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Background and PurposeHematoma expansion has been identified as a crucial predictor for the progress and outcome of intracranial hemorrhage(ICH). MicroRNAs (miRNAs) are associated with hematoma expansion and play important roles in regulating the mechanism of ICH. Here, we identified a miRNA, hsa-miR-1278, as a predictor of hematoma expansion and earlier estimation of ICH prognosis.MethodsThe participants who had been diagnosed with ICH by brain imaging were divided into hematoma enlargement(HE) group and non-HE group. A total of 10 samples from 2 groups were extracted and subjected to high-throughput sequencing. The differentially expressed microRNAs (DEMs) were identified by bioinformatics and quantitated by reverse transcription-polymerase quantitive chain reaction(RT-qPCR). To further validate the DEMs, We searched the Targescan database to find the target gene of the DEM and cultured the QSG7701 cells line and performed western blotting to validated the target miRNA. The Continuous variables were expressed as mean ± SD and analyzed by unpaired Student’s t-test; categorical variables were analyzed by chi-square test, and P values < 0.05 were considered statistically significant.ResultsWe performed miRNA sequencing of HE and non-HE in 10 patients with cerebral hemorrhage. We found 18 differentially expressed miRNAs in HE group. We then performed RT-qPCR verification and identified that hsa-miR-1278 was significantly increased in the HE group (P ConclusionsThe expression of hsa-miR-1278 was still significantly up-regulated in the hematoma expansion group, and therefore made the hsa-miR-1278 as a novel predictor of ICH prognosis.

BackgroundThe outcome of deploying balloon-mounted stents for symptomatic intracranial atherosclerotic stenosis (ICAS) has not been fully investigated. In this study we evaluate the safety and long-term outcome of using balloon-mounted stents to treat symptomatic ICAS in comparison with the WEAVE/WOVEN study.MethodsIn a multicenter registry study of stenting for symptomatic intracranial artery stenosis in China, 159 patients treated with an intracranial balloon-mounted stent approved by the China Food and Drug Administration were evaluated. The morphological features of the lesions were categorized by Mori classification. The endpoints, including periprocedural and long-term clinical and radiological outcomes, were the same as those in the WEAVE/WOVEN study.ResultsIn the present study the mean percent stenosis before and after stenting was 84.0% and 6.1%, respectively. The proportions of Mori A, Mori B, and Mori C lesions were 33.3%, 52.2%, and 14.5%, respectively. The 72-hour rates of stroke and mortality after the procedure were 0%. The 1-year rates of any stroke, ischemic stroke, hemorrhagic stroke, and death were 6.3% (10/159), 5.7% (9/159), 0.6% (1/159), and 0.6% (1/159), respectively. The 1-year rate of in-stent restenosis (ISR) was 23.4% (15/64). The rate of ISR in Mori C lesions (53.8%, 7/13) was significantly higher than that in Mori A (15.8%, 3/19) or Mori B lesions (15.6%, 5/32) (p=0.024).ConclusionsThe short-term and long-term outcomes of using a balloon-mounted stent for symptomatic ICAS with focal and non-angular lesions (Mori A and B type) and smooth arterial access were comparable to the results of the WEAVE/WOVEN trial.

Background Cytotoxic edema (CE) is an important form of perihematomal edema (PHE), which is a surrogate marker of secondary injury after intracerebral hemorrhage (ICH). However, knowledge about CE after ICH is insufficient. Whether CE has adverse effects on clinical outcomes of patients with ICH remains unknown. Therefore, we aimed to investigate the temporal pattern of CE and its association with clinical outcomes in patients with ICH. Methods Data were derived from a randomized controlled study (comparing the deproteinized calf blood extract with placebo in patients with ICH). Intervention in this original study did not show any impact on hematoma and PHE volume, presence of CE, or clinical outcomes. We conducted our analysis in 20 patients who underwent magnetic resonance imaging with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) images at day 3 and within 7–12 days after symptom onset. CE was defined as an elevated DWI b1000 signal and an ADC value reduced by > 10% compared with the mirror area of interest in the perihematomal region. The modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel Index (BI) were performed face to face at 30-day and 90-day follow-ups after ICH onset to assess the clinical outcomes of the patients. Results CE was detected in nearly two thirds of patients with ICH in our study and seemed to be reversible. CE within 7–12 days, rather than at day 3 after symptom onset, was associated with poor clinical outcome (mRS 3–6) at the 30-day follow-up (P = 0.020). In addition, compared with those without CE, patients with CE within 7–12 days had more severe neurological impairment measured by NIHSS score (P = 0.024) and worse daily life quality measured by BI (P = 0.004) at both the 30- and 90-day follow-ups. Conclusions CE appears in the acute phase of ICH and might be reversible. CE within 7–12 days post ICH was related to poor outcomes, which provides a novel therapeutic target for ICH intervention.

Circulating microRNAs have been shown to be biomarkers of various diseases. We aimed to investigate whether circulating microRNA can serve as a biomarker to predict ischemic stroke risk in asymptomatic intracranial artery stenosis. A total of 716 participants from the Asymptomatic Polyvascular Abnormalities Community study who had asymptomatic intracranial artery stenosis at baseline were enrolled (2010-11). Patients who suffered incident ischemic stroke were classified into the case group, and age- and sex-matched individuals without stroke were used as controls. MicroRNA microarrays were used to distinguish baseline circulating serum microRNA levels between the case and the control groups (GEO accession number GSE201860). The differentially expressed microRNAs were validated by real-time PCR. MicroRNA microarrays were performed in baseline serum samples from12 subjects who developed ischemic stroke and 12 age- and sex-matched subjects without stroke during the 2014-15 follow-up period. Twenty microRNAs were differentially expressed between the two groups (fold change 1.3 and p 0.05 for all). Hsa-miR-486-5p, hsa-miR-92a-3p, hsa-miR-6089 from them were selected and validated in the baseline serum samples of ten subjects with incident ischemic stroke and another ten age- and sex-matched subjects without stroke during the 2016-17 follow-up period. Hsa-miR-1225-5p, with a large fold change value and a reported relationship with cardiovascular or cerebrovascular diseases, was also validated. Ultimately, only hsa-miR-6089 was differentially downregulated among patients with intracranial artery stenosis who developed ischemic stroke (p 0.05). In patients with asymptomatic intracranial artery stenosis, downregulated serum hsa-miR-6089 may be associated with the risk of ischemic stroke.

Background and Purpose We investigated the relationship between basilar artery (BA) atherosclerotic stenosis features and vertebral artery (VA) stenosis and explored whether BA stenosis features are associated with perforator stroke after stenting. Methods Patients with BA stenosis who underwent HRMRI and DSA were recruited. Patients were divided into proximal BA stenosis and middle-or-distal BA stenosis groups, and then subgroup analyses were performed based on whether they had VA stenosis. BA plaque features were evaluated by HRMRI. Artery stenosis was measured by DSA. The incidence of perforator stroke after BA stenting was recorded, and the potential association between BA stenosis features and perforator stroke was analyzed. Results One hundred and seventy-four patients were consecutively enrolled. Patients with proximal BA stenosis had a higher proportion of severe stenosis than those with middle-or-distal BA stenosis ( P = 0.027). In the subgroup analysis, this difference mainly existed in patients complicated with VA stenosis ( P = 0.023). Patients with proximal BA stenosis had a higher proportion of strong plaque enhancement than those with middle-or-distal BA stenosis ( P Conclusion Patients with proximal BA stenosis had a higher proportion of severe stenosis and strong plaque enhancement, particularly in patients complicated with VA stenosis and VBJ stenosis. Perforator stroke after BA stenting may be related to distribution, burden and characteristics of BA lesions.

Objective: MicroRNAs (miRNAs) in exosomes had been implicated differentially expressed in patient with moyamoya disease (MMD), but the miRNAs expression in circulating leukocytes remains unclear. This study was investigated on the differential expression of miRNAs in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD.Materials and methods: A total of 30 patients with MMD and 10 healthy adults were enrolled in a stroke center from October 2017 to December 2018. The gene microarray was used to detect the differential expression profiles of miRNA in leukocytes between MMD patients and controls, and the differentially expressed miRNAs were verified by the method of real-time PCR. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the key signaling pathways and possible pathogenesis of MMD.Results: The microarray results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change >2.0, p < 0.05 and FDR p < 0.05), of which 4 miRNAs (miRNA-29b-3p, miRNA-142-3p, miRNA-340-5p, miRNA-582-5p) were upregulated, and 3 miRNAs (miRNA-363-3p, miRNA-451a and miRNA-486-5p) were downregulated. Both GO and KEGG analysis suggested that the Wnt signaling pathway may be involved in the pathogenesis of MMD. In addition, miRNAs were also differentially expressed among patients with subtypes of MMD.Conclusion: This study indicated that miRNAs are differentially expressed in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. The Wnt signaling pathway is probably involved in the pathogenesis of MMD.

Intracranial vertebrobasilar atherosclerotic stenosis (IVBAS) is a major cause of posterior circulation stroke. Some patients suffer from stroke recurrence despite receiving medical treatment. This study aimed to determine the prognostic value of a new score for the posterior communicating artery and the P1 segment of the posterior cerebral artery (PCoA-P1) for predicting stroke recurrence in IVBAS.We retrospectively enrolled patients with severe IVBAS (70%-99%). According to the number of stroke recurrences, patients were divided into no-recurrence, single-recurrence, and multiple-recurrences groups. We developed a new 5-point grading scale, with the PCoA-P1 score ranging from 0 to 4 based on magnetic resonance angiography, in which primary collaterals were dichotomized into good (2-4 points) and poor (0 or 1 point). Stroke recurrences after the index stroke were recorded. Patients who did not experience stroke recurrence were compared with those who experienced single or multiple stroke recurrences.From January 2012 to December 2019, 176 patients were enrolled, of which 116 (65.9%) had no stroke recurrence, 35 (19.9%) had a single stroke recurrence, and 25 (14.2%) had multiple stroke recurrences. Patients with single stroke recurrence (odds ratio [OR]=4.134, 95% confidence interval [CI]=1.822-9.380,The new PCoA-P1 score appears to provide improve predictions of stroke recurrence in patients with IVBAS.

OBJECTIVE Endovascular treatment is one of the choices for symptomatic chronic intracranial total occlusion (CITO); however, its safety and efficacy remain unclear. The present study was performed to evaluate the safety and long-term outcome of endovascular treatment for CITO at a high-volume stroke center. METHODS Data about patients with symptomatic CITO who received endovascular treatment were retrospectively collected. Technique success was regarded as ≤ 30% residual stenosis. Periprocedural complications within 30 days were used to evaluate safety. Baseline characteristics and lesion features were compared between patients with successful recanalization and those with recanalization failure. Stroke recurrence and in-stent restenosis (ISR) of the culprit arteries during follow-up were used to evaluate long-term efficacy. RESULTS From June 2012 to September 2019, 117 patients (mean ± SD age 55.8 ± 9.6 years) were included. The successful recanalization rate was 82.9% (97/117 patients). The combined rate of periprocedural stroke, myocardial infarction, and death was 8.5% (10/117). Compared with patients with successful recanalization, patients with recanalization failure had longer occlusion time and longer lesion length (27.0 mm vs 15.4 mm, p = 0.001). In the median 23.0-month clinical follow-up period, recurrent stroke occurred in 12.6% (11/87) of patients with successful recanalization. In the median 5-month imaging follow-up period, ISR was detected in 26.6% (21/79) of patients. CONCLUSIONS Endovascular treatment was relatively safe for patients with symptomatic CITO. Shorter occlusion time and shorter lesion length may be associated with higher recanalization rate. The rates of stroke recurrence and symptomatic ISR were acceptable but need to be confirmed in future studies.

In this study, we aimed to disclose the association of pre- and post-stroke glycemic status with clinical outcome in patients with spontaneous intracerebral hemorrhage (sICH). It was a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. The association of admission random blood glucose (RBG), fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) with clinical outcome at 90 days after sICH onset were analyzed comprehensively. Poor outcome was defined as death or modified Rankin Scale (mRS) score >2. The results showed that elevated RBG and FBG were associated with larger hematoma volume, lower GCS, higher NIHSS (P P > 0.05). In stratified analysis, the association of poor outcome with elevated FBG or RBG retained statistical significance just in patients without diabetes. Kaplan-Meier curve and Cox regression showed that patients with elevated FBG or RBG had significantly higher risk of death within 90 days (P

OBJECTIVE This study aimed to identify predictors of intracranial in-stent restenosis (ISR) after stent placement in symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS The authors retrospectively collected data from consecutive patients who suffered from symptomatic ICAS and underwent successful stent placement in Beijing Tiantan hospital. Eligible patients were classified into “ISR,” “indeterminate ISR,” or “no-ISR” groups by follow-up digital subtraction angiography or CT angiography. A multivariate logistic regression model was used to explore the predictors of intracranial ISR after adjustments for age and sex. In addition, ISR and no-ISR patients were divided into two groups based on the strongest predictor, and the incidence of ISR, recurrent stroke, and symptomatic ISR was compared between the two groups. RESULTS A total of 511 eligible patients were included in the study: 80 ISR, 232 indeterminate ISR, and 199 no-ISR patients. Elevated high-sensitivity C-reactive protein (hs-CRP; odds ratio [OR] 4.747, 95% confidence interval [CI] 2.253–10.01, p < 0.001), Mori type B and C (Mori type B vs Mori type A, OR 3.119, 95% CI 1.093–8.896, p = 0.033; Mori type C vs Mori type A, OR 4.780, 95% CI 1.244–18.37, p = 0.023), coronary artery disease (CAD; OR 2.721, 95% CI 1.192–6.212, p = 0.017), neutrophil/lymphocyte ratio (NLR; OR 1.474 95% CI 1.064–2.042, p = 0.020), residual stenosis (OR 1.050, 95% CI 1.022–1.080, p = 0.001) and concurrent intracranial tandem stenosis (OR 2.276, 95% CI 1.039–4.986, p = 0.040) synergistically contributed to the occurrence of intracranial ISR. Elevated hs-CRP (hs-CRP ≥ 3 mg/L) was the strongest predictor for ISR, and the incidence of ISR in the elevated hs-CRP group and normal hs-CRP group (hs-CRP < 3 mg/L) was 57.14% versus 21.52%, respectively, with recurrent stroke 44.64% versus 16.59%, and symptomatic ISR 41.07% versus 8.52%. CONCLUSIONS Elevated hs-CRP level, NLR, residual stenosis, Mori type B and C, CAD, and concurrent intracranial tandem stenosis are the main predictors of intracranial ISR, and elevated hs-CRP is crucially associated with recurrent stroke in patients with symptomatic ICAS after intracranial stent implantation.

Background: Hematoma expansion (HE) is associated with poor clinical outcomes following intracerebral hemorrhage (IcH). Existing predictors of HE from non-contrast computed tomography (NCCT) have low sensitivity and high inter-observer variability. Availability of an objective, standardized method to predict HE remains an unmet need. Methods: This multicenter observational cohort study analyzed a retrospective dataset of 2350 patients (December 2011 to June 2018, NCCT only, 86 centers), and a prospective dataset of 460 patients (March 2018 to February 2019, NCCT plus clinical data, 28 centers) with acute IcH . Prediction of HE, defined as a hematoma growth of > 6ml within 48 hours was the primary outcome of the study. A deep learning system (DLS) was developed and validated to autonomously predict HE based on the NCCT images using retrospectively collected data. A multivariate logistic regression model and a five-point score based on clinical variables and DLS prediction score were then developed using prospectively collected data. Findings: The DLS, using only NCCT, achieved HE prediction AUC of 0·783 (95% CI, 0·693-0·871) on the prospective validation dataset. Multivariate analysis of clinical variables indicated a higher risk of HE in patients with higher baseline NIHSS (OR: 4·37(1·56-12·25)), shorter onset-to-NCCT time (OR: 2·92(1·13-7·56)), and lack of antihypertensive therapy history (OR: 2·61 (1·05-6·53)) . Inclusion of these clinical variables along with DLS prediction, further improved the HE prediction accuracy, achieving an AUC of 0·812 (0·732-0·891) which was higher than all the previous methods. Finally, an easy-to-use five-point score was developed, which achieved an AUC of 0·789 (0·707-0·871). Interpretation: Deep learning systems could provide an automated, objective, multicenter generalizable, and observer bias-free solution for HE prediction from NCCT images. Inclusion of clinical factors may further improve the prediction accuracy and the system can be used to identify patients at risk of HE leading to a personalized treatment planning. Funding: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, Beijing Municipal Committee of Science and Technology, Ministry of Science and Technology of the People’s Republic of China, National Natural Science Foundation of China, and Beijing Nova Program. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Institutional Review Board of Beijing TianTan hospital which covers all the hospitals contributing data to this study as part of the Chinese Stroke Center Alliance

Background and purposeIn-stent restenosis (ISR) is one of the long-term adverse outcomes of endovascular angioplasty and stenting for symptomatic intracranial arterial stenosis. In this study, we try to evaluate the safety and efficacy of endovascular treatment for intracranial ISR.MethodsWe retrospectively collected patients with intracranial ISR who underwent endovascular treatment from June 2012 to August 2019 at a high-volume stroke center. Successful recanalization was defined as ≤30% residual stenosis. Stroke, myocardial infarction, and death after stenting within 30 days were used to evaluate periprocedural safety. Recurrent stroke in the territory of the culprit vessel and re-ISR in patients with clinical and vascular imaging follow-up data were used to evaluate the long-term outcome.Results32 patients (59.6±7.2 years old) with ISR were recruited, including 22 patients (68.8%) treated with balloon dilatation, 8 patients (25%) with stenting, and 2 patients (6.3%) with failed procedures. Successful recanalization was achieved in 71.9% (23/32) of patients. There was no stroke, myocardial infarction or death within 30 days after the procedure. Recurrent stroke was found in 10.7% (3/28) of the patients, and re-ISR was found in 42.1% (8/19) of the patients. The re-ISR rate was lower in patients with stenting than in those with balloon dilatation (0% vs 57.1%, p=0.090), and in patients with successful recanalization than in those with unsuccessful recanalization (33.3% vs 75.0%, p=0.352), but with no statistically significant difference.ConclusionsThe periprocedural safety of endovascular treatment for intracranial ISR may be acceptable, but the long-term rates of recurrent stroke and re-ISR remain at high levels.

Diabetes may be one of the risk factors of cognitive impairment. In this study, we aimed to investigate the relationship between diabetes status and cognitive impairment among the middle-aged and elderly population (≥40 years) in Chinese rural communities.A sample of 3392 participants aged 40 years or older from the China National Stroke Prevention Project (CSPP) between 2015 and 2017 were enrolled in this study. Cognitive function was assessed by the Beijing edition of the Montreal cognitive assessment (MoCA) scale. Cognitive impairment was diagnosed as a MoCA score 26. Diabetes status was divided into three groups------Normal: fasting plasma glucose (FPG) ≤ 5.5 mmol/L, Prediabetes: 5.6 ≤ FPG ≤ 6.9 mmol/L, Diabetes: FPG ≥ 7.0 mmol/L or with a history of diabetes. Multivariate logistic regression was used to analyze the association between diabetes status and cognitive impairment.Out of the 3392 enrolled participants, 2023(59.6%) had cognitive impairment, 1586(46.8%) had abnormal fasting plasma glucose including 867(25.6%) prediabetes and 719(21.2%) diabetes. After adjusting for potential risk factors, we found prediabetes (OR: 1.22, 95%CI: 1.03-1.45) and diabetes (OR: 1.28, 95%CI: 1.06-1.55) are all associated with cognitive impairment, especially in the domains of language (prediabetes: OR: 1.14, 95%CI: 1.05-1.25; diabetes: OR:1.13, 95%CI: 1.03-1.24), visuospatial/executive functions (diabetes: OR: 1.50, 95%CI: 1.22-1.84) and attention (diabetes: OR: 1.15, 95%CI: 1.02-1.31).In this large community-based study, we found diabetes status may be an independent risk factor for cognitive impairment, particularly in domains of language, visuospatial/executive functions, and attention.

Patients with intracerebral hemorrhage are susceptible to venous thromboembolism, but the relationship between venous thromboembolism and outcome is largely unknown. We aim to investigate the association of in-hospital venous thromboembolism with functional outcome in patients with intracerebral hemorrhage.From September 2014 through August 2016, we conducted a hospital-based, prospective study by consecutively recruiting eligible patients with first-ever acute spontaneous intracerebral hemorrhage. In-hospital venous thromboembolism was defined as observation of pulmonary embolism or deep vein thrombosis during initial hospitalization. The primary end point was death or disability (modified Rankin Scale 3 to 6) at discharge, 3-month and 1-year follow-up. Logistic analysis was conducted to evaluate the association of venous thromboembolism and poor functional outcome.Among 637 participants included in the analysis, the prevalence of venous thromboembolism was 22.6%. After adjusting for confounding factors, venous thromboembolism was independently associated with death or disability at discharge (odds ratio 2.09, 95% confidence interval 1.12-3.85), 3-month follow-up (2.00 [1.12-3.54]) and 1-year follow-up (2.00 [1.14-3.49]). Venous thromboembolism was also an independent indicator of disability (modified Rankin Scale 3-5) among ICH survivors, with odds ratios ranging from 1.93 to 2.08 (all P0.05). The relationship was stronger in patients with hematoma volume10 ml (3.24 [1.11-9.46]) and ≥30 ml (2.57 [1.03-6.44]) (P for interaction=0.002) at 1-year follow-up. The results were confirmed by sensitivity analysis.In-hospital venous thromboembolism was independently associated with poor outcome at discharge, 3-month and 1-year in patients with intracerebral hemorrhage.

We elucidated the clinical and radiological characteristics and analyzed the risk factors for hemorrhage and poor outcomes of cerebral venous malformations (CVMs) in a northern Chinese population.We included 60 consecutive patients with CVM patients in Beijing Tiantan Hospital from January 2011 to February 2018. The clinical manifestations, radiological characteristics, management, and outcomes were elucidated and analyzed. The patients were followed up for 5-64 months (median, 26). Poor outcomes included repeat bleeding, secondary infarction, severe disability (modified Rankin scale score ≥3), and death.Infratentorial CVMs were more prone to intracranial hemorrhage (75% vs. 28.6%; P0.001), dizziness (37.5% vs. 10.7%; P = 0.017), and focal neurological deficits (65.6% vs. 25%; P = 0.002) than were supratentorial CVMs. Supratentorial CVMs were more prone to seizure (32.1% vs. 0%; P = 0.001) than were infratentorial CVMs. Multivariate logistic regression revealed that the major risk factors for intracranial hemorrhage in CVMs were infratentorial lesions (P = 0.003) and complicated cavernous angiomas (P = 0.016). Compared with conservative treatment, resection of hematoma or cavernous angiomas with CVM preservation did not increase the risk of poor outcomes (P = 0.646). However, CVM resection significantly increased that risk (odds ratio, 44.0; P = 0.003).Our results have shown that conservative treatment of CVMs results in a relatively good prognosis. For those complicated by hemorrhage or cavernous angiomas requiring surgical interventions, the integrity of the CVM should be preserved, irrespective of the treatment. In exceptional cases, before CVM resection, the CVM drainage should be comprehensively evaluated.