Development and validation of a novel nomogram for predicting good neoangiogenesis after encephaloduroarteriosynangiosis in patients with moyamoya disease and type 2 diabetes mellitus: a case-control study.

OBJECTIVE: Diabetes is often linked to poorer outcomes in patients with moyamoya disease (MMD). However, experience has shown that certain individuals with diabetes have favorable outcomes after encephaloduroarteriosynangiosis (EDAS). The authors aimed to develop a nomogram to predict good neoangiogenesis in patients with MMD and type 2 diabetes mellitus (T2DM) to aid neurosurgeons in the identification of suitable candidates for EDAS. METHODS: Adults with MMD and T2DM who underwent EDAS between June 2004 and December 2018 were included in the analysis. In total, 126 patients (213 hemispheres) with MMD and T2DM from the Fifth Medical Centre of the Chinese PLA General Hospital were included and randomly divided into training (152 hemispheres) and internal validation (61 hemispheres) cohorts at a ratio of 7:3. Univariate logistic and least absolute shrinkage and selection operator regression analyses were used to identify the significant factors associated with good neoangiogenesis, which were used to develop a nomogram. The discrimination, calibration, and clinical utility were assessed. RESULTS: A total of 213 hemispheres in 126 patients were reviewed, including 152 (71.36%) hemispheres with good postoperative collateral formation and 61 (28.64%) with poor postoperative collateral formation. The authors selected 4 predictors (FGD5 rs11128722, VEGFA rs9472135, Suzuki stage, and internal carotid artery [ICA] moyamoya vessels) for nomogram development. The C-indices of the nomogram in the training and internal validation cohorts were 0.873 and 0.841, respectively. The nomogram exhibited a sensitivity of 84.5% and specificity of 81.0%. The positive and negative predictive values were 92.1% and 66.7%, respectively. The calibration curves indicated high predictive accuracy, and receiver operating characteristic curve analysis showed the superiority of the nomogram. The decision-making analysis validated the fitness and clinical application value of this nomogram. Then a web-based calculator to facilitate clinical application was generated. CONCLUSIONS: The nomogram developed in this study accurately predicted neoangiogenesis in patients with MMD and T2DM after EDAS and may assist neurosurgeons in identifying suitable candidates for indirect revascularization surgery.

Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD). METHODS: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding. RESULTS: Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively. CONCLUSIONS: EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.

A long-term study of posterior circulation changes after revascularization in patients with moyamoya disease.

OBJECTIVE: This study aimed to explore the long-term course of posterior circulation changes and predictors in patients with moyamoya disease (MMD). METHODS: The authors retrospectively enrolled patients who were diagnosed with MMD and underwent encephaloduroarteriosynangiosis (EDAS) surgery at the authors' department from December 2002 to September 2011. A comparative study between short-term (6-12 months) and long-term (≥ 9 years) follow-up angiography was conducted. The progression of lesions was defined from lower to higher stages of the posterior cerebral artery (PCA). RESULTS: Eighty-eight patients who received indirect EDAS were enrolled in the study. The mean age at first surgery was 28.1 ± 15.0 years. Among these 88 patients with MMD, 39 (44.3%) exhibited transient ischemic attack and 27 (30.7%) exhibited infarction, comprising 5 with occipital lobe infarction, 14 (15.9%) with hemorrhagic symptoms, and 8 (9.1%) with atypical symptoms as the initial symptoms. Heterozygous mutations occurred significantly more frequently in the cases that presented with PCA involvement. During follow-up, stage progression of PCA was observed in 21 patients (28 hemispheres). At short-term follow-up, 21/176 (11.9%) hemispheres had progression of steno-occlusive lesions in the PCA. At long-term follow-up, 7 (4.0%) hemispheres had progression of steno-occlusive lesions in the PCA. At short-term follow-up, the progression of steno-occlusive lesions in the PCA was associated with progression of the internal carotid artery. Stage progression of PCA occurred significantly more frequently in the cases with PCA involvement on preoperative angiography. Nine strokes (10.2%) occurred in 88 patients during long-term follow-up. Four patients (4.5%) presented with ischemic stroke, including 2 with occipital lobe infarctions. CONCLUSIONS: Progression of PCA stenosis is common in patients with MMD, even if the PCA is normal initially. Mutations of RNF213 p.R4810K may predict PCA involvement or progression. Follow-up of the PCA in MMD patients should be conducted, and timely surgical revascularization is needed.

Epidural Pulsation Accelerates the Drainage of Brain Interstitial Fluid.

Unhindered transportation of substances in the brain extracellular space (ECS) is essential for maintaining brain function. Regulation of transportation is a novel strategy for treating ECS blockage-related brain diseases, but few techniques have been developed to date. In this study, we established a novel approach for accelerating the drainage of brain interstitial fluid (ISF) in the ECS using minimally invasive surgery, in which a branch of the external carotid artery is separated and implanted epidurally (i.e., epidural arterial implantation [EAI]) to promote a pulsation effect on cerebrospinal fluid (CSF) in the frontoparietal region. Tracer-based magnetic resonance imaging was used to evaluate the changes in ISF drainage in rats 7 and 15 days post-EAI. The drainage of the traced ISF from the caudate nucleus to ipsilateral cortex was significantly accelerated by EAI. Significant increases in the volume fraction of the ECS and molecular diffusion rate were demonstrated using the DECS-mapping technique, which may account for the mechanisms underlying the changes in brain ISF. This study provides a novel perspective for encephalopathy treatment via the brain ECS.

40 Hz Light Flicker Alters Human Brain Electroencephalography Microstates and Complexity Implicated in Brain Diseases.

Previous studies showed that entrainment of light flicker at low gamma frequencies provided neuroprotection in mouse models of Alzheimer's disease (AD) and stroke. The current study was set to explore the feasibility of using 40 Hz light flicker for human brain stimulation for future development as a tool for brain disease treatment. The effect of 40 Hz low gamma frequency light on a cohort of healthy human brains was examined using 64 channel electroencephalography (EEG), followed by microstate analyses. A random frequency light flicker was used as a negative control treatment. Light flicker at 40 Hz significantly increased the corresponding band power in the O1, Oz, and O3 electrodes covering the occipital areas of both sides of the brain, indicating potent entrainment with 40 Hz light flicker in the visual cortex area. Importantly, the 40 Hz light flicker significantly altered microstate coverage, transition duration, and the Lempel-Ziv complexity (LZC) compared to the rest state. Microstate metrics are known to change in the brains of Alzheimer's disease, schizophrenia, and stroke patients. The current study laid the foundation for the future development of 40 Hz light flicker as therapeutics for brain diseases.

The Alteration of Brain Interstitial Fluid Drainage with Myelination Development.

The integrity of myelination is crucial for maintaining brain interstitial fluid (ISF) drainage in adults; however, the mechanism of ISF drainage with immature myelin in the developing brain remains unknown. In the present study, the ISF drainage from the caudate nucleus (Cn) to the ipsilateral cortex was studied at different developmental stages of the rat brain (P 10, 20, 30, 40, 60, 80, 10-80). The results show that the traced ISF drained to the cortex from Cn and to the thalamus in an opposite direction before P30. From P40, we found impeded drainage to the thalamus due to myelin maturation. This altered drainage was accompanied by enhanced cognitive and social functions, which were consistent with those in the adult rats. A significant difference in diffusion parameters was also demonstrated between the extracellular space (ECS) before and after P30. The present study revealed the alteration of ISF drainage regulated by myelin at different stages during development, indicating that a regional ISF homeostasis may be essential for mature psychological and cognitive functions.

Feasibility of occipital condyle screw placement in patients with Chiari malformation type I: a computed tomography-based morphometric study.

BACKGROUND: The occipital condyle (OC) screw is an alternative technique for occipitocervical fixation that is especially suitable for revision surgery in patients with Chiari malformation type I (CMI). This study aimed to investigate the feasibility and safety of this technique in patients with CMI. METHODS: The CT data of 73 CMI patients and 73 healthy controls were retrospectively analyzed. The dimensions of OCs, including length, width, height, sagittal angle, and screw length, were measured in the axial, sagittal, and coronal planes using CT images. The OC available height was measured in the reconstructed oblique parasagittal plane of the trajectory. RESULTS: The mean length, width, and height of OCs in CMI patients were 17.79 ± 2.31 mm, 11.20 ± 1.28 mm, and 5.87 ± 1.29 mm, respectively. All OC dimensions were significantly smaller in CMI patients compared with healthy controls. The mean screw length and sagittal angle were 19.13 ± 1.97 mm and 33.94° ± 5.43°, respectively. The mean OC available height was 6.36 ± 1.59 mm. According to criteria based on OC available height and width, 52.1% (76/146) of OCs in CMI patients could safely accommodate a 3.5-mm-diameter screw. CONCLUSIONS: The OC screw is feasible in approximately half of OCs in CMI patients. Careful morphometric analyses and personalized surgical plans are necessary for the success of this operation in CMI patients.

A morphometric study of the atlanto-occipital joint in adult patients with Chiari malformation type I.

BACKGROUND: There are many morphometric studies on Chiari malformation type I (CMI) patients, most of which focus on the posterior cranial fossa (PCF). Less attention has been paid to the atlanto-occipital joint. In this study, we aim to evaluate the morphological characteristics of the atlanto-occipital joint in CMI patients. MATERIALS AND METHODS: The cervical CT imaging data of adult patients diagnosed with CMI but without any bony malformation in craniovertebral junction (CVJ) who were treated by the authors between January 2014 and December 2019 were retrospectively analyzed. The equal number of sex and age-matched healthy individuals were included as the control group. The morphometric analysis was performed by measuring the length and depth of the atlanto-occipital joint, and the depth/length ratio was calculated to evaluate the curvature of the joint. RESULTS: A total of 47 patients (15 males and 32 females) were included. The mean age of patients was 47.49 ± 9.01 years (range 19-62 years). The mean depth/length ratio of the atlanto-occipital joint in CMI patients was 0.141 ± 0.065 (range 0.027 - 0.274), which was smaller than that of control individuals (0.228 ± 0.057, range 0.069 - 0.379). And the difference was statistically significant (p < .01). CONCLUSIONS: The atlanto-occipital joints in CMI patients are significantly flatter compared with those in healthy controls. This morphological variation could lead to differences of the atlanto-occipital stability between CMI patients and normal population, which may be related to the pathogenesis of CMI.

Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation.

Lupeol has been reported to exhibit anti-inflammatory and anti-tumor activities in many diseases, but its potential effects in cerebral ischemia injury have not been studied to date. In this work we present evidence for a beneficial effect of lupeol in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) injury and provide some histological and biochemical evidence for its mechanism of action. A cerebral MCAO rat model was established by vascular occlusion for 2 h, followed by 24 h reperfusion period. The infarct volume, neurological deficits, and brain water content were compared with animals treated during reperfusion with different concentrations of lupeol. Macroscopic parameters, cell viability, pro-inflammatory factors generation, as well as oxidative stress parameters and associated apoptotic signaling cascades were evaluated. Treatment with lupeol significantly reduced the cerebral infarct volume and water content and recovered neuro behavioral functions in affected rats. Lupeol treatment down-regulated the expression of oxidative stress and inflammation factors. In addition, lupeol activated Nrf2, suppressed caspase-3 activity, reduced BAX/Bcl-2 ratio and inhibited phosphorylation of p38 MAPK. The data suggest that lupeol may exert protective effects against cerebral ischemia by suppressing oxidative stress and reduction of inflammation factors possible via activation of nuclear transcription factors and inhibition of cell death pathways.

Can Posterior Reduction Replace Odontoidectomy as Treatment for Patients With Congenital Posterior Atlantoaxial Dislocation and Basilar Invagination?

BACKGROUND: For patients with odontoid process protrusion and basilar invagination, posterior screw-rod fixation can usually achieve satisfactory horizontal reduction, but in some cases satisfactory reduction in the vertical direction cannot be achieved at the same time. OBJECTIVE: To propose a method for calculation of the theoretical maximum vertical reduction possible in individual patients. METHODS: The computed tomography imaging data of patients with occipitalization and basilar invagination who were treated at our institute between January 2013 and June 2016 were retrospectively analyzed. The direction of odontoid reduction was decided by the inclination of the lateral joint. The atlanto-dental distance was assumed to be the maximum possible reduction in the horizontal direction. The maximum vertical reduction possible was calculated based on these values. RESULTS: A total of 82 patients (34 males and 48 females) were included. The theoretical vertical reduction value was 4.2 ± 3.0 mm, which was significantly smaller than that of the dental protrusion (14.5 ± 3.8 mm, P = .000). Analysis of follow-up data (29 cases) showed that, the difference between the theoretical vertical reduction value H (4.7 ± 3.5 mm) and the actual vertical reduction value Ha (5.6 ± 3.5 mm) was not significant (P = .139). CONCLUSION: The theoretical calculation method we proposed can well predict the actual degree of vertical reduction. The theoretical vertical reduction value is significantly lower than the odontoid protrusion value, indicating that satisfactory reduction in the vertical direction is difficult with a posterior approach alone.

Usefulness of 3D Printed Models in the Management of Complex Craniovertebral Junction Anomalies: Choice of Treatment Strategy, Design of Screw Trajectory, and Protection of Vertebral Artery.

OBJECTIVE: To evaluate the usefulness of 3-dimensional (3D) printed models as an aid for the treatment of complex CVJ anomalies. METHODS: 3D printed models were fabricated for 21 patients with complex CVJ anomalies, including vertebral artery anomaly, thin C2 pedicle, vertical atlantoaxial facet joint, or rotational dislocation combined with atlantoaxial dislocation and basilar invagination. Preoperative planning, surgical simulation, and intraoperative reference were achieved using the 3D model during the surgical treatment. The usefulness of 3D printed models, and postoperative clinical and radiological outcomes were assessed. RESULTS: Direct posterior reduction and atlantoaxial fixation were achieved in 19 patients. Transoral odontoidectomy followed by posterior fixation was implemented for 2 patients with vertical facet joint and rotational dislocation. All screws were safely inserted with no complication, and 90% patients achieved a >60% reduction of both horizontal and vertical dislocation. Clinical symptoms improved in all patients, with the averaged Japanese Orthopedic Association scores increasing from 11.14 to 14.43 (P < 0.01). CONCLUSIONS: The patient-specific 3D printed model would be an effective tool for evaluation of the reducibility of the atlantoaxial dislocation and basilar invagination, decision making in choosing the optimal surgical approach and way of fixation, and precise placement of the screw while protecting the vertebral artery and spinal cord. The risk of neurovascular injury was minimized, and encouraging outcomes were achieved with the aid of this technique.

Comparison of Therapeutic Efficacy Between Isolated Encephaloduroarteriosynangiosis and Medical Treatment in Patients with Atherosclerotic Middle Cerebral Artery Occlusion.

BACKGROUND: Encephaloduroarteriosynangiosis (EDAS) as a form of indirect revascularization has been recently proposed as a potentially promising alternative for patients with intracranial atherosclerotic disease (ICAD). The object of this study was to compare the prognostic roles between isolated EDAS and medical therapy in patients with atherosclerotic middle cerebral artery occlusion (MCAO). METHODS: From January 2014 to June 2017, 125 patients with atherosclerotic MCAO were enrolled in this prospective nonrandomized controlled cohort study. Patients who underwent EDAS (n = 60) were compared with those treated medically (n = 65). Early and late adverse events and functional outcomes including memory ability were compared between groups. RESULTS: During 23.7 months of mean follow-up, rates of adverse events, including ischemic events in the territory of the qualifying middle cerebral artery, and death from any causes, were not significantly different in patients treated with EDAS and with medical therapy (6.7% vs. 12.3%; P = 0.285). Landmark analyses showed that at initial 6-month follow-up, there was no significant difference for adverse event rates, whereas the opposite finding was shown for the subsequent period (EDAS 1/57 [1.7%] vs. medical management 7/64 [10.9%]; P = 0.024). The P value for the interaction between time (first 6 months vs. subsequent period) was 0.044. No significant differences were found with respect to neural function status and cognitive ability. CONCLUSIONS: In the long-term, isolated EDAS can be considered effective and safe for patients with atherosclerotic MCAO, whereas it may need additional medical therapy support in the short-term.

First clinical results of minimally invasive vector lumbar interbody fusion (MIS-VLIF) in spondylodiscitis and concomitant osteoporosis: a technical note.

PURPOSE: First description of MIS-VLIF, a minimally invasive lumbar stabilization, to evaluate its safety and feasibility in patients suffering from weak bony conditions (lumbar spondylodiscitis and/or osteoporosis). METHODS: After informed consent, 12 patients suffering from lumbar spondylodiscitis underwent single level MIS-VLIF. Eight of them had a manifest osteoporosis, either. Pre- and postoperative clinical status was documented using numeric rating scale (NRS) for leg and back pain. In all cases, the optimal height for the cage was preoperatively determined using software-based range of motion and sagittal balance analysis. CT scans were obtained to evaluate correct placement of the construct and to verify fusion after 6 months. RESULTS: Since 2013, 12 patients with lumbar pyogenic spondylodiscitis underwent MIS-VLIF. Mean surgery time was 169 ± 28 min and average blood loss was less than 400 ml. Postoperative CT scans showed correct placement of the implants. Eleven patients showed considerable postoperative improvement in clinical scores. In one patient, we observed screw loosening. After documented bony fusion in the CT scan, the fixation system was removed in two cases to achieve lower material load. CONCLUSIONS: The load-bearing trajectories (vectors) of MIS-VLIF are different from those of conventional coaxial pedicle screw implantation. The dorsally converging construct combines the heads of the dorsoventral pedicle screws with laminar pedicle screws following cortical bone structures within a small approach. In case of lumbar spondylodiscitis and/or osteoporosis, MIS-VLIF relies on cortical bony structures for all screw vectors and the construct does not depend on conventional coaxial pedicle screws in the presence of inflamed, weak, cancellous or osteoporotic bone. MIS-VLIF allows full 360° lumbar fusion including cage implantation via a small, unilateral dorsal midline approach.

Occipital Condyle-C1 Complex Screw for Fixation of Basilar Invagination Patients with Atlas Assimilation.

AIM: To investigate whether C1-occipital condyle complex (CC complex) screws can be safely and rapidly placed without guidance in basilar invagination patients with atlas assimilation. MATERIAL AND METHODS: The occipital-cervical (OC) junction was fixed posteriorly in 8 basilar invagination patients with atlas assimilation using polyaxial titanium screws inserted unicortically into the CC complex and C2 pedicles and subsequent fixation to a 3-mm rod. Anatomic landmarks were used during the drilling. The screw angles and lengths of the CC complex were analyzed. RESULTS: The width, length, and height values of the left-side CC complex were 7.96±2.23, 16.06±2.73, and 13.76±2.06 mm; those of the right-side CC complex were 7.84±1.38, 16.66±2.58, and 12.81±2.62 mm. The CC complex entry point was at the central point of posterior surface of the CC complex. The angle used for medialization was 10-15°, which was also the maximal superior screw angulation in the sagittal plane. The screw length required for unicortical purchase was 16-22 mm. The screw was not misplaced or poorly positioned, and no neurovascular complications associated with screw insertion were detected. CONCLUSION: In patients with atlas assimilation, CC complex screws can be placed safely. The CC complex screws can be safely inserted assisted by microscope without image guidance.

Indirect Revascularization for Non-Moyamoya Disease Anterior Circulation Arterial Steno-occlusion: Clinical Features, Surgical Treatment, and Medium-Term Outcomes in Adults.

BACKGROUND: Symptomatic anterior arterial steno-occlusion is often associated with neurofunctional deficits or a high risk of recurrent stroke or both. Although both medical and endovascular treatments are useful and suitable, few studies have investigated the continued use of indirect encephaloduroarteriosynangiosis (EDAS) bypass in patients with non-moyamoya disease ischemia. We retrospectively investigated clinical features, surgical treatments, and medium-term outcomes of indirect revascularization for patients with non-moyamoya disease anterior circulation arterial steno-occlusion in China. METHODS: EDAS without burr holes was performed in 51 adult patients with cerebral ischemic events and diagnosed nonmoyamoya anterior circulation arterial steno-occlusion. Preoperative, postoperative, and follow-up neurologic status was evaluated using the National Institutes of Health Stroke Scale; changes on angiography and perfusion-weighted magnetic resonance imaging were evaluated. RESULTS: Unilateral EDAS was performed in 48 patients, and bilateral EDAS was performed in 3 patients. Four patients experienced complications before hospital discharge; only 23 patients underwent follow-up angiograms. Of the 51 patients, 44 (86.3%) exhibited improved muscle strength; 21 of 23 patients (91.3%) with follow-up angiography data exhibited evidence of new visible branches from the superficial temporal artery or middle meningeal artery or both. Preoperative and postoperative perfusion-weighted magnetic resonance imaging was performed for 5 patients. Despite clinical improvement in all patients, only 2 exhibited hemodynamic improvement. CONCLUSIONS: Indirect revascularization may be safe and effective for improving blood flow to the ischemic region following nonmoyamoya anterior circulation arterial steno-occlusion, especially in patients with residual postinfarction neurologic deficits. Our study demonstrates that improvements in ischemic symptoms after EDAS correspond to neovascularization from the superficial temporal artery or middle meningeal artery in ischemic brain areas.

Posterior Reduction of Fixed Atlantoaxial Dislocation and Basilar Invagination by Atlantoaxial Facet Joint Release and Fixation: A Modified Technique With 174 Cases.

BACKGROUND: Treatment of fixed atlantoaxial dislocation (AAD) with basilar invagination (BI) is challenging. OBJECTIVE: To introduce a modified technique to reduce fixed AAD and BI through a posterior approach. METHODS: From 2007 to 2013, 174 patients with fixed AAD and BI underwent surgical reduction by posterior atlantoaxial facet joint release and fixation technique. RESULTS: There was 1 death in the series, and 3 patients were lost to follow-up. The follow-up period ranged from 12 to 52 months (mean: 35.2 months) for the remaining 170 patients. Neurological improvement was observed in 168 of 170 patients (98.8%), and was stable in 1 (0.06%) and exacerbated in 1 (0.06%), with the Japanese Orthopedic Association scores increasing from 11.4 preoperatively to 15.8 postoperatively (P < .01). Radiologically, complete or >90% reduction was attained in 107 patients (62.9%), 60% to 90% reduction was attained in 51 patients (30%), and <50% reduction was attained in 12 patients (7.1%), who underwent additional transoral decompression. Complete decompression was demonstrated in all 170 patients. Solid bony fusion was demonstrated in 167 patients at follow-up (98.2%). CONCLUSION: This series showed the safety and efficacy of the posterior C1-2 facet joint release and reduction technique for the treatment of AAD and BI. Most fixed AAD and BI cases are reducible via this method. In most cases, this method avoids transoral odontoidectomy and cervical traction. Compared with the occiput-C2 screw method, this short-segment C1-2 technique exerts less antireduction shearing force, guarantees longer bone purchase, and provides more immediate stabilization.

Downregulation of solute carriers of glutamate in gliosomes and synaptosomes may explain local brain metastasis in anaplastic glioblastoma.

Advanced grades of glioblastoma are highly aggressive, especially in terms of multisite spread within the brain or even to distant sites at the spinal cord. In advanced grades of glioblastoma, glutamate and glutamine are reported to be increased in concentration in the extracellular fluid. It has been reported that glutamate acts as an extracellular signaling molecule for facilitating local spread of advanced grades of glioblastoma. In the present study, we aimed to examine whether glutamate uptake mechanisms is impaired in advanced glioblastoma. The possible downregulated mechanisms of glutamate uptake would facilitate persistence of glutamate in the extracellular environment, rather than intracellular uptake. We obtained biobanked human specimens of glioblastoma and tested expression of proteins belonging to the solute carrier families of proteins that are known to function as membrane-located excitatory amino acid like glutamate transporters. The present study provides preliminary evidence of the downregulation of membrane expression of excitatory amino acid transporters solute carrier family 1 member 3 (SLC1A3) and its palmitoylated form in gliosomes, as well as SLC1A2 in the glio-synaptosomes. Compounds like riluzole used in the treatment of amyotrophic lateral sclerosis and the antibiotic ceftriaxone have the potential to facilitate glutamate uptake. These medications may be examined as adjunct chemotherapy in the massively aggressive tumor glioblastoma multiforme.

On the preparation of transferrin modified artesunate nanoliposomes and their glioma-targeting treatment in-vitro and in-vivo.

OBJECTIVE: To prepare transferrin modified artesunate nanoliposomes (Tf-ART-LPs) and study their glioma U87 cells-targeting treatment in-vitro and in-vivo. METHODS: Ammonium sulfate transmembrane gradient method was used to prepare Tf-ART-LPs, whose size and stability was detected by a Nanosizer. Besides, the encapsulation efficiency and release rate of artesunate (ART) were tested by a ultraviolet spectrophotometer. Further, isothiocyanate (FITC) was used to label nanoliposomes and the cell-targeting property of Tf-ART-LP in-vitro was observed under a fluorescence microscope. In addition, CCK-8 method was used to detect the effect of single nanoliposomes and Tf-ART-LPs on the viability of glioma U87 cells. At last, a subcutaneously implanted tumor model in nude mouse was established for studying the in-vivo anti-tumor effect of Tf-ART-LPs by caudal vein injection. The tumor volume and mice weight were monitored and pathological sections of their major organs were analyzed. RESULTS: Tf-ART-LPs were spherical with an average diameter of 94.2 nm. They showed no aggregation after being stored in a refrigerator for 14 days at 4°C. The encapsulation efficiency and highest releasing rate (48 hours after being placed in normal saline under 37°C) of ART was 85.9% and 58.7±2.9%, respectively. The uptake rate of U87 cells was 59.8±3.8% for Tf-ART-LPs and only 18.7±4.5% for ART-LPs. While single liposomes almost showed no toxicity, Tf-ART-LP had a concentration-dependent killing effect on U87 cells. Within 32 days of treatment, the growth of U87 cells was well inhibited by Tf-ART-LPs without significant toxicity. CONCLUSION: In this study, transferrin modified artesunate liposomes we prepared have a good targeting property to glioma U87 cells and good effect on glioma both in-vitro and in-vivo.

[Exploratory study of 3D printing technique in the treatment of basilar invagination and atlantoaxial dislocation].

OBJECTIVE: To investigate the clinical application value of the 3D printing technique in the treatment of basilar invagination and atlantoaxial dislocation. METHODS: From January 2013 to September 2013, 10 patients with basilar invagination and atlantoaxial dislocation needing posterior fixation undertook 3D printing modes at the Department of Neurosurgery in PLA General Hospital. The 1:1 size models were established from skull base to C4 level with different colors between bone structures and vertebral arteries. The simulation of screw insertion was made to investigate the fixation plan and ideal entry point to avoid vertebral artery injury. After obtaining the individual screw insertion data in 3D printing modes, the according surgical operations were performed. The actual clinical results and virtual screw data in 3D printing mode were compared with each other. RESULTS: The 3D printing modes revealed that all the 10 patients had the dysplasia or occipitalized C1 posterior arch indicating C1 posterior arch screw implantation was not suitable. C1 lateral masses were chosen as the screws entry points. C2 screws were designed individually based on the 3D printing modes as follows: 3 patients with aberrant vertebral artery or narrow C2 pedicle less than 3.5 mm were not suitable for pedicle screw implantation. Among the 3 patients, 1 was fixed with C2 laminar screw, and 1 with C2-3 transarticular screw and 1 with C3 pedicle screw (also combined with congenital C2-3 vertebral fusion). Two patients with narrow C2 pedicle between 3.5 and 4mm were designed to choose pedicle screw fixation after 3D printing mode evaluation. One patient with C1 lateral mass vertically dislocated axis was planned with C1-2 transarticular screw fixation. All the other patients were planned with C2 pedicle screws. All the 10 patients had operation designed as the 3D printing modes schemes. The follow-up ranged from 12 to 18 months and all the patients recovered from the clinical symptoms and the bony fusion attained to 100%. CONCLUSIONS: 3D printing mode could provide thorough information of the bony structure abnormalities and route of vertebral artery. It is helpful for setting operation strategy and designing screw entry point and trajectory and avoiding vertebral artery and spinal cord injury and thus deserves generalization.