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Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease.

ABSTRACT: AIM:Previous studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis. METHODS:We retrospectively analyzed 214 MMD patients from January 2014 to January 2016. Clinical characteristics and LMC status were compared between the pediatric and adult patients. LMC status was graded as good or poor depending on the retrograde flow from the posterior cerebral artery (PCA) on digital subtraction angiography (DSA). RESULTS:A total of 83 pediatric and 131 adult (1:1.6) MMD patients were analyzed. Pediatric patients were more likely to experience a transient ischemic attack (81%), whereas adult patients were more likely to experience infarction (51%). Regarding the different MMD stages (the early, medium, and advanced stages corresponded to Suzuki stages 1-2, 3-4, and 5-6, respectively), the prevalence of good LMC status was higher for pediatric patients than for adult patients in the early stage (P = 0.047) and the medium stage (P = 0.001), but there were no differences between these patient groups in the advanced stage (P = 0.547). Worse postoperative angiographic outcomes (P = 0.017) were found in adult patients than in pediatric patients in the medium stage. Poor LMC status had strong correlations with infarction (P < 0.001 and P = 0.017) and poor postoperative outcomes (P = 0.003 and P = 0.043) in both pediatric and adult patients. CONCLUSIONS:Pediatric MMD patients have greater patency and a greater ability to establish good LMC status than adult patients, and poor LMC status has a strong correlation with severe clinical symptoms and poor postoperative outcomes. LMC status may be an important factor in the differences in clinical characteristics and prognosis between pediatric and adult MMD patients.

SUBMITTER: Liu ZW

PROVIDER: S-EPMC6930821 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease.

Liu Zhi-Wen ZW Han Cong C Wang Hui H Zhang Qian Q Li Si-Jie SJ Bao Xiang-Yang XY Zhang Zheng-Shan ZS Duan Lian L

CNS neuroscience & therapeutics 20190413 1

<h4>Aim</h4>Previous studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis.<h4>Methods</h4>We retrospectively analyzed 214 MMD patients ...[more]

PMID: 31875482

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Project description:ObjectiveMoyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive steno-occlusion within the terminal segment of the internal carotid artery. However, good collaterals from an external carotid artery are essential to compensate for the ischemia in moyamoya disease. This study aimed to investigate the transforming growth factor-beta 1 (TGFβ1) in plasma as a potential biomarker for predicting collateral formation in ischemic MMD.MethodsThe transcriptome profile downloaded from Gene Expression Omnibus (GEO) was used to analyze the differential expression of genes between the ischemic MMD and the control groups. We prospectively recruited 23 consecutive patients with ischemic MMD that was diagnosed via digital subtraction angiography (DSA). Nine patients with intracranial aneurysms and four healthy people served as controls. The collaterals from the external carotid artery were examined using DSA. We evaluated whether the collateral formation was associated with TGFβ1 in patients with ischemic MMD. Western blot, RT-qPCR, ELISA, and tube formation assay were used to explore the relationship between TGFβ1 and angiogenesis, as well as the potential mechanisms.ResultsThe mRNA levels of TGFβ1 were upregulated in the patients with ischemic MMD. The plasma TGFβ1 levels were higher in the patients with ischemic MMD than in the aneurysm and healthy patients (p < 0.05). The collateral formation group has higher levels of serum TGFβ1 than the non-collateral formation group (p < 0.05). The levels of vascular endothelial growth factor (VEGF) are positively correlated with TGFβ1 levels in the plasma (R 2 = 0.6115; p < 0.0001). TGFβ1 regulates VEGF expression via the activation of the TGFβ pathway within HUVEC cells, as well as TGFβ1 stimulating HUVEC cells to secrete VEGF into the cell culture media. An in vitro assay revealed that TGFβ1 promotes angiogenesis within the endothelial cells.ConclusionOur findings suggest that TGFβ1 plays a vital role in promoting collateral formation by upregulating VEGF expression in ischemic MMD.

Project description:Background: The use of antiplatelet agents in ischemic moyamoya disease (MMD) is controversial. This study aimed to investigate the effectiveness and safety of antiplatelet therapy compared with conservative treatment and surgical revascularization in ischemic MMD patients. Methods: Ischemic MMD patients were retrospectively enrolled from eight clinical sites from January 2013 to December 2018. Follow-up was performed through clinical visits and/or telephone interviews from first discharge to December 2019. The primary outcome was the episodes of further ischemic attacks, and the secondary outcome was the individual functional status. Risk factors for future stroke were identified by the LASSO-Cox regression model. Propensity score matching was applied to assemble a cohort of patients with similar baseline characteristics using the TriMatch package. Results: Among 217 eligible patients, 159 patients were included in the analyses after a 1:1:1 propensity score matching. At a mean follow-up of 33 months, 12 patients (7.5%) developed further incident cerebral ischemic events (surgical:antiplatelet:conservative = 1:3:8; p = 0.030), 26 patients (16.4%) developed a poor functional status (surgical:antiplatelet:conservative = 7:12:7; p = 0.317), and 3 patients (1.8%) died of cerebral hemorrhage (surgical:antiplatelet:conservative = 1:2:0; p = 0.361). The survival curve showed that the risk of further cerebral ischemic attacks was lowest with surgical revascularization, while antiplatelet therapy was statistically significant for preventing recurrent risks compared with conservative treatment (χ2 = 8.987; p = 0.011). No significant difference was found in the functional status and bleeding events. The LASSO-Cox regression model revealed that a family history of MMD (HR = 6.93; 95% CI: 1.28-37.52; p = 0.025), a past history of stroke or transient ischemic attack (HR = 4.35; 95% CI: 1.09-17.33; p = 0.037), and treatment (HR = 0.05; 95% CI: 0.01-0.32; p = 0.001) were significantly related to the risk of recurrent strokes. Conclusions: Antiplatelet agents were effective and safe in preventing further cerebral ischemic attacks in adult patients with ischemic MMD. They may be a replacement therapy for patients with surgical contraindications and for patients prior to revascularization.

Project description:BackgroundMixed data exist regarding the association between hyperglycemia and functional outcome after acute ischemic stroke when accounting for the impact of leptomeningeal collateral flow. We sought to determine whether collateral status modifies the association between treatment group and functional outcome in a subset of patients with large vessel occlusion enrolled in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial.MethodsIn this post-hoc analysis, we analyzed patients enrolled into the SHINE trial with anterior circulation large vessel occlusion who underwent imaging with CT angiography prior to glucose control treatment group assignment. The primary analysis assessed the degree to which collateral status modified the effect between treatment group and functional outcome as defined by the 90-day modified Rankin Scale score. Logistic regression was used to model the data, with adjustments made for thrombectomy status, age, post-perfusion thrombolysis in cerebral infarction (TICI) score, tissue plasminogen activator (tPA) use, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Five SHINE trial centers contributed data for this analysis. Statistical significance was defined as a p-value < 0.05.ResultsAmong the 1151 patients in the SHINE trial, 57 with angiographic data were included in this sub-analysis, of whom 19 had poor collaterals and 38 had good collaterals. While collateral status had no effect (p = 0.855) on the association between glucose control treatment group and functional outcome, patients with good collaterals were more likely to have a favorable functional outcome (p = 0.001, OR 5.02; 95% CI 1.37-16.0).ConclusionsIn a post-hoc analysis using a subset of patients with angiographic data enrolled in the SHINE trial, collateral status did not modify the association between glucose control treatment group and functional outcome. However, consistent with prior studies, there was a significant association between good collateral status and favorable outcome in patients with large vessel occlusion stroke.Trial registrationClinicalTrials.gov Identifier is NCT01369069. Registration date is June 8, 2011.

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Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease.

Publications

Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease.

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