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

INTRODUCTION: 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). MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Asymptomatic parenchymal haemorrhage following endovascular treatment: Impact on functional outcome in patients with acute ischaemic stroke.

BACKGROUND AND PURPOSE: In patients with acute ischaemic stroke (AIS), haemorrhagic transformation (HT) following endovascular treatment (EVT) is associated with poor functional outcome. However, the impact of asymptomatic HT, not linked to neurological deterioration in the acute phase, is unknown. We aimed to investigate the impact of asymptomatic PH1 (aPH1) and PH2 (aPH2) subtypes of HT on the functional outcome of patients treated with EVT. METHODS: We conducted a retrospective study of patients with AIS who were consecutively admitted to our comprehensive stroke centre between January 2019 and December 2022, and who underwent EVT. We collected clinical, radiological, and procedural data. HTs were categorized according to the Heidelberg classification. The primary outcome was the shift on the modified Rankin Scale (mRS) at 3 months of follow-up. We performed bivariate and multivariable ordinal regression analyses to test the association between aPH1/aPH2 and the primary outcome. RESULTS: We included 314 patients (mean age = 72.5 years [SD = 13.6], 171 [54.5%] women). We detected 54 (17.2%) patients with HT; 23 (7.3%) were classified as PH2 (11 asymptomatic) and 17 (5.4%) as PH1 (16 asymptomatic). The adjusted common odds ratio for aPH2 of worsening 1 point on the 3-month mRS was 3.32 (95% confidence interval = 1.16-9.57, p = 0.026). No association was observed for aPH1. aPH2 was also independently associated with lower odds of achieving a favourable outcome (mRS = 0-2). Neither aPH1 nor aPH2 was associated with mortality. CONCLUSIONS: In patients with AIS treated with EVT, aPH2 is independently associated with unfavourable functional outcome.

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

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

Analysis of the prognostic value of emergency blood tests in ischaemic stroke.

OBJECTIVES: This study aims to evaluate the prognostic value of emergency blood test results in patients with acute ischaemic stroke. METHODS: We evaluated 592 prospectively patients with neuroimaging-confirmed ischaemic stroke admitted to our stroke unit between 2015 and 2018. We gathered emergency blood test results and calculated the neutrophil-to-lymphocyte ratio and the neutrophil-to-platelet ratio (neutrophils × 1.000/platelets). The association between blood test results and functional prognosis (as measured with the modified Rankin Scale) and such complications as haemorrhagic transformation was evaluated by logistic regression analysis. The additional predictive value of blood test parameters was assessed with receiver operating characteristic curves and the net reclassification index. RESULTS: An neutrophil-to-lymphocyte ratio ≥ 3 at admission was associated with a two-fold increase in the risk of functional dependence at 3 months (OR: 2.24; 95% CI: 1.35-3.71) and haemorrhagic transformation (OR: 2.11; 95% CI: 1.09-4.05), while an neutrophil-to-lymphocyte ratio ≥ 3.86 resulted in an increase of 2.4 times in the risk of mortality at 3 months (OR: 2.41; 95% CI: 1.37-4.26) after adjusting for the traditional predictors of poor outcomes. Patients with neutrophil-to-platelet ratio ≥ 32 presented 3 times more risk of haemorrhagic transformation (OR: 3.17; 95% CI: 1.70-5.92) and mortality at 3 months (OR: 3.07; 95% CI: 1.69-5.57). Adding these laboratory parameters to standard clinical-radiological models significantly improved discrimination and prognostic accuracy. CONCLUSIONS: Basic blood test parameters provide important prognostic information for stroke patients and should therefore be analysed in combination with standard clinical and radiological parameters to optimise ischaemic stroke management.

Risk factors for infarct growth and haemorrhagic or oedematous complications after endovascular treatment - a literature review.

INTRODUCTION: Acute ischaemic stroke (AIS) is caused by significant disturbances in the cerebral bloodflow (CBF) that lead to brain ischaemia and eventually result in irreversible brain tissue damage. The main goal of its treatment is to restore bloodflow to the areas at risk of necrosis. Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are the mainstay of current therapy, with the latter being widely employed in selected patients with radiologically proven large vessel occlusion (LVO). Despite convincing evidence of its efficacy, up to half of patients undergoing endovascular treatment (EVT) still do not achieve a beneficial functional outcome; this is mainly due to unfavourable brain tissue sequelae. Therefore, factors associated with known adverse brain changes, such as larger infarct size or haemorrhagic and oedematous complications, should be adequately addressed. OBJECTIVE: To review the available literature describing AIS brain tissue outcome assessed by computed tomography (CT) and/ or magnetic resonance imaging (MRI) in patients undergoing MT treatment. Additionally, to evaluate the association of post-MT tissue changes with short- and long-term prognosis. MATERIAL AND METHODS: We searched the PubMed, Scopus, EMBASE, and Google Scholar databases according to established criteria. RESULTS: We found a total of 264 articles addressing the most common types of AIS tissue sequelae after EVT (i.e. MT with or without IVT as bridging therapy) by brain CT and MRI. These were: follow-up infarct volume (FIV), cerebral oedema (COD) and haemorrhagic transformation (HT). As the next step, 37 articles evaluating factors associated with defined outcomes were selected. Several non-modifiable factors such as age, comorbidities, pretreatment neurological deficit, and collateral circulation status were found to affect stroke tissue sequelae, to varying degrees. Additionally, some factors including time to treatment initiation, selection of treatment device, and periprocedural systemic blood pressure, the modification of which can potentially reduce the occurrence of an unfavourable tissue outcome, were identified. Some recently revealed biochemical and serological parameters may play a similar role. CONCLUSIONS: The identification of factors that affect post-MT ischaemic area evolution may result in studies assessing the effects of their modification, and potentially improve clinical outcomes. Modifiable parameters, including periprocedural systemic blood pressure and some biochemical factors, may be of particular importance.

Prognostic significance of the clinical and radiological haemorrhagic transformation subtypes in acute ischaemic stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The aim was to investigate the associations of haemorrhagic transformation (HT) and its clinical and radiological subtypes with functional outcome, mortality, early neurological deterioration (END) and neurological complications in patients with acute ischaemic stroke (AIS). METHODS: A systematic review and meta-analysis of observational studies on the associations of overall HT, clinical HT subtypes (asymptomatic intracerebral haemorrhage [aICH] and symptomatic intracerebral haemorrhage [sICH]) or radiological HT subtypes (haemorrhagic infarction [HI-1 or HI-2] and parenchymal haemorrhage [PH-1 or PH-2]) with prognosis in patients with AIS was performed. PubMed, Web of Science and Embase were systematically searched. Random effects models were used to calculate pooled estimates. RESULTS: Fifty-one studies with 100,510 patients were pooled in the meta-analysis. Overall HT was associated with worse functional outcome (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.55-2.90), increased mortality (OR 1.87, 95% CI 1.52-2.30), END (OR 2.35, 95% CI 1.46-3.77), early-onset seizures (OR 2.58, 95% CI 1.63-4.10) and post-stroke epilepsy (OR 2.23, 95% CI 1.11-4.49). For clinical subtypes, sICH remained significantly associated with the aforementioned poor prognoses except post-stroke epilepsy, and aICH was associated with worse functional outcome but was unrelated to mortality. For radiological subtypes, PH (especially PH-2) was strongly associated with poor prognosis. HI-2 was associated with worse functional outcome, and HI-1 was associated with a lower risk of mortality and END. CONCLUSIONS: Regardless of whether AIS patients undergo thrombolysis or thrombectomy, overall HT, sICH and PH (especially PH-2) are associated with a substantially increased risk of worse functional outcome, mortality, END or neurological complications. The presence of aICH is related to worse functional outcome but is independent of increased mortality. HI-2 impairs functional independence, and HI-1 does not cause neurological impairment.

Mathematical modelling of haemorrhagic transformation within a multiscale microvasculature network.

Objective.Haemorrhagic transformation (HT) is one of the most common complications after ischaemic stroke, caused by damage to the blood-brain barrier (BBB) that could be the result of stroke progression or a complication of stroke treatment with reperfusion therapy. The aim of this study is to develop further a previous simple HT mathematical model into an enlarged multiscale microvasculature model in order to investigate the effects of HT on the surrounding tissue and vasculature. In addition, this study investigates the relationship between tissue displacement and vascular geometry.Approach.By modelling tissue displacement, capillary compression, hydraulic conductivity in tissue and vascular permeability, we establish a mathematical model to describe the change of intracranial pressure (ICP) surrounding the damaged vascular bed after HT onset, applied to a 3D multiscale microvasculature. The use of a voxel-scale model then enables us to compare our HT simulation with available clinical imaging data for perfusion and cerebral blood volume (CBV) in the multiscale microvasculature network.Main results. We showed that the haematoma diameter and the maximum tissue displacement are approximately proportional to the diameter of the breakdown vessel. Based on the voxel-scale model, we found that perfusion reduces by approximately13-17%andCBVreduces by around20-25%after HT onset due to the effect of capillary compression caused by increased interstitial pressure. The results are in good agreement with the limited experimental data.Significance. This model, by enabling us to bridge the gap between the microvascular scale and clinically measurable parameters, providing a foundation for more detailed validation and understanding of HT in patients.

Early recurrence of ischaemic stroke of cardioembolic cause and delayed anticoagulation: a case report.

Introduction: Anticoagulation therapy is used for the management of atrial fibrillation to prevent new clots from developing. However, neurologists face the challenge of when to initiate/reintroduce treatment after a recent episode of stroke without increasing haemorrhagic risk, especially if the stroke is large and/or complicated with haemorrhagic transformation. Case presentation: This report describes the case of a 72-year-old man who had an ischaemic stroke of the right posterior cerebral artery. The patient had permanent atrial fibrillation, discovered in hospital. He was not on chronic anticoagulation therapy before stroke. His anticoagulation therapy was postponed due to a haemorrhagic lesion, leading to new ischaemic stroke. The patient suddenly had right hemiplegia with aphasia for which a mechanical thrombectomy was performed but complicated by embolization into the left posterior cerebral artery with failure of thromboaspiration of this clot. Finally, the patient presented with intracranial hypertension due to ischaemic lesions and died 3 days after his readmission. Conclusion: When to start anticoagulation therapy after ischaemic stroke is an unresolved question but should be discussed at least twice weekly in a stroke unit based on the clinical evolution of the patient.

Does ASTRAL score at hospital admission predict symptomatic haemorrhagic transformation in acute ischaemic stroke after revascularisation? A pilot single-centre study.

INTRODUCTION: Accurately predicting outcomes after acute ischaemic stroke (AIS) is a major clinical goal. The aim of this pilot study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in predicting symptomatic haemorrhagic transformation (sHT) in patients with AIS who have undergone revascularisation. MATERIAL AND METHODS: Consecutive patients hospitalised for AIS who underwent treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were identified, and their ASTRAL scores at hospital admission were estimated. The study endpoint was sHT within 24 hours of stroke onset. The predictive performance of the ASTRAL score was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Sixty-eight AIS patients, with a median age of 69 (58-79) years, were included. sHT occurred in 20 (29.4%) of the 68 patients. The ASTRAL score was significantly higher in patients who developed sHT compared to non-sHT patients [36 (34-38) versus 24 (17-32); p<0.001]. The ASTRAL score was an independent predictor of sHT, and showed good discriminative power (area under the curve 0.88; 95% confidence interval, 0.789-0.965). CONCLUSIONS AND CLINICAL IMPLICATIONS: ASTRAL score is an independent predictor of sHT and shows high predictive accuracy in patients with AIS. Future studies are warranted to confirm these results.

Incidence, prognosis, and prediction of haemorrhagic transformation after revascularisation for stroke.

INTRODUCTION: Haemorrhagic transformation is a major complication of acute ischaemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial haemorrhage (ICH) after revascularisation therapy. METHODS: We conducted a retrospective, single-centre study including 235 patients with AIS who underwent intravenous recombinant tissue plasminogen activator (IV-rtPA) therapy and/or endovascular treatment. A binary logistic regression model was used to determine the variables associated with ICH, parenchymal haematomas (PH), modified Rankin Scale (mRS) scores, and mortality. RESULTS: ICH was detected in 57 (30 with PH) of 183 patients included. Mechanical thrombectomy, either alone (OR 3.3 [1.42-7.63], P=.005) or in combination with IV-rtPA (OR 3.39 [1.52-7.56], P=.003), was associated with higher risk of ICH, while higher Alberta Stroke Program Early CT scores (OR 0.71 [0.55-0.91], P=.007) were associated with lower risk. Patients with older age (OR 1.07 [1.02-1.13], P=.006) and occlusion of the terminal branch of the internal carotid artery (OR 4.03 [1.35-11.99], P=.012) had a higher risk of PH, while the use of IV-rtPA alone (OR 0.24 [0.08-0.68], P=.008) was associated with lower risk of PH. Only PH was associated with disability as measured by the mRS (OR 3.2 [1.17-8.76], P=.02) and higher mortality (OR 5.06 [1.65-15.5], P=.005). CONCLUSIONS: Greater understanding about the predictors of ICH, mRS scores, and mortality could enable better selection of patients and treatments.

Incidencia, pronóstico y predicción de la transformación hemorrágica tras el tratamiento revascularizador del ictus / Incidence, prognosis, and prediction of haemorrhagic transformation after revascularisation for stroke

Introducción: La transformación hemorrágica es una complicación importante del ictus isquémico agudo (IIA). El propósito del trabajo es analizar el impacto clínico y los factores predictores de las hemorragias intracraneales (HIC) tras terapia revascularizadora.MétodosAnálisis retrospectivo monocéntrico de 235 pacientes con IIA tratados mediante trombólisis intravenosa (TIV) o tratamiento endovascular (TE). Se ha realizado un modelo de regresión logística binaria para determinar los factores asociados con las HIC, las hemorragias parenquimatosas (HP), la escala mRS y la mortalidad.ResultadosDe los 183 pacientes incluidos, 57 tuvieron HIC (30 HP). El TE mecánico (OR 3,3 [1,42-7,63], p = 0,005) y la TIV junto con TE mecánico (OR 3,39 [1,52-7,56], p = 0,003) se han asociado a mayor riesgo de HIC, mientras que valores altos de ASPECTS (OR 0,71 [0,55-0,91], p = 0,007) se han asociado a menor riesgo. Mayor edad (OR 1,07 [1,02-1,13], p = 0,006) y la oclusión de la carótida interna terminal (OR 4,03 [1,35-11,99], p = 0,012) han sido factores predictores de HP, mientras que haber recibido TIV exclusivamente (OR 0,24 [0,08-0,68], p = 0,008) se ha asociado con menor riesgo. Solo las HP se han asociado a valores invalidantes de mRS (OR = 3,2 [1,17-8,76], p = 0,02) y mayor mortalidad (OR 5,06 [1,65-15,5], p = 0,005).ConclusionesUna mejor comprensión de los factores predictores de HIC, mRS y mortalidad puede permitir una mejor selección de pacientes y tratamientos. (AU)

Introduction: Haemorrhagic transformation is a major complication of acute ischaemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial haemorrhage (ICH) after revascularisation therapy.MethodsWe conducted a retrospective, single-centre study including 235 patients with AIS who underwent intravenous recombinant tissue plasminogen activator (IV-rtPA) therapy and/or endovascular treatment. A binary logistic regression model was used to determine the variables associated with ICH, parenchymal haematomas (PH), modified Rankin Scale (mRS) scores, and mortality.ResultsICH was detected in 57 (30 with PH) of 183 patients included. Mechanical thrombectomy, either alone (OR 3.3 [1.42-7.63], P=.005) or in combination with IV-rtPA (OR 3.39 [1,52-7.56], P=.003), was associated with higher risk of ICH, while higher Alberta Stroke Program Early CT scores (OR 0.71 [0.55-0.91], P=.007) were associated with lower risk. Patients with older age (OR 1.07 [1.02-1.13], P=.006) and occlusion of the terminal branch of the internal carotid artery (OR 4.03 [1.35-11.99], P = .012) had a higher risk of PH, while the use of IV-rtPA alone (OR 0.24 [0.08-0.68], P=.008) was associated with lower risk of PH. Only PH was associated with disability as measured by the mRS (OR 3.2 [1.17-8.76], P=.02) and higher mortality (OR 5.06 [1.65-15.5], P=.005).ConclusionsGreater understanding about the predictors of ICH, mRS scores, and mortality could enable better selection of patients and treatments. (AU)

Mathematical modelling of haemorrhagic transformation after ischaemic stroke.

With an increasingly elderly population globally, the impacts of cerebrovascular diseases, such as stroke and dementia, become increasingly significant. Haemorrhagic transformation (HT) is one of the most common complications of ischaemic stroke that is caused by dysfunction of endothelial cells in the blood-brain barrier (BBB) and that can be exacerbated by thrombolytic therapy. Recent studies also suggest that HT can lead to an increase in intracranial pressure (ICP) and result in capillary compression. The aim of this study is to develop a mathematical model that can be used to simulate the consequence of HT over a range of vasculature length scales. We use a 2D vasculature model to investigate the severity of HT with different vascular geometry. The resulting model shows that the haematoma radius is approximately constant across different length scales (100-1000µm) and in good agreement with the available experimental data. In addition, this study identified that the effects of capillary compression do appear to have a significant impact on the leakage fraction of blood and hence act to restrain the development of a haematoma.

Efficacy and safety of Cerebrolysin after futile recanalisation therapy in patients with severe stroke.

INTRODUCTION: Golden standard of acute stroke treatment is recanalisation therapy. However, opening the occluded blood vessel sometimes does not show the expected clinical result or leads to haemorrhagic complications. As neuroinflammation and neurotoxicity play an important role in the pathophysiology of stroke, neuroprotective agents might preserve brain tissue after futile recanalisation. PATIENTS AND METHODS: After recanalisation therapy and not later than 24 h after symptoms onset, patients with initial NIHSS of ≥ 8 were assigned to the investigational and control group. The investigational group received intravenous Cerebrolysin as add-on therapy. The primary objective was to assess the clinical efficacy of Cerebrolysin. The secondary objective was to investigate its effect on haemorrhagic transition and to confirm its safety profile. RESULTS: Baseline characteristics of patients showed no significant differences between the two groups. No difference could be detected between the two groups in the mRS scale though the Cerebrolysin group showed descriptive superiority over the control group. We found a statistically significant difference considering haemorrhagic transition and mortality rate in favour of the Cerebrolysin group. DISCUSSION: The multimodal neurotrophic agent Cerebrolysin holds promise to impact on the late consequences of a reperfusion syndrome. Its influence on reducing neuroinflammation, promoting neuronal cell viability and neurogenesis as well as the stabilising effect on the blood-brain barrier suggests a protective effect on the neurovascular unit even when no recanalisation occurs. We confirmed the excellent safety profile of Cerebrolysin. CONCLUSION: Cerebrolysin as add-on therapy might be beneficial and safe for patients with acute stroke in terms of lowering risk for haemorrhagic complications after recanalisation therapy.

The relationship of leukoaraiosis, haemorrhagic transformation and prognosis at 3 months after intravenous thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction.

BACKGROUD: As the elderly stroke population continues to increase, we will have to confront greater challenges regarding how to choose suitable patients to reduce thrombolysis-related bleeding events and accurately judge their prognosis. Therefore, we evaluated the relationship among leukoaraiosis (LA), haemorrhagic transformation (HT) and the prognosis at 3 months after intravenous (IV) thrombolysis in elderly patients aged ≥ 60 years with acute cerebral infarction (ACI). METHODS: We prospectively and consecutively chose 125 elderly patients aged ≥ 60 years with ACI who could accept and be suitable for IV recombinant tissue plasminogen activator (rtPA) after excluding 6 cases. Brain computed tomography(CT) was used to assess LA by using the modified Van Swieten scale (mVSS) before treatment and the modified Rankin scale (mRS) to appraise prognosis at 3 months after IV rtPA. Binary logistic regression was used to analyse the predictors of HT and the prognosis of ACI. RESULTS: Our data indicated that by brain CT, 26.4% of all patients showed severe LA, and the rate of HT and symptomatic intracranial haemorrhage (sICH) were 12.0% and 9.6%, respectively. Severe LA was evidently associated with HT (odds ratio [OR] 3.272, 95% confidence interval [CI] 1.010-10.598, P = 0.048) rather sICH (P > 0.05). Moreover, we also found that severe LA was associated with poor functional prognosis (OR 5.266, 95% CI 1.592-17.419, P = 0.006). CONCLUSION: Our results showed that LA was associated with HT and adverse clinical prognosis rather sICH after IV rtPA in elderly patients aged ≥60 years with ACI. Although LA may increase the risk of bleeding but not fatal haemorrhage after IV thrombolysis, therefore, we should actively select an appropriate elderly population for thrombolytic treatment and have reasonable judgments on the outcomes.

Diagnostic accuracy of computed tomography perfusion in the prediction of haemorrhagic transformation and patient outcome in acute ischaemic stroke: A systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of computed tomography brain perfusion in the prediction of haemorrhagic transformation and patient outcome in acute ischaemic stroke. METHOD: Electronic databases and grey literature published over the last 10 years related to healthcare and radiology were searched using the key terms: 'computed tomography perfusion', 'haemorrhagic transformation', 'acute ischaemic stroke', 'functional outcome' and their synonyms using both UK and American spellings. Inclusion criteria were: sample size at least 30 patients, original research, evaluate ability of computed tomography perfusion to predict haemorrhagic transformation, reports diagnostic accuracy or provide relevant data for a 2 × 2 contingency table, use follow-up non-contrast computed tomography (NCCT) or magnetic resonance imaging as reference standard. FINDINGS: Twelve studies were included in the review; studies cover a total of 808 patients. Haemorrhagic transformation occurred in 30.2% of patients. Pooled sensitivity and specificity were 85.9% (95% CI; 65-97%), 73.9% (95% CI; 45-92%) and accuracy of 79.1% (95% CI; 57-98%). Pooled NPV was 92.9% with a high false positive rate (19.8%), which could be explained in terms of outcome classification, acquisition artefact and computed tomography perfusion processing algorithms. DISCUSSION: This review evaluated the importance of using pre-defined threshold measurement for optimal prediction of HT, the relevance of patient pre-treatment clinical parameters to HT occurrence, the CTP parameters and the measurements that are independent predictors of HT, the significance of rtPA rather as an exacerbator of HT and the impact of both minor and major HT/PH on patient 20 functional outcome. CONCLUSION: Computed tomography perfusion has a high sensitivity and moderately high specificity for prediction of haemorrhagic transformation in acute ischaemic stroke. Pre-treatment clinical decision making requires consideration of clinical factors in addition to imaging findings. This systematic review and meta-analysis highlights that pre-treatment computed tomography perfusion adds to clinical confidence by predicting potential for haemorrhage, both in thrombolysed and un-thrombolysed patients, and also influences decisions about alternative treatments for acute ischaemic stroke patients.

Association between non-high-density lipoprotein cholesterol and haemorrhagic transformation in patients with acute ischaemic stroke.

BACKGROUND: It is unclear whether non-high-density lipoprotein cholesterol (Non-HDL-C) is associated with haemorrhagic transformation (HT) after acute ischaemic stroke (AIS). We aimed to explore the association between Non-HDL-C and HT, as well as compare the predictive values of Non-HDL-C and low-density lipoprotein cholesterol (LDL-C) for HT. METHODS: We consecutively enrolled AIS patients within 7 days of stroke onset. Participants were divided into four categories according to quartiles of Non-HDL-C. HT was assessed by follow-up brain imaging. We assessed the association between Non-HDL-C, LDL-C and HT in multivariate logistic regression analysis. RESULTS: A total of 2043 patients were included, among whom 232 were identified as HT. Compared with the highest quartiles, the first, second and third quartiles of Non-HDL-C were associated with increased risk of HT (adjusted odds ratios [ORs] 1.74 [95% confidence interval [CI] 1.09-2.78], 2.01[95% CI 1.26-3.20], and 1.76 [95% CI 1.10-2.83], respectively, P for trend = 0.024). Similar results were found for LDL-C. There was significant interaction between Non-HDL-C and age (P for interaction = 0.021). The addition of Non-HDL-C and LDL-C to conventional factors significantly improved predictive values [Non-HDL-C, net reclassification index (NRI) 0.24, 95%CI 0.17-0.31, P < 0.001; LDL-C, NRI 0.15, 95%CI 0.08-0.22, P = 0.03]. CONCLUSIONS: Low Non-HDL-C was associated with increased risks of HT. In addition, Non-HDL-C has similar effects as LDL-C for predicting HT.

The effect of HMG-CoA reductase inhibitors on thrombolysis-induced haemorrhagic transformation.

Thrombolysis-induced haemorrhagic transformation is the most challenging preventable complication in thrombolytic therapy. This condition is often associated with poor functional outcome and long-term disease burden. Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are controversially suggested to either increase or decrease the odds of better primary outcomes compared to treatment without statins after thrombolysis in patients or animals; statins are thought to act by influencing lipid levels, the inflammatory response, blood brain barrier permeability and cell apoptosis. Statins are the cornerstone of secondary prevention of cardiovascular and cerebrovascular diseases. However, the role of statins in acute phase stroke, and the necessity of their use, remains unclear. Currently, whether statins can increase the risk of haemorrhagic transformation is of great concern for patients treated with tissue plasminogen activator (t-PA). Herein, we thoroughly summarize the recent advances that address whether the administration of statins in ischaemic stroke increases haemorrhagic transformation in patients or animals who received thrombolysis at an early stage and the related mechanisms. This review will provide more clinical and preclinical evidence to address questions regarding the exercise of caution in the use of high dose statins in patients who received thrombolysis and if low dose statins may be beneficial in decreasing thrombolysis-induced haemorrhagic transformation.

Absolute blood eosinophil count could be a potential biomarker for predicting haemorrhagic transformation after intravenous thrombolysis for acute ischaemic stroke.

BACKGROUND: Immune cells are involved in all stages of acute ischaemic stroke (AIS) and possess both neuroprotective and neurodamaging properties. It has been suggested that immune system activation after stroke may be associated with the development of haemorrhagic transformation (HT), which is the main complication limiting the clinical use of intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) for AIS. The purpose of our study was to analyse the association between absolute eosinophil count (AEC) at admission and the occurrence of HT after intravenous rtPA therapy for AIS. METHODS: In this retrospective study we enrolled AIS patients who were treated with rtPA within 4.5 h of symptom onset. Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients underwent head computed tomography scans at admission which were repeated 24 h after treatment with rtPA or promptly in case of clinical deterioration. HT was defined as blood at any site in the brain on follow-up head computed tomography scans. Spearman's rank correlation test was used to analyse the correlation between AEC and NIHSS scores. The optimal AEC cut-off value for predicting HT was calculated using the area under the receiver operating characteristic curve. Multiple logistic regression was used to determine the association between AEC included as a binary variable and the incidence of HT. RESULTS: The data of 201 patients was analysed (59.7% females; median age 77 years); 23 (11.4%) of them developed HT. The median of AEC was 62.5% greater in the non-HT group compared to the HT group (0.13 ×  109/l and 0.08 × 109/l, respectively, p = 0.026). No correlation was found between AEC and baseline NIHSS scores (r = 0.061, p = 0.393). AEC ≥ 0.11 × 109/l predicted the occurrence of HT with 69.6% sensitivity and 60.7% specificity. AEC ≥ 0.11 × 109/l was independently associated with a 78% reduction in the odds of developing HT (adjusted odds ratio = 0.223, 95% confidence interval = 0.069-0.723, p = 0.012). CONCLUSION: Higher values of AEC were associated with lower odds of developing HT, thus, AEC at admission could be considered an independent predictive marker of HT after treatment with rtPA for AIS.

Cathepsin K Knockout Exacerbates Haemorrhagic Transformation Induced by Recombinant Tissue Plasminogen Activator After Focal Cerebral Ischaemia in Mice.

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk-/- mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood-brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk-/- than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk-/- than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood-brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

Effects of the blood urea nitrogen to creatinine ratio on haemorrhagic transformation in AIS patients with diabetes mellitus.

BACKGROUND: The effect of the blood urea nitrogen (BUN) to creatinine (Cr) ratio (henceforth BUN/Cr) on haemorrhagic transformation (HT) of acute ischaemic stroke (AIS) patients is unclear. METHODS: AIS patients in the West China Hospital, Sichuan University, Chengdu, China, admitted within seven days from stroke onset (2012-2016) were included in the study. Baseline data, including BUN and Cr levels, were collected. The outcome was defined as HT during hospitalization. RESULTS: In this study, 1738 participants with an average age of 62.7 ± 14.0 years were included. After adjusting potential confounders (age, blood platelet, albumin, stroke severity, triglycerides and low-density lipoprotein [LDL]), multivariate logistic regression analyses indicated that BUN/Cr is independently associated with HT. The nonlinear relation between BUN/Cr and HT was explored in a dose-dependent manner, with an apparent inflection point of 30.71. On the left and right sides of the inflection point, the odds ratio (OR) and 95% confidence interval (CI) were 1.05 (1.02-1.08) and 0.96 (0.88-1.05), respectively. Interaction between BUN/Cr and diabetes mellitus (DM) and HT (P for interaction = 0.0395) was noted. BUN/Cr showed positive correlation with HT in DM patients (OR = 1.07; 95% CI: [1.02, 1.12]) but no significant relationship with HT in patients without DM. CONCLUSION: BUN/Cr is significantly associated with HT in AIS patients in a linear fashion, with an apparent cut point demarcating the HT difference. When the patients have DM, BUN/Cr is positively correlated with HT. These results support a revision in how we anticipate the prognosis for AIS patients.