Correlation Between Tumor Molecular Markers and Perioperative Epilepsy in Patients With Glioma: A Systematic Review and Meta-Analysis.

Purpose: Tumors derived from the neuroepithelium are collectively termed gliomas and are the most common malignant primary brain tumor. Epilepsy is a common clinical symptom in patients with glioma, which can impair neurocognitive function and quality of life. Currently, the pathogenesis of glioma-related epilepsy is not fully described. Therefore, it is necessary to further understand the mechanism of seizures in patients with glioma. In this study, a comprehensive meta-analysis was conducted to investigate the relationship between five commonly used tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma. Methods: PubMed, EMBASE, and Cochrane Library databases were searched for related research studies. Odds ratio and the corresponding 95% confidence interval were used as the main indicators to evaluate the correlation between tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma. Results: A total of 12 studies were included in this meta-analysis. The results showed that isocitrate dehydrogenase 1 (IDH1) mutation was significantly correlated with the incidence of perioperative epilepsy. A subgroup analysis showed that IDH1 was significantly correlated with the incidence of preoperative epilepsy, but not with intraoperative and postoperative epilepsy. There was no correlation between O6-methylguanine-DNA methyltransferase methylation and 1p/19q deletion and the incidence of perioperative epilepsy. Tumor protein p53 and epidermal growth factor receptor could not be analyzed because of the limited availability of relevant literature. There was no significant heterogeneity or publication bias observed among the included studies. Conclusion: The present meta-analysis confirms the relationship between tumor molecular markers and the incidence of perioperative epilepsy in patients with glioma. The present results provide more comprehensive evidence for the study of the pathogenesis of glioma-related epilepsy. Our research may offer a new method for the treatment of perioperative seizures in patients with glioma.

Reduction of Autophagosome Overload Attenuates Neuronal Cell Death After Traumatic Brain Injury.

Previous studies have shown that alterations in autophagy-related proteins exist extensively after traumatic brain injury (TBI). However, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, a controlled cortical impact was used to establish a model of moderate TBI in rats. We found that a significant increase in protein levels of LC3-II and SQSTM1 in the injured cortex group. However, there were no significant differences in protein levels of VPS34, Beclin-1, and phosphor-ULK1, which are the promoters of autophagy. Lysosome dysfunction after TBI might lead to autophagosome accumulation. In addition, the highly specific autophagy inhibitor SAR405 administration reduced TBI-induced apoptosis-related protein cleaved caspase-3 and cleaved caspase-9 levels in the ipsilateral cortex, as well as brain edema and neurological defects accessed by mNSS. Furthermore, chloroquine treatment reversed the beneficial effects of SAR405 by increasing the accumulation of autophagosomes. Finally, our data showed that autophagy inhibition by VPS34 gene knockout method attenuated cell death after TBI. Our findings indicate that impaired autophagosome degradation is involved in the pathological reaction after TBI, and the inhibition of autophagy contributes to attenuate neuronal cell death and functional defects.

Inflammation and behavioral symptoms in preoperational glioma patients: Is depression, anxiety, and cognitive impairment related to markers of systemic inflammation?

PURPOSE: Behavioral symptoms, including depression, anxiety, and cognitive impairment, are common clinical symptoms of patients with glioma. However, the mechanisms underlying the behavioral symptoms of glioma patients remain unclear. In this study, we explore the correlation between markers of systemic inflammation and preoperational behavioral symptoms in glioma patients. PATIENTS AND METHODS: Patients (n = 71) who had recently undertaken imaging (i.e., CT, MRI) for suspected glioma had a face-to-face interview, completed self-report scales, and provided blood samples. Furthermore, we tested blood samples by a protein chip to select differential inflammatory cytokines and further confirm such differences using liquid-phase chip technology. RESULTS: The prevalence of depression, anxiety, and cognitive impairment in glioma patients prior to surgery in this study was 53.5%, 70.4%, and 32.4%, respectively. The increased levels of IFN-γ were positively correlated with clinical symptoms of depression in the glioma patients. Moreover, increased IL-2 levels were negatively associated with anxiety symptoms (p = .00) and positively correlated with cognitive impairment in glioma patients. CONCLUSION: This study suggests that systemic inflammation is associated with behavioral symptoms in glioma patients. This provides further evidence of the contribution of inflammatory markers to psychological symptoms in the context of physical conditions and lays the foundation for the development of further treatments of the behavioral symptoms in glioma patients.

Subperiosteal versus Subdural Drain After Burr Hole Drainage for Chronic Subdural Hematomas: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of drains has been considered to be superior to no drains after burr hole drainage of chronic subdural hematomas (CSDHs). Therefore, routine placement of a subdural drain (SDD) is supported by most neurosurgeons. However, whether the drain location after CSDH burr hole evacuation influences patient outcomes is unclear. Therefore, we compared the efficacy and safety of subperiosteal drains (SPDs) with those of SDDs for patients with CSDHs. METHODS: Using the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, eligible studies reported up to September 2019 were identified through a search of MEDLINE, EMBASE, and Cochrane Central. Pooled estimates, confidence intervals (CIs), and odds ratios (ORs) were calculated for all outcomes. RESULTS: Ten studies with 3169 patients were included. The use of a SPD after CSDH burr hole drainage resulted in a significant decrease in recurrences compared with the use of a SDD (OR, 0.73; 95% CI, 0.58-0.92; I2, 14%; P = 0.007). No significant differences were identified between the SPD and SDD groups in the favorable outcomes (OR, 1.29; 95% CI, 1-1.68; I2, 0%; P = 0.05). Adverse event rates, including mortality, seizures, and surgical infection, were not significantly different between the 2 groups. However, the use of SPDs was associated with a lower risk of parenchymal injuries compared with SDDs (OR, 0.29; 95% CI, 0.11-0.76; I2, 0%; P = 0.01). CONCLUSIONS: The results from the present meta-analysis suggest that the use of an SPD is safer and might be more effective than an SDD in the treatment of CSDH. However, more large randomized controlled trials are needed to investigate the use of SPDs in the management of CSDH.

Recurrent Acute Subdural Hematoma Due to Middle Meningeal Artery Bleeding Treated by Embolization.

BACKGROUND: Recurrent acute subdural hematomas (ASDHs) are a common complication of neurosurgical operations. However, ASDHs associated with middle meningeal artery (MMA) injury are extremely rare. We encountered a rare case of recurrent ASDH due to MMA bleeding after craniotomy for a nontraumatic ASDH and successfully performed MMA embolization for treatment of it. CASE DESCRIPTION: A 56-year-old woman was admitted to our department with progressively worsening headache and vomiting approximately 1 week. She had no history of head trauma and illness. A head computed tomography (CT) scan revealed an ASDH on the right hemisphere. The patient underwent a right-sided craniotomy for evacuation of the hematoma. Two days later, she exhibited impaired consciousness and a repeat CT scan showed a recurrent ASDH. To clarify the cause, we performed cerebral digital subtraction angiography for the patient. Obvious contrast extravasation from the anterior branch of the right MMA was noticed. It was considered to be related to the recurrent ASDH. Embolization of the MMA was performed using Onyx 18 (Micro Therapeutics, Inc., Irvine, California, USA). Follow-up CT scans showed progressive resolution of the ASDH and no recurrence. The patient was discharged without any neurologic deficits. CONCLUSIONS: In our case, the relationship between the recurrent ASDH and MMA was observed via angiography and MMA embolization was successfully performed to avoid surgery for reevacuation, suggesting that active bleeding of MMA may be a cause of recurrent ASDH after neurosurgical operations and endovascular exploration, and possible treatment is necessary for an unexplained ASDH.

[The Mechanism Study on Histone Acetylation Activating Glioblastoma-derived Neurotrophic Factor Transcription].

OBJECTIVE: To study the regulation role and mechanism of protein acetylation on the expression of glioblastoma-derived neurotrophic factor (GDNF) in human glioma. METHODS: Six normal brain tissue samples, six low-grade glioma brain tissue (LG-glioma), and six high-grade glioma brain tissue (HG-glioma) were collected for study. Human glioma U251 cells were treated with histone acetylase inhibitor and histone deacetylase inhibition. The mRNA level of GDNF in glioma and normal controls was detected by Real-time PCR. H3K9 acetylation level of cAMP-response element binding protein (CREB) binding region on GDNF promoter and the ability of CREB combining to GDNF promoter were detected by ChIP-PCR. The effects of histone acetylase and deacetylase inhibitors on transcription factor binding ability and GDNF expression were detected. RESULTS: The mRNA level of GDNF in HG-glioma was significantly higher than those in normal brain tissue and LG-glioma (P < 0.01). The H3K9 acetylation level of GDNF promoter region in the glioma was increased compared to that in the normal brain tissue (P < 0.01), and the acetylation level in CREB-binding region on the GDNF promoter was higher than that in the non-CREB-binding region (P < 0.01). The binding activity of CREB and GDNF promoter in HG-glioma was higher than those in normal brain tissue and LG-glioma (P < 0.05). After treatment of U251 cells with histone acetyltransferase inhibition, the level of acetylation in CREB-binding region on GDNF promoter, the binding activity of CREB and GDNF promoter was decreased, and GDNF transcription and expression were down-regulated, while histone deacetylase inhibitors had the opposite effect (P < 0.01). CONCLUSION: Histone acetylation promotes the transcription expression of GDNF in glioma by promoting the binding of transcription factor CREB to the promoter region of GDNF gene.

Long non­coding RNA DLEU1 promotes cell proliferation of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common malignant tumor with high morbidity and mortality. This study investigated the role of long non­coding RNAs (lncRNAs) in glioblastomagenesis progression. Using the GSE2223 and GSE59612 datasets, and RNA sequencing data of GBM from The Cancer Genome Atlas, differentially expressed (DE) genes including DE messenger RNAs (DEmRNAs) and DElncRNAs between GBM and normal controls were identified. Based on the competing endogenous RNA hypothesis, DElncRNA­micro RNA (miRNA)­DEmRNA interactions were obtained by target gene prediction. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes pathway analysis of DEmRNAs in the DElncRNA­miRNA­DEmRNA network was performed. Expression and function analyses of DElncRNAs were performed by reverse transcription­polymerase chain reaction (RT­PCR) and an established viability assay, respectively. In total, 712 DE genes were identified. Significant upregulation of lncRNA deleted in lymphocytic leukemia 1 (DLEU1) was revealed in GBM and a number of other types of cancer. DLEU1 interacted with 315 miRNAs and 105 DEmRNAs. The DEmRNAs were mainly enriched in tumorigenesis­associated GO terms (angiogenesis, positive regulation of cell proliferation, positive regulation of fibroblast apoptotic processes and regulation of neutrophil migration) and pathways (Hippo signaling pathway, cancer pathways, and Wnt signaling pathway). Correlation analysis revealed that mRNA TNF receptor associated factor 4 (TRAF4) was associated with DLEU1 expression. RT­PCR demonstrated that the expression levels of DLEU1 and TRAF4 were increased in GBM tissues. Small interfering RNA demonstrated that silencing DLEU1 downregulated TRAF4. The viability of GBM cells was significantly decreased following RNA interference with DLEU1 and TRAF4 production. The results demonstrate that DLEU1 and TRAF4 is highly expressed in GBM tissues and promotes proliferation of GBM cells. It may act as a competing endogenous RNA and influence tumorigenesis of GBM.

Analysis of the Factors Affecting the Prognosis of Glioma Patients.

This retrospective study was carried out to investigate factors affecting the prognosis of gliomas for better management of treatment. Clinical data from 186 glioma patients treated in our hospital from January 2013 to June 2016 were analyzed. There was slightly more male than female patients in the cohort. The main clinical symptoms included sudden limb twitching, headache and fatigue, vomiting, vision reduction and speaking disorders. The malignancy was high and the prognosis was poor in the patients, with an overall survival rate of 54.84 % by October 2017. Univariate analysis showed that the prognosis was mainly affected by age, tumor grade, preoperative Karnofsky performance status (KPS), surgical method, postoperative radiotherapy and chemotherapy, and postoperative use of temozolomide (TMZ). Multivariate Cox regression analysis showed that the independent risk factors for the prognosis were old age (≥ 60), advanced tumor, partial tumor resection, KPS of < 70, no chemotherapy after operation and < 4 courses of postoperative TMZ. The prognosis is negatively affected by age, tumor grade, KPS, and partial tumor resection. Surgical resection combined with chemotherapy and multi-course use of TMZ prolongs the survival time of patients.