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| Summary of hemorrhagic transformation data from major clinical trials of AIS intervention.
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Acute ischemic stroke is a devastating disease that is often complicated by hemorrhagic transformation. While significant advances have been made over the past two decades with regard to emergent treatment of AIS, many of the therapeutic options are limited by an increased risk of hemorrhage. Here, we sought to review the rates of hemorrhagic trans...
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Context 1
... any homogenous hyperdensity located beyond the borders of the infarct zone recanalization against the added risk of hemorrhage due to the particular therapy that is used. In the remainder of this manu- script, we will review the rates of hemorrhagic transformation in the major clinical trials of AIS (summarized in Table 2). It is important to emphasize that there is a significant degree of het- erogeneity between the design and eligibility criteria of each of the clinical trials that will be discussed. ...
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Introduction
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Background
Intravenous administration of recombinant tissue plasminogen activator (rt-PA) fails to succeed in a subset of acute ischemic stroke (AIS) patients, while in approximately 6–8% of cases intracerebral hemorrhage (ICH) occurs as side effect.
Objective
Here, we aimed to investigate α2-plasmin inhibitor (α2-PI) levels during thrombolysis an...
Background: Widespread quick access to mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is one of the main challenges in stroke care. It is unclear if newly established MT units are required 24 h/7 d. We explored the diurnal admission rate of patients with AIS potentially eligible for MT to provide a basis for discussion of daytime-adap...
Objective:
To evaluate the effectiveness of minimally invasive craniopuncture with local fibrinolysis in the management of supratentorial spontaneous intracerebral hemorrhage (SICH).
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Citations
... Radiological features of cardioembolic stroke include massive infarction and multiple infarctions which affect both hemispheres or the anterior and posterior circulation territories combined. Large artery occlusion and hemorrhagic transformation are common in cardioembolic stroke [10]. In a study that examined factors associated with lack of early recanalization after intravenous thrombolysis in patients with an occluded cerebral artery, the prevalence of AF was lower among those who experienced early recanalization [11]. ...
Cardioembolic stroke accounts for over 20% of ischemic strokes and is associated with worse outcomes than other types of strokes. Atrial fibrillation (AF) is the most common risk factor for cardioembolic stroke. In this narrative review, we present an update about cardioembolic stroke mainly related to AF and atrial cardiopathy. Direct oral anticoagulants (DOACs) have revolutionized stroke prevention in patients with AF; however, their efficacy in preventing recurrent embolic stroke of unknown source remains uncertain. Various cardiac monitoring methods are used to detect AF, which is crucial for preventing stroke recurrence. DOACs are preferred over warfarin for AF-related stroke prevention; however, the timing of initiation after acute ischemic stroke is debated. Resuming anticoagulation after intracerebral hemorrhage in AF patients requires careful assessment of the risks. While catheter ablation may reduce the incidence of cardiovascular events, its effect on stroke prevention is unclear, especially in heart failure patients. Atrial cardiopathy is the emerging cause of embolic stroke of unknown source, which indicates atrial structural and functional disorders that can precede AF. Future research should focus on refining stroke risk prediction models, optimizing AF detection, understanding the roles of ablation and anticoagulation in stroke prevention, and establishing atrial cardiopathy as a therapeutic target, which could significantly reduce the burden of stroke.
... acute cerebral infusion (ACI). The incidence rate reported in the literature is 8.5%-30% [4]. Studies have shown that platelet-induced inflammation plays a vital role in the pathogenesis of ACI [5], and lymphocyte levels decrease because of various pathological changes during acute ischemic events [6]. ...
Background
The increasing incidence of acute ischemic stroke (AIS) necessitates a comprehensive understanding of the related factors. Hemorrhagic transformation (HT), a severe complication of AIS, is influenced by platelet-induced inflammation and lymphocyte levels.
Objective
To measure the predictive value of platelet-to-lymphocyte ratio (PLR) in the occurrence of HT in young AIS patients.
Methods
Data of young AIS patients (n = 157) admitted to the hospital for the first time were retrospectively collected. The patients were divided into HT (63 patients) and non-HT groups (94 patients) on the basis of whether HT had occurred after admission. The National Institute of Health stroke scale (NIHSS) score was used to determine the severity of clinical symptoms. The relationship between PLR and HT and NIHSS scores was analyzed to evaluate the predictive value of PLR in the occurrence of HT using receiver operating characteristic (ROC) and area under the curve (AUC).
Results
Multivariate analysis showed that PLR and NIHSS are independent risk factors of HT. The PLR value of the observation group was positively associated with the NIHSS score ( r = 0.8075, P < 0.0001). According to the PLR prediction about the occurrence of HT, an AUC of 0.713 (95% CI, 0.652–0.781), a cut-off value of 109.073, and a sensitivity and specificity of 0.806 and 0.674, respectively, were obtained.
Conclusions
PLR value can predict the possibility of HT in young AIS patients to a certain extent. To take effective measures to prevent HT in advance has crucial clinical significance according to PLR value.
... The hemorrhagic infarction that arises following venous or arterial thrombosis and embolism is known as hemorrhagic transformation [55]. Hemorrhagic transformation exhibits a wide array of severity levels, from minor pinpoint bleeding within the affected tissue to a substantial hematoma that sprawls past the infarcted area's edges [56]. This transformation's radiological categorization stemmed from the initiatives taken by the European Cooperative Acute Stroke Study (ECASS), which discerns between various forms: minor petechial hemorrhagic infarction (HI1), extensive petechial hemorrhagic infarction (HI2), modest parenchymal hemorrhage (PH1) (constituting less than 30% of the infarct with a slight mass effect), and significant parenchymal hemorrhage (PH2), which accounts for more than 30% of the infarct and exhibits a pronounced mass effect [57]. ...
The number of scholarly articles continues to rise. The continuous increase in scientific output poses a challenge for researchers, who must devote considerable time to collecting and analyzing these results. The topic modeling approach emerges as a novel response to this need. Considering the swift advancements in computed tomography perfusion (CTP), we deem it essential to launch an initiative focused on topic modeling. We conducted a comprehensive search of the Scopus database from 1 January 2000 to 16 August 2023, to identify relevant articles about CTP. Using the BERTopic model, we derived a group of topics along with their respective representative articles. For the 2020s, linear regression models were used to identify and interpret trending topics. From the most to the least prevalent, the topics that were identified include “Tumor Vascularity”, “Stroke Assessment”, “Myocardial Perfusion”, “Intracerebral Hemorrhage”, “Imaging Optimization”, “Reperfusion Therapy”, “Postprocessing”, “Carotid Artery Disease”, “Seizures”, “Hemorrhagic Transformation”, “Artificial Intelligence”, and “Moyamoya Disease”. The model provided insights into the trends of the current decade, highlighting “Postprocessing” and “Artificial Intelligence” as the most trending topics.
... OAC treatment is initially withheld after admission to reduce the risk of hemorrhagic transformation (HT), a potential complication of AIS often occurring within the first few days after stroke onset [85]. Symptomatic HT has been reported in 2% to 20% of patients in RCTs [86], and it is associated with increased stroke mortality and morbidity. ...
Atrial fibrillation (AF) is an important risk factor for ischemic stroke (IS). Oral anticoagulation (OAC) significantly reduces the risk of IS in AF but also increases the risk of systemic bleeding, including intracerebral hemorrhage (ICH). AF-related strokes are associated with greater disability and mortality compared to non-AF strokes. The management of patients with AF-related strokes is challenging, and it involves weighing individual risks and benefits in the acute treatment and preventive strategies of these patients. This review summarizes the current knowledge of the acute management of ischemic and hemorrhagic stroke in patients with AF, and the prognosis and potential implications for management both in the acute and long-term setting.
... Минимально определяемое отношение шансов (ОШ) для любой ГТ принималось равным 0,5. Вероятность любой ГТ среди контрольной группы ожидалась равной 0,2 [12]. Уровень значимости, мощность и корреляция любой ГТ между группами были установлены на значения, рекомендованные руководством по программному обеспечению, которые составляли 0,05, 0,8 и 0,3 соответственно [11]. ...
... Таким образом, полученные результаты полностью согласуются с обоснованием исследования. Частота симптомной ГТ в настоящем исследовании была несколько выше, чем сообщалось ранее [1,12]. Это мо- ...
Objective:
The study aimed to assess effects of the simultaneous use of Cerebrolysin and intravenous thrombolysis (Alteplase) on hemorrhagic transformation (HT) and functional outcome as well as to analyze the treatment safety in acute stroke patients.
Material and methods:
It was a prospective, randomized, open-label, multicenter, parallel-group, active-controlled pilot study (Trial Registration Number: ISRCTN87656744, https://doi.org/10.1186/ISRCTN87656744, Trial registration date: 16/02/2021). The intervention group (n=126) was treated with Cerebrolysin infusion (30 mL) started simultaneously with Alteplase (0.9 mg/kg) via a separate IV line. The Cerebrolysin treatment continued for 14 consecutive days with the baseline therapy along. The control group (n=215) received only Alteplase and the baseline therapy. The primary endpoints were the rate of any and symptomatic hemorrhagic transformation (HT) from admission to day 14. Secondary endpoints were treatment safety and functional outcome measured with the National Institutes of Health stroke scale (NIHSS) in 24 h and on day 14, and with the modified Rankin scale (mRS) on day 90.
Results:
Treatment with Cerebrolysin resulted in a significant reduction of the symptomatic HT rate with an odds ratio of 0.248 (95% CI: 0.072-0.851; p=0.019). No serious adverse events related to Cerebrolysin were observed. On day 14, the intervention group showed a significant reduction in the NIHSS score (p=0.045). However, no difference in the mRS score was observed on day 90, but there was a trend towards its improvement.
Conclusion:
The combination of Cerebrolysin and Alteplase was safe and significantly reduced the rate of symptomatic HT and improved early neurological deficit. However, no difference in functional outcome was found on day 90, but there was a trend towards favorable functional outcome.
... This rate of sICH was slightly higher than the 5-8% reported in pivotal randomized clinical trials that evaluated either IVT or MT [20]. A meta-analysis based on 4254 patients with acute ischemic stroke who received bridging therapy found a rate of hemorrhagic transformation of 6.8% [21]. ...
(1) Background: bridging revascularization therapy is now the standard of care in patients with ischemic stroke due to large vessel occlusion. This study aimed to determine the frequency of symptomatic intracranial hemorrhage (sICH) related to this treatment, and to assess contributing factors and patients’ outcomes. (2) Methods: consecutive ischemic stroke patients treated with bridging therapy were prospectively enrolled. sICH (intracranial hemorrhage with an increase in NIHSS score of ≥4 points) was assessed on imaging at 24 h. The functional status of patients was measured at 6 months using the mRS score; (3) Results: 176 patients were included (mean age 68.7 ± 1.2 years, 52.3% women), among whom 15 (8.5%) had sICH. Patients with sICH had more frequent alcohol abuse (30.1% versus 9.7%, p = 0.023), prestroke use of dual antiplatelet therapy (14.3% versus 1.3%, p = 0.002), higher NIHSS scores at admission (median score 20.5 versus 15, p = 0.01), greater systolic blood pressure upon admission, more frequent vascular intracranial calcifications (p = 0.004), leukoaraiosis (p = 0.001), and intracranial atheroma (p = 0.02), and higher neutrophil-to-lymphocyte ratios (p = 0.02) and neutrophil-to-platelet ratios (p = 0.04). At 6-month follow-up, 9 (60%) patients with sICH died, versus 18% of patients without sICH (p < 0.001). Only 1 (7%) patient with sICH had a good functional outcome, defined as an mRS score of 0 to 2, versus 51% of patients without sICH. (4) Conclusions: one in twelve ischemic stroke patients treated with bridging therapy suffered sICH. Given the observed poor outcomes after sICH, further studies are required to better identify patients at risk to help clinicians in guiding therapeutic strategies.
... The minimum detectable odds ratio (OR) for any HT was assumed as low as 0.5. The probability of any HT among controls was expected as high as 0.2 [16]. The significance level, power, and correlation of any HT between the arms were set at the values recommended by the software manual, which were 0.05, 0.8, and 0.3, respectively [15]. ...
... p = 0.022), respectively. In the ITT population, the NNT (benefit) to reduce any and symptomatic HT with Cerebrolysin was 13.545 (95% CI, 68.282 (harm) to 6.161 (benefit)) and 16.319 (95% CI, 8.536 (benefit) to 184.973 (benefit)), respectively. ...
... However, the rate of symptomatic HT observed in our study was higher than it was reported in other IVT clinical trials [1,16]. The difference could be attributed to a peculiar set of HT predictors in the recruited patients (Table 4) and required a separate sub-analysis beyond the scope of the current research. ...
Background
Cerebrolysin could mitigate reperfusion injury and hemorrhagic transformation (HT) in animal models of acute ischemic stroke.
Methods
This was a prospective, randomized, open-label, parallel-group with active control, multicenter pilot study. Cerebrolysin (30 mL/day over 14 days) was administered concurrently with alteplase (0.9 mg/kg) in 126 patients, whereas 215 control patients received alteplase alone. The primary outcomes were the rate of any and symptomatic HT assessed from day 0 to 14. The secondary endpoints were drug safety and functional outcome measured with the National Institutes of Health Stroke Scale (NIHSS) on day 1 and 14, and the modified Rankin scale (mRS) on day 90. Advanced brain imaging analysis was applied on day 1 and 14 as a marker for in vivo pharmacology of Cerebrolysin.
Results
Cerebrolysin treatment resulted in a substantial decrease of the symptomatic HT rate with an odds ratio (OR) of 0.248 (95% CI: 0.072–0.851; p = 0.019). No serious adverse events attributed to Cerebrolysin occurred. On day 14, the Cerebrolysin arm showed a significant decrease in the NIHSS score (p = 0.045). However, no difference in the mRS score was observed on day 90. A substantial improvement in the advanced brain imaging parameters of the infarcted area was evident in the Cerebrolysin group on day 14.
Conclusions
Early add-on of Cerebrolysin to reperfusion therapy was safe and significantly decreased the rate of symptomatic HT as well as early neurological deficit. No effect on day 90 functional outcome was detected. Improvements in the imaging metrics support the neuroprotective and blood–brain barrier stabilizing activity of Cerebrolysin.
Trial registration
Name of Registry: ISRCTN.
Trial Registration Number: ISRCTN87656744.
Trial Registration Date: 16/02/2021.
... Cardioembolic stroke is a subtype of ischemic stroke with a high rate of neurologic disability upon discharge, a high mortality rate, and a tendency for both early and late embolic recurrence [9] . Hemorrhagic transformation is a type of cerebral hemorrhage caused by infarction that is a common spontaneous complication of prolonged, untreated acute ischemic stroke [10] . The clinical presentation (neurologic deterioration or deterioration as measured by the National Institutes of Health Stroke Scale scores) and radiological findings of bleeding on CT-Scan or magnetic resonance imaging within 48 hours of the ischemic stroke can be used to suspect hemorrhagic transformation [ 11 ,12 ]. ...
Cardioembolic stroke is the second leading cause of mortality and the leading cause of long-term morbidity. Embolisms of cardiac origin, such as atrial fibrillation, represent about one-fifth of all ischemic strokes. Patients with acute atrial fibrillation frequently require anticoagulation, which increases the risk of hemorrhagic transformation. A 67-year-old woman was brought to the Emergency Department with decreased consciousness, weakness on the left side, facial expression, and slurred speech. The patient had a history of atrial fibrillation and was taking regular medications acarbose, warfarin, candesartan and bisoprolol. She has had an ischemic stroke about a year ago. Left hemiparesis, hyperreflexias, pathologic reflexes, and central type of facial nerve palsy were found. The CT-Scan results revealed hyperacute to acute thromboembolic cerebral infraction in the frontotemporoparietal lobe to the right basal ganglia accompanied by hemorrhagic transformation. Massive cerebral infarction, history of previous stroke, and use of anticoagulants are among the greatest risk factors for hemorrhagic transformation in these patients. The use of warfarin should be of particular concern to the clinician, because hemorrhagic transformation is associated with poorer functional outcome and morbidity and mortality.
... Hemorrhagic complications, especially symptomatic intracranial hemorrhage (sICH), are the most feared and least treatable consequences of thrombolytic therapy, which may limit the use of rt-PA in patients with AIS. The risk of sICH varies from 2 to 8% depending on the definition used (based on NINDS, ECASS-II, III, ATLANTIS, and SITS-MOST studies) (10), while asymptomatic hemorrhagic transformation (HT) occurs in 18% (11). Several studies have demonstrated that HT after AIS is associated with poor functional outcomes and higher mortality rates (12). ...
Introduction
Acute ischemic stroke (AIS) is a potentially devastating disease with high disability and mortality. Recombinant tissue plasminogen activator (rt-PA) is an effective treatment with a 2–8% possible risk for symptomatic intracranial hemorrhage (sICH). Our aim was to investigate the risk factors and long-term clinical outcomes of ICH in patients after rt-PA treatment.
Methods
Consecutive patients with AIS, thrombolysed at the Department of Neurology, University of Debrecen, between 1 January 2004 and 31 August 2016 were enrolled prospectively. Risk factors, stroke severity based on the National Institute of Health Stroke Scale (NIHSS), functional outcome using the modified Rankin scale, and mortality at 1 year were compared in patients with and without ICH following rt-PA treatment. We evaluated clinical characteristics and prognosis by hemorrhage type based on the Heidelberg Bleeding Classification. Descriptive statistics, the chi-square test, the Mann–Whitney U-test, ANOVA, the Kruskal–Wallis test, a survival analysis, and logistic regression were performed as appropriate.
Results
Out of 1,252 patients with thrombolysis, ICH developed in 138 patients, with 37 (2.95%) being symptomatic. Mean ages in the ICH and non-ICH groups differed significantly (p = 0.041). On admission, the 24-h NIHSS after thrombolysis was higher in patients with ICH (p < 0.0001). Large vessel occlusion was more prevalent in patients with ICH (p = 0.0095). The ICH risk was lower after intravenous thrombolysis than intra-arterial or combined thrombolysis (p < 0.0001). Both at 3 months and 1 year, the outcome was worse in patients with ICH compared to patients without ICH group (p < 0.0001). Mortality and poor outcome were more prevalent in all hemorrhage types with a tendency for massive bleeding associated with unfavorable prognosis. At 3 months with the logistic regression model, the worse outcome was detected in patients with ICH after thrombolysis, at 1 year in patients with ICH after thrombolysis and smoking.
Discussion
Older age, higher NIHSS, large vessel occlusion, and intra-arterial thrombolysis may correlate with ICH. The unfavorable outcome is more common in patients with ICH. Precise scoring of post-thrombolysis bleeding might be a useful tool in the evaluation of the patient's prognosis. Our findings may help to identify predictors and estimate the prognosis of ICH in patients with AIS treated with rt-PA.
... In contrast, several studies also found MT to be safe and effective in both M1 [13,15,19] and M2 occlusions [6]. In our study, 1 out of 11 in the MT group (9.1%) and 6 out of 35 (17.1%) in the MM subgroup resulted in post treatment hemorrhage, which are both within the range of prior reports [33,34]. The higher percentages in both subgroups may be a function of the small sample size. ...
Background and purpose:
Minor acute ischemic stroke (AIS) patients-defined by an NIHSS score < 6-presenting with proximal middle cerebral artery large vessel occlusions (MCA-LVO) is a subgroup for which treatment is still debated. Although these patients present with minor symptoms initially, studies have shown that several patients afflicted with MCA-LVO in this subgroup experience cognitive and functional decline. Although mechanical thrombectomy (MT) is the standard of care for patients with an NIHSS score of 6 or higher, treatment in the minor stroke subgroup is still being explored. The purpose of this preliminary study is to report our center's experience in evaluating the potential benefit of mechanical thrombectomy (MT) in minor stroke patients when compared to medical management (MM).
Methods:
We performed a retrospective study with two comprehensive stroke centers within our hospital enterprise of consecutive patients presenting with minor AIS secondary to MCA-LVO (defined as M1 or proximal M2 segments of MCA). We subsequently evaluated patients who received MT versus those who received MM.
Results:
Between January 2017 and July 2021, we identified 46 AIS patients (11 treated with MT and 35 treated with MM) who presented with an NIHSS score < 6 secondary to MCA-LVO (47.8% 22/46 female, mean age 62.3 years, range 49-75 years). MT was associated with a significantly lower mRS at 90 days (median: 1.0 [IQR 0.0-2.0] versus 3.0 [IQR 1.0-4.0], p = <0.001), a favorable NIHSS shift (-4.0 [IQR -10.0--2.0] versus 0.0 [IQR -2.0-1.0], p = 0.002), favorable NIHSS shift dichotomization (5/11, 45.5% versus 3/35, 8.6%, p = 0.003) and favorable mRS dichotomization (7/11, 63.6% versus 14/35, 40.0%, p = 0.024).
Conclusions:
In our center's preliminary experience, for AIS patients presenting with an NIHSS score < 6 secondary to MCA-LVO, MT may be associated with improved clinical outcomes when compared to MM only.
