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ObjectiveOpen microsurgery, often with bypass techniques, is indispensable for complex aneurysms. To date, it remains unknown whether arterial anatomy or quantitative blood flow measurements can predict insufficient flow-related stroke (IRS). The present study aimed to evaluate the risk factors for IRS in patients treated with open microsurgery with bypass procedures for complex internal carotid artery aneurysms.MethodsPatients with complex aneurysms undergoing bypass surgery were retrospectively reviewed. The recipient/donor flow index (RDFI) was preoperatively evaluated using colour-coding angiography. RDFI was defined as the ratio of the cerebral blood volume of the recipient and donor arteries. The sizes of the recipient and donor arteries were measured. The recipient/donor diameter index (RDDI) was then calculated. IRS was defined as the presence of new postoperative neurological deficits and infarction on postoperative CT scans. We assessed the association between RDFI and other variables and the IRS.ResultsTwenty patients (38±12 years) were analysed. IRS was observed in 12 patients (60%). Patients with postoperative IRS had a higher RDFI than those without postoperative IRS (p2.3 were more likely to develop IRS (pConclusionQuantitative digital subtraction angiography enables preoperative evaluation of cerebral blood volume. RDFI >2.3, rather than RDDI, was significantly associated with postoperative IRS. This preoperative evaluation allows appropriate decisions regarding the treatment strategy for preventing postoperative IRS.

ObjectSuperficial temporal artery to middle cerebral artery (STA-MCA) bypass is the most effective treatment for Moyamoya disease (MMD). In this study, we aimed to assess whether aspirin improves STA-MCA bypass patency and is safe in patients with MMD.MethodsWe performed a retrospective medical record review of patients with ischaemic-onset MMD who had undergone STA-MCA bypass at two hospitals between January 2011 and August 2018, to clarify the effects and safety of aspirin following STA-MCA bypass. The neurological status at the last follow-up (FU) was compared between patients with FU bypass patency and occlusion.ResultsAmong 217 identified patients (238 hemispheres), the mean age was 41.4±10.2 years, and 51.8% were male; the indications for STA-MCA bypass were stroke (48.2%), followed by a transient ischaemic attack (44.0%). Immediate bypass patency was confirmed in all cases. During the FU period (1.5±1.5 y), 15 cases were occluded at FU imaging, resulting in an overall cumulative patency rate of 94%. The patency rates were 93% and 94% in the short-term FU group (n=131, mean FU time 0.5±0.2 years) and long-term FU group (n=107, mean FU time 4.1±3.5 years), respectively. The STA-MCA bypass patency rate in the aspirin group was higher than that in the non-aspirin group (98.7% vs 89.7%; HR 1.57; 95% CI 1.106 to 2.235; p=0.012). No significant difference in the FU haemorrhagic events was observed between the aspirin and non-aspirin groups.ConclusionsAmong adult patients with ischaemic-onset MMD undergoing STA-MCA bypass procedures, aspirin might increase the bypass patency rate, without increasing the bleeding risk. FU bypass patency may be associated with a better outcome. Additional studies, especially carefully designed prospective studies, are needed to address the role of aspirin after bypass procedures.

Frailty is known to be influenced by genetics, however, little evidence on the association of Apolipoprotein E (ApoE) genotype and frailty exists which we aim to investigate. This study is a cross-sectional analysis from a prospective longitudinal study cohort. Community-dwelling individuals aged 55 years and older from Beijing region in China. A total of 3,569 older adults with a mean age of 75.06(±6.79) years were included. We investigated the association between ApoE polymorphism and frailty syndrome using the frailty index (FI) and frailty phenotype (including association with individual components of the frailty phenotype). Logistic regressions were performed to investigate the relation between ApoE variants and frailty. There was no significant association between ApoE variants and frailty as assessed by the FI. In the age and sex-adjusted model, compared to the ApoE e3/e3 carriers ApoE e4 carriers had almost 1.5 times higher odds of being frail as assessed by the frailty phenotype. However, the significance was lost on the model with adjustment for cognitive impairment. Compared to the ApoE e3/e3 carriers ApoE e4 carriers had almost two times higher odds of fatigue. ApoE e4 heterozygotes had higher odds of fatigue compared to ApoE e4 non-carriers. No significant association was found between ApoE variants and other components of frailty phenotype. Our findings do not support an association between ApoE genotype and frailty irrespective of the frailty assessment tools. Fatigue in older adults is the only component of frailty phenotype influenced by ApoE genotype.

China faces the greatest challenge from stroke in the world. The death rate for cerebrovascular diseases in China was 149.49 per 100 000, accounting for 1.57 million deaths in 2018. It ranked third among the leading causes of death behind malignant tumours and heart disease. The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100 000 population and 246.8 per 100 000 person-years, respectively. According to the Global Burden of Disease Study 2017, the years of life lost (YLLs) per 100 000 population for stroke increased by 14.6%; YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017. The absolute numbers and rates per 100 000 population for all-age disability-adjusted life years (DALYs) for stroke increased substantially between 1990 and 2017, and stroke was the leading cause of all-age DALYs in 2017. The main contributors to cerebrovascular diseases include behavioural risk factors (smoking and alcohol use) and pre-existing conditions (hypertension, diabetes mellitus, dyslipidaemia and atrial fibrillation (AF)). The most prevalent risk factors among stroke survivors were hypertension (63.0%-84.2%) and smoking (31.7%-47.6%). The least prevalent was AF (2.7%-7.4%). The prevalences for major risk factors for stroke are high and most have increased over time. Based on the latest national epidemiological data, 26.6% of adults aged ≥15 years (307.6 million adults) smoked tobacco products. For those aged ≥18 years, age-adjusted prevalence of hypertension was 25.2%; adjusted prevalence of hypercholesterolaemia was 5.8%; and the standardised prevalence of diabetes was 10.9%. For those aged ≥40 years, the standardised prevalence of AF was 2.31%. Data from the Hospital Quality Monitoring System showed that 3 010 204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018. Of those, 2 466 785 (81.9%) were ischaemic strokes (ISs); 447 609 (14.9%) were intracerebral haemorrhages (ICHs); and 95 810 (3.2%) were subarachnoid haemorrhages (SAHs). The average age of patients admitted was 66 years old, and nearly 60% were male. A total of 1555 (0.1%), 2774 (0.6%) and 1347 (1.4%) paediatric strokes (age

ObjectiveExtra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown.MethodsWhole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model.ResultsWe detected somaticGJA4mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that theGJA4mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing theGJA4mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683.ConclusionsWe identified a somaticGJA4mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due toGJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.

For moyamoya disease (MMD) patients who suffered an acute ischemic attack, the infarction patterns on DWI and its association with recurrent adverse cerebrovascular events (ACEs) after bypass surgery remain unknown. 327 patients who suffered an acute ischemic attack and received following revascularization surgery were retrospectively reviewed and were divided into three patterns according to the lesion number and distribution on DWI that obtained within 7 days of onset: no acute infarction (NAI), single acute infarction (SAI), and multiple acute infarctions (MAIs). We used Cox proportional hazard models to estimate hazard ratios (HR) for associations of infarction patterns and the risk of recurrent ACEs and strokes. Over a median follow-up of 41 months (IQR 26-60), there were 61 ACEs and 27 strokes. Compared to the NAI cohort, patients with SAI (HR, 2.92; 95% CI, 1.41-6.05; p = 0.004 ) and MAIs (HR, 4.44; 95% CI, 2.10-9.41; p < 0.001 ) were associated with higher risk of ACEs recurrences. In analysis adjusted for age and surgery modalities, the corresponding HR was 2.90 (95% CI: 1.41-5.98) for SAI and 4.10 (95% CI: 1.95-8.63) for MAIs, and this effect remained persistent on further adjustment for several potential confounders. Similar but less precise association was found in separate analysis that only takes into account stroke recurrences. Thus, different infarction patterns on DWI imply different risks of recurrent ACEs, and more attention should be paid to prevent ACEs in MMD patients with MAIs.

China faces the greatest challenge from stroke in the world. According to results from the Global Burden of Disease Study 2019, there were 3.94 million new stroke cases, 28.76 million prevalent cases and 2.19 million deaths due to stroke in China in 2019. Furthermore, stroke is also the leading cause of disability-adjusted life-year (DALY) in China, the number of DALYs reached 45.9 million in 2019. Several recent large-scale epidemiological surveys have updated the data on pre-existing conditions contributed to stroke. The age-adjusted prevalence of overweight among Chinese adults aged 18–69 years was 34.4%, and the prevalence of obesity was 16.8% in 2018. 50.9% of Chinese adults ≥18 years of age without history of hypertension had prehypertension in 2018. The weighted prevalence of hypertension in adults was 27.5% in 2018. The weighted prevalence of total diabetes and pre-diabetes diagnosed by the American Diabetes Association criteria were 12.8% and 35.2%, respectively, among Chinese adults ≥18 years of age in 2017. The weighted atrial fibrillation prevalence was 1.8% among Chinese adults ≥45 years of age and equates to being present in an estimated 7.9 million people in China. Data from 1672 tertiary public hospitals in the Hospital Quality Monitoring System (HQMS) showed that 3 411 168 stroke cases were admitted during 2019. Of those, 2 818 875 (82.6%) were ischaemic strokes (ISs), 485 474 (14.2%) were intracerebral haemorrhages (ICHs), 106 819 (3.1%) were subarachnoid haemorrhages (SAHs). The average age was 66 years old, and 59.6% were male. A total of 1379 (

ObjectiveThe long-term postoperative language outcomes for brain arteriovenous malformations (bAVMs) have not been well characterised. With fibres scattered in the Broca’s, Wernicke’s and Geschwind’s area, the arcuate fasciculus (AF) is considered as a crucial structure of language function. This study aimed to observe the language outcomes, determine the risk factors and construct a grading system for long-term postoperative language deficits (LDs) in patients with bAVMs involving the AF (AF-bAVMs).MethodsWe retrospectively reviewed 135 patients with AF-bAVMs. Based on the course of the AF and our clinical experience, three boundary lines were drawn to divide the AF into segments I, II, III and IV in spatial order from the frontal lobe to the temporal lobe. Surgery-related LD evaluations were performed 1 week (short term) and at the last follow-up (long term) after surgery. Finally, based on multivariable logistic regression analysis, a grading system was constructed to predict long-term postoperative LD. The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC).ResultsSixty-two (45.9%) patients experienced short-term postoperative LD. After a mean follow-up of 50.2±24.9 months, long-term LD was found in 14 (10.4%) patients. Nidus size (p=0.007), LD history (p=0.009) and segment II involvement (p=0.030) were independent risk factors for short-term LD. Furthermore, segment II involvement (p=0.002), anterior choroidal artery (AChA) feeding (p=0.001), patient age (p=0.023) and LD history (p=0.001) were independent risk factors for long-term LD. A grading system was developed by combining the risk factors for long-term LD; its predictive accuracy was 0.921.ConclusionsThe involvement of the trunk of the AF between Broca’s area and the inferior parietal lobule, a nidus supplied by the AChA, older patient age and history of LD were associated with long-term postoperative LD. The grading system combining these factors demonstrated favourable predictive accuracy for long-term language outcomes.

Background An epidemic of COVID-19 broke out in Wuhan, China, since December 2019. The ordinary medical services were hindered. However, the emergency cases, including aneurysmal subarachnoid hemorrhage (aSAH), still required timely intervention. Thus, it provoked challenges to the routine management protocol. In this study, we summarized our experience in the emergency management of aSAH (Beijing Tiantan Protocol, BTP) in Beijing, China. Methods Demographic, clinical, and imaging data of consecutive emergency aSAH patients who underwent craniotomy clipping during the COVID-19 epidemic season were reviewed and compared with the retrospective period last year. Subgroup analysis was further performed to assess the outcomes of different screening results and several detailed protocols. Neurological outcomes were evaluated by the modified Rankin Scale (mRS). Results A total of 127 aSAH were referred to our emergency department, and 42 (33.1%) underwent craniotomy clipping between January 20, 2020, and March 25, 2020. The incidence of preoperative hospitalized adverse events and the perioperative outcomes were similar (− 0.1, 95% CI − 1.0 to 0.8, P = 0.779) to the retrospective period last year (January 2019–March 2019). After the propensity score matching (PSM), there were still no statistical differences in prognostic parameters between the two groups. Eight (19.0%) of the 42 individuals were initially screened as preliminary undetermined COVID-19 cases, in which 2 of them underwent craniotomy clipping in the negative pressure operating room (OR). The prognosis of patients with varied COVID-19 screening results was similar (F(2, 39) = 0.393, P = 0.678). Since February 28, 12 cases (28.6%) received COVID-19 nucleic acid testing (NAT) upon admission, and all showed negative. The false-negative rate was 0.0%. The preoperative hospitalized adverse events and postoperative prognosis were still similar between patients with and without COVID-19 NAT (− 0.3, 95% CI − 1.4 to 0.9, P = 0.653). Conclusions Our emergency surgery management protocol (BTP) is reliable for scheduling emergency aneurysm craniotomy clipping in non-major epidemic areas.

Background: Treatments on middle cerebral arterial occlusions (MCAO) remain controversial. This study aims at investigating efficacies of surgical revascularizations in young and middle-aged patients (aged 18-65 y) with symptomatic MCAO, and making comparisons between surgical procedures.Methods: From a seven-year prospective consecutive registry, 115 cases were enrolled in this study. Patient individually received medical therapy alone (medical group, n=64) and medical therapy plus direct or indirect revascularization (surgical group, n=51). The secondary ischemic events (SIE) was defined as the primary outcome. SIE incidences and SIE-free survival rates were compared between groups. Risk factors were analyzed using the Cox regression analysis.Results: During a follow-up of 42.7 months on average, SIE occurred in 11cases of medical group and 10 cases of surgical group. SIE incidences were indifferent between groups (surgical:medical = 19.6%:17%, P=0.810, 95%CI 0.455-3.034). SIE incidences were 29.4% and 0% in direct revascularization subgroup and indirect revascularization subgroup, respectively. Indirect revascularization induced a higher SIE-free survival rate than direct revascularization (Log-rank P=0.015) and medical therapy (Log-rank P=0.044). An age>43y, with concomitant intracerebral arterial stenosis, and hyperlipidaemia history were correlated to the occurrence of SIE, while presences of compensatory arteries and taking antihypertensive drugs reduced risks of SIE.Conclusions: Indirect revascularization plus medical therapy was suggested to be more effective on SIE prevention than both medical treatments alone and direct revascularization plus medical therapy in young and middle aged patients with symptomatic MCAO. Direct revascularization was not recommended, for its similar efficacy to medical therapy alone.

AimThis evidence-based guideline aims to present current and comprehensive recommendations for the diagnosis and management of spontaneous intracerebral haemorrhage (ICH).MethodsA formal literature search was conducted on MEDLINE (1 January 1990 to 30 June 2019). Data were synthesised using evidence tables. The members of the working group met by teleconference to update and formulate data-based recommendations. The recommendations are graded according to levels of evidence grading algorithm of the Chinese Stroke Association. The guideline draft has been reviewed by Chinese Stroke Association Stroke Council Guideline Writing Committee.ResultsEvidence-based guideline is proposed for the management of patients with ICH. The focus of the guideline is divided into the diagnosis and aetiology of ICH, management of ICH in emergency department, surgical treatment for removal of hematoma, management of complications and prevention of secondary ICH.ConclusionsThis guideline provides a framework for ICH management. Early active and reasonable treatment may improve the clinical outcome of patients.

BackgroundIn June 2015, the Chinese Stroke Association (CSA) initiated the Chinese Stroke Center Alliance (CSCA) to establish the national hospital-based stroke care quality assessment and improvement platform. This article outlines its objectives, operational structure, patient population, quality improvement (QI) intervention tools, data elements, data collection methodology and current patient and hospital data.MethodsThe CSCA is a national, hospital-based, multicentre, voluntary, multifaceted intervention and continuous QI initiative. This multifaceted intervention includes stroke centre development, written care protocols, workshops and a monitoring/feedback system of evidence-based performance measures. The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital.ResultsAs of July 2017, 1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433 264 patients with acute stroke/transient ischaemic attacks (TIA), including 352 572 (81.38%) acute ischaemic stroke, 30 362 (7.01%) TIA, 42 080 (9.71%) spontaneous intracranial haemorrhage, 5505 (1.27%) subarachnoid haemorrhage and 2745 (0.63%) not specified stroke.ConclusionThe CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and, ultimately, improve patient outcomes. It supports the CSA mission to reduce stroke burden in China.

ObjectiveWe initiated a multicenter, prospective cohort study to test the hypothesis that aspirin is safe for patients with ischemic cerebrovascular disease (ICVD) harboring unruptured intracranial aneurysms (UIAs) MethodsThis prospective, multicenter cohort study consecutively enrolled 1,866 eligible patients with ICVD harboring UIAs ResultsAfter a total of 4,411.4 person-years, 643 (37.2%) patients continuously received aspirin treatment. Of all included patients, rupture occurred in 12 (0.7%). The incidence rate for rupture (IRR) was 0.27 (95% confidence interval [CI] 0.15–0.48) per 100 person-years. The IRRs were 0.39 (95% CI 0.21–0.72) and 0.06 (95% CI 0.010–0.45) per 100 person-years for the nonaspirin and aspirin groups, respectively. In the multivariate analysis, uncontrolled hypertension and UIAs 5 to ConclusionAspirin is a safe treatment for patients with concurrent small UIAs and ICVD. Patients who are not taking aspirin in the high-risk group warrant intensive surveillance.ClinicalTrials.gov IdentifierNCT02846259.Classification of EvidenceThis study provides Class III evidence that for patients harboring UIAs

Background and Purpose- Evidence on the natural history of hemorrhagic moyamoya disease is still insufficient. We investigated the incidence of recurrent intracranial bleeding, mortality, and risk factors for rebleeding in patients with moyamoya disease. Methods- A total of 128 conservatively managed patients with hemorrhagic presentation and complete follow-up data were included. Recurrent hemorrhages during long-term follow-up were documented. Annual and cumulative incidence rate of bleeding was generated via Kaplan-Meier survival analysis, and risk factors were analyzed using logistic regression analysis. Results- The median follow-up time was 10.1 (1-27) years. During a total of 1300.7 patient-years, 47 (36.7%) patients experienced 59 occurrences of recurrent hemorrhages, rendering an average annual incidence of 4.5%. Among them, 9 patients (19.1%) died from rebleeding and 12 patients sustained severe disability (modified Rankin Scale score of ≥3). The cumulative risk of rebleeding was 7.8% at 5 years, 22.6% at 10 years, and 35.9% at 15 years. Only 4 (3.1%) patients experienced ischemic stroke, yielding an average annual incidence of 0.3%. Multivariate analysis showed that smoking (odds ratio, 4.85; P=0.04) was an independent risk factor of rebleeding. Rebleeding (hazard ratio, 11.04; P=0.02) and hypertension (hazard ratio, 4.16; P=0.04) were associated with increased mortality. Age, type of initial bleeding, digital subtraction angiography staging, family history, and coexisting cerebral aneurysms were not associated with increased risk of rebleeding. Conclusions- Rebleeding events were common and the main cause of death in patients with hemorrhagic moyamoya disease. The risk of rebleeding steadily increased during long-term follow-up. Smoking was a risk factor for rebleeding, and hypertension was associated with increased mortality.

In this study, we determined serum 25-hydroxyvitamin D [25(OH) D] levels in serum, and investigated their associations with risk of recurrent stroke and mortality in a 24-month follow up study in Chinese patients with first-ever ischemic stroke. In this preplanned post hoc analysis, serum levels of 25(OH) D and NIH stroke scale (NIHSS) were measured at the time of admission in a cohort of patients with ischemic stroke. We used logistic regression model to assess the relationship between 25(OH) D levels and risk recurrent stroke or mortality. The follow-up rate was 98.2% in 220 stroke patients. Of 216 patients, 18.5% (95%CI: 13.3%–23.7%) patients had a stroke recurrence, and 30.1% (95% CI: 24.0%–36.2%) died. After adjustment for traditional risk factors, serum 25(OH) D levels were negatively associated with the risk of stroke recurrence (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.70–0.85; P< 0.001) and negatively associated with mortality during 24 months of follow-up (OR, 0.72; 95% CI, 0.64–0.80; P< 0.001). Compared with the first quartile of serum 25(OH) D levels, the ORs for stroke recurrence and mortality were as follows: second quartile, 0.80 (95% CI, 0.63–0.93) and 0.77 (95% CI, 0.65–0.89); third quartile, 0.42 (95% CI, 0.31–0.55) and 0.39 (95% CI, 0.30–0.52); fourth quartile, 0.12 (95% CI, 0.07–0.19) and 0.10 (95% CI, 0.06–0.15), respectively. Lower serum levels of 25(OH) D are independently associated with the stroke recurrence and mortality at 24 months in ischemic stroke patients.

Irisin was discovered as a PGC-1a-activated messenger of myocytes that links sedentary lifestyle, obesity, and diabetes. In this study, we investigated the short-term prognostic value of early measurement of irisin concentration in 1530 Han Chinese patients with acute ischemic stroke (AIS) from three stroke centers. The subjects were the first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Clinical information and stroke severity were collected at admission. Neurological evaluations were conducted at the 6-month follow-up. Serum levels of irisin, National Institutes of Health Stroke Scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 6 months. Multivariate analyses were performed using logistic regression models. During follow-up, a poor functional outcome was found in 588 patients (38.4%; 95% confidence interval (CI), 36.0-40.9%), and 325 patients died (21.2%; 95% CI, 19.2-23.3%). The stroke patients included in the study were divided into four groups according to irisin quartiles (first is the lowest level). Poor outcome across the irisin quartiles ranged from 54.5% (first quartile) to 21.7% (fourth quartile), and mortality rate ranged from 39.3% (first quartile) to 6.3% (fourth quartile). In a multivariate model using the first quartile (Q1) of irisin vs. Q2-Q4 together with the clinical variables, the marker displayed prognostic information and increased odds ratios of poor outcome by 58% (OR for Q1, 1.58 [95% CI, 1.12-2.43]) and mortality by 185% (OR for Q1, 2.85 [95% CI, 1.79-4.02]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability to predict poor outcome (the area under the curve (AUC) with an increase from 0.73 to 0.75 [95% CI, 0.70-0.81]) and mortality (the AUC increased from 0.80 to 0.83 [95% CI, 0.78-0.87]). Irisin is a novel, independent prognostic marker improving currently used risk stratification of stroke patients. Further studies are needed to confirm this association, which may pave the way to new therapeutic options. Trial registration: ChiCTR-OPC- 17013501.

Objective To observe the effect of Xiaozhong Sanyu pills (XZSY) on neurological severity score (NSS), brain water content and expression level of water channel aquaporin 4 (AQP4) in rats with intracerebral hemorrhage (ICH). Methods ICH model was reproduced by Rosenberg method in 150 SD rats, then the animals were randomly divided into model group (n=50), XZSY high dose group (n=50, 40 mg/kg of XZSY suspension was given by intragastric administration, bid) and XZSY low dose group (n=50, 20 mg/kg of XZSY suspension was given by intragastric administration, bid), and the latter two groups were further randomly divided into 12-h and 1-, 3-, 7-, and 10-d subgroups. The differences in NSS, brain water content and expression level of AQP4 among 3 groups were analyzed. Results Compared with control group, the NSS, brain water content and expression level of AQP4 were lowered at 3, 7 and 10 d in XZSY low dose group, and lowered at 1, 3, 7 and 10 d in XZSY high dose group (P

Previous studies suggested that insulin resistance (IR) may be a significant causal risk factor for cardiovascular events and depression independent of other risk factors. In this prospective, we assess the value of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at admission to predict post-stroke depression (PSD) later developed at 3 months follow-up.This prospective, multicenter cohort study was conducted from January 2015 through December 2016 in China. Clinical information and HOMA-IR was assessed at admission. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up.In the study population, 56.6% were male and the median age was 59 years (interquartile range [IQR]: 51-69). One hundred and eighty-six patients (26.6%) showed depression at 3 months after admission and in 53 patients (28.5%) this depression was classified as severe. For each 1-unit increase of HOMA-IR, the unadjusted and adjusted risk of PSD increased by 63% (odds ratios [OR]: 1.63; 95% confidence interval [CI]:1.44-1.85; P0.001) and 27% (1.27; 1.13-1.39; P = 0.002). In a multivariate model using the fourth quartiles of HOMA-IR vs. quartiles 1 through 3 together with the clinical variables, the marker displayed prognostic information (PSD: OR for fourth quartile, 2.76 [95% CI, 1.66-3.73; P = 0.003]).The data suggests that the HOMA-IR may be of potential clinical relevance in identifying stroke patients at risk of developing depression, independent of the well-established predictors.

Long noncoding RNAs (lncRNAs) have been proved as important regulators in many diseases, including cancers. HOXA11 antisense RNA (HOXA11-AS) is a novel identified lncRNA associated with cancer progression. However, the role of HOXA11-AS in glioma remains poorly understood and needs to be elucidated. The purpose of this study is to investigate the role and regulating mechanism of HOXA11-AS on gliomagenesis. Expression of HOXA11-AS was significantly upregulated in glioma tissue and cell lines compared with the adjacent normal tissue and cells. Moreover, patients with high HOXA11-AS expression had a shorter survival and poorer prognosis than that of lower expression. Loss-of-function experiments revealed that HOXA11-AS knockdown inhibited the proliferation, induced cell cycle arrest at G0/G1 phase, and enhanced the apoptosis. Bioinformatics prediction forecast that miR-140-5p directly targeted HOXA11-AS at 3'-UTR, which was confirmed by luciferase reporter assay. In vitro rescue experiment assays, miR-140-5p inhibitor transfection, could reverse the function of HOXA11-AS knockdown on the proliferation, cell cycle arrest, and apoptosis. Taken together, the present study illustrates that the pathway of HOXA11-AS sponging miR-140-5p might play a vital regulating role in the development and progression of glioma.

AIM For cerebral arteriovenous malformations (AVMs) involving language areas, right-sided language lateralization on functional magnetic resonance imaging (fMRI) has been reported, which is regarded as language cortex reorganization. The authors attempted to study if this right-sided language lateralization affects postoperative language outcome. MATERIAL AND METHODS Clinical and imaging data of 43 right-handed AVM patients who underwent preoperative fMRI were retrospectively reviewed. All lesions involved the language cortex, with the Broca area involved in 13 patients and the Wernicke area involved in 30 patients. Lateralization indices (LI) of BOLD signal activations were calculated to determine language lateralization. All patients underwent craniotomy and total resection. Western aphasia battery (WAB) was used to evaluate language functions preoperatively, 1-2 weeks after surgery and 6-30 months after surgery. RESULTS On preoperative fMRI, right-sided lateralization was observed in 18 patients (41.9%, R Group), including 3 with rightsided lateralization in the Broca area alone, 14 in the Wernicke area alone, and 1 in both areas. The other 25 patients were non-rightsided lateralized (NR Group). One week after surgery, 7 patients in the R Group (38.9%) and 11 patients in the NR Group (44.0%) had language function deterioration, and no significant difference was found (p=0.983). At long-term follow-up, 3 patients in the R Group (16.7%) and 4 patients in the NR Group (16.0%) still had aphasia, and no significant difference was observed (p=1.000). CONCLUSION Although right-sided lateralization on fMRI might suggest language cortex reorganization, it is not a factor predicting better postoperative language outcome for AVM patients.

Spinal extradural arachnoid cyst is extremely rare. The longest SEACs that have been reported in previous studies involved no more than 5 spinal segments. This study presents a case of SEAC diagnosed from T9 to L4 and excised through a novel laminectomy/laminoplasty. A 22-year-old female presented with a 5-year history of progressive paraparesis and numbness in both lower limbs. MRI revealed posterolateral epidural cystic mass extending from T9-L4 with a length of 190 mm and width of 15 mm. The cyst was totally removed through surgery. The patient’s symptom was completely relieved 1 year after the surgery. There was no recurrence, compression on the spinal cord, or kyphotic deformity based on MRI and CT taken 1 year after. Spinal extradural arachnoid cysts are relatively uncommon but surgically curable causes of myelopathy. For symptomatic patients, early surgical intervention is suggested for restoring neurological functions. Performing laminectomy by using crainotome is safe and efficient.

Objective The purpose of this study was to investigate the feasibility and value of the intraoperative contrast-enhanced ultrasound (CEUS) in resection for brain tumors. Materials and methods Intraoperative CEUS was performed in 29 patients with brain tumors pre-resection, in whom 9 (of 29) patients underwent second intraoperative CEUS for assessing remained tumor tissue after initial resection. Gray-scale and color-flow images of the brain tumors on both conventional and CEUS were analyzed and compared with the results of surgical pathology. Results The border of the tumor and remained tumor tissue was more distinguishable from healthy brain on CEUS than that on conventional ultrasound during the operation. Improving definition of the tumor tissue from normal brain with CEUS was demonstrated in all cases. Conclusion Intraoperative CEUS has the potential to be a very useful imaging technique not only in defining the border between the tumor and healthy brain pre resection but also in detecting remained tumor tissues after the initial resection.

Rictor upregulation and mTORC complex 2 (mTORC2) over-activation participate in glioma cell progression, yet the underling mechanisms are not known. We here identified microRNA-153 (miR-153) as a potential anti-Rictor miRNA, which was downregulated in multiple human glioma tissues and glioma cell lines (U87MG, T98G, U373MG and U251MG). miR-153 downregulation was correlated with Rictor (mRNA and protein) upregulation and p-Akt Ser473 (the mTORC2 indicator) over-activation in the glioma tissues and cells. Our in vitro evidences suggested that Rictor could be one primary target of miR-153 in glioma cells. Exogenous overexpression of miR-153 downregulated Rictor (mRNA and protein) and decreased p-Akt Ser473 in U87MG cells, leading to significant growth inhibition and apoptosis activation. Notably, U87MG cells with Rictor shRNA knockdown showed similar phenotypes of cells with miR-153 overexpression. More importantly, in Rictor-silenced U87MG cells, miR-153 expression failed to further affect cell growth nor apoptosis. In vivo, we showed that miR-153 overexpression dramatically inhibited U87MG tumor growth in nude mice. Together, these results suggest that miR-153 downregulation could be one important reason of Rictor upregulation and mTORC2 over-activation in glioma cells. Further, miR-153-induced anti-glioma cell activity is possibly via downregulating Rictor.

Background and Purpose— It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study. Methods— We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and Hin fI digestion. Results— Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 μmol/L; P P P P =0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78). Conclusions— The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.

Objective To investigate the effect of irrigation through burr hole with siphonage drainage on chronic subdural hematoma(CSDH).Methods The clinical data of 139 patients with CSDH(89 males and 50 females,aged from 48 to 87 with mean of 66.4 years) hospitalized from Jan.2006 to Dec.2010 were retrospectively reviewed.All the patients were finally diagnosed by radiology,and divided into 3 groups according to the operative method,i.e.parietal burr hole irrigation with drainage group(group A,n=47),parietal burr hole irrigation and aspiration group(group B,n=41),and frontal burr hole irrigation with siphonage drainage group(group C,n=51).All the patients were treated with closed drainage for 2-6 days.The activity of daily living(ADL) scores was measured before and 7 days after operation in all patients.The patients were followed-up for 12-36 months to observe the treatment results.Results No death occurred in the 3 groups during the follow-up period.The improvement of ADL was markedly better in group C than in group B(P < 0.05) and group A(P < 0.01),and in group B than in group A(P < 0.05).The recurrence rate was significantly lower in group C(0.02%) than in group B(12.19%,P < 0.05) and group A(29.79%,P < 0.01),and in group B than in group A(P < 0.05).No significant difference was found regarding length of hospital stay among the 3 groups(P > 0.05).Conclusion The frontal burr hole irrigation with siphonage drainage has a definite treatment effect for CSDH with a low recurrence rate and less complications,and is appropriate to use in most of CSDH patients.

To investigate the role and molecular mechanism of membrane-associated guanylate kinase inverted 3 (MAGI3) in glioma cell proliferation.The expression levels of MAGI3 and PTEN were assessed in glioma samples by Western blotting. MAGI3 was stably transfected into C6 glioma cells to obtain C6-MAGI3 cells. Then, the proliferation, the expression levels of MAGI3 and PTEN, and Akt phosphorylation were evaluated in C6 and C6-MAGI3 cells. Xenograft tumor models were established by subcutaneous injection of C6 and C6-MAGI3 cells into nude mice, and the growth rates of xenografts in the mice were compared. The potential role of MAGI3 expression in PI3K/Akt signaling activation was further investigated by examining the correlation between MAGI3 expression and the expression of PI3K/Akt signaling downstream target genes in a glioma dataset using gene set enrichment analysis (GSEA).Expression levels of MAGI3 and PTEN were significantly downregulated in gliomas. Overexpression of MAGI3 in the glioma C6 cell line upregulated PTEN protein expression, inhibited the phosphorylation of Akt, and suppressed cell proliferation. MAGI3 overexpression also inhibited the growth of C6 glioma tumor xenografts in nude mice. Analysis based on the GEO database confirmed the negative correlation between activation of PI3K/Akt pathway and MAGI3 mRNA levels in human glioma samples.The loss of MAGI3 expression in glioma may enhance the proliferation of glioma cells via downregulation of PTEN expression, leading to the activation of the PI3K/Akt pathway. MAGI3 is a potential glioma suppressor.

To analyze the clinical characteristics and surgical outcomes of ruptured cerebellar arteriovenous malformations (AVM).The clinical data were retrospectively analyzed for 676 brain AVM patients. Among them, 616 cases were treated at Beijing Tiantan Hospital from January 2003 to December 2009 and 32 cases of them were of cerebellar AVM. Another 60 cases of intracranial AVM were managed at Beijing Chaoyang Hospital from January 2003 to December 2011 and there were 8 cases of cerebellar AVM. Microsurgery was performed to remove hematoma and excise AVM. And the postoperative outcomes were evaluated.Statistics analysis of activities of daily living (ADL) scores for 636 cases of cerebral AVM and 40 cases of cerebellar AVM showed no significant difference. Among 40 cases of cerebellar AVM, hemorrhage occurred first in 35 (87.5%) patients. Postoperative re-examinations of computed tomography revealed the resolution of hematoma and the absence of re-hemorrhage. Digital subtraction angiography (DSA) examinations were performed in 39 cases and no residual nidus was observed. Tonsillar herniation occurred preoperatively in 1 case and DSA was not re-examined. There were balance dysfunction (n = 3), dysarthria (n = 2) and dystaxia and dysphasia (n = 1). The postoperative ADL degrees were I(n = 26), II(n = 10), III(n = 3) and IV(n = 1). During a follow-up period of 6 months, no re-hemorrhage occurred and there was no worsening function of central nerve system.Emergency microsurgery is effective in the treatment of ruptured cerebellar AVM.

To design a set of functional magnetic resonance imaging (fMRI) tasks to activate the major Chinese language functional areas.Eight volunteers and 3 patients received fMRI studies with the tasks of semantic judgment, word reading and listening comprehension. Brain activation map of each task was obtained after standard fMRI data processing.The fMRI examination with 3 tasks activated middle frontal gyrus (BA 9), Broca area and Wernicke area respectively.A set of fMRI examinations, including semantic judgment, word reading and listening comprehension, can activate the major Chinese language functional areas steadily and may be used as a preoperative localizer of language areas.

To explore the clinical manifestations, diagnosis, treatment and prognostic features of melanocytic neoplasms of central nervous system (CNS).A total of 24 patients with melanocytic neoplasms of CNS underwent surgery and were confirmed pathologically our hospital during 2006 - 2012. Their clinical data were collected. There were primitive melanocytic neoplasms (n = 8) and metastatic melanoma (n = 16) according to the diagnostic criteria of Willis. The scans of magnetic resonance imaging (MRI) showed hyper-intensity on T1 weighted image (n = 15) and hypo-intensity on T2 weighted image (n = 20).The outcomes were total resection (n = 11), subtotal resection (n = 9) and partial resection (n = 4). All 8 primitive melanocytic neoplasms were followed up. Among them, 2 cases died postoperatively at 15 and 40 months respectively. The remaining 6 cases survived 13 - 56 months after craniotomy. And 14/16 patients of metastatic melanoma were followed up, 8 cases died and the mean survival period was 4.5 months. The remaining 6 cases survived 1-7 months after craniotomy. Immunohistochemical staining demonstrated that the positive rate of HMB-45 was 9/10, S-100 9/11 and Vimentin 8/11.Melanocytic neoplasms of CNS are rare lesions with characteristic MRI features. Immunohistochemical staining helps to reach a definite pathological diagnosis. Surgical excision is recommended. Differentiation of primary and metastatic neoplasm is critical for prognostic evaluations.

Cerebral amyloid angiopathy (CAA) is one of the main causes of spontaneous intracranial hemorrhage (ICH). No established link is available between pathological scores of CAA and its outcome. This study aimed to identify the correlations between pathological severity and poor postoperative outcome in the Chinese population.Between May 2006 and April 2011, 367 consecutive patients who underwent surgery for CAA-related ICH in 71 hospitals throughout the mainland of China were enrolled in this study. Twelve months after surgery, we evaluated these patients' outcomes according to the modified Rankin Scale (mRS) and statistically correlated risk factors (demographics, medical history, pathological results, and surgical details) that are associated with a favorable (mRS3) and poor (mRS ≥ 3) outcome groups.Risk factors for poor postoperative outcome in 367 patients with CAA-related ICH included advanced age (OR 1.034, 95%CI 1.001 - 1.067, P = 0.042), CAA pathology severity (OR 2.074, 95%CI 7.140 - 16.25, P0.001), lobar hematoma (OR 0.225, 95%CI 0.104 - 0.486, P0.001), presence of intraventricular hemorrhage (OR 0.478, 95%CI 0.229 - 1.001, P = 0.050), and/or subarachnoid hemorrhage (OR 2.629, 95%CI, 1.051 - 6.577, P = 0.039).Poor postoperative outcome of patients with CAA-related ICH was more related to the severe pathological manifestation instead of other factors. Prior ischemia may present an early stage of CAA.

To explore the changes of regional cerebral blood flow at the site of anastomosis of superficial temporal artery-middle cerebral artery (STA-MCA) to guide the preventive treatment of symptomatic hyperperfusion.A total of 35 patients with Moyamoya disease were recruited from Beijing Tiantan Hospital. There were 22 males and 13 females with an average age of 29 years (range: 5 - 55). And there were 10 children. Regional cortical blood flow (rCBF) was measured by Laser Doppler flowmeter (LDF) before, after and at Day 1, 2, 3, 4, 5 and 6 postoperation of STA-MCA anastomosis. The probe of LDF was implanted adjacent to the area of anastomosis for 144 hours to record the values of rCBF.The baseline LDF values of cortical rCBF near the area of anastomosis were (69 ± 24) PU before anastomosis, (66 ± 74) PU immediately after anastomosis, (123 ± 23) PU at the conscious time after anesthesia postoperation, (297 ± 17) PU at Day 1 postoperation. And the LDF values of the following 5 days were (302 ± 31), (317 ± 26), (272 ± 46), (363 ± 54) and (367 ± 24) PU respectively.As a safe and effective treatment for Moyamoya disease, STA-MCA anastomosis has great risks for symptomatic hyperperfusion. The highest risk time for hyperperfusion is identified after STA-MCA.