Thrombolysis For Acute Ischemic Stroke Research Articles

Comparative Assessment of the Proteolytic Stability and Impact of Poly-Arginine Peptides R18 and R18D on Infarct Growth and Penumbral Tissue Preservation Following Middle Cerebral Artery Occlusion in the Sprague Dawley Rat.

Poly-arginine peptides R18 and R18D have previously been demonstrated to be neuroprotective in ischaemic stroke models. Here we examined the proteolytic stability and efficacy of R18 and R18D in reducing infarct core growth and preserving the ischaemic penumbra following middle cerebral artery occlusion (MCAO) in the Sprague Dawley rat. R18 (300 or 1000nmol/kg), R18D (300nmol/kg) or saline were administered intravenously 10min after MCAO induced using a filament. Serial perfusion and diffusion-weighted MRI imaging was performed to measure changes in the infarct core and penumbra from time points between 45- and 225-min post-occlusion. Repeated measures analyses of infarct growth and penumbral tissue size were evaluated using generalised linear mixed models (GLMMs). R18D (300nmol/kg) was most effective in slowing infarct core growth (46.8mm3 reduction; p < 0.001) and preserving penumbral tissue (21.6% increase; p < 0.001), followed by R18 at the 300nmol/kg dose (core: 29.5mm3 reduction; p < 0.001, penumbra: 12.5% increase; p < 0.001). R18 at the 1000nmol/kg dose had a significant impact in slowing core growth (19.5mm3 reduction; p = 0.026), but only a modest impact on penumbral preservation (6.9% increase; p = 0.062). The in vitro anti-excitotoxic neuroprotective efficacy of R18D was also demonstrated to be unaffected when preincubated for 1-3h or overnight, in a cell lysate prepared from dying neurons or with the proteolytic enzyme, plasmin, whereas the neuroprotective efficacy of R18 was significantly reduced after a 2-h incubation. These findings highlight the capacity of poly-arginine peptides to reduce infarct growth and preserve the ischaemic penumbra, and confirm the superior efficacy and proteolytic stability of R18D, which indicates that this peptide is likely to retain its neuroprotective properties when co-administered with alteplase during thrombolysis for acute ischaemic stroke.

Golden Hour Thrombolysis in Acute Ischemic Stroke: The Changing Pattern in South Korea.

Golden Hour Thrombolysis in Acute Ischemic Stroke: The Changing Pattern in South Korea.

An automatic machine learning approach for ischemic stroke onset time identification based on DWI and FLAIR imaging

Current thrombolysis for acute ischemic stroke (AIS) treatment strictly relies on the time since stroke (TSS) less than 4.5 h. However, some patients are excluded from thrombolytic treatment because of the unknown TSS. The diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch can simply identify TSS since lesion intensities are not identical at different onset time. In this paper, we propose an automatic machine learning method to classify the TSS less than or more than 4.5 h. First, we develop a cross-modal convolutional neural network to accurately segment the stroke lesions from DWI and FLAIR images. Second, the features are extracted from DWI and FLAIR according to the segmentation regions of interest (ROI). Finally, the features are fed to machine learning models to identify TSS. In DWI and FLAIR ROI segmentation, the networks obtain high Dice coefficients with 0.803 and 0.647. The classification test results show that our model achieves an accuracy of 0.805, with a sensitivity of 0.769 and a specificity of 0.840. Our approach outperforms human reading DWI-FLAIR mismatch model, illustrating the potential for automatic and fast TSS identification.

Off-label use of intravenous thrombolysis for acute ischemic stroke: a critical appraisal of randomized and real-world evidence.

Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary.

Successful intravenous thrombolysis for acute ischemic stroke caused by aortic dissection with severe hypofibrinogenemia: a case report and literature review

Background Intravenous thrombolysis (IVT) for acute brain infarctions caused by aortic dissection (AD) may lead to fatal outcomes; thus, it should be ruled out, especially if hypofibrinogenemia occurs after IVT. Successful management of AD-related acute brain infarction with hypofibrinogenemia after IVT has not been reported previously. Case report An 84-year-old woman developed sudden left limb weakness and aphasia for almost 4 h. Alteplase was administered intravenously immediately after cerebral hemorrhage was ruled out by emergent head computed tomography (CT). An anomaly suspected to be AD was detected during subsequent routine chest CT, which was confirmed by CT angiography to be a thoracoabdominal aortic dissecting aneurysm (DeBakey type I). Severe hypofibrinogenemia was also noted. After effective blood pressure control, intramuscular injection of vitamin K, and rehydration therapy, her brain cell metabolism improved, hemiplegia improved slightly, and hypofibrinogenemia recovered gradually. The patient’s cerebral hemorrhage did not progress, there was no chest pain or no aggravation of hemiplegia, and the fibrinogen level gradually returned to normal. The condition was stable during hospitalization. At 1.5 months after discharge, the patient showed minimal change in condition. Conclusion The symptoms of AD may be nonspecific and latent. IVT may be allowed to perform for some patients with AD related ischemical stroke, And IVT can improve the neural symptoms of AD-related ischemic stroke, but close monitoring is needed to avoid aneurysm rupture. Fibrinogen levels should also be monitored periodically after IVT for early detection of hypofibrinogenemia.

Examining outcomes following thrombolysis in an increasingly older and dependent stroke population.

Thrombolysis for acute ischaemic stroke (AIS) patients aged ˜80 years is evidence based, although its use in previously dependent patients is controversial. Data from 831 thrombolysed AIS patients in our centre from 2009-2017 were used to compare demographic trends and outcomes (haemorrhage, mortality, three-month independence) in patients aged <80 and ˜80 years and with prior dependency. Comparison with UK and world registry data regarding age and pre-stroke dependency was made. The percentage of treated patients aged ˜80 years increased year-on-year, doubling from 25% to 50% (p <0.01), with increasing average age and pre-stroke dependency in world centres. Patients ˜80 years had higher (p <0.001) stroke severity, symptomatic intracerebral haemorrhage (5% vs. 1.5%), mortality (35% vs. 13%) and lower three month independent survival (24% vs. 60%). Patients with pre-stroke dependency had especially higher three month mortality (57-71%, OR 3.75 [95% CI 1.97-7.15]) in both age groups. Patients aged ˜80 years and with dependency increasingly receive thrombolysis. Given poorer outcomes thrombolysis trials are needed in pre-stroke dependent patients.

Identifying and Addressing Barriers to Systemic Thrombolysis for Acute Ischemic Stroke in the Inpatient Setting: A Quality Improvement Initiative.

ObjectivesTo identify barriers to inpatient alteplase administration and implement an interdisciplinary program to reduce time to systemic thrombolysis.Patients and MethodsCompared with patients presenting to the emergency department with an acute ischemic stroke (AIS), inpatients are delayed in receiving alteplase for systemic thrombolysis. Institutional AIS metrics were extracted from the electronic medical records of patients presenting as an inpatient stroke alert. All patients who received alteplase for AIS were included in the analysis. A gap analysis was used to assess institutional deficiencies. An interdisciplinary intervention was initiated to address these deficiencies. Efficacy was measured with pre- and postintervention surveys and institutional AIS metric analysis. Statistical significance was determined using the Student t test. We identified 5 patients (mean age, 73 years; 100% (5/5) male; 80% (4/5) white) who met inclusion criteria for the preintervention period (January 1, 2017, to December 31, 2017) and 10 patients (mean age, 71 years; 50% male; 80% white) for the postintervention period (October 31, 2018, to July 1, 2020).ResultsWe found barriers to rapid delivery of thrombolytic treatment to include alteplase availability and comfort with bedside reconstitution. Interdisciplinary intervention strategies consisted of stocking alteplase on additional floors as well as structured education and hands-on alteplase reconstitution simulations for resident physicians. The mean time from stroke alert to thrombolysis was shorter postintervention than preintervention (57.4 minutes vs 77.8 minutes; P=.03).ConclusionA coordinated interdisciplinary approach is effective in reducing time to systemic thrombolysis in patients experiencing AIS in the inpatient setting. A similar program could be implemented at other institutions to improve AIS treatment.

Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples.

Rationale: More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success.Hypothesis: We hypothesize that individual patient plasmin potential, as measured by in vitro response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early.Methods: This study will use historical samples from the Barcelona Stroke Thrombolysis Biobank, comprised of 350 pre-thrombolysis plasma samples from ischaemic stroke patients who received serial transcranial-Doppler (TCD) measurements before and after thrombolysis. The plasmin potential of each patient will be measured using the level of plasmin-antiplasmin complex (PAP) generated after in-vitro addition of rt-PA. Levels of antiplasmin, plasminogen, t-PA activity, and PAI-1 activity will also be determined. Association between plasmin potential variables and time to recanalization [assessed on serial TCD using the thrombolysis in brain ischemia (TIBI) score] will be assessed using Cox proportional hazards models, adjusted for potential confounders.Outcomes: The primary outcome will be time to recanalization detected by TCD (defined as TIBI ≥4). Secondary outcomes will be recanalization within 6-h and recanalization and/or haemorrhagic transformation at 24-h. This analysis will utilize an expanded cohort including ~120 patients from the Targeting Optimal Thrombolysis Outcomes (TOTO) study.Discussion: If association between proteolytic response to rt-PA and recanalization is confirmed, future clinical treatment may customize thrombolytic therapy to maximize outcomes and minimize adverse effects for individual patients.

Reader response: Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window.

The timely meta-analysis by Tsivgoulis et al.1 is an illustration of the transformative shift in hyperacute stroke management that has characterized the last several years. Focus has appropriately expanded beyond the classic mantra, “time is brain,” to view time as a necessary, but no longer sufficient, surrogate for predicting functional outcome and to recognize that, perhaps, now “penumbra is key.” Ultimately, this is an extraordinary advance for the more than 13 million people having new stroke each year2 and the first-line health care professionals who help treat them. The summation of these studies prompted the American Heart Association to update recommendations about thrombolysis in an extended time window. 2019 Guidelines now provide a Class IIa recommendation, supporting IV alteplase administration in select patients with unclear time of onset and MRI diffusion-positive FLAIR-negative lesions who have symptom recognition within 4.5 hours.3

Editors' note: Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window

In their recent meta-analysis of 4 randomized-controlled trials (RCTs) evaluating the safety and efficacy of IV alteplase for patients treated beyond 4.5 hours after last known well, Dr. Tsivgoulis et al. confirm each trial's reported advantage of treatment over placebo. Although the risk-to-benefit ratio of IV alteplase undoubtedly dwindles with time—as prior trials and meta-analyses have demonstrated—there is a population of slow—or perhaps, slower—progressors who may yet benefit from treatment in the extended treatment window. Important to note is the 4 included RCTs from this meta-analysis restricted patient inclusion based on the presence of a reversible ischemic lesion, as identified via perfusion CT or diffusion-weighted MRI. Among patients who meet these imaging and other clinical criteria, the risk of symptomatic hemorrhage following thrombolysis is considerable (adjusted odds ratio 6.22, 95% confidence interval 1.37–28.26), and yet the long-term outcomes demonstrate a clear functional benefit without a higher probability of mortality. In response, Dr. Ishida cautions readers that these data do not indicate a shift in the paradigm of acute treatment for all-comers. Instead, they should be used to extend treatment opportunities for historically ineligible patients. What's more is that we should not use these data to justify treatment delays or to curtail stroke education emphasizing rapid evaluation and triage for stroke-like symptoms. Time is still tissue, although it may be more or less tissue on the individual patient level. In their recent meta-analysis of 4 randomized-controlled trials (RCTs) evaluating the safety and efficacy of IV alteplase for patients treated beyond 4.5 hours after last known well, Dr. Tsivgoulis et al. confirm each trial's reported advantage of treatment over placebo. Although the risk-to-benefit ratio of IV alteplase undoubtedly dwindles with time—as prior trials and meta-analyses have demonstrated—there is a population of slow—or perhaps, slower—progressors who may yet benefit from treatment in the extended treatment window. Important to note is the 4 included RCTs from this meta-analysis restricted patient inclusion based on the presence of a reversible ischemic lesion, as identified via perfusion CT or diffusion-weighted MRI. Among patients who meet these imaging and other clinical criteria, the risk of symptomatic hemorrhage following thrombolysis is considerable (adjusted odds ratio 6.22, 95% confidence interval 1.37–28.26), and yet the long-term outcomes demonstrate a clear functional benefit without a higher probability of mortality. In response, Dr. Ishida cautions readers that these data do not indicate a shift in the paradigm of acute treatment for all-comers. Instead, they should be used to extend treatment opportunities for historically ineligible patients. What's more is that we should not use these data to justify treatment delays or to curtail stroke education emphasizing rapid evaluation and triage for stroke-like symptoms. Time is still tissue, although it may be more or less tissue on the individual patient level.

Association between chronic kidney disease and outcomes among admissions for acute ischemic stroke receiving thrombolysis

Abstract Background Patients with chronic kidney disease may have hemostatic defects that increase the risk of bleeding following the administration of thrombolysis. Purpose We assessed the association between chronic kidney disease and intracerebral hemorrhage in acute ischemic stroke admissions receiving thrombolysis. Methods Using administrative data from the 2013 and 2014 National Inpatient Sample, adult acute ischemic stroke admissions treated with thrombolysis were identified. Patients with chronic kidney disease were identified via diagnostic coding. We used multivariable logistic regression to estimate the odds of intracerebral hemorrhage in patients with chronic kidney disease after adjustment for age and comorbidities. The association between chronic kidney disease and in-hospital mortality was also evaluated. Results Of 13,993 admissions treated with thrombolysis for acute ischemic stroke, 12.4% (n=1,739) had chronic kidney disease. Intracerebral hemorrhage occurred in 7.6% of patients and 7.0% experienced in hospital mortality. Chronic kidney disease did not increase the odds of intracerebral hemorrhage (odds ratio [OR]=1.00; 95% confidence interval [CI]=0.83–1.20). The adjusted odds of in-hospital mortality were also no different in those with versus without chronic kidney disease (OR=1.19; 95% CI=0.99–1.42). Conclusions Among admissions treated with thrombolysis for acute ischemic stroke, chronic kidney disease was not associated with a higher adjusted odd of intracerebral hemorrhage. Chronic kidney disease did not increase the odds of in-hospital mortality. Funding Acknowledgement Type of funding source: Other. Main funding source(s): SmartState Medication Safety

Serum homocysteine level is an independent predictor for hemorrhagic transformation within 24 h of intravenous thrombolysis in acute ischemic stroke

The study aimed to investigate the role of serum homocysteine in hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 h of intravenous (IV) recombinanttissueplasminogenactivator(rt-PA) in acute ischemic stroke (AIS) patients. 236 consecutive AIS patients (169 men, median 65 years old) who underwent to IV rt-PA within 4.5 h of symptom onset were retrospectively recruited and analyzed. The serum homocysteine levels ranged from 4.45 to 67.71 (median 12.05) μmol/L. HT was observed in 28 (11.9%) patients, including 7 (3.0%) sICH patients within 24 h of IV rt-PA. Multiple parameters were compared between HT and non-HT patients as well as sICH and non-sICH patients. The serum homocysteine levels were higher in patients with HT than in those without HT (13.00 vs. 11.70 μmol/L, P = 0.025) and an independent association between serum homocysteine level and HT within 24 h of IV rt-PA was identified via multivariable logistic regression analysis (odds ratio [OR] = 1.103, 95% confidence interval [CI] = 1.021–1.191, P = 0.013). Moreover, serum homocysteine levels were also significantly higher in patients with sICH than in those without sICH (15.19 vs. 11.73 μmol/L, P = 0.005).Our study suggests that serum homocysteine level is an independent predictor for HT within 24 h of IV rt-PA in AIS patients.

Effect of off-hour versus work-hour thrombolysis for acute ischemic stroke on emergency department patients' outcome: a retrospective study.

Early management of patients with acute ischemic stroke is crucial regardless of the time of presentation. The aim of the study was to evaluate the effect of off-hours management of patients with ischemic stroke that underwent thrombolytic therapy in the emergency department. This is a single-center retrospective study included ischemic stroke patients who received thrombolysis in the emergency department from January 2009 to April 2017. Patients who presented between 08:00 and 17:00 Monday to Friday were in the 'work-hour group (group 1)' versus others who were considered 'off-hours (group 2)'. Primary endpoint was 3-month mortality. Secondary endpoints included the National Institutes of Health Stroke Scale and dramatic recovery rate at 24 h, intracranial hemorrhage, systemic hemorrhage and modified Rankin Scale at the 3 months. Symptom-to-needle time, door-to-computed tomography time, and door-to-needle time were also compared between groups. A total of 399 ischemic stroke patients were included in the analysis, 137 (34%) during work-hours and 262 (66%) during off-hours. The mortality rate was not different at 3 months between groups: 24 (17.5%) in the work-hours group versus 38 (14.5%) in the off-hours group [odds ratio 1.25; 95% confidence interval (CI), 0. 72-2.19]. There were no differences between groups on secondary endpoints. The mean time of symptom-to-needle was significantly higher during off-hours (mean difference: 18.4 min; 95% CI, 7.81-29.0). In this study, there were no significant differences in mortality and functional outcomes at 3 months between patients who underwent off-hour or work-hour thrombolysis in the emergency department.

Treatment with Delipid Extracorporeal Lipoprotein Filter from Plasma after Intravenous Thrombolysis for Acute Ischemic Stroke: A Single-Center Experience

Introduction: The delipid extracorporeal lipoprotein filter from plasma (DELP) has been approved for the treatment of acute ischemic stroke (AIS) by the China Food and Drug Administration, but its effectiveness and mechanism are not yet fully determined. The purpose of this study was to evaluate the effect of DELP treatment on AIS patients after intravenous thrombolysis. Methods: A retrospective study was performed on AIS patients with no improvement within 24 h after intravenous thrombolysis who were subsequently treated with or without DELP. Primary outcome was the proportion with a modified Rankin scale (mRS) of 0–1 at 90 days. Secondary outcomes were changes in National Institute of Health Stroke Scale (NIHSS) score from 24 h to 14 days after thrombolysis, and the rate of improvement in stroke-associated pneumonia (SAP). The main safety outcomes were the rates of symptomatic intracranial hemorrhage and mortality. To investigate its mechanisms, serum biomarkers were measured before and after DELP. Results: A total of 252 patients were recruited, 63 in the DELP group and 189 matched patients in the NO DELP group. Compared with the NO DELP group, the DELP group showed an increase in the proportion of mRS 0–1 at 90 days (p = 0.042). More decrease in NIHSS from 24 h to 14 days (p = 0.024), a higher rate of improvement in SAP (p = 0.022), and lower mortality (p = 0.040) were shown in DELP group. Furthermore, DELP decreased levels of interleukin (IL)-1β, E-selectin, malondialdehyde, matrix metalloprotein 9, total cholesterol, low-density lipoprotein, and fibrinogen, and increased superoxide dismutase (p< 0.05). Conclusions: DELP following intravenous thrombolysis should be safe, and is associated with neurological function improvement, possibly through multiple neuroprotective mechanisms. Prospective trials are needed.

Brain imaging abnormalities and outcome after acute ischaemic stroke: the ENCHANTED trial

ObjectiveTo test the hypothesis that imaging signs of ‘brain frailty’ and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the...

Prognostic significance of early systolic blood pressure variability after endovascular thrombectomy and intravenous thrombolysis in acute ischemic stroke: A systematic review and meta-analysis.

ObjectivesPrevious studies have shown inconsistent results regarding the effect of early systolic blood pressure variability (SBPV) after endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) on functional outcome in acute ischemic stroke (AIS). The systematic review and meta‐analysis aimed to determine the effect of early SBPV after EVT and IVT on outcome in AIS.Materials and MethodsWe searched for articles published before February 2020 in the following databases: PubMed, Web of Science, EMBASE, Medline, and Google Scholar. The pooled multivariate odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs) were obtained using STATA 13.0 software.ResultsIncreased early SBPV after EVT was significantly associated with worse functional outcome in AIS (OR = 1.42, 95% CI 1.02 to 1.99, I 2 = 82.4%, p value of Q test < .001), whereas no significant associations were indicated between SBPV after IVT and functional outcome, symptomatic intracerebral hemorrhage (sICH) in AIS [functional outcome: RR = 1.08, 95% CI 0.96 to 1.22, I 2 = 0.0%, p value of Q test = 0.793; sICH: RR = 2.40, 95% CI 0.71 to 8.03, I 2 = 78.2%, p value of Q test = 0.01].ConclusionsThe present study provided evidence that increased early SBPV after EVT is related to worse longer‐term functional outcome in AIS, but the association is not significant in AIS patients treated with IVT. Furthermore, individualized BP management strategies were essential for AIS patients after EVT or IVT.

Implementation of regional Acute Stroke Care Map increases thrombolysis rates for acute ischaemic stroke in Chinese urban area in only 3 months

BackgroundThe rate of intravenous thrombolysis for acute ischaemic stroke remains low in China. We investigated whether the implementation of a citywide Acute Stroke Care Map (ASCaM) is associated with an...

Analysis of thrombolysis in acute ischemic stroke in economically developed and developing regions in Guangdong, China

Analysis of thrombolysis in acute ischemic stroke in economically developed and developing regions in Guangdong, China

Neutrophil Counts to High-Density Lipoprotein Cholesterol Ratio: a Potential Predictor of Prognosis in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Neutrophil counts to high-density lipoprotein cholesterol ratio (NHR) is a relatively new and readily available indicator, and our study aimed to demonstrate its relationship with short-term prognosis after intravenous thrombolysis in acute ischemic stroke (AIS) patients and to make a simple comparison with other prognostic indicators. We compared demographic and laboratory characteristics of AIS patients and healthy controls and grouped AIS patients according to NHR tertiles to contrast 3-month outcomes. Univariate and multivariate regression analyses were carried to further analyze the relationship between NHR and prognosis. Moreover, we compared the accuracy of several factors using receiver-operating characteristic curve. NHR levels of AIS patients were higher than those of healthy controls (p < 0.001). The NHR levels were significantly higher in AIS patients with poor prognosis than those with good prognosis (p = 0.001) and were higher in patients with severe stroke than those with mild stroke (p = 0.011). Multivariate logistic regression analysis indicated that elevated NHR was an independent predictor of poor outcomes (odds ratio = 4.570; 95% CI, 1.841-11.340; p = 0.001). High NHR levels were associated with poor 3-month outcomes after intravenous thrombolysis in AIS patients.

Low Serum Magnesium Levels Are Associated With Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke.

Background: In patients with acute ischemic stroke, hemorrhagic transformation is a major complication after intravenous thrombolysis. This study aimed to investigate the relationship between serum magnesium levels and hemorrhagic transformation (HT) after thrombolytic therapy.Methods: We retrospectively analyzed data from 242 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China. Baseline serum magnesium levels were measured before intravenous thrombolysis, and the occurrence of HT was evaluated using computed tomography images reviewed within 24–36 h after therapy. The relationship between serum magnesium levels and HT was examined using multivariate logistic regression, subgroup analysis, and restricted cubic spline models.Results: Of the 242 included patients, 43 (17.8%) developed HT. Patients with HT had significant lower serum magnesium levels than those without HT (0.81 ± 0.08 vs. 0.85 ± 0.08 mmol/L, p = 0.007). Multivariable logistic regression analysis indicated that patients with higher serum magnesium levels had lower risk of HT (OR per 0.1-mmol/L increase 0.43, 95% CI 0.27–0.73, p = 0.002). However, this association did not persist when baseline levels of serum magnesium were higher than the median value (0.85 mmol/L) in subgroup analysis (OR per 0.1-mmol/L increase 0.58, 95% CI 0.14–2.51, p = 0.47). This threshold effect was also observed in the restricted cubic spline model when serum magnesium levels were above 0.88 mmol/L. No association between symptomatic HT and serum magnesium levels was observed in our study (OR per 0.1-mmol/L increase 0.52, 95% CI 0.25–1.11, p = 0.092).Conclusions: Lower serum magnesium levels in patients with ischemic stroke are associated with an increased risk of HT after intravenous thrombolysis, but perhaps only when serum magnesium is below a certain minimal concentration.