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

So what the fuck is the solution?

1. Test for magnesium deficiency?

2. How would you bring low levels up fast enough to not slow down thrombolysis intervention?

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

Zicheng Cheng¹, Xiaoyan Huang¹, Farah Mohamed Muse¹, Lingfan Xia¹, Zhenxiang Zhan¹, Xianda Lin², Yungang Cao¹ and Zhao Han^1*

• ¹Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
• ²Department of Neurology, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, China

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.

Introduction

Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the preferred treatment for acute ischemic stroke patients in super earlier period (≤ 4.5 h) (1). However, hemorrhagic transformation (HT) is common in patients with IVT, occurring as a consequence of coagulation dysfunction and blood-brain barrier (BBB) disruption induced by rt-PA (2, 3). Limited administration of thrombolytic drugs in stroke patients is largely due to the fear of HT. Since patients with HT are susceptible to early death or long-term disability (4, 5), it is imperative to identify the modifiable risk factors of HT after IVT.

Magnesium is an abundant endogenous neuroprotective agent that has close association with ischemic stroke (6). It also maintains the integrity of the vascular endothelial barrier through anti-inflammatory and anti-oxidation effects (7). Brain microvascular endothelium is the fundamental component of BBB and the initiation of ischemia-related BBB disruption is predominantly triggered by endothelial damage (8). Recent evidence indicates the protective effect of magnesium on BBB in rats with transient focal cerebral ischemia (9). In addition, magnesium is involved in the coagulation cascade (10, 11) and platelet activation (12); magnesium deficiency would lead to dysfunction of coagulation system. The relationship between serum magnesium levels and functional outcomes in patients with acute ischemic stroke has been widely studied. But two large-sample randomized controlled trials [the IMAGES (Intravenous Magnesium Efficacy in Stroke) trial and the FAST-MAG (Field Administration of Stroke Therapy–Magnesium) trial] showed regrettable results, which early intravenous magnesium sulfate therapy did not improve the outcomes for patients with acute stroke (13, 14). By contrast, there are very few studies on the association between serum magnesium levels and the occurrence of HT. These studies had inconsistent conclusions and did not specifically address patients with IVT (15, 16). Thus, we investigated the association of serum magnesium levels with development of HT in patients with acute ischemic stroke after IVT.

 

Early prediction of the 3-month outcome for individual acute ischemic stroke patients who received intravenous thrombolysis using the N2H3 nomogram model

 In what magical universe do you live in where ANYTHING here is going to get survivors better recovery?

Early prediction of the 3-month outcome for individual acute ischemic stroke patients who received intravenous thrombolysis using the N2H3 nomogram model

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Shan Lv, Yu Song, Fu-Liang Zhang, ...

First Published September 4, 2020 Research Article 

https://doi.org/10.1177/1756286420953054

Article information

 

Abstract

Background:

The aim of this study was to establish a nomogram model for individualized early prediction of the 3-month prognosis in patients with acute ischemic stroke (AIS) who were treated with intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis.

Methods:

A total of 691 patients were included in this study; 564 patients were included in the training cohort, while 127 patients were included in the test cohort. The main outcome measure was a 3-month unfavorable outcome (modified Rankin Scale 3–6). To construct the nomogram model, stepwise logistic regression analysis was applied to select the significant predictors of the outcome. The discriminative performance of the model was assessed by calculating the area under the receiver operating characteristic curve (AUC-ROC). A decision curve analysis was used to evaluate prognostic value of the model.

Results:

The initial National Institutes of Health Stroke Scale [NIHSS, odds ratio (OR), 1.35; 95% confidence interval (CI), 1.28–1.44; p < 0.001], delta NIHSS (changes in the NIHSS score from baseline to 24 h, OR, 0.75; 95% CI, 0.70–0.79; p < 0.001), hypertension (OR, 2.07; 95% CI, 1.32–3.31; p = 0.002), hyperhomocysteinemia (Hhcy, OR, 2.18; 95% CI, 1.20–4.11; p = 0.013), and the ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) (HDL-C/LDL-C, OR, 3.29; 95% CI, 1.00–10.89; p = 0.049) (N2H3) were found to be independent predictors of a 3-month unfavorable outcome from multivariate logistic regression analysis and were incorporated in the N2H3 nomogram model. The AUC-ROC of the training cohort was 0.872 (95% CI, 0.841–0.902), and the AUC-ROC of the test cohort was 0.900 (95% CI, 0.848–0.953).

Conclusion:

The study presented the N2H3 nomogram model, with initial NIHSS score, delta NIHSS, hypertension, Hhcy, and HDL-C/LDL-C as predictors. It therefore provides an individualized early prediction of the 3-month unfavorable outcome in AIS patients treated with intravenous rt-PA thrombolysis.

Keywords acute ischemic stroke, intravenous thrombolysis, nomogram, prognosis

Introduction

Ischemic stroke is highly prevalent worldwide. As one of the leading causes of disability and mortality, ischemic stroke places a significant burden on patients and caregivers. Thrombolysis has been found to be the most effective medical treatment for acute ischemic stroke (AIS) patients. The primary thrombolytic agent, recombinant tissue plasminogen activator (rt-PA), is the most widely used thrombolytic drug worldwide.^1–4 Unfortunately, some patients still experience functional deficits after rt-PA thrombolysis. Accurate and early prediction of the clinical outcome for individual AIS patients who receive rt-PA treatment is needed to provide a reasonable approach to patient management.⁵

A series of prognostic models established using various statistical methods have been reported in the past few decades with the aim of predicting long-term patient outcome after intravenous thrombolysis.^6–11 As a graphical statistical instrument, nomograms make it possible to individually predict outcomes by calculating the scores of each individual based on their own characteristics. The nomogram has been used widely for clinical decision making in multiple clinical conditions, including ischemic stroke, myocardial infarction, and cancer.^5,12–16 Nomograms have also been used to predict outcome of patients receiving thrombolysis, including the START (National Institutes of Health Stroke Scale score, age, pre-stroke mRS score, onset-to-treatment time) nomogram for prediction of unfavorable outcome and the STARTING-SICH (systolic blood pressure, age, onset-to-treatment time for thrombolysis, National Institutes of Health Stroke Scale score, glucose, aspirin alone, aspirin plus clopidogrel, anticoagulant with INR ⩽1.7, current infarction sign, hyperdense artery sign) nomogram for prediction of symptomatic intracerebral hemorrhage.^5,17

The aim of this present study was to develop and validate a simple and reliable nomogram model for early and individual prediction of 3-month prognosis in AIS patients who treated with intravenous thrombolysis. To obtain a stronger power of prediction, we use both clinical characteristics and laboratory tests as variables.

 

Mild Hypothermia Reduces Tissue Plasminogen Activator-Related Hemorrhage and Blood Brain Barrier Disruption After Experimental Stroke

Maybe we will finally have enough information on whether or not hypothermia should be applied to stroke patients. And then wait 20 years to get it rolled out. There are 15 ways to apply hypothermia right now.
http://online.liebertpub.com/doi/abs/10.1089/ther.2013.0010

ABSTRACT

Therapeutic hypothermia has shown neuroprotective promise, but whether it can be used to improve outcome in stroke has yet to be determined in patients. Recombinant tissue plasminogen activator (rt-PA) is only given to a minority of patients with acute ischemic stroke, and is not without risk, namely significant brain hemorrhage. We explored whether mild hypothermia, in combination with rt-PA, influences the safety of rt-PA. Mice were subjected to middle cerebral artery occlusion (MCAO) using a filament model, followed by 24 hours reperfusion. Two paradigms were studied. In the first paradigm, cooling and rt-PA treatment began at the same time upon reperfusion, whereas in the second paradigm, cooling began soon after ischemia onset, and rt-PA began after re-warming and upon reperfusion. Experimental groups included: tPA treatment at normothermia (37°C), rt-PA treatment at hypothermia (33°C), no rt-PA at normothermia, and no rt-PA treatment at hypothermia. Infarct size, neurological deficit scores, blood brain barrier (BBB) permeability, brain hemorrhage, and expression of endogenous tissue plasminogen activator (tPA) and its inhibitor, plasminogen activator inhibitor (PAI-1) were assessed. For both paradigms, hypothermia reduced infarct size and neurological deficits compared to normothermia, regardless of whether rt-PA was given. rt-PA treatment increased brain hemorrhage and BBB disruption compared to normothermia, and this was prevented by cooling. However, mortality was higher when rt-PA and cooling were administered at the same time, beginning 1–2 hours post MCAO. Endogenous tPA expression was reduced in hypothermic mice, whereas PAI-1 levels were unchanged by cooling. In the setting of rt-PA treatment, hypothermia reduces brain hemorrhage, and BBB disruption, suggesting that combination therapy with mild hypothermia and rt-PA appears safe.