Associations between adiposity, diabetes, lifestyle factors and the risk of gliomas.

Background: Despite numerous observational studies linking adiposity, diabetes, and lifestyle factors with gliomas, the causal associations between them remain uncertain. Methods: This study aimed to use two-sample Mendelian randomization (MR) analysis to investigate whether these associations are causal. Specifically, independent genetic variants in body mass index (BMI), waist circumference (WC), type 2 diabetes (T2D), smoking, alcohol, and coffee consumption were extracted from the published genome-wide association studies (GWASs) with genome-wide significance. The corresponding summary-level data for gliomas were available from a GWAS of 1,856 cases and 4,955 controls of European descent from the GliomaScan consortium. Additionally, glioma pathogenesis-related protein 1 data were used for validation, and Radial MR analysis was conducted to examine the potential outlier single-nucleotide polymorphisms (SNPs). Results: One standard deviation (SD) increase in BMI had an odds ratio (OR) of 1.392 (95% confidence interval (CI), 0.935-2.071) for gliomas, while one SD increase in WC had an OR of 0.967 (95% CI, 0.547-1.710). For T2D, a one-unit increase in log-transformed OR had an OR of 0.923 (95% CI, 0.754-1.129). The prevalence of smoking initiation had an OR of 1.703 (95% CI, 0.871-3.326) for gliomas, while the prevalence of alcohol intake frequency had an OR of 0.806 (95% CI, 0.361-1.083), and the prevalence of coffee intake had an OR of 0.268 (95% CI, 0.033-2.140) for gliomas. Conclusion: This study provides evidence that adiposity, T2D, smoking, alcohol drinking, and coffee intake do not play causal roles in the development of gliomas. The findings highlight the importance of reconsidering causal relationships in epidemiological research to better understand the risk factors and prevention strategies for gliomas.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied. METHODS: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality. RESULTS: A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval [CI], 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy. CONCLUSIONS: Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).

Saikosaponin-d improved the stemness of mouse neural stem cells and increased their thermotolerance potential.

PURPOSE: To investigate the effect of saikosaponin-d (Ssd) on proliferation, differentiation, and stemness of neural stem cells (NSCs), and to observe whether Ssd has a protective effect on NSCs at medium-high and high temperature. MATERIALS AND METHODS: NSCs were extracted from 15-day fetal mice. After subculture, Ssd treatment was performed. Cell cycle and apoptosis rate were detected by flow cytometry. Western Blot and immunofluorescence assay were used to detect the expression and spatial distribution of Nestin, NSE, GFAP, Oct4, and SOX2. Cell growth morphology was observed under a microscope; the concentration of extracellular lactate dehydrogenase (LDH) was determined by ELISA. RESULTS: Compared with the control group, the proportion of NSCs in the G0/G1 phase increased in the Ssd treatment group; on the contrary, the proportion in the G2/M phase significantly decreased. Microscopically, our results also suggested the sphere-formation rate increased significantly. Besides, the percentage of dead cells in the Ssd group at 38.5, 40°C were reduced, and the level of LDH release was dropped. CONCLUSION: Ssd improved the stemness of NSCs, inhibited their differentiation into neural cells, and reduced cell damage under high temperature. Therefore, we speculate that Ssd can improve the thermotolerance of NSCs and protect the nervous system of children with fever.

Risk Factors of Transient Cortical Blindness After Cerebral Angiography: A Multicenter Study.

Background: Although transient cortical blindness is a rare complication following cerebral angiography, identification of risk factors for the development of transient cortical blindness after cerebral angiography is an important clinical issue. Material and methods: Between January 2008 and April 2018, 5,126 patients at five high-volume medical centers who underwent cerebral angiography procedures were enrolled in this multicenter cohort study. Patient baseline characteristics and surgery-related factors were analyzed. We used multivariate logistic regression to examine factors associated with transient cortical blindness. Results: Eighteen patients (0.35%) in the total cohort of 5,126 suffered transient cortical blindness. After univariate statistical analysis, no significant differences were determined between the transient cortical blindness group and the control group regarding gender (p = 0.454), age (p = 0.872), smoking (p = 0.170), diabetes (p = 0.800), and hypertension (p = 0.100). Compared with the control group, the transient cortical blindness group weighed less (p = 0.020), and had a larger dose of contrast agent (p = 0.034) and more instances of contrast agent injected into the posterior circulation (p < 0.001). Logistic regression analysis identified contrast agent dose and contrast agent injected into posterior circulation as independent predictive factors for transient cortical blindness (P < 0.05). Conclusion: Larger doses off contrast agent and contrast agent injected into the posterior circulation are potential independent predictive factors for transient cortical blindness following cerebral angiography.

Efficacy of endovascular intervention in patients with unruptured posterior communicating artery aneurysm-related oculomotor nerve palsy.

OBJECTIVES: Oculomotor nerve palsy (ONP) is commonly encountered in daily neurosurgical activities. The ONP secondary to un-ruptured PComA aneurysm might be a unique entity that was different in diagnosis, treatment and prognosis from its ruptured counterparts. Perhaps as a result of the limitation in sample size, studies that solely focused on factors affecting recovery of ONP in patients with unruptured corresponding PComA aneurysms were scarce. METHODS: In this study, we would like to report a relatively larger case series of patients with un-ruptured PComA aneurysm-related ONP. A retrospective review of medical records of 39 patients with un-ruptured PComA aneurysm-related ONP was performed with endovascular coiling. RESULTS: All 39 consecutive patients underwent endovascular coiling. Eighteen (46%) patients had a complete resolution of ONP, 14 (36%) patients had a partial resolution. Time interval from onset of ONP to endovascular intervention (P=0.004), degree of ONP (P=0.015) and age (P=0.016) were predictors of ONP recovery with statistical significance. Sex, aneurysm size and risk factor exposure (smoking, alcohol abuse and hypertension) were not associated with ONP outcomes. CONCLUSION: ONP secondary to un-ruptured aneurysm should be treated as a unique entity from its ruptured counterparts. A prospective study that contains surgical clipping and endovascular coiling, and comparison between two treatment modalities would be more convincing and is anticipated.

Diagnosis and treatment of a dural arteriovenous fistula presenting with progressive parkinsonism and dementia: A case report and literature review.

A dural arteriovenous fistula (DAVF) presenting with parkinsonism and dementia is rare; thus, is easily misdiagnosed. The present study reports the case of a 62-year-old male with mobility disabilities and a cognitive disorder. The initial symptoms were progressive symmetrical limb stiffness and weakness without significant limb tremor, and subsequently the appearance of progressive memory loss, behavioral abnormalities and a decline in the activities of daily living. Cranial magnetic resonance imaging (MRI) revealed an enlarged vascular shadow at the meninges of the left temporal lobe. In addition, digital subtraction angiography (DSA) revealed a DAVF in the left temporal region, fed by the bilateral middle meningeal arteries and meningeal branches of the vertebral artery, which were enlarged abnormally, with poor venous reflux to the superior sagittal sinus. The patient was treated with transarterial embolization therapy. Intraoperative angiography showed almost complete embolization of the DAVF. At day 3 following the surgery, the muscle tension of the bilateral limbs decreased significantly. After two weeks, the memory ability of the patient had recovered to the level prior to the onset, and the gait was stable. At one month post-surgery, the patient was able to take care of himself completely, and after three months, a stereotactic treatment was conducted for the residual fistula. At the one year follow-up, neurological examination revealed that the patient had recovered normally. In conclusion, progressive parkinsonism and dementia with an abnormal flow void shadow on cranial MRI films should be considered as a possible diagnosis of a DAVF. In these cases, DSA and endovascular treatment are recommended as soon as possible.

Endovascular treatment of severe acute basilar artery occlusion.

Severe acute basilar artery occlusion (BAO) has a high mortality rate but as yet no effective treatment has been developed. This study aimed to evaluate the feasibility and safety of combined mechanical thrombectomy, intra-arterial thrombolysis, and emergent stent placement for patients with severe acute BAO. Eighteen patients who were unconscious after confirmed onset of BAO and who were given arterial interventional treatment from March 2011 to June 2013 at our department were included in this study. The mean age was 59.56 years (range: 31-76 years) and patients were in a critical physical condition upon admission, and had a mean National Institutes of Health Stroke Scale (NIHSS) score of 25.94 (range: 18-35). All patients were treated with mechanical thrombectomy, 10 of whom received mechanical thrombectomy only. Of the others, eight were also treated with intra-arterial thrombolysis, three were treated with emergent stent placement, and 17 were treated with recanalization with an achieved recanalized rate of 94.4%. The average number of passes through the stent was 1.5 (range: 1-3) and five patients died (27.8%). Thirteen patients survived, and the mean NIHSS score was 6.54 (range: 0-16). Seven patients showed a modified Rankin Scale score ⩽ 2, and the rate of good prognoses was 38.9%. In the treatment of patients with severe acute BAO, intra-arterial mechanical thrombectomy combined with thrombolysis or stent placement are effective strategies to restore blood flow and preserve life, and these strategies have a low incidence of complications.

Identification of a hemodynamic parameter for assessing treatment outcome of EDAS in Moyamoya disease.

This work is a novel attempt to incorporate computational fluid dynamics (CFD) techniques in the analysis of hemodynamic parameters of Moyamoya disease (MMD). Highly prevalent in Asian countries, MMD is characterised by progressive occlusion of the intracranial Internal Carotid Arteries (ICA). We intend to identify a reliable hemodynamic parameter that can be used to gauge treatment outcome. This will aid surgeons in the perioperative management of MMD patients. We carried out CFD analysis on eight patients (5 female, 3 male) with MMD treated by EDAS (encephalo-duro-arterio-synangiosis) between 2011 and 2012. All the eight patients presented with haemorrhage, with subsequent 4-12 month follow-up done using Magnetic Resonance Angiography (MRA) to capture auto-remodelling. We calculated percentage change in flow rate and pressure drop indicator (ΡDI) across the Left and Right ICA. Pressure drop indicator (PDI) is defined as the difference of pressure reduction within the carotid arteries, measured at post-op and follow up, using patient specific inflow rates. The measured percentage flow change and pressure reduction showed an increase at follow up for improved patients (characterised by angiography according to the method of Matsushima), who did not develop any complications after surgery. The inverse was observed in patients who were clinically classified as no change and retrogressed (according to the method of Matsushima) cases post-operation. This elucidates that our findings have instituted a new parameter that may well play a critical role as an assistive clinical decision making tool in MMD.

A meta-analysis of carotid endarterectomy versus stenting in the treatment of symptomatic carotid stenosis.

BACKGROUND: Carotid stenosis is one of the common reasons for patients with ischemic stroke, and the two invasive options carotid endarterectomy (CEA) and carotid artery stenting (CAS) are the most popular treatments. But the relative efficacy and safety of the methods are not clear. METHODS: About 521 articles related to CAS and CEA for carotid stenosis published in 1995 - 2011 were retrieved from MEDLINE, Cochrane Library (CL), and China National Knowledge Infrastructure (CNKI) China Journal Full-Test database. Of them, eight articles were chosen. Meta-analysis was used to assess the relative risks. RESULTS: The eight studies included 3873 patients with symptomatic carotid artery stenosis, including 1941 cases in the carotid stent angioplasty group, and 1932 cases in the carotid endarterectomy group. Fixed effect model analysis showed that within 30 days of incidence of all types of strokes, surgery was significantly highly preferred in CAS patients (CAS group) than the CEA patients (CEA group), and the difference was statistically significant (relative ratio (RR) = 1.80, 95% confidence interval (CI): 1.380 - 2.401, P < 0.0001). But the incidence of death in the two groups is not showed and is not statistically significant after 30 days (RR = 1.52, 95%CI: 0.82 - 2.82, P = 0.18). The rate of cranial nerve injury in the CAS group is lower than the CEA group (RR = 0.14, 95%CI: 0.05 - 0.43, P = 0.0005). The incidence of CAS patients with myocardial infarction is lower than the CEA group after 30 days, but statistically meaningless (RR = 0.22, 95%CI: 0.05 - 1.02, P = 0.05). The stroke or death in CAS patients were higher than the CEA group after 1 year of treatment (RR = 2.58, 95%CI: 1.03 - 6.48, P = 0.04). CONCLUSIONS: Compared to CAS, carotid endarterectomy is still the preferred treatment methodology of symptomatic carotid artery stenosis. Future meta-analyses should then be performed in long-term follow-up to support this treatment recommendation.

Moyamoya disease in China: its clinical features and outcomes.

BACKGROUND AND PURPOSE: Here we describe the clinical features and outcomes of patients with moyamoya disease who were surgically treated at a single institution in China. METHODS: Our cohort included 802 patients with moyamoya disease. Demographic and clinical characteristics were obtained by retrospective chart review; follow-up information and outcome were obtained through clinical visits, telephone, or letter interview. We used the Kaplan-Meier methods to estimate stroke risk by treatment status. RESULTS: The median age for the onset of symptoms was 28 (range, 0.5-77) years. Two definite peaks in age distribution were found. The ratio of women to men was 1:1 (398/404). Familial occurrence of moyamoya disease was 5.2%. The initial symptom was ischemia, hemorrhage, or others in 564, 113, and 125 patients, respectively. Twenty-nine of the 802 patients (3.6%) received conservative management. The remaining 773 patients (96.4%) underwent neurosurgical revascularization procedures, and 502 of these were bilateral. The median follow-up after surgery (n=773) or conservative management (n=26) was 26.3 months (range, 6.0-101.9 months). Most subsequent ischemic events appeared in the first 2 years after surgery. The Kaplan-Meier estimated stroke risk was 10.1% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 12.7% after surgery for all patients treated with surgical revascularization. CONCLUSIONS: This study on the clinical features of moyamoya disease in mainland China indicated bimodal incidence distribution with women-to-men ratios of 1:1 and lower rate of hemorrhages in adults compared with in children. Patients had low rates of postoperative ischemic or hemorrhagic strokes, and the majority of patients had preserved functional status after revascularization.

Pain reduction in osteoporotic patients with vertebral pain without measurable compression.

INTRODUCTION: Non-compression osteoporotic vertebral pain (NCOVP) can also cause pain and severe immobilization, such as typical vertebral compression fracture (VCF). The aim of this study was to evaluate whether patients with NCOVP refractory to medical treatment and severely affecting normal daily activities could be offered therapeutic benefit with percutaneous vertebroplasty. METHODS: We conducted a retrospective review of the records of consecutive percutaneous vertebroplasty procedures performed at our institutions during a 28-month period to define a population of patients who suffered from severe NCOVP. Nine such patients were identified based on physical examination, computed tomography, magnetic resonance (MR) imaging, and bone scans. Initial clinical outcomes were assessed by comparing quantitative measurements of pain (10-point scale) and mobility (5-point scale) 1 day before the operation with those 1 day post-operation. A second follow-up took place between 2 weeks and 1 month after the operation, with a third follow-up between 6 and 10 months post-operative. Biopsy was taken in each case. RESULTS: Each patient demonstrated point tenderness over radiographically normal-shaped vertebra. Every patient showed a low signal on T1W images, and seven cases showed a high signal on T2W images inside the vertebra, indicating bone marrow edema. All patients experienced a reduction in pain and an increase in mobility after percutaneous vertebroplasty, with a mean pain reduction of 7.0 points and an average improved mobility of 2.8 points. Biopsy results indicated necrotic and/or degenerative changes in eight cases. CONCLUSION: The clinical outcomes of our patients suggest that NCOVP, mainly verified by abnormal MR signals and biopsy results, can be successfully treated by percutaneous vertebroplasty.

[Treatment of severe vertebral compressive fractures in the elderly with percutaneous vertebroplasty].

OBJECTIVE: To evaluate the efficacy of treating severe and chronic vertebral compressive fractures in the elderly with percutaneous vertebroplasty. METHODS: Sixteen patients who suffered from severe back pain and whose daily living was badly affected were retrospectively reviewed. The average age was 72.5 years, the average disease history was 19 months, and the average compressive rate of the affected vertebral bodies was 74.1%. RESULTS: Nineteen affected compressive vertebral bodies in 16 cases were treated with percutaneous vertebroplasty. All the procedures were successful without any complication. After 3.5-7 ml of cement was injected into the lesions, complete relief was achieved in 3 cases, remarkable relief was achieved in 11 cases, and improvement was observed in 2 cases. The scores of 6-point Behavioral Rating Scale and Activity of Daily Living (ADL) declined significantly after the treatment (P < 0.001). CONCLUSION: Percutaneous vertebroplasty can significantly improve the symptoms and quality of life in the elderly patients with severe and chronic vertebral compressive fractures.