Low-intensity pulsed ultrasound delays the progression of osteoarthritis by regulating the YAP-RIPK1-NF-κB axis and influencing autophagy.

BACKGROUND: Osteoarthritis (OA) is a degenerative disease characterized by chronic inflammation of the joint. As the disease progresses, patients will gradually develop symptoms such as pain, physical limitations and even disability. The risk factors for OA include genetics, gender, trauma, obesity, and age. Unfortunately, due to limited understanding of its pathological mechanism, there are currently no effective drugs or treatments to suspend the progression of osteoarthritis. In recent years, some studies found that low-intensity pulsed ultrasound (LIPUS) may have a positive effect on osteoarthritis. Nonetheless, the exact mechanism by which LIPUS affects osteoarthritis remains unknown. It is valuable to explore the specific mechanism of LIPUS in the treatment of OA. METHODS: In this study, we validated the potential therapeutic effect of LIPUS on osteoarthritis by regulating the YAP-RIPK1-NF-κB axis at both cellular and animal levels. To verify the effect of YAP on OA, the expression of YAP was knocked down or overexpressed by siRNA and plasmid in chondrocytes and adeno-associated virus was injected into the knee joint of rats. The effect of LIPUS was investigated in inflammation chondrocytes induced by IL-1ß and in the post-traumatic OA model. RESULTS: In this study, we observed that YAP plays an important role in the development of osteoarthritis and knocking down of YAP significantly inhibited the inflammation and alleviated cartilage degeneration. We also demonstrated that the expression of YAP was increased in osteoarthritis chondrocytes and YAP could interact with RIPK1, thereby regulating the NF-κB signal pathway and influencing inflammation. Moreover, we also discovered that LIPUS decreased the expression of YAP by restoring the impaired autophagy capacity and inhibiting the binding between YAP and RIPK1, thereby delaying the progression of osteoarthritis. Animal experiment showed that LIPUS could inhibit cartilage degeneration and alleviate the progression of OA. CONCLUSIONS: These results showed that LIPUS is effective in inhibiting inflammation and cartilage degeneration and alleviate the progression of OA. As a result, our results provide new insight of mechanism by which LIPUS delays the development of osteoarthritis, offering a novel therapeutic regimen for osteoarthritis.

A novel lncRNA TCONS_00071187 upregulated by activated GSK3ß promotes high glucose-induced mesangial cell proliferation in the diabetic nephropathy.

Inhibiting mesangial cell proliferation is one of the strategies to control the early progression of diabetic nephropathy (DN). GSK3ß is closely related to cell apoptosis as well as the development of DN, but whether it acts on the proliferation of mesangial cells is unclear. This study aimed to elucidate the role and mechanism of GSK3ß-mediated lncRNA in high glucose-induced mesangial cell proliferation. HBZY-1 cells were used to establish the cell model of DN. The automatic cell counter was applied to assess cell proliferation. Flow cytometry was used to detect cell apoptosis and intracellular ROS levels. High-throughput transcriptomics sequencing was performed to detect the different expressions of long noncoding RNAs (lncRNAs) in the cell model of DN after knocking down the expression of GSK3ß by the transfection of siRNA. The expression of RNA was detected by real-time PCR. In the cell model of DN using HBZY-1 cells, cell proliferation was enhanced accompanied by GSK3ß activation and elevated apoptosis rate and reactive oxygen species (ROS) levels. A panel of novel lncRNAs, which were differentially expressed after GSK3ß knockdown in the cell model of DN, were identified by high-throughput transcriptomics sequencing. Among them, the expression of TCONS_00071187 was upregulated under high glucose conditions while the knockdown of the GSK3ß expression led to the downregulation of TCONS_00071187. The knockdown of TCONS_00071187 resulted in reduced mesangial cell proliferation, and decreased apoptosis rates and ROS levels. In conclusion, GSK3ß promoted mesangial cell proliferation by upregulating TCONS_00071187, which led to enhanced ROS production under high glucose conditions in the cell model of DN. This study revealed the role of GSK3ß medicated lncRNAs in the development of DN.

Resting-state functional alterations in patients with brain arteriovenous malformations involving language areas.

Brain arteriovenous malformations (AVMs) may involve language areas but usually do not lead to aphasia. This study evaluated resting-state functional alterations and investigated the language reorganization mechanism in AVM patients. Thirty-nine patients with AVMs involving language areas and 32 age- and sex-matched healthy controls were prospectively enrolled. The AVM patients were categorized into three subgroups according to lesion location: the frontal (15 patients), temporal (14 patients), and parietal subgroups (10 patients). All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI), and the amplitude of low-frequency fluctuation (ALFF) approach was applied to analyze rs-fMRI data. Language abilities were normal in all participants based on the Western Aphasia Battery. Compared with those of healthy subjects, ALFF values significantly increased (FDR corrected p < .01) in the anterior part of the right putamen in the frontal AVM subgroup, in the posterior part of the right inferior and middle temporal gyrus in the temporal AVM subgroup, and in the inferior lateral part of the left cerebellar hemisphere (lobule VIII) and the right inferior parietal lobule in the parietal AVM subgroup. Functional annotation using Neurosynth indicated that the ALFF t-map was only significantly positively associated with the language-related domain (FDR corrected p < .01). In patients with AVMs involving the language cortex, language network reorganization occurs to maintain normal language abilities. The brain areas recruited into the reorganized language network were located in the right cerebral and left cerebellar hemispheres, both of which are nondominant hemispheres. Differences in lesion location led to distinct reorganization patterns.

Impairment and Plasticity of Language-Related White Matter in Patients With Brain Arteriovenous Malformations.

BACKGROUND: Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas. METHODS: Thirty-three patients with AVMs involving language areas were prospectively enrolled. Patients were categorized into 3 groups according to the lesion locations: the frontal (14 patients), temporal (15 patients), and parietal groups (4 patients). Thirty age- and sex-matched healthy controls were enrolled as comparison. All participants underwent diffusion tensor imaging scans, and automated fiber quantification method was applied to quantitatively study the difference of segmented language-related white matter connectivity between 3 AVM groups and control group. RESULTS: Language functions were normal in all subjects according to Western Aphasia Battery test. In the frontal group, fractional anisotropy (FA) value decreased in the left arcuate fascicle and increased in left superior longitudinal fasciculus and uncinate fascicle; in the temporal group, FA values decreased in left inferior fronto-occipital fascicle and inferior longitudinal fascicle and increased in right anterior thalamic radiation and uncinate fascicle; in the parietal group, FA values decreased in left arcuate fascicle and inferior longitudinal fascicle and increased in bilateral anterior thalamic radiations and uncinate fascicles and right inferior fronto-occipital fascicle. In fascicles with decreased FA values, the increase of radial diffusivity was common, and fascicles with increased FA values usually presented along with increased axial diffusivity values. CONCLUSIONS: Remodeling of language-related white matter occurs when traditional language areas are involved by AVM nidus, and its reorganization patterns vary with locations of AVM nidus. Fascicle impairment is mainly caused by the myelin deficits, and its plasticity may be dominated by the axon remodeling procedure.

Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the three major cancers in the world and is the cancer with the most liver metastasis. The present study aimed to investigate the role of metallothionein 2A (MT2A) in the modulation of CRC cell proliferation and liver metastasis, as well as its molecular mechanisms. METHODS: The expression profile of metallothionein 2A (MT2A) in colorectal cancer retrieved from TCGA, GEO and Oncomine database. The biological effect of MT2A overexpression was investigated mainly involving cell proliferation and migration in CRC cells as well as growth and metastasis in CRC animal models. To explore the specific mechanism of MT2A metastasis in CRC, transcriptome sequencing was used to compare the overall expression difference between the control group and the MT2A overexpression group. RESULTS: Metallothionein 2A (MT2A) was downregulated in the tumor tissues of patients with CRC compared to adjacent normal tissues and was related to the tumor M stage of patients. MT2A overexpression inhibited CRC cell proliferation and migration in cells, as well as growth and metastasis in CRC animal models. While knockdown of MT2A had the opposite effect in cells. Western blotting confirmed that MT2A overexpression promoted the phosphorylation of MST1, LAST2 and YAP1, thereby inhibiting the Hippo signaling pathway. Additionally, specific inhibitors of MST1/2 inhibited MT2A overexpression-mediated phosphorylation and relieved the inhibition of the Hippo signaling pathway, thus promoting cell proliferation. Immunohistochemistry in subcutaneous grafts and liver metastases further confirmed this result. CONCLUSIONS: Our results suggested that MT2A is involved in CRC growth and liver metastasis. Therefore, MT2A and MST1 may be potential therapeutic targets for patients with CRC, especially those with liver metastases.

lncRNA Nuclear Factor of Activated T Cells Knockdown Alleviates Hypoxia/Reoxygenation-induced Cardiomyocyte Apoptosis by Upregulating HIF-1α Expression.

ABSTRACT: Acute myocardial infarction (AMI) has become the most common cause of death in the developed countries. However, its pathogenesis is poorly understood. Increasing studies have revealed that lncRNAs are important modulators of AMI development. This study aimed to explore the function of lncRNA noncoding repressor of nuclear factor of activated T cells (NRON) in hypoxia/reoxygenation (H/R)-stimulated H9c2 cells. NRON expression in peripheral blood of AMI patients and H/R-stimulated H9c2 cells was measured by quantitative real-time polymerase chain reaction. H9c2 cells were transfected with si-NRON or cotransfected with si-NRON and si-hypoxia-inducible factor-1 alpha (HIF-1α). The viability and apoptosis of these cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay and flow cytometer, respectively. In addition, HIF-1α, AKT/mTOR signal pathways and ERK1/2 were detected by western blot. NRON knockdown in the myocardial infarction mouse model was conducted through adeno-associated virus injection, and cardiac function was evaluated by motion-mode echocardiography. The results showed that NRON was highly expressed in peripheral blood of AMI patients and H/R-stimulated H9c2 cells. NRON knockdown promoted cell viability and inhibited cell apoptosis of H/R-stimulated H9c2 cells. Meanwhile, NRON knockdown also significantly attenuated heart damage and improved cardiac function in an AMI mouse model. Furthermore, compared with si-normal control, NRON knockdown increased the levels of HIF-1α, p-AKT, p-mTOR, and p-ERK1/2. HIF-1α knockdown reversed the effects of NRON knockdown in H/R-stimulated-H9c2 cells damage. Overall, our study revealed that NRON knockdown alleviated H/R-induced cardiomyocyte apoptosis by upregulating HIF-1α expression, suggesting that NRON might be a novel therapeutic target for AMI.

The downregulation of miR-22 and miR-372 may contribute to gestational diabetes mellitus through regulating glucose metabolism via the PI3K/AKT/GLUT4 pathway.

BACKGROUND: Identifying effective regulatory mechanisms will be significant for Gestational diabetes mellitus (GDM) diagnosis and treatment. METHODS: The expressions of miR-22 and miR-372 in placenta tissues from 75 pregnant women with GDM and 75 matched healthy controls and HRT8/SVneo cells (a model of insulin resistance) were analyzed by qPCR. The expressions of PI3K, AKT, IRS, and GLUT4 in high glucose-treated HRT8/SVneo cells transfected with miR-22 or miR-372 mimics or inhibitors was assessed by Western blot. A luciferase gene reporter assay was employed to verify miRNAs' target genes. RESULTS: The expressions of miR-22 and miR-372 in placental tissues from GDM patients and HRT8/SVneo cells were significantly decreased compared with the respective controls. The GLUT4 expression was significantly decreased in the placenta tissues of GDM and HRT8/SVneo cells with high glucose transfected with miR-22 and miR-372 inhibitors. We confirmed that SLC2A4, the gene encoding GLUT4, was a direct target of miR-22 and miR-372. In this study, we report that the lower expressions of miR-22 and miR-372 in placental tissue from GDM patients. CONCLUSION: Our results further suggested that the downregulations of miR-22 and miR-372 may contribute to GDM through regulating the PI3K/GLUT4 pathway.

Right-hemispheric language reorganization in patients with brain arteriovenous malformations: A functional magnetic resonance imaging study.

Brain arteriovenous malformation (AVM), a presumed congenital lesion, may involve traditional language areas but usually does not lead to language dysfunction unless it ruptures. The objective of this research was to study right-hemispheric language reorganization patterns in patients with brain AVMs using functional magnetic resonance imaging (fMRI). We prospectively enrolled 30 AVM patients with lesions involving language areas and 32 age- and sex-matched healthy controls. Each subject underwent fMRI during three language tasks: visual synonym judgment, oral word reading, and auditory sentence comprehension. The activation differences between the AVM and control groups were investigated by voxelwise analysis. Lateralization indices (LIs) for the frontal lobe, temporal lobe, and cerebellum were compared between the two groups, respectively. Results suggested that the language functions of AVM patients and controls were all normal. Voxelwise analysis showed no significantly different activations between the two groups in visual synonym judgment and oral word reading tasks. In auditory sentence comprehension task, AVM patients had significantly more activations in the right precentral gyrus (BA 6) and right cerebellar lobule VI (AAL 9042). According to the LI results, the frontal lobe in oral word reading task and the temporal lobe in auditory sentence comprehension task were significantly more right-lateralized in the AVM group. These findings suggest that for patients with AVMs involving language cortex, different language reorganization patterns may develop for different language functions. The recruitment of brain areas in the right cerebral and cerebellar hemispheres may play a compensatory role in the reorganized language network of AVM patients.

High performance OCTA enabled by combining features of shape, intensity, and complex decorrelation.

Motion contrast optical coherence tomography angiography (OCTA) entails a precise identification of dynamic flow signals from the static background, but an intermediate region with voxels exhibiting a mixed distribution of dynamic and static scatterers is almost inevitable in practice, which degrades the vascular contrast and connectivity. In this work, the static-dynamic intermediate region was pre-defined according to the asymptotic relation between inverse signal-to-noise ratio (iSNR) and decorrelation, which was theoretically derived for signals with different flow rates based on a multi-variate time series (MVTS) model. Then the ambiguous voxels in the intermediate region were further differentiated using a shape mask with adaptive threshold. Finally, an improved OCTA classifier was built by combining shape, iSNR, and decorrelation features, termed as SID-OCTA, and the performance of the proposed SID-OCTA was validated experimentally through mouse retinal imaging.

The effects of statins on hyperandrogenism in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.

Several clinical studies showed that statins were potential to treat polycystic ovary syndrome (PCOS). Through comprehensive search PubMed, EMBASE, the Web of Science, BIOSIS, the ClinialTrails.gov, and the Cochrane Library database up to 14 Feb 2020, we identified the randomized controlled trials about the treatment of statins on hyperandrogenism in PCOS women, and performed a systematic review and meta-analysis. The quality of the included studies was assessed by the Cochrane risk of bias tool and the Jadda score. Subgroup analysis and sensitivity analysis were conducted to analyze the pooled results. Nine trials included 682 PCOS patients were identified. Statins showed a significant potential to reduce testosterone (SMD = -0.47; 95% CI, - 0.76-- 0.18; P = 0.002) and dehydroepiandrosterone (SMD = -0.51; 95% CI, - 0.97-- 0.05; P = 0.03) levels, compared to the control treatments. The cutaneous symptoms hirsutism (SMD = -0.61; 95% CI, - 1.13-- 0.10; P = 0.02) and acne (SMD = -0.92; 95% CI, - 1.49-- 0.34; P = 0.002) were significantly improved by statins in PCOS women. Subgroup analysis showed that the two types of statins, and the different control treatments as well, presented no significantly different effect on testosterone and dehydroepiandrosterone. Sensitivity analysis confirmed the stability of the findings from the meta-analysis. In conclusion, statin treatment could significantly reduce androgen levels and improve cutaneous manifestations of hyperandrogenism of PCOS.

Risk factors for postoperative ischemic complications in pediatric moyamoya disease.

BACKGROUND: Ischemic events are the most common postoperative complication in bypass surgery for moyamoya disease (MMD), but the risk factors for pediatric MMD remain unclear. The goal of the study was to investigate the risk factors for postoperative ischemic complications in pediatric MMD patients. METHODS: We retrospectively reviewed a consecutive series of pediatric MMD cases at Beijing Tiantan Hospital, Capital Medical University from June 2010 through June 2019. Preoperative clinical variables and radiographic findings were recorded, and logistic regression analysis was carried out to identify the risk factors for postoperative ischemic events. RESULTS: A total of 533 operations in 336 patients were included in this study. Postoperative complications occurred after 51 operations (9.6%), including 40/447 indirect bypass procedures, 9/70 direct bypass procedures, and 2/16 combined bypass procedures. Postoperative ischemic events were the most common complication and occurred in 30 patients after 31 procedures (8.9% per patient; 5.8% per operation), including 26/447 indirect bypass procedures, 4/70 direct bypass procedures, and 1/16 combined bypass procedures, and the incidence of these events did not differ significantly between indirect and non-indirect bypass (5.8% vs 5.8%; p = 0.999). Multivariate logistic regression analyses revealed that older age at operation (OR 1.129, 95% CI 1.011-1.260, p = 0.032) and posterior cerebral artery involvement (OR 2.587, 95% CI 1.030-6.496, p = 0.043) were significantly associated with postoperative ischemic events. CONCLUSION: We speculate that older age at operation and posterior cerebral artery involvement are risk factors for postoperative ischemic events in pediatric MMD patients.

Modifiable Risk Factors Associated With Moyamoya Disease: A Case-Control Study.

BACKGROUND AND PURPOSE: The cause of moyamoya disease (MMD) remains unknown. We aimed to investigate the association between modifiable risk factors and MMD in a prospective, case-control study. METHODS: Clinical and laboratory characteristics were evaluated in consecutively recruited adult patients with MMD and age-matched healthy control individuals. The potential risk factors for MMD were estimated by logistic regression analysis. RESULTS: Our prospective study included 138 adult patients and 138 healthy control subjects. Logistic regression analyses showed that increased body mass index (odds ratio [OR], 1.121 [95% CI, 1.018-1.234]; P=0.020) and homocysteine (OR, 1.201 [95% CI, 1.081-1.334]; P=0.001) were associated with higher risk of MMD. Whereas increased albumin (OR, 1.043 [95% CI, 1.004-1.082]; P=0.028) and high-density lipoprotein cholesterol (OR, 1.043 [95% CI, 1.004-1.082]; P=0.028) were correlated with a lower risk of MMD. Furthermore, homocysteine (OR, 1.070 [95% CI, 1.010-1.134]; P=0.023) was significantly related to unilateral lesions. CONCLUSIONS: Increased body mass index and homocysteine were associated with a higher risk of MMD. In contrast, increased albumin and high-density lipoprotein cholesterol were correlated with a lower risk of MMD. Furthermore, increased homocysteine was related to a higher prevalence of unilateral MMD. More attention should be paid to the modifiable risk factors of MMD, as these might help us finding its cause and new therapeutic regimen. Registration: URL: http://www.chictr.org. Unique identifier: ChiCTR2000031412.

Different subtypes of collateral vessels in hemorrhagic moyamoya disease with p.R4810K variant.

BACKGROUND: The aim of this study was to investigate the hemorrhgic sites and collateral vessels in hemorrhagic MMD with the p.R4810K variant. METHODS: Hemorrhage sites were classified as either anterior or posterior. Collateral vessels were classified into three subtypes according to origin: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. Hemorrhage sites and collateral vessels were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching. RESULTS: A total of 130 hemorrhagic MMD patients were included in present study, 21 pairs (42 hemorrhagic hemispheres) were obtained after 1:1 propensity score. In GA group, 16 hemispheres (76.2%) presented anterior hemorrhage, and 5 hemispheres (23.8%) presented with posterior hemorrhage. In GG group, 13 hemispheres (61.9%) presented anterior hemorrhage, and 8 hemispheres (38.1%) presented with posterior hemorrhage. No significant differences were found in hemorrhagic sites between two matched groups (P > 0.05). Of 21 hemispheres in GA group, 10 (47.6%) exhibited lenticulostriate anastomosis, 6 (28.6%) thalamic anastomosis, and 6 (28.6%) choroidal anastomosis. Of 21 hemispheres in GG group, 3 (14.3%) exhibited lenticulostriate anastomosis, 5 (23.8%) thalamic anastomosis, and 9 (42.9%) choroidal anastomosis. There was significant difference in lenticulostriate anastomosis between two matched groups (P = 0.045). After adjustment the age, sex, and PCA involvement, we found that lenticulostriate anastomosis was associated with p.R4810K variant (OR, 5.995; 95% CI, 1.296-27.737; P = 0.022). CONCLUSION: Lenticulostriate anastomosis might be associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis might not be associted withp.R4810K variant.

Postoperative collateral formation after indirect bypass for hemorrhagic moyamoya disease.

BACKGROUND: The research on postoperative collateral formation for hemorrhagic moyamoya disease (MMD) evaluated by using digital subtraction angiography (DSA) is limited. Our study objective was to investigate the postoperative collateral formation after indirect bypass for hemorrhagic MMD. METHODS: All consecutive inpatients with hemorrhagic MMD who received indirect bypass at Beijing Tiantan Hospital, Capital Medical University from January 2010 through December 2018 were screened. The site of the hemorrhage was classified as either anterior or posterior. Postoperative collateral formation was evaluated on lateral views using the Matsushima scale. Univariate and multivariate logistic regression analyses were carried out to determine the factors influencing postoperative collateral formation. RESULTS: Six-four patients (64 hemispheres) were included in this study. After a median 8.5 months DSA follow-up, 14 (21.9%) hemispheres had grade A collateral circulation, 13 (20.3%) had grade B, and 37 (57.8%) had grade C. Twenty-seven (42.2%) hemispheres had good postoperative collateral formation and 37 (57.8%) had poor postoperative collateral formation. The univariate logistic regression analyses showed that age at operation (OR, 0.954; 95% CI, 0.908-1.003; p = 0.066), hemorrhagic site (OR, 4.694; 95% CI, 1.582-13.923; p = 0.005), and PCA involvement (OR, 3.474; 95% CI, 0.922-13.086; p = 0.066) may effect postoperative collateral formation. The multivariate logistic regression analyses showed that only anterior hemorrhage (OR, 5.222; 95% CI, 1.605-16.987; p = 0.006) was significantly related to good postoperative collateral formation. CONCLUSION: Anterior hemorrhage was significantly related to good postoperative collateral formation after indirect bypass.

Clinical characteristics and surgical outcomes of spinal myxopapillary ependymomas.

Spinal myxopapillary ependymoma (SME) is a rare pathological variant of ependymoma, which most commonly occurs in the cauda equina and filum terminale of the spinal cord. Although SME is considered as a benign entity, histologically corresponding to WHO grade I, local recurrence and metastasis have been reported in many cases. The purpose of this large-scale, single-center study was to investigate the clinical characteristics and surgical outcomes of SME. A total of 34 consecutive patients diagnosed with SME were enrolled in this retrospective study. All patients underwent magnetic resonance imaging (MRI) and were treated with surgical resection. Individual clinical data were collected, and surgical outcomes were evaluated during the follow-up period. There were 21 males and 13 females, with an average age of 29.97 years. Clinical symptoms included back pain (82.4%), weakness (44.1%) and numbness (20.6%) in extremities, and sphincter dysfunction (26.5%). The tumor locations included lumbar segments (52.9%), thoracolumbar segments (23.5%), lumbosacral segments (17.6%), and thoraco-lumbo-sacral segments (5.9%). On MRI, all SMEs appeared hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, with remarkable enhancement. Gross total resection was achieved in 18 patients, and subtotal resection (STR) was achieved in 16 patients. After an average follow-up period of 41.5 months, recurrence was noted in 5 patients (5 of 16) who underwent STR. SMEs have some characteristic features on MRI which can facilitate the preoperative diagnosis. Complete surgical resection is the best treatment of choice with a favorable outcome. In cases of incomplete resection, postoperative radiotherapy may be an effective alternative.

Altered Brain Structural Networks in Patients with Brain Arteriovenous Malformations Located in Broca's Area.

Focal brain lesions, such as stroke and tumors, can lead to remote structural alterations across the whole-brain networks. Brain arteriovenous malformations (AVMs), usually presumed to be congenital, often result in tissue degeneration and functional displacement of the perifocal areas, but it remains unclear whether AVMs may produce long-range effects upon the whole-brain white matter organization. In this study, we used diffusion tensor imaging and graph theory methods to investigate the alterations of brain structural networks in 14 patients with AVMs in the presumed Broca's area, compared to 27 normal controls. Weighted brain structural networks were constructed based on deterministic tractography. We compared the topological properties and network connectivity between patients and normal controls. Functional magnetic resonance imaging revealed contralateral reorganization of Broca's area in five (35.7%) patients. Compared to normal controls, the patients exhibited preserved small-worldness of brain structural networks. However, AVM patients exhibited significantly decreased global efficiency (p = 0.004) and clustering coefficient (p = 0.014), along with decreased corresponding nodal properties in some remote brain regions (p < 0.05, family-wise error corrected). Furthermore, structural connectivity was reduced in the right perisylvian regions but enhanced in the perifocal areas (p < 0.05). The vulnerability of the left supramarginal gyrus was significantly increased (p = 0.039, corrected), and the bilateral putamina were added as hubs in the AVM patients. These alterations provide evidence for the long-range effects of AVMs on brain white matter networks. Our preliminary findings contribute extra insights into the understanding of brain plasticity and pathological state in patients with AVMs.

Association between p.R4810K Variant and Postoperative Collateral Formation in Patients with Moyamoya Disease.

OBJECT: To investigate the association between p.R4810K variant and postoperative collateral formation (PCF) in patients with moyamoya disease. METHODS: The p.R4810K variant was detected in 254 Chinese moyamoya patients. Surgically treated 273 hemispheres with preoperative and postoperative digital subtraction angiography were included. PCF was evaluated on lateral and anteroposterior views using angiography. Univariate and multivariate logistic regression analyses were performed to determine the influence factors for PCF. RESULTS: Among 254 patients, 191 (75.2%) patients carried wild-type p.R4810K variant (GG) and 63 patients (24.8%) carried the heterozygous p.R4810K variant (GA). PCF was better in patients with GA than in patients with GG both on lateral views and anteroposterior views (p < 0.001 and p < 0.001). Over the median 7 months follow-up after discharge, good PCF was observed in 201 hemispheres (73.6%), and poor PCF was observed in 72 hemispheres (26.4%). The univariable logistic regression showed that patients with GA (OR 4.681; 95% CI 1.925-11.383; p = 0.001) was associated with good PCF. On the other hand, the increasing age (OR 0.971; 95% CI 0.952-0.989; p = 0.002) and the presence of hemorrhage (OR 0.189; 95% CI 0.096-0.374; p = 0.000) were associated with poor PCF. Multivariate logistic regression analyses of p.R4810K variant and clinical variables showed that GA (OR 3.671; 95% CI 1.452-9.283; p = 0.006) was associated with a good PCF, while the presence of hemorrhage (OR 0.258; 95% CI 0.065-0.362; p = 0.000) was identified as a predictor of poor PCF. CONCLUSIONS: The heterozygous p.R4810K variant was associated with better PCF.

Shunt dependency syndrome and acquired Chiari malformation secondary to cerebrospinal fluid diversion procedures: a 9-year longitudinal observation.

BACKGROUND: Shunt dependency syndrome is a rare long-term complication of cystoperitoneal (CP) shunting for intracranial arachnoid cysts, which is characterized by acute intracranial hypertension with normal-sized or small ventricles. Additionally, acquired Chiari type I malformations (ACIM) could be infrequently secondary to extrathecal shunt drainage of cerebrospinal fluid. CASE REPORT: We described a 12-year-old boy who developed shunt dependency syndrome following a CP shunting for treating a temporal arachnoid cyst. To manage this rare complication, we placed a lumboperitoneal (LP) shunt. During the follow-up period, shunt-induced ACIM and concomitant syringomyelia were noted. CONCLUSION: Shunt dependency syndrome is a rare complication secondary to CP shunting in the treatment of temporal arachnoid cysts, and LP shunting is an effective option to relieve the intracranial hypertension. However, the clinicians should be alert to the ACIM as a rare late complication of cerebrospinal fluid diversion procedures, and the potential protecting effect of the programmable valve should be emphasized.

Clinical features and neurosurgical treatment of trigonal cavernous malformations.

The goals of this study were to analyze the incidence, clinical manifestations, neuroimaging findings, surgical treatments, and neurological outcomes of trigonal cavernous malformations (TCMs). Among 1395 cases of intracranial and intraspinal cavernous malformations (CMs) surgically treated between 2003 and 2016 at Beijing Tiantan Hospital, a series of 12 patients with TCM was chosen for analysis and their records were reviewed. We also performed an exhaustive literature search using PubMed to identify all previously reported cases in the literatures. TCMs accounted for 0.86% of the entire series of the central nervous system (CNS) CMs. The case series consisted of five male and seven female patients (ratio 1:1.4), with an average age at presentation of 32.9 years (7-53 years). In all the cases, headache was the most common initial symptom (66.7%). Complete resection without surgical mortality was achieved in all the cases. Postoperative complications included fever, lower limb weakness, sensory aphasia, and calculational capacity declination. Follow-up period after diagnosis was 15 to 74 months (mean 48.3 months); no patient was lost to follow-up. All the patients were considered to be in excellent clinical condition. TCMs are rare lesions; they can reach large size, and their symptoms and signs commonly resulted from mass effect. Surgical intervention is the treatment of choice for TCMs; patients can obtain favorable neurological outcomes after complete resection.

Neurosurgical management of cavernous malformations located at the foramen of Monro.

Cavernous malformations (CMs) located at the foramen of Monro (FM) are relatively rare benign vascular malformations. Knowledge of FM CM is poor. The aims of this study were to describe the incidence, clinical presentation, radiological features, surgical approaches, and neurological outcomes for FM CM patients and to discuss the treatment strategy for this disease. We present a series of nine FM CM patients (four males, five females; mean age 29.3 years) who were treated at a single neurosurgical center. FM CM accounted for 0.56% of the entire series of the central nervous system (CNS) CMs. Headache accompanied by nausea and vomiting was the most common initial symptom (55.6%). The mean preoperative Karnofsky Performance Scale (KPS) score was 84.4 (range 70-100). In all but one patient, the lesions were surgically resected. Postoperatively, two patients developed obstructive hydrocephalus, and one experienced motor aphasia and right hemiparesis. At the time of discharge, the KPS score improved to a mean of 88.9. Follow-up period after diagnosis was 18 to 131 months (mean 69.7 months); all the patients were considered to be in excellent clinical condition. FM CMs are rare and challenging lesions; they have a female predilection. The most common clinical manifestations of FM CM are the symptoms of mass effect. The seizure risk of FM CMs seems to be significantly lower than that of general intraventricular CMs. Early surgical intervention should be offered to symptomatic cases, and gross total resection is associated with favorable neurological outcomes.