Guobiao Liang

Neuroform stent-assisted coiling of intracranial aneurysms: a 5 year single-center experience and follow-up

Abstract Background and purpose: Wide-necked and fusiform aneurysms still remain a therapeutic challenge both surgically and endovascularly. The authors report their clinical experience and 5 year follow-up results using Neuroform stent, as an adjunct in the treatment of wide-necked and fusiform aneurysms. Methods: One hundred and seven consecutive patients with 110 wide-necked or fusiform intracranial aneurysms were treated with the Neuroform stent-assisted coiling. Both sequential technique and parallel technique were used. In all cases, embolization was completed by packing the aneurysm sac with a variety of commercially available coils. The technical feasibility of the procedure, procedure-related complications, angiographic results, clinical outcome and follow-up angiography were evaluated. Results: In every case, the Neuroform stent system was delivered and deployed accurately, and occlusion was achieved. Immediate angiography demonstrated complete occlusion in 57·2%, neck remnant in 27·3% and incomplete occlusion in 15·5%. Procedure-related morbidity was 5·6% and procedural-related mortality was 0·9%. Favorable clinical outcome (modified Rankin scale score: 0–2) was observed in 90·7% of the patients (average follow-up time: 47·3 months). No rehemorrhage of treated aneurysm occurred. Angiography follow-up was obtained in 45·8% (49/107 patients; 51/110 aneurysms; average follow-up time: 37·2 months). The overall recanalization rate was 13·7%. Comparison of occlusion class immediately after treatment and at last follow-up showed that 86·3% of the 51 aneurysms had stable or improved class. Eight aneurysms (36·4%) that were not initially completely occluded converted to complete occlusion on follow-up. No delayed coil or stent migration was found. One patient with in-stent stenosis and one with penetrating artery occlusion occurred as delayed complications. Conclusion: In treating complex intracranial aneurysms, the Neuroform stent-assisted coiling is a secure and effective technique.

Complications and adverse events associated with Neuroform stent-assisted coiling of wide-neck intracranial aneurysms

Abstract Background: Successful experiences of the Neuroform stent-assisted coiling have been reported by many teams in endovascular neurosurgery centers throughout the world. However, most of the reported complications involved a limited number of patients. Objective: To systematically report the complications of Neuroform stent-assisted coiling of intracranial aneurysms and to tentatively assess the efficacy and safety of this method. Methods: A retrospective study of 232 consecutive patients with 239 wide-neck aneurysms treated with Neuroform stent-assisted coil embolization at our institution over a 6-year period was performed. Angiographic results and clinical outcome were evaluated. Cases with complications were analyzed. Results: Stenting was successful in 237 of 239 aneurysms. Favorable clinical outcome (modified Rankin score: 0-2) was observed in 88·3% of the patients. Procedure-related complications included thromboembolism (n = 13), intraprocedural rupture (n = 8), coil protrusions (n = 5), new mass effect (n = 3), vessel injury (n = 3), and stent dislodgement (n = 2). Procedure-related morbidity and mortality were 4·2 and 1·3%, respectively. Non-procedural complications attributable to subarachnoid hemorrhage in 129 patients with ruptured aneurysms were symptomatic vasospasm (18·6%) and shunt-dependent hydrocephalus (6·9%). Angiography follow-up was obtained in 67·1% of the treated aneurysms. The overall recanalization rate was 14·5%. Delayed complications included in-stent stenosis (n = 2) and penetrating artery occlusion (n = 2) in follow-up period. Conclusion: Neuroform sent-assisted coiling of intracranial aneurysm is a safe technique with relatively low recanalization rate. The main cause of morbidity and mortality is thromboembolism. Long-term effect on parent artery should be observed carefully.

Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption.

Expression of Pro-Inflammatory Cytokines and the Risk of Intracranial Aneurysm

Intracranial aneurysm (IA) lingers as a potentially devastating clinical problem, in which inflammation acts as a critical contributor to the pathogenesis of this disease. Cytokines play a major role in regulating inflammation. The aim of this study was to gain insight in the inflammatory response in IA by assessing plasma cytokine profiles. Plasma levels of 10 cytokines were quantified by multiplex protein arrays in 66 patients with IA and 78 healthy controls. Results showed that plasma level of interleukin 1 beta (IL-1β) was 2.4-fold higher in patients than in controls (p < 0.05). The level of monocyte chemoattractant protein-1 (MCP-1) was 2.8-fold higher in patient than in controls (p < 0.01). The level of tumor necrosis factor-alpha (TNF-α) was 2.1-fold higher in cases than in controls (p < 0.001). When comparing the expression of cytokines in IA patients with different characteristics, cases with ruptured aneurysm revealed increased level of MCP-1 than those with unruptured aneurysm (p < 0.05), whereas cases with multiple numbers of aneurysms demonstrated higher levels of MCP-1 and TNF-α than those with single aneurysm (p < 0.05 and p < 0.05, respectively). These data indicated that IL-1β, MCP-1, and TNF-α were associated with increased risk of IA and may affect the development of this disease.

Endovascular treatment for dural arteriovenous fistula at the foramen magnum: report of five consecutive patients and experience with balloon-augmented transarterial Onyx injection.

BACKGROUND Foramen magnum dural arteriovenous fistulas (DAVF) with perimedullary venous drainage represent a small minority of intracranial DAVF, and only a number of small series with limited cases have been reported. The purpose of this retrospective study is to summarize experience of transarterial Onyx embolisation in the treatment of these lesions, with emphasis on the balloon-augmented technique. METHODS Five consecutive patients with DAVF at the foramen magnum were treated by transarterial embolisation using the Onyx system. Their symptoms included myelopathy (n=4) and SAH (n=1). Suppliers were from the vertebral artery (VA) (n=4), occipital artery (OA) (n=4), and ascending pharyngeal artery (APA) (n=2), with drainage to the perimedullary veins. After catheterization of the dilated supplier, the fistulous connections, proximal draining veins and appropriate distal segment of the feeders of these DAVF were transarterial embolized using Onyx-18. In three patients, balloon-augmented technique was used to assist embolisation. The technical feasibility of the procedure, angiographic results, and clinical outcome were evaluated. RESULTS In every case, complete obliteration was achieved. Neither intraprocedural vessel rupture nor other procedure-related complications occurred. The results remained stable in all patients on follow-up angiograms (mean, 7.2 months). At the last clinical follow-up (mean, 17.6 months), two patients showed complete resolution of the initial symptoms, and three patients showed significant improvement. CONCLUSION We found that Onyx embolisation is a feasible and safe alternative to open surgery in the treatment of selective DAVF at the foramen magnum. The balloon-augmented technique widens indications for transarterial Onyx packing of these lesions, and improved safety of the procedure.

Stanniocalcin-1, a new biomarker of glioma progression, is associated with prognosis of patients

Stanniocalcin-1 (STC1) is a secreted glycoprotein hormone and highly expressed in various types of human malignancies. Although evidence points to the role of STC1 in human cancers, the clinical significance of STC1 expression in glioma has not been established. Here, we investigated the relationship between STC1 expression and clinicopathological significance in glioma. In our study, we selected 60 cases of different grades glioma tissues to detect the expression of STC1. Data showed that the mRNA and protein levels of STC1 in high-grade glioma tissues were significantly higher than that in low-grade tissues. The results of double immunofluorescent staining disclosed STC1 distribution in vascular endothelial cells and the cytoplasm in high-grade glioma, but almost distributed only in vascular endothelial cells in low-grade glioma. By immunohistochemistry, we got the same results and the expression of STC1 has significant difference in high-grade gliomas and low-grade gliomas. Furthermore, the results of Kaplan–Meier analysis indicated that cases with high STC1expression had significantly worse overall survival than those with low level of STC1. These results suggested that STC1 may be a valuable biomarker in diagnosing malignant degree of glioma and evaluating prognostic following surgery. Next, we would study the pathophysiological mechanism of STC1 in glioma.

Lysyl oxidase genetic variants and the prognosis of glioma

Lysyl oxidase (LOX) is a copper‐dependent amine oxidase that plays important roles in the development and homeostasis of primary brain tumors such as glioma. The aim of this study was to investigate whether polymorphisms in the LOX gene were associated with susceptibility to glioma. We tested two functional polymorphisms of LOX, −22G/C and 473G/A, and compared them between 466 glioma cases and 502 healthy controls in the Chinese population. Results showed that the prevalence of 473AA genotype was significantly increased in cases than in controls (p = 0.001). Individuals who carried 473A allele had a 1.44‐fold of increased risk for glioma than those with 473G allele (p = 0.002). In addition, when analyzing the survival time of glioma patients with LOX 473G/A polymorphism, cases with AA genotype had significantly shorter survival time compared to the patients carrying G allele (25.0 months vs 43.0 months, p = 0.0009). These results suggested that polymorphism in LOX gene was associated with increased susceptibility to glioma and could be used as prognostic factor for this malignancy.

β-elemene inhibits stemness, promotes differentiation and impairs chemoresistance to temozolomide in glioblastoma stem-like cells

Accumulating evidence indicates that glioblastoma stem-like cells (GSCs) are key factors in tumour development, recurrence and chemoresistance. The impairment of stemness and the enhancement of differentiation contributes to the weakening of radiation and chemotherapy resistance of GSCs. We previously found that β-elemene was an effective anti-glioblastoma agent and chemosensitizer. In this study, we examined the distribution of CD133(+) cells in human glioblastoma tissues by immunohistochemistry. Following treatment with β-elemene, the formation of GSC spheres was investigated by manual counting, the proliferation of GSCs was measured with a Cell Counting Kit-8 (CCK-8) assay, and the dispersion of GSC spheres was observed with an inverted microscope. GSC spheres were treated with β-elemene, and the expression levels of CD133, ATP-binding cassette subfamily G member 2 (ABCG2) and glial fibrillary acidic protein (GFAP) were examined by western blotting. After treatment with β-elemene, the volumes and weights of GSC xenografts were measured, and the expression of CD133, ABCG2 and GFAP was evaluated through immunohistochemistry analysis. After treatment with β-elemene and temozolomide (TMZ), GSC viability was examined by the CCK-8 assay, and the volumes and weights of xenografts were measured. We found that CD133(+) cells were assembled in some vascular walls and also sparsely distributed in other parts of glioblastoma tissues. β-elemene decreased the formation of GSC spheres, dispersed GSC spheres and inhibited the proliferation of GSCs in vitro and in vivo. In the GSC spheres and xenografts treated with β-elemene, the expression of CD133 and ABCG2 was significantly downregulated, and the expression of GFAP increased. Furthermore, the sensitivity of GSCs to TMZ was enhanced in vitro and in vivo. These results suggest that β-elemene impaired the stemness of GSC spheres, promoted their differentiation and sensitized GSCs to TMZ. β-elemene will hopefully become a valuable agent to enhance the effects of radiotherapy and chemotherapy.

Fangchinoline suppresses the growth and invasion of human glioblastoma cells by inhibiting the kinase activity of Akt and Akt-mediated signaling cascades.

Glioblastoma multiforme (GBM) is one of the most palindromic and malignant central nervous system neoplasms, and the current treatment is not effectual for GBM. Research of specific medicine for GBM is significant. Fangchinoline possesses a wide range of pharmacological activities and attracts more attentions due to its anti-tumor effects. In this study, two WHO grade IV human GBM cell lines (U87 MG and U118 MG) were exposed to fangchinoline, and we found that fangchinoline specifically inhibits the kinase activity of Akt and markedly suppresses the phosphorylation of Thr308 and Ser473 of Akt in human GBM cells. We also observed that fangchinoline inhibits tumor cell proliferation and invasiveness and induces apoptosis through suppressing the Akt-mediated signaling cascades, including Akt/p21, Akt/Bad, and Akt/matrix metalloproteinases (MMPs). These data demonstrated that fangchinoline exerts its anti-tumor effects in human glioblastoma cells, at least partly by inhibiting the kinase activity of Akt and suppressing Akt-mediated signaling cascades.

Using Onyx in endovascular embolization of internal carotid artery large or giant aneurysms

BACKGROUND AND PURPOSE Internal carotid artery (ICA) large or giant saccular aneurysms is challenging for endovascular coil embolization and surgical clipping with a high recanalization and rebleeding rate. We report our results using Onyx in the endovascular treatment of ICA large or giant saccular aneurysms. METHODS During 2008-2010, 5 patients with 5 large or giant saccular aneurysms in ICA were treated with a liquid embolic agent (Onyx; Micro Therapeutics, Irvine, CA). One aneurysm was small (<10mm), 2 were large (≥10mm, <25mm) and 2 were giant saccular aneurysms (≥25mm). Of 3 female and 2 male patients, 3 were incidental and 2 had bleeding. Selective embolization was performed with Onyx alone or a combination with coils. Clinical and anatomic outcomes were assessed with the Modified Glasgow Outcome Scale and follow-up angiography was performed at 4-21 months (mean 12.2 months). RESULTS Complete aneurysm occlusion was obtained in all of the aneurysms on immediate control angiogram. There was not any procedure-related complication. No recanalization was observed at the follow- up periods. There were 2 ICA occlusions in giant ICA aneurysms. The 5 patients were all clinically asymptomatic at follow-up. CONCLUSION Endovascular embolization with Onyx is a useful treatment for ICA large or giant aneurysms, which is unsuitable for coiling or surgical treatment.