Endovascular embolization for basal ganglia and thalamic arteriovenous malformations.

Background: Basal ganglia and thalamic arteriovenous malformations (AVMs) represent a special subset of malformations. Due to the involvement of vital brain structures and the specifically fine and delicate angioarchitecture of these lesions, it presents unique therapeutic challenges and technical difficulties that require thorough treatment planning, individualized treatment strategies, and advanced techniques for good clinical outcome. Method: In this study, we presented a series of ruptured basal ganglia and thalamic AVMs embolized via a transarterial, transvenous or combined approach. Herein, we summarized our treatment experience and clinical outcomes to further evaluate the effectiveness and safety of endovascular embolization for these AVMs as well as the indications, therapy strategies, and techniques of embolization procedures. Results: Twelve patients with basal ganglia and thalamus AVMs were included in the study. Their average age was 23.83 ± 16.51 years (range, 4-57 years) with a female predominance of 67% at presentation. The AVMs were located in the thalamus in 3 (25%) patients, in the basal ganglia in 3 (25%) patients, and in both sites of the brain in 6 (50%) patients. There were 5 AVMs located on the left side and 7 on the right. The mean nidus diameter was 3.32 ± 1.43 cm (range 1.3-6.1 cm). According to the Spetzler-Martin grading classification, 4 (33.3%) brain AVMs were Grade III, 7 (58.3%) were Grade IV, and 1 (8.3%) was Grade V. All of them presented with bleeding at admission: four of these patients presented with an intracerebral hemorrhage (ICH), 8 ICH in combination with intraventricular hemorrhage (IVH), and no patient with subarachnoid hemorrhage (SAH). Among these patients treated with endovascular embolization, 7 patients were treated by the transarterial approach, 4 patients transvenous approach, and 1 patient underwent the combined approach. A single embolization procedure was performed in 6 patients (50%) and the other 6 cases (50%) were treated in a staged manner with up to three procedures. Procedure-related complications occurred only in two patient (16.7%). Complete AVM obliteration was obtained in 7 patients (58.3%), and partial obliteration was in 4 patients (33.3%). Overall, good or excellent outcomes were obtained in 7 patients (58.3%), and poor functional outcome was observed in 5 patients (41.7%) at the last follow-up. All survived patients achieved anatomic stabilization and there was no postoperative bleeding or recurrence in the follow-up. Conclusion: The management of the basal ganglia and thalamic AVMs is a great challenge, which needs multimodal individualized treatment to improve the chances of radiographic cure and good outcomes. Endovascular therapy is safe and effective in the treatment of cerebral AVMs particularly for deep-seated AVMs such as the basal ganglia and thalamus. Our results demonstrate a high rate of anatomic obliteration with an acceptable rate of complications in the endovascular treatment of these vasculopathies via a transarterial approach or a transvenous approach.

Development and Validation of a Deep Learning Predictive Model Combining Clinical and Radiomic Features for Short-Term Postoperative Facial Nerve Function in Acoustic Neuroma Patients.

OBJECTIVE: This study aims to construct and validate a predictable deep learning model associated with clinical data and multi-sequence magnetic resonance imaging (MRI) for short-term postoperative facial nerve function in patients with acoustic neuroma. METHODS: A total of 110 patients with acoustic neuroma who underwent surgery through the retrosigmoid sinus approach were included. Clinical data and raw features from four MRI sequences (T1-weighted, T2-weighted, T1-weighted contrast enhancement, and T2-weighted-Flair images) were analyzed. Spearman correlation analysis along with least absolute shrinkage and selection operator regression were used to screen combined clinical and radiomic features. Nomogram, machine learning, and convolutional neural network (CNN) models were constructed to predict the prognosis of facial nerve function on the seventh day after surgery. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate model performance. A total of 1050 radiomic parameters were extracted, from which 13 radiomic and 3 clinical features were selected. RESULTS: The CNN model performed best among all prediction models in the test set with an area under the curve (AUC) of 0.89 (95% CI, 0.84-0.91). CONCLUSION: CNN modeling that combines clinical and multi-sequence MRI radiomic features provides excellent performance for predicting short-term facial nerve function after surgery in patients with acoustic neuroma. As such, CNN modeling may serve as a potential decision-making tool for neurosurgery.

Combined Endovascular and Surgical Treatment for Brain Arteriovenous Malformations in Biplanar Hybrid Operating Room.

OBJECTIVE: Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years. However, reports on one-session hybrid surgery for arteriovenous malformations (AVMs) are relatively rare. The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room (OR) at one stage. METHODS: We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018. The data for resection rate, microcatheter adhesion, surgical position and postoperative outcomes were analyzed. Total resection or near-total resection was achieved in all cases. RESULTS: A total of 13 patients were under combined endovascular and surgical procedures, and 7 experienced surgery with intraoperative digital subtraction angiography. Sitting position was applied in 3 of them; 2 niduses in cerebellum, and 1 in parietal lobe. Compared with admission modified Rankin Scale (mRS) in all patients, postoperative 12-month mRS showed a significant decline. Besides, 3 patients experienced microcatheter adhesion after endovascular embolization, thereafter underwent surgical adhesion removal while nidus resection was done. CONCLUSION: Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs. The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position. It also reduces the risk of microcatheter adhesion, which enables interventional radiologists to perform aggressively.

Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma.

Long non-coding RNA (lncRNA) are a class of non-coding RNAs demonstrated to play pivotal roles in regulating tumor progression. Therefore, deciphering the regulatory role of lncRNA in the development of glioma may offer a promising therapeutic target for treatment of glioma. We performed RT-qPCR analysis on the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-365 in glioma tissues and cell lines. Cell proliferation and viability was assessed with CCK8 assay. Cell migration was assessed by wound healing assay. Transwell assay was used to assess cell invasion capacity. Expression of CD133+ cells was detected by flow cytometry. Western blot assay was used to detection the expression of ELF4 and stemness-related protein SOX2, Oct4 and Nanog. Bioinformatics and dual-luciferase assay were used to predict and validate the interaction between PVT1 and miR-365. Elevated PVT1 expression was observed in glioma tissues and cells. Knockdown of PVT1 and overexpression of miR-365 inhibited proliferation, migration, invasion and promoted stemness and Temozolomide (TMZ) resistance of glioma cells. PVT1 regulated ELF4 expression by competitively binds to miR-365. PVT1 regulated the stemness and sensitivity of TMZ of glioma cells through miR-365/ELF4/ SOX2 axis. This study identified that PVT1 promoted glioma stemness through miR-365/ELF4/SOX2 axis.

Moyamoya Disease Associated With Morning Glory Disc Anomaly and Other Ophthalmic Findings: A Mini-Review.

Moyamoya disease (MMD) is a chronic cerebrovascular disease that frequently results in intracranial ischemia or hemorrhage. Its concurrence with varying ophthalmic findings is relatively rare yet may lead to irreversible blindness. We performed a search and review of the literature to characterize the relevance of MMD (excluding moyamoya syndrome) and ophthalmic findings. As a result, a total of 38 articles identified from PubMed and Web of Science were included in this mini-review. Patients with MMD sometimes present with decreased visual acuity or visual field defects before the onset of symptomatic cerebrovascular dysfunction. The most predominant ophthalmic condition in MMD patients is the morning glory disc anomaly (MGDA). Deficiency during neuroectodermal genesis and subsequent mesodermal changes may be responsible for the association between these two diseases. Thus, it may be beneficial for patients with MGDA to receive cerebral vascular examinations as the precaution against life-threatening intracranial angiopathy. Other ophthalmic findings reported in cases of MMD include retinal vascular occlusion, optic disc pallor, cortical blindness, etc. For most of the patients with MMD, retinal examinations would be recommended to prevent potential loss of vision. It is essential for both neurologists and ophthalmologists to be aware of the correlation between cerebrovascular diseases such as MMD and ocular manifestations to achieve a comprehensive diagnosis.

Endovascular Treatment of Cavernous Sinus Dural Arteriovenous Fistulas via Direct Transorbital Puncture Using Cone-Beam Computed Tomography Image Guidance: Report of 3 Cases.

BACKGROUND: Certain cavernous sinus (CS) dural arteriovenous fistulas (DAVFs) are difficult to access through transarterial or transvenous routes and may necessitate access through direct transorbital puncture of the superior ophthalmic vein (SOV) or the CS. However, to be successful, the accurate design of the puncture route and guidance are crucial. This study aimed to report our preliminary clinical experience using cone-beam computed tomography (CT) with real-time fluoroscopic overlays for image guidance during transorbital needle puncture. METHODS: Between December 2017 and July 2018, 3 patients with CS DAVFs were treated via a transorbital puncture to establish access to the CS under the guidance of XperGuide planning software either via direct CS puncture or through the SOV. The guidance trajectory was superimposed onto the real-time fluoroscopic image during needle puncture. Once access was established, the CS DAVFs were treated with a combination of liquid embolic materials and coils. RESULTS: Image guidance aided to avoid at-risk structures and treatment resulted in all cases in complete obliteration of the CS DAVFs as verified by control angiography without peri- or postprocedural complications. CONCLUSIONS: Endovascular embolization of CS DAVFs via direct transorbital puncture aided by image guidance provided an alternative option when more conventional approaches are deemed not possible.

Sustained antidepressant action of the N-methyl-D-aspartate receptor antagonist MK-801 in a chronic unpredictable mild stress model.

(5S,10R)-5-methyl-10,11-dihydro-5H-dibenzo(A,D)cyclohepten-5,10-imine hydrogen maleate (MK-801) is an N-methyl-D-aspartate non-competitive antagonist that possesses useful biological properties, including anticonvulsant and anesthetic activities. Studies have indicated the rapid antidepressant effects of MK-801 in animal models. However, there are no reports concerning a sustained antidepressant effect in the chronic unpredictable mild stress (CUMS) model. Furthermore, the antidepressant mechanism remains unclear. The aim of the present study was to examine the effects of MK-801 (0.1 mg/kg) and rapastinel (10 mg/kg) on depression-like behavior in CUMS mice and measure the protein expression of brain-derived neurotrophic factor (BDNF), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (GluA1) and phosphorylated mammalian target of rapamycin (p-mTOR). In the tail suspension and forced swim tests, MK-801 significantly attenuated the increased immobility time in CUMS mice compared with the vehicle group. In the sucrose preference test, a single-dose injection of MK-801 significantly ameliorated the decreased sucrose preference in CUMS mice compared with the vehicle group. Western blot analyses indicated that MK-801 significantly attenuated the decreased BDNF, GluA1 and p-mTOR protein levels in the medial prefrontal cortex (mPFC), dentate gyrus (DG) and CA3 of the hippocampi of CUMS mice. Conversely, this compound had no effect on increased BDNF, GluA1 and p-mTOR protein levels in the nucleus accumbens of CUMS mice. Therefore, the present study revealed the sustained antidepressant effects of MK-801 in the CUMS model. Furthermore, synaptogenesis and neuronal regeneration in the prelimbic regions of mPFC, DG and CA3 of the hippocampus may be implicated as mechanisms that promote a sustained antidepressant response.

Giant Serpentine Aneurysm of the Middle Cerebral Artery.

BACKGROUND: Giant serpentine aneurysms (GSAs) are a subgroup of giant intracranial aneurysms, distinct from saccular and fusiform varieties, that are defined as partially thrombosed giant aneurysms with tortuous internal vascular channel. Clinicopathologic characteristics of middle cerebral artery GSAs have been rarely reported in the literature, with discussion of radiologic characteristics only. We clarify patient clinical and neuroradiologic features and discuss the mechanism of formation and progression. CASE DESCRIPTION: A 43-year-old woman presented with a GSA arising from the middle cerebral artery. There was a separate inflow and outflow channel of the aneurysm, with the outflow channel feeding the distal branches of the parent artery and supplying normal brain parenchyma. The GSA was treated successfully by aneurysmectomy and superficial temporal artery-middle cerebral artery bypass followed by proximal occlusion and vascular reconstruction. An aneurysm specimen was examined to correlate pathologic findings and morphologic characteristics. RESULT: Pathologic results showed that thickness of the aneurysmal wall was typically increased and varied, and no internal elastic lamina or endothelial lining could be identified. The sac contained thrombi of various ages with recanalizing vessel formation and chronic inflammation infiltration. Intimal hyperplasia and neoangiogenesis in the wall and hyaline degeneration of the media were observed. Vessels coursing in their adventitia showed mucoid changes, which are responsible for the contrast enhancement of the aneurysmal rim on computed tomography scan. CONCLUSIONS: GSAs are a specific pathologic entity with unique morphologic and pathologic characteristics that can affect intracranial blood vessels. The pathogenic mechanisms are unclear; this report suggests that GSAs may be associated with degeneration of the vascular wall.

Bisperoxovandium (pyridin-2-squaramide) targets both PTEN and ERK1/2 to confer neuroprotection.

BACKGROUND AND PURPOSE: We and others have shown that inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) or activating ERK1/2 confer neuroprotection. As bisperoxovanadium compounds are well-established inhibitors of PTEN, we designed bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and determined whether and how bpV(pis) exerts a neuroprotective effect in cerebral ischaemia-reperfusion injury. EXPERIMENTAL APPROACH: Malachite green-based phosphatase assay was used to measure PTEN activity. A western blot assay was used to measure the phosphorylation level of Akt and ERK1/2 (p-Akt and p-ERK1/2). Oxygen-glucose deprivation (OGD) was used to injure cultured cortical neurons. Cell death and viability were assessed by LDH and MTT assays. To verify the effects of bpV(pis) in vivo, Sprague-Dawley rats were subjected to middle cerebral artery occlusion, and brain infarct volume was measured and neurological function tests performed. KEY RESULTS: bpV(pis) inhibited PTEN activity and increased p-Akt in SH-SY5Y cells but not in PTEN-deleted U251 cells. bpV(pis) also elevated p-ERK1/2 in both SH-SY5Y and U251 cells. These data indicate that bpV(pis) enhances Akt activation through PTEN inhibition but increases ERK1/2 activation independently of PTEN signalling. bpV(pis) prevented OGD-induced neuronal death in vitro and reduced brain infarct volume and promoted functional recovery in stroke animals. This neuroprotective effect of bpV(pis) was blocked by inhibiting Akt and/or ERK1/2. CONCLUSIONS AND IMPLICATIONS: bpV(pis) confers neuroprotection in OGD-induced injury in vitro and in cerebral ischaemia in vivo by suppressing PTEN and activating ERK1/2. Thus, bpV(pis) is a bi-target neuroprotectant that may be developed as a drug candidate for stroke treatment.

Histopathological features of middle cerebral artery and superficial temporal artery from patients with moyamoya disease and enlightenments on clinical treatment.

The histopathological features of the middle cerebral artery (MCA) and superficial temporal artery (STA) from moyamoya disease (MMD) and their relationships with gender, age, angiography stage were explored. The causes and the clinical significance of vasculopathy of STA were also discussed. The clinical data and specimens of MCA and STA from 30 MMD patients were collected. Twelve samples of MCA and STA from non-MMD patients served as control group. Histopathological examination was then performed by measuring the thickness of intima and media, and statistical analysis was conducted. The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group. There was no significant pathological difference between the hemorrhage group and non-hemorrhage group, and between the males and females in MMD patients. Neither the age nor the digital subtraction angiography (DSA) stage was correlated with the thickness of intima in MCA and STA. MMD is a systemic vascular disease involving both intracranial and extracranial vessels. Preoperative external carotid arteriography, especially super-selective arteriography of the STA, benefits the selection of donor vessel.

Glycine Potentiates AMPA Receptor Function through Metabotropic Activation of GluN2A-Containing NMDA Receptors.

NMDA receptors are Ca2+-permeable ion channels. The activation of NMDA receptors requires agonist glutamate and co-agonist glycine. Recent evidence indicates that NMDA receptor also has metabotropic function. Here we report that in cultured mouse hippocampal neurons, glycine increases AMPA receptor-mediated currents independent of the channel activity of NMDA receptors and the activation of glycine receptors. The potentiation of AMPA receptor function by glycine is antagonized by the inhibition of ERK1/2. In the hippocampal neurons and in the HEK293 cells transfected with different combinations of NMDA receptors, glycine preferentially acts on GluN2A-containing NMDA receptors (GluN2ARs), but not GluN2B-containing NMDA receptors (GluN2BRs), to enhance ERK1/2 phosphorylation independent of the channel activity of GluN2ARs. Without requiring the channel activity of GluN2ARs, glycine increases AMPA receptor-mediated currents through GluN2ARs. Thus, these results reveal a metabotropic function of GluN2ARs in mediating glycine-induced potentiation of AMPA receptor function via ERK1/2 activation.

Significance of cyclooxygenase-2 elevation in middle cerebral artery for patients with hemorrhagic moyamoya disease.

The etiology and pathogenesis of moyamoya disease (MMD) remain elusive. Some inflammatory proteins, such as cyclooxygenase (COX)-2, are believed to be implicated in the development of MMD. So far, the relationship between COX-2 and MMD is poorly understood and reports on the intracranial vessels of MMD patients are scanty. In this study, tiny pieces of middle cerebral artery (MCA) and superficial temporal artery (STA) from 13 MMD patients were surgically harvested. The MCA and STA samples from 5 control patients were also collected by using the same technique. The expression of COX-2 was immunohistochemically detected and the average absorbance (A) of positively-stained areas was measured. High-level COX-2 expression was found in all layers of the MCA samples from all 5 hemorrhagic MMD patients, while positive but weak expression of COX-2 was observed only in the endothelial layer of the MCA samples from most ischemic MMD patients (6/8, 75%). The average A values of COX-2 in the hemorrhagic MMD patients were substantially higher than those in their ischemic counterparts (t=4.632, P=0.001). There was no significant difference in the COX-2 expression among the "gender" groups, or "radiographic grade" groups, or "lesion location" groups (P>0.05 for all). The COX-2 expression was detected neither in the MCA samples from the controls nor in all STA specimens. Our results suggested that COX-2 was up-regulated in the MCA of MMD patients, especially in hemorrhagic MMD patients. We are led to speculate that COX-2 may be involved in the pathogenesis of MMD and even contribute to the hemorrhagic stroke of MMD patients.

Treatment strategies for huge central neurocytomas.

Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.

Stromal cell-derived factor 1α decreases ß-amyloid deposition in Alzheimer's disease mouse model.

ß-amyloid (Aß) aggregates are known to induce neuronal and synaptic dysfunction, and thus are involved in learning and memory deficits in Alzheimer's disease (AD), making Aß deposits a potential target for prevention or treatment. Microglia, especially bone marrow-derived microglia (BMDM), has been recently thought to play important roles in internalizing and phagocytozing Aß. BMDM originate in the bone marrow, migrate into the blood as hematopoietic progenitor cells (HPCs) and enter the brain in a chemokine-dependent manner. An effective chemoattractant for HPCs is stromal cell-derived factor 1 (SDF-1), which is also involved in regulating HPCs differentiation. Therefore, we hypothesize that SDF-1 might have influence on the migration of BMDM from peripheral cycle to brain. To explore whether treatment with SDF-1α can decrease Aß burden, APP/PS1 double transgenic mice were given intracerebroventricular injection of SDF-1α weekly from the age of 28 to 32 weeks (4 weeks of injections) or from 28 to 36 weeks (8 weeks of injections). The results of our study showed that SDF-1α treatment decreased the area and the number of Aß deposits, increased the level of Iba-1, a marker of microglia, and increased the number of plaque associated microglia in the parenchyma of APP/PS1 transgenic mice. These results suggest that SDF-1 could provide a novel and promising target for the purpose of lowering Aß pathology in AD.

Diagnosis and endovascular treatment of spontaneous direct carotid-cavernous fistula.

BACKGROUND: Spontaneous direct carotid-cavernous fistula (CCF) is relatively rare and few reports have been found in the literature. The aim of this paper was to report the clinical characteristics, imaging findings and curative effect of endovascular treatment for patients with spontaneous direct CCF. METHODS: We retrospectively analyzed the clinical data of nine patients with spontaneous direct CCF admitted between May 2003 and November 2007 and the outcomesof endovascular treatment. Sudden neuro-ophthalmological symptoms were the most common clinical presentation at diagnosis (n=8). No patients had a history of head trauma. Cerebral digital subtraction angiography (DSA) was performed on all cases under local anesthesia and seven cases received endovascular treatment. RESULTS: In eight patients, internal carotid angiograms recorded during the early arterial phase revealed aneurysms located in the cavernous sinuses, and in one patient, a dilated internal carotid artery (ICA) was seen. Among the nine cases, seven received endovascular treatment via a transarterial approach and complete occlusion of the fistula was obtained with no technique-related complications, one died suddenly before treatment and one gave up treatment. A detachable balloon was used as the embolic material in two cases, a detachable balloon and detachable coil as the embolic material in two cases, balloon-assisted coil embolization in two cases and covered stents were successfully placed in the parent vessel to exclude the aneurysm and fistula from circulation in one case. During a follow-up period of 3-48 months, all treated patients remained asymptomatic except for one patient who suffered from ipsilateral decreased vision. CONCLUSIONS: Most spontaneous direct CCF may be caused by a ruptured intracavernous aneurysm with direct shunting into the cavernous sinus. Endovascular treatment seems to be a safe and effective method for treating spontaneous direct CCF.