were 63.34±12.901 years old. There were 41 patients in the END group and 209 in the non-END group. The usage rate of PCSK9 inhibitors was significantly different between the END group and non-END group (29.268% vs 58.852% P<0.001). The White blood cell count (WBC) and homocysteine levels showed a significant difference between the two groups (all P<0.05). Patients not using PCSK9 inhibitors (OR=0.282 95%CI: 0.127-0.593) and white blood cell count (OR=1.197, 95%CI: 1.085-1.325) were independently associated with END. Receiver-operating characteristic curve analysis suggested that the sensitivity specificity and area under the curve for PCSK9 inhibitors used for END were 88.9%, 80.7% and 0.648 respectively. The use of PCSK9 inhibitors can reduce the incidence of early neurological deterioration in patients with acute non-cardioembolism and non-hemorrhagic transformation after intravenous thrombolysis.

Extended Length of Stay After Mechanical Thrombectomy for Stroke: A Single-Center Analysis of 703 Patients.

Mechanical thrombectomy (MT) is crucial for improving functional outcomes for acute ischemic stroke. Length of stay (LOS) is a reimbursement metric implemented to incentivize value-based care. Our study aims to identify predictors of LOS in patients undergoing MT at a high-volume center in the United States. This was a retrospective study of patients who underwent MT at a single institution from 2017 to 2023. Patients who experienced mortality during their course of hospital stay were excluded from this study. Extended LOS (eLOS) was defined as the upper quartile (≥75th) of the median duration of hospital stay. Univariate and multivariate analyses were performed, with P values < .05 denoting statistical significance. Seven hundred three patients met criteria for inclusion. The median age of the cohort was 72 years (IQR: 61-82), and 57.2% was female. The median LOS was 6, IQR: 4-10. A total of 28.9% of the cohort (n = 203) patients experienced eLOS. The multivariate regression model identified age (odds ratio [OR]: 0.98, 95% CI: 0.97-0.99), diabetes mellitus (OR: 1.68, 95% CI: 1.15-2.44), and hemorrhagic transformation of stroke (OR: 2.89, 95% CI: 0.39-0.90) as predictors of eLOS, whereas antiplatelet use before admission (OR: 0.55, 95% CI: 0.34-0.89) and higher baseline modified Rankin Scale before stroke were associated with lower odds (OR: 0.59 [0.39-0.90]; P < .05) of eLOS. By identifying predictors of eLOS, we provide a foundation for targeted interventions aimed at optimizing post-thrombectomy care pathways and improving patient outcomes. The implications of our study extend beyond clinical practice, offering insights into healthcare resource utilization, reimbursement strategies, and value-based care initiatives.

Artificial intelligence/machine learning for neuroimaging to predict hemorrhagic transformation: Systematic review/meta-analysis.

Early and reliable prediction of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) is crucial for treatment decisions and early intervention. The purpose of this study was to conduct a systematic review and meta-analysis on the performance of artificial intelligence (AI) and machine learning (ML) models that utilize neuroimaging to predict HT. A systematic search of PubMed, EMBASE, and Web of Science was conducted until February 19, 2024. Inclusion criteria were as follows: patients with AIS who received reperfusion therapy; AI/ML algorithm using imaging to predict HT; or presence of sufficient data on the predictive performance. Exclusion criteria were as follows: articles with less than 20 patients; articles lacking algorithms that operate solely on images; or articles not detailing the algorithm used. The quality of eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 and Checklist for Artificial Intelligence in Medical Imaging. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a random-effects model, and a summary receiver operating characteristic curve was constructed using the Reitsma method. We identified six eligible studies, which included 1640 patients. Aside from an unclear risk of bias regarding flow and timing identified in two of the studies, all studies showed low risk of bias and applicability concerns in all categories. Pooled sensitivity, specificity, and DOR were.849,.878, and 45.598, respectively. AI/ML models can reliably predict the occurrence of HT in AIS patients. More prospective studies are needed for subgroup analyses and higher clinical certainty and usefulness.