Huijian Ge

Circulating microRNA: a novel potential biomarker for early diagnosis of Intracranial Aneurysm Rupture a case control study

ObjectiveTo investigate warning effect of serum miRNA for intracranial aneurysm rupture through microarray hybridization.Methods24 were selected from 560 patients in our department and divided into group A, B, C and D. They are aneurysms with daughter aneurysms group, aneurysm without daughter aneurysms group, ruptured aneurysms group and angiography negative group. Then a microarray study was carried out using serum miRNA. Differentially expressed miRNAs were identified. Cluster analysis was performed in order to make the results looks more intuitive and potential gene targets were retrieved from miRNA target prediction databases.ResultsMicroarray study identified 86 miRNAs with significantly different (p < 0.05) expression levels between three experimental groups and control group. Among them 69 are up-regulated and 17 are down-regulated. All miRNAs in group A are up-regulated, while there are up and down-regulated in group B and C. A total of 8291 predicted target genes are related to these miRNAs. Bioinformatic analysis revealed that several target genes are involved in apoptosis and activation of cells associated with function of vascular wall.ConclusionOur gene level approach reveals several different serum miRNAs between normal people and aneurysm patients, as well as among different phases of aneurysm, suggesting that miRNA may participate in the regulation of the occurrence and development of intracranial aneurysm, and also have warning effect for intracranial aneurysm rupture. All differently expressed miRNA in group A are up-regulated, which may suggesting protective function of miRNA for intracranial vascular wall.

Intracranial Aneurysms Associated with Moyamoya Disease in Children: Clinical Features and Long-Term Surgical Outcome

BACKGROUND Moyamoya disease (MMD) in children was rarely associated with intracranial aneurysms. The purpose of this study was to report the clinical characteristics and long-term surgical outcomes of pediatric intracranial aneurysms accompanied with MMD. METHODS Between October 2002 and October 2013, our department treated 9 pediatric MMD patients (aged ≤17 years) with intracranial aneurysms. Clinical and angiographic features, treatment selection, as well as follow-up information were obtained and analyzed. The efficacy of vascularization and the changes of intracranial aneurysms were evaluated with digital subtraction angiography (DSA). We also collected 7 previously published reports to analyze the characteristics of this rare condition. RESULTS In our series of 9 patients, 7 were male. The mean age was 11 ± 3.4 years (range 5-16). Seven patients presented with intracranial hemorrhage as the initial manifestation, while 2 patients suffered transient ischemic attacks. The most common aneurysm location was the posterior choroidal artery (4, 44.4%). One anterior choroidal artery aneurysm was completely embolized with Onyx (ev3, Irvine, California, USA). One posterior choroidal artery aneurysm failed due to inaccessibility to the parent artery. Bilateral encephalo-duro-arterio-synangiosis (EDAS) surgery was performed for all the children. During the follow-up period of 6.4 ± 2.2 years (range 3-11), spontaneous occlusion of aneurysm was observed in 4 children, including 1 child with middle cerebral artery aneurysm, 1 with lenticulostriate artery aneurysm, and 2 with posterior choroidal artery aneurysm. Good or fair vascularization was observed in all the 9 children with DSA follow-up. No patients suffered intracranial hemorrhage during the follow-up period. CONCLUSIONS The long-term survey showed EDAS surgery could effectively increase the cerebral blood flow and maintain good outcomes in children, which may further result in the disappearance of the intracranial aneurysms and decrease the incidence of recurrent hemorrhage.

Difference in Angiographic Characteristics Between Hemorrhagic And Nonhemorrhagic Hemispheres Associated with Hemorrhage Risk of Moyamoya Disease in Adults: A Self-Controlled Study.

BACKGROUND Here, we compare the angiographic characteristics of hemorrhagic and nonhemorrhagic hemispheres within the same adult patient with moyamoya disease (MMD) and identify the possible risk factors for initial and recurrent hemorrhage during the long-term follow-up period. METHODS We retrospectively collected and analyzed the clinical and angiographic data of 145 consecutive adults with hemorrhagic MMD between 2004 and 2011. Separate angiographic characteristics of the hemorrhagic and nonhemorrhagic hemispheres were analyzed based on digital subtraction angiography. Multivariate logistic regression analysis was used to study the risk factors related to initial hemorrhage. In addition, clinical follow-up for at least 5 years was obtained in all the 145 patients. Cox regression analysis was used to determine the predictors for the subsequent recurrent hemorrhagic strokes. RESULTS With regard to the 145 consecutive patients in our cohort, multivariate analysis indicated that the dilation grade of anterior choroidal artery (odds ratio [OR], 2.449; 95% confidence interval [CI], 1.617-3.862), the dilation grade of the posterior communicating artery (PComA) (OR, 1.491; 95% CI, 1.071-2.075), and the involvement of the posterior cerebral artery (OR, 4.623; 95% CI, 1.273-16.792) were significantly associated with initial hemorrhage. After a median follow-up of 6.33 ± 1.81 years, 20 of the 145 patients (13.8%) developed 22 recurrent episodes of hemorrhage. No significant correlation was found between rebleeding and the above significant factors associated with the initial hemorrhage. CONCLUSIONS Compared with the nonhemorrhagic hemispheres, hemorrhagic hemispheres are more prone to recurrent hemorrhage. Our case-control study showed the dilation of the anterior choroidal artery or posterior communicating artery, as well as the involvement of the posterior cerebral artery, is associated with the initial hemorrhage of MMD, but not for the episode of recurrent hemorrhage. Longer and more detailed clinical and angiographic follow-up are still needed to delineate the specific mechanism underlying the recurrent hemorrhage in hemorrhagic MMD.

Adjunct to Embolize the High-Flow Fistula Part of Arteriovenous Malformation Using a Double-Lumen Balloon Catheter

OBJECTIVE The purpose of this study is to report our initial experience of Onyx embolization of the high-flow fistula part of arteriovenous malformation (AVM) using a double-lumen balloon catheter. METHODS A Scepter C balloon catheter was used in 2 patients with AVMs associated with high-flow fistulas. The fistulas were located in the anterior cerebral artery and the middle cerebral artery. RESULTS Onyx embolization was successful in 2 cases, resulting in elimination of the high-flow fistula part of the AVM. There were no treatment-related events. CONCLUSIONS The double-lumen Scepter balloon appears to be a safe and convenient device for Onyx embolization of high-flow fistulas.

Anterior inferior cerebellar artery aneurysms: Segments and results of surgical and endovascular managements.

Background Anterior inferior cerebellar artery (AICA) aneurysms are rare and published clinical experience with these aneurysms is limited. Objective The objective of this article is to report angiographic characteristics and results associated with premeatal, meatal and postmeatal segments, surgical and endovascular therapies. Methods A literature review was performed through PubMed using “anterior inferior cerebellar artery aneurysm” through January 2016. Clinical data, angiograms, management techniques, and patient outcomes were reviewed for 47 collected cases in 30 previous reports. Results Of these aneurysms, 21 (44.7%) were associated with meatal segment, 10 (21.3%) were postmeatal and 16 (34.0%) were premeatal. Patients with meatal aneurysms are more likely to present with subarachnoid hemorrhage and hearing loss and facial palsy (77.8%). Patient outcomes of meatal aneurysms presented with more neuropathies (51.7%) and cerebellar symptoms (14.3%) (p = 0.049). Four cases of meatal aneurysm with preoperative cranial nerve deficits (two VII and two VIII) showed improvement after surgery. Endovascular treatment achieved outcomes similar to surgical treatment (p = 0.327). Conclusions AICA aneurysms have a predilection for meatal segment. Patients with meatal aneurysms are more likely to present with subarachnoid hemorrhage and hearing loss and facial palsy. Patient outcomes of meatal aneurysms presented with more neuropathies and cerebellar symptoms. Endovascular treatment achieved outcomes similar to surgical treatment.

Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling.

Objective To investigate the influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling. Methods Between September 2014 and October 2015, we prospectively recruited 215 patients with intracranial aneurysms who were treated with stent-assisted coiling. CYP2C19 genotypes were determined and clopidogrel response was tested. The primary endpoints included symptomatic or silent ischemic events, and bleeding events. The secondary endpoint was clinical outcome at 3 months. Results Of the 215 patients, 108 (50.2%) were classified as intermediate metabolizers (IMs, CYP2C19*1/*2, *1/*3), 76 (35.3%) as extensive metabolizers (EMs, CYP2C19*1/*1) and 31 (14.4%) as poor metabolizers (PMs, CYP2C19*2/*2, *2/*3, *3/*3). Carriers of CYP2C19 loss-of-function (LOF) alleles (*2 or *3, p=0.001), especially PMs (p=0.004), had an increased risk for clopidogrel resistance. After the procedures, cerebral ischemic events occurred in 69 patients (32.1%) and bleeding was seen in 20 patients (9.3%). In comparison with IMs and PMs, EMs had a lower risk for ischemic events (21.1% vs 37.0% and 41.9%, p=0.02 and 0.027, respectively) and a relatively higher risk for bleeding events (18.4% vs 5.6% and 0%, p=0.006 and 0.01, respectively). Based on multivariate analysis, the carriage of CYP2C19 LOF alleles (p=0.032) and clopidogrel resistance (p=0.047) were considered as predictors of cerebral ischemic events, and EMs were significantly associated with bleeding (p=0.002). Posterior circulation aneurysms (p=0.038), hemorrhagic history (p=0.001) and poor metabolic genotypes (p=0.001) could result in poor clinical outcomes (modified Rankin Scale >2). Conclusions CYP2C19 genetic polymorphisms had significant influence on the antiplatelet effect of clopidogrel, and could be considered as risk factors of ischemic or bleeding events and even clinical outcomes of patients with intracranial aneurysms treated with stent-assisted coiling.

The role of endovascular treatment in unruptured basilar tip aneurysms

Objective This study was to evaluate the safety and efficiency of endovascular treatment of unruptured basilar tip aneurysms. Methods We retrospectively reviewed consecutive 79 cases of unruptured basilar tip aneurysms in our center between 2009 and 2014. The patients’ clinical and imaging information were recorded. Complications, initial occlusion rate, clinical outcomes and the predictors were retrospectively analyzed. Results Thirty-five cases received conservative treatment and 44 cases were treated by endovascular embolization. In the conservative treatment group, six (19.4%) of 31 basilar tip aneurysms ruptured and resulted in five deaths (16.1%) during the mean 18.1-month follow-up (range from 1 to 60 months). Among the endovascularly treated cases, 24 (54.5%) achieved initial complete occlusion and no delayed hemorrhagic events occurred during the mean 33.6-month follow-up (range from 10 to 68 months). For 20 (45.5%) incompletely occluded cases, five postoperative or delayed hemorrhagic events and two mass effect events resulted in six deaths. There were no statistical significant differences in hemorrhagic events (p = 0.732) and mortality (p = 0.502) between the incomplete occlusion group and untreated group. Large aneurysm size (≥10 mm) was an independent predictor for incomplete occlusion (p = 0.002), which had a potential risk of postoperative or delayed hemorrhage. On univariate analysis, initial occlusion rate and aneurysm size were found to be associated with clinical outcomes (p = 0.042 and 0.015). Conclusion Complete occlusion for unruptured basilar tip aneurysm proved to be a safe and effective therapeutic method that could eliminate the potential risk of postoperative or delayed hemorrhage.

A challenging entity of endovascular embolization with ONYX for brainstem arteriovenous malformation: Experience from 13 cases:

Objective Brainstem arteriovenous malformations (AVMs) are rare lesions with a high risk of intracranial hemorrhage and are challenging to treat. We present our experience of endovascular embolization with Onyx in these aggressive lesions. Materials and methods Between 2007 and 2016, 13 patients with brainstem AVMs were embolized with Onyx at our center. Twelve patients presented with intracranial hemorrhage and one with headache. Retrospective examinations of patient demographics, clinical presentation, angiographic features, treatment modalities, postoperative complications and outcomes were carried out. Results The AVMs were in the midbrain in 10 patients (one anterior and nine posterior or dorsal), in the posterior pons in two and pontomedullary in one. Complete occlusion was achieved in three patients. Gamma knife radiosurgery was performed in six patients who were near-completely or partially embolized. Postoperative complications, including five cases of ischemia and one case of hemorrhage, resulted in four cases of neurological deterioration and two deaths. Clinical follow-up was obtained in 10 patients at a mean period of 45.2 months (range 3 to 93 months). During the follow-up, good clinical outcomes were observed in seven patients with posterior or dorsal midbrain AVMs, and one patient with a posterior pons AVM that was partially occluded died of intracranial hemorrhage. Conclusion Endovascular embolization for brainstem AVM with Onyx is a technical challenge and the reflux of Onyx may cause severe complications. Individualized treatment is needed based on the specific subtype of brainstem AVM.

Aberrant Expression of microRNA-9 Contributes to Development of Intracranial Aneurysm by Suppressing Proliferation and Reducing Contractility of Smooth Muscle Cells

Background MiR-9 is reportedly involved with many diseases, such as acute myeloid leukemia and liver oncogenesis. In the present study we investigated the molecular mechanism, including the potential regulator and signaling pathways, of MYOCD, which is the gene that in humans encodes the protein myocardin. Material/Methods We searched the online miRNA database (www.mirdb.org) with the “seed sequence” located within the 3′-UTR of the target gene, and then validated MYOCD to be the direct gene via luciferase reporter assay system, and further confirmed it in cultured cells by using Western blot analysis and realtime PCR. Results We established the negative regulatory relationship between miR-9 and MYOCD via studying the relative luciferase activity. We also conducted realtime PCR and Western blot analysis to study the mRNA and protein expression level of MYOCD between different groups (intracranial aneurysm vs. normal control) or cells treated with scramble control, miR-9 mimics, MYOCD siRNA, and miR-9 inhibitors, indicating the negative regulatory relationship between miR-9 and MYOCD. We also investigated the relative viability of smooth muscle cells when transfected with scramble control, miR-9 mimics, MYOCD siRNA, and miR-9 inhibitors to validate that miR-9 t negatively interferes with the viability of smooth muscle cells. We then investigated the relative contractility of smooth muscle cells when transfected with scramble control, miR-9 mimics, MYOCD siRNA, and miR-9 inhibitors, and the results showed that miR-9 weakened contractility. Conclusions Our findings show that dysregulation of miR-9 is responsible for the development of IA via targeting MYOCD. miR-9 and its direct target, MYOCD, might novel therapeutic targets in the treatment of IA.

Role of endovascular embolization for trigeminal neuralgia related to cerebral vascular malformation

Objective The objective of this article is to describe the trigeminal neuralgia related to cerebral vascular malformation that is rarely reported and the experience referring to endovascular treatment. Patients and methods A total of 10 patients who had cerebral vascular malformation (AVM and dAVF) in a single center presented with trigeminal neuralgia. Clinical and angiographic presentations as well as their clinical outcomes after embolization were reviewed. Results Of the 10 cases, seven dAVFs and three AVMs were detected. In contrast to the dilated feeding arteries, an ectasia of the draining vein that is adjacent to the root entry zone of the trigeminal nerve such as the petrosal vein and lateral mesencephalic vein has the major role in causing the trigeminal neuralgia. All of these patients had relief of facial pain after endovascular embolization during follow-up (mean 57.3 months, range 5 to 100 months). There were no permanent neurological deficits. Conclusions Endovascular embolization is an effective method in treating trigeminal neuralgia related to cerebral vascular malformation.