Wenjun Ji

Aneurysm Characteristics Associated with the Rupture Risk of Intracranial Aneurysms: A Self-Controlled Study

This study analyzed the rupture risk of intracranial aneurysms (IAs) according to aneurysm characteristics by comparing the differences between two aneurysms in different locations within the same patient. We utilized this self-controlled model to exclude potential interference from all demographic factors to study the risk factors related to IA rupture. A total of 103 patients were diagnosed with IAs between January 2011 and April 2015 and were enrolled in this study. All enrolled patients had two IAs. One IA (the case) was ruptured, and the other (the control) was unruptured. Aneurysm characteristics, including the presence of a daughter sac, the aneurysm neck, the parent artery diameter, the maximum aneurysm height, the maximum aneurysm width, the location, the aspect ratio (AR, maximum perpendicular height/average neck diameter), the size ratio (SR, maximum aneurysm height/average parent diameter) and the width/height ratio (WH ratio, maximum aneurysm width/maximum aneurysm height), were collected and analyzed to evaluate the rupture risks of the two IAs within each patient and to identify the independent risk factors associated with IA rupture. Multivariate, conditional, backward, stepwise logistic regression analysis was performed to identify the independent risk factors associated with IA rupture. The multivariate analysis identified the presence of a daughter sac (odds ratio [OR], 13.80; 95% confidence interval [CI], 1.65–115.87), a maximum aneurysm height ≥7 mm (OR, 4.80; 95% CI, 1.21–18.98), location on the posterior communicating artery (PCOM) or anterior communicating artery (ACOM; OR, 3.09; 95% CI, 1.34–7.11) and SR (OR, 2.13; 95% CI, 1.16–3.91) as factors that were significantly associated with IA rupture. The presence of a daughter sac, the maximum aneurysm height, PCOM or ACOM locations and SR (>1.5±0.7) of unruptured IAs were significantly associated with IA rupture.

miR-23b improves cognitive impairments in traumatic brain injury by targeting ATG12-mediated neuronal autophagy.

HighlightsMiR‐23b was frequently downregulated in TBI patients and experimental TBI model.Overexpression of miR‐23b attenuated brain injury in rat model of TBI.Overexpression of miR‐23b improved TBI‐induced neurological and cognitive impairmentss.Overexpression of miR‐23b inhibited TBI‐induced the activation of neuronal autophagy in the rat hippocampus CA1 region.Autophagy‐related gene, ATG12, was a novel target of miR‐23b.miR‐23b improved TBI‐induced cognitive impairments by directly targeting ATG12 to suppress neuronal autophagy. ABSTRACT Dysregulated microRNAs (miRNAs) have been reported to involve in the pathophysiological process of traumatic brain injury (TBI), and modulate autophagy‐related genes (ATGs) expression. Our previous studies showed that neuronal autophagy was activated in the injury hippocampus post‐ TBI and associated with neurological and cognitive impairments. The present study was designed to investigate the possible role of miR‐23b in TBI‐induced cognitive impairments. We found the overexpression of miR‐23b conferred a better neuronprotective effects after TBI by decreasing lesion volume, alleviating brain edema, inhibiting neuron apoptosis and attenuating long‐term neurological deficits, and most interestingly, improving cognitive impairments. To further explore the molecular underlying this neuronprotection, we evaluated autophagic activity and ATG12 expression in the injury hippocampus CA1 region. The results identified that miR‐23b directly targeted to the 3′UTR region of ATG12 mRNA to suppress the activation of neuronal autophagy by a dual‐luciferase reporter system. Notably, overexpression of ATG12 abrogated the neuronprotective effects of miR‐23b on TBI‐induced neurological and cognitive impairments. Taken together, these date revealed inhibition of ATG12‐mediated autophagic activity by miR‐23b overexpression might be involve in cognitive improvement after TBI, indicating that miR‐23b might be a potential therapeutic target for TBI.

Risk Score for Neurological Complications After Endovascular Treatment of Unruptured Intracranial Aneurysms

Background and Purpose— Procedure-related neurological complications are common after endovascular treatment of unruptured intracranial aneurysms. We aimed to develop a score to quantify individual patient risk. Methods— We retrospectively analyzed consecutive patients who underwent endovascular treatment for unruptured intracranial aneurysms between January 2012 and September 2015. After excluding those who lost to follow-up and those with fusiform unruptured intracranial aneurysms, included patients were randomly divided into a derivation group (60%) and a validation group (40%). A neurological complication was defined as any transient or permanent increase in the modified Rankin Scale score after aneurysm embolization. A risk score for neurological complications was derived from multivariable logistic regression analyses in the derivation group and validated in the validation group. Results— Overall, 1060 patients were included (636 in the derivation group and 424 in the validation group). The incidence of neurological complications was 5.5% (95% confidence interval, 3.8%–7.4%). A 3-point risk score (S-C-C) was derived to predict neurological complications (size [≥10 mm=1], core areas [yes=1], and cerebral ischemic comorbidity [yes=1]). The incidence of neurological complications varied from 2.2% in 0-point patients to 25.0% in 3-point patients. The score demonstrated significant discrimination (C-statistic, 0.714; 95% confidence interval, 0.624–0.804) and calibration (McFadden R2, 0.102) in the derivation group. Excellent prediction, discrimination, and calibration properties were reproduced in the validation group. Conclusions— One in 20 patients will develop neurological complications after endovascular treatment of unruptured intracranial aneurysms. The S-C-C score may be useful for predicting these adverse outcomes based on variables in daily practice.

A case of two pial arteriovenous fistulas with giant venous pouches treated by endovascular coil embolization: Therapy with and without anticoagulation.

Background Endovascular coil embolization of pial arteriovenous fistulas (AVF) has been reported as an effective treatment. However, venous thrombosis and intracranial hemorrhage developing after endovascular occlusion of a pial AVF have not been adequately reported. Case description A 37-year-old man presented with left middle cerebral artery (MCA) AVF and right posterior cerebral artery (PCA) AVF with giant venous pouches. Staged endovascular coil embolization was performed. The MCA AVF was completely occluded by coils at the first stage. Intravenous heparin (3000 IU) was administered during the procedure, and then low molecular weight heparin (subcutaneous injection, 0.4 mL/12 hours) was administered for two days. The PCA AVF was near completely occluded by coils without anticoagulation therapy at the second stage. Rapid progressive venous thrombosis and intracranial hemorrhage were confirmed by computerized tomography brain scan postoperatively, and the patient was then transferred to the neurological intensive care unit for further treatment. Finally, the patient recovered well at the five-month follow-up. Conclusions Endovascular occlusion of a high-flow pial AVF with a giant venous pouch resulting in significant blood stasis could precipitate thrombosis in the venous system. Further studies are required to establish whether anticoagulation therapy is necessary.

MiR-144 promotes β-amyloid accumulation-induced cognitive impairments by targeting ADAM10 following traumatic brain injury

The dysregulation expression of microRNAs (miRNAs) including miR-144, has been widely documented in TBI. However, little is known about the potential roles of miR-144 in the pathogenesis of TBI. In this study, we investigated the potential effects of miR-144 on cognitive function in vivo and in vitro. The results indicated that inhibition of miR-144 conferred a better neurological outcome after TBI in vivo, as evidenced by reduced lesion volume, alleviated brain edema and increased mNSS, of particular importance, improved cognitive deficits. In vitro, miR-144 knockdown protected neuron against Glu-induced injury, by enhancing cell viability, suppressing LDH release and caspase-3 activity, and reducing cognitive-related proteins levels. However, overexpression of miR-144 in vivo and in vitro showed the opposite effects. To further explore the molecular mechanisms underlying miR-144-induced cognitive dysfunctions, we found a significant inverse correlation between miR-144 and ADAM10 expression. Moreover, the direct interaction between miR-144 and ADAM10 3’-UTR was identified by dual-luciferase reporter assay. Also, we found miR-144 negatively regulated ADAM10 protein expression. Additionally, ADAM10 could modulate β-amyloid formation involved in cognitive deficits. Notably, ADAM10 knockdown by siRNA apparently abrogated miR-144 inhibitor-mediated neuroprotection. Taken together, these findings demonstrated that elevated miR-144 promoted cognitive impairments induced by β-amyloid accumulation post-TBI through suppressing of ADAM10 expression.

Incidence and predictors of headache relief after endovascular treatment in patients with unruptured intracranial aneurysms.

Objective Patients with unruptured intracranial aneurysms often present with headaches. We retrospectively determined the incidence of headache relief in patients with unruptured intracranial aneurysms after endovascular treatment, with the main goals of preventing aneurysmal haemorrhage and identifying factors associated with headache relief in a cohort study. Methods From a cohort of patients with unruptured intracranial aneurysms who were treated with endovascular coiling and admitted between January 2012 and December 2014, we included 123 patients who had headaches and underwent regular follow-up. The severity of headache was assessed by a quantitative 11-point headache scale for all patients before and after the endovascular treatment. Headache relief was defined as a decrease in the headache score. We determined the incidence and predictors of headache relief using Kaplan–Meier curves and Cox regression analysis. Results Of the 123 patients with a mean follow-up of 14.1 months (range 1–39 months), 69 had headache relief. The overall cumulative incidence of headache relief was 62.3% (95% confidence interval (CI) 54.2%, 69.4%). On multivariate Cox regression analysis, the side of headache ipsilateral to the aneurysm (adjusted hazard ratio 0.540; 95% CI 0.408, 0.715; P < 0.001) and aneurysm size (adjusted hazard ratio 1.753; 95% CI 1.074, 2.863; P = 0.025) were significant predictors of headache relief. Conclusions Endovascular treatment relieved preoperative headaches for most patients with unruptured intracranial aneurysms. The side of headache ipsilateral to the aneurysm and aneurysm size >10 mm were significant predictors of headache relief.

Stent-assisted coiling of very small wide-necked intracranial aneurysms: Complications, anatomical results and clinical outcomes

BACKGROUND AND OBJECTIVE Treatment of very small (≤3mm) wide-necked intracranial aneurysms remains controversial, we investigated the efficacy and safety of stent-assisted coiling of such aneurysms. METHODS From September 2008 to December 2012, 112 very small wide-necked intracranial aneurysms in 108 patients were embolized with stent-assisted coiling. We assessed the initial neurological conditions, complications and anatomic results. The follow-up results were evaluated with DSA and mRS. RESULTS Stent deployment was successful in 104 of 108 procedures (96.3%). 11 complications (10.2%) occurred during procedures, including 5 events of aneurysm rupture, 3 events of thromboembolism. The rate of complication, rupture and thromboembolism was not statistically different between the ruptured and unruptured patients (P=0.452, P=0.369, P=1.000, respectively). The initial aneurysmal occlusion was Raymond scale (RS) 1 in 34 patients (31.5%), RS2 in 53 patients (49.1%), and RS3 in 21 patients (19.4%). 79 aneurysms were available for anatomic follow-up of 12-47 months, stable occlusion in 45 aneurysms (57.0%), progressive complete occlusion in 34 aneurysms (43.0%). 95 patients(88.0%) were available for a clinical follow-up of 12-52 months, 92 patients (96.8%) had favorable clinical outcomes (mRS ≤2), 3 patients (3.2%) had morbidity (mRS: 3-5). The morbidity was not statistically different between the ruptured and unruptured patients (P=1.000). CONCLUSIONS Stent-assisted coiling of very small wide-necked intracranial aneurysms may be effective and safe. Because of low risk of rupture in such aneurysms, the coiling of unruptured such aneurysms must be selective. The long-term efficacy and safety of coiling such aneurysms remains to be determined in larger prospective series.

Larger inflow angle and incomplete occlusion predict recanalization of unruptured paraclinoid aneurysms after endovascular treatment.

Background Unruptured paraclinoid aneurysms have a high incidence of aneurysm recanalization (AR) after endovascular treatment. We aimed to identify the incidence and predictors of AR in these lesions. Methods We retrospectively analyzed consecutive patients with unruptured paraclinoid aneurysms who underwent endovascular treatment between January 2013 and December 2014. Patients with fusiform aneurysms, dissection aneurysms, traumatic aneurysms, or without digital subtraction angiography (DSA) at follow-up, were excluded. AR was defined as any aneurysm remnant that had increased in size or contrast filling that was observed via DSA at the follow-up. Univariate and multivariate logistic regression analyses were performed to assess the predictors of AR. Results We included 145 patients with 150 unruptured paraclinoid aneurysms in the analysis. The incidence of AR was 8.7% (95% confidence interval (CI): 4.7–13.3%) at a mean follow-up of 7.4 months. In the univariate analysis, AR was associated with aneurysm size (odd ratio (OR): 6.098; 95% CI: 1.870–19.886; p = 0.003), location (OR: 3.88; 95% CI: 1.196–12.583; p = 0.024), inflow angle (OR: 6.852; 95% CI: 1.463–32.087; p = 0.015), and Raymond scale (OR: 12.473; 95% CI: 2.7496–56.59; p < 0.001). In the adjusted multivariate analysis, AR was independently predicted by Raymond scale (OR: 9.136; 95% CI: 1.683–49.587; p = 0.001) and inflow angle (OR: 16.159; 95% CI: 3.211–81.308; p = 0.01). Conclusions Unruptured paraclinoid aneurysms had a high incidence of AR after endovascular treatment. An inflow angle of ≥90 degrees and incomplete occlusion were significant predictors of AR.

De novo aneurysm formation of a feeder artery after embolization of a dural arteriovenous fistula and rupture during second embolization

Objective Hemorrhage during embolization of dural arteriovenous fistula (DAVF) is a rare but devastating complication. This study was undertaken to analyze the causes of hemorrhage and avoid complication. Methods The clinical data of a case of DAVF with hemorrhagic complication were retrospectively collected and analyzed. Results The patient in this case presented with DAVF and two de novo aneurysms of a feeder artery after the first embolization. One de novo aneurysm ruptured during the second embolization of the DAVF because of hemodynamic change. Computed tomography showed a subdural hematoma, and surgical exploration was emergently performed. However, the patient died at postoperative day 10. Conclusions De novo aneurysm of a feeder artery may form after embolization of DAVF because of hemodynamic change. It has a high risk of rupture and should be a primary consideration in embolization of DAVF.

The Considerable Burden of Unruptured Intracranial Aneurysms in China

In China, the incidence of disease has undergone a remarkable epidemiologic and demographic transition during the past three decades, resulting in cerebrovascular diseases emerging as the leading cause of mortality [1]. Although hypertension, the most important cause of cerebrovascular diseases, is well studied and controlled in China, the common use of CT and MR angiography has led to increasing identification of unruptured intracranial aneurysms (UIAs), the main cause of acute subarachnoid hemorrhage that is associated with high mortality. A cross-sectional study in China showed that the prevalence of UIAs is 7%, [2] which is much higher than the 1-2% observed in the general population worldwide [3]. Surgical clipping, endovascular coiling, and conservative management are the primary treatment strategies for UIAs. The clinical management of UIAs has greatly improved in the past several decades in China. However, UIAs have not received enough attention across the country, and have not been treated reasonably and economically, which could drastically increase the future healthcare burden in China.