Association between leukoaraiosis and hemorrhagic transformation after cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease

Wei, Chuanliang; Zhang, Shuting; Wang, Yunhan; Liu, Junfeng; Li, Jie; Yuan, Ruozhen; Tan, Ge; Liu, Ming

doi:10.1016/j.jns.2017.05.001

Cited by 13 publications

(22 citation statements)

References 47 publications

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“…Patients in our study were more likely to have HT if they presented with only one marker of SVD. Several studies have reported that a single MRI marker of SVD, such as WMHs or CMBs, is associated with an increased risk of HT (16, 17, 33, 34). Cerebral SVD is associated with increased blood–brain barrier leakage in acute ischemic stroke (35), while HT is believed to result from abnormal permeability of the blood–brain barrier, which allows extravasation of blood products in or out of the ischemic region after restoration of blood flow (36).…”

Section: Discussionmentioning

confidence: 99%

A Non-linear Association Between Total Small Vessel Disease Score and Hemorrhagic Transformation After Ischemic Stroke With Atrial Fibrillation and/or Rheumatic Heart Disease

Wei

Liu

et al. 2019

Front. Neurol.

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Background: Previous studies have investigated the association between a single marker of cerebral small vessel disease (SVD) and hemorrhagic transformation (HT). However, the effect of the total SVD burden on HT has not been evaluated yet. We aimed to investigate the association between the total SVD score and HT in ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD). Methods: Ischemic stroke patients with AF and/or RHD admitted within 7 days after onset were enrolled at two hospitals in China. The total SVD score was based on the presence of lacunes, extensive white matter hyperintensities, cerebral microbleeds, and moderate to severe enlarged perivascular spaces in the basal ganglia. One point was awarded for the presence of each marker, with the total SVD score ranging from 0 to 4 points. HT was assessed based on follow-up imaging scans during hospitalization and was classified according to the radiographic appearance and associated neurological deterioration. Results: Of 207 enrolled patients (mean age, 67.79 years; 58.9% female), 89 (43.0%) developed HT. The distribution of the total SVD score was significantly different between patients with and without HT in the univariate analysis ( p = 0.04). After adjustment for confounders, a SVD score of 1 was independently associated with an increased risk of HT [odds ratio (OR), 3.23; 95% confidence interval (CI), 1.48–7.04; p = 0.003], while a SVD score ≥2 was inversely related to the occurrence of HT (OR, 0.41; 95% CI, 0.19–0.91; p = 0.03). These independent associations remained significant in the subgroups of hemorrhagic infarction and asymptomatic HT (all p < 0.05). Conclusions: In our study, the relationship between the total SVD score and HT was not linear, since the presence of only one marker of SVD was associated with an increased risk of HT, while the presence of two or more markers of SVD was a potential protective factor for HT. These results indicate the need to take the total SVD score into account, not only a single SVD marker, when assessing the risk of HT. Further studies with larger samples are required to validate these findings.

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Section: Discussionmentioning

confidence: 99%

A Non-linear Association Between Total Small Vessel Disease Score and Hemorrhagic Transformation After Ischemic Stroke With Atrial Fibrillation and/or Rheumatic Heart Disease

Wei

Liu

et al. 2019

Front. Neurol.

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“…On the other hand, there is clinical evidence that moderate to severe leukoaraiosis ((LA) or white matter lesions) presence may be related with endothelial dysfunction and blood brain barrier (BBB) damage (15)(16)(17)(18). LA presence is known to contribute to long-term functional decline, morbidity, and death in independent outpatients and in stroke patients (19).…”

Section: Introductionmentioning

confidence: 99%

sTWEAK as Predictor of Stroke Recurrence in Ischemic Stroke Patients Treated With Reperfusion Therapies

et al. 2021

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Aim: The purpose of this study was to investigate clinical and neuroimaging factors associated with stroke recurrence in reperfused ischemic stroke patients, as well as the influence of specific biomarkers of inflammation and endothelial dysfunction.Methods: We conducted a retrospective analysis on a prospectively registered database. Of the 875 patients eligible for this study (53.9% males; mean age 69.6 ± 11.8 years vs. 46.1% females; mean age 74.9 ± 12.6 years), 710 underwent systemic thrombolysis, 87 thrombectomy and in 78, systemic or intra-arterial thrombolysis together with thrombectomy was applied. Plasma levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) were analyzed as markers of inflammation, and soluble tumor necrosis factor-like inducer of apoptosis (sTWEAK) as an endothelial dysfunction marker. The main outcome variables of the study were the presence and severity of leukoaraiosis (LA) and stroke recurrence.Results: The average follow-up time of the study was 25 ± 13 months, during which 127 patients (14.5%) showed stroke recurrence. The presence and severity of LA was more severe in the second stroke episode (Grade III of the Fazekas 28.3 vs. 52.8%; p < 0.0001). IL-6 levels at the first admission and before reperfusion treatment in patients with and without subsequent recurrence were similar (9.9 ± 10.4 vs. 9.1 ± 7.0 pg/mL, p = 0.439), but different for TNFα (14.7 ± 5.6 vs. 15.9 ± 5.7 pg/mL, p = 0.031) and sTWEAK (5,970.8 ± 4,330.4 vs. 8,660.7 ± 5,119.0 pg/mL, p < 0.0001). sTWEAK values ≥7,000 pg/mL determined in the first stroke were independently associated to recurrence (OR 2.79; CI 95%: 1.87–4.16, p < 0.0001).Conclusions: The severity and the progression of LA are the main neuroimaging factors associated with stroke recurrence. Likewise, sTWEAK levels were independently associated to stroke recurrence, so further studies are necessary to investigate sTWEAK as a therapeutic target.

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“…In this line, there are clinical evidences that moderate to severe LA presence may be related to endothelial dysfunction and BBB damage. [9][10][11][12] We have recently identified an endothelial dysfunction marker, the soluble tumor necrosis factor-like inducer of apoptosis (sTWEAK), as a possible biomarker related to LA presence in patients with IS. 13 sTWEAK is constitutively expressed by monocytes, tumor cell lines, and endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

“…This suggests that the degrees of LA may indicate several pathogenesis and influence differentially the prognosis of the patients. In this line, there are clinical evidences that moderate to severe LA presence may be related to endothelial dysfunction and BBB damage 9–12 …”

Section: Introductionmentioning

confidence: 99%

The presence of leukoaraiosis enhances the association between sTWEAK and hemorrhagic transformation

Silva‐Candal

Pérez‐Mato

Rodríguez‐Yáñez

et al. 2020

Ann Clin Transl Neurol

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Objective: To investigate whether elevated serum levels of sTWEAK (soluble tumor necrosis factor-like inducer of apoptosis) might be involved in a higher frequency of symptomatic hemorrhagic transformation (HT) through the presence of leukoaraiosis (LA) in patients with acute ischemic stroke (IS) undergoing reperfusion therapies. Methods: This is a retrospective observational study. The primary endpoint was to study the sTWEAK-LA-HT relationship by comparing results with biomarkers associated to HT and evaluating functional outcome at 3-months. Clinical factors, neuroimaging variables and biomarkers associated to inflammation, endothelial/atrial dysfunction or blood-brain barrier damage were also investigated. Results: We enrolled 875 patients (mean age 72.3 AE 12.2 years; 46.0% women); 710 individuals underwent intravenous thrombolysis, 87 endovascular therapy and 78 both. HT incidence was 32%; LA presence was 75.4%. Patients with poor functional outcome at 3-months showed higher sTWEAK levels at admission (9844.2 [7460.4-12,542.0] vs. 2717.3 [1489.7-5852.3] pg/mL, P < 0.0001). By means of logistic regression models, PDGF-CC and sTWEAK were associated with mechanisms linked simultaneously to HT and LA. Serum sTWEAK levels at admission ≥6700 pg/ mL were associated with an odds ratio of 13 for poor outcome at 3-months (OR: 13.6; CI 95%: 8.2-22.6, P < 0.0001). Conclusions: Higher sTWEAK levels are independently associated with HT and poor functional outcome in patients with IS undergoing reperfusion therapies through the presence of LA. sTWEAK could become a therapeutic target to reduce HT incidence in patients with IS.

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Association between leukoaraiosis and hemorrhagic transformation after cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease

Cited by 13 publications

References 47 publications

A Non-linear Association Between Total Small Vessel Disease Score and Hemorrhagic Transformation After Ischemic Stroke With Atrial Fibrillation and/or Rheumatic Heart Disease

A Non-linear Association Between Total Small Vessel Disease Score and Hemorrhagic Transformation After Ischemic Stroke With Atrial Fibrillation and/or Rheumatic Heart Disease

sTWEAK as Predictor of Stroke Recurrence in Ischemic Stroke Patients Treated With Reperfusion Therapies

The presence of leukoaraiosis enhances the association between sTWEAK and hemorrhagic transformation

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