Associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) Polymorphisms and TRAF2, TAB2, IKBKB Protein Levels with Clinical and Morphological Features of Pituitary Adenomas.

AIM: The aim of this study was to determine associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) gene polymorphisms and TRAF2, TAB2, IKBKB protein levels with clinical and morphological features of pituitary adenomas (PAs). METHODS: This case-control study included 459 individuals divided into two groups: a control group (n = 320) and a group of individuals with PAs (n = 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used for TRAF2 (rs867186), TAB2 (rs237025), and IKBKB (rs13278372) SNP genotyping, and TRAF2, TAB2, IKBKB protein concentration measurements were performed by immunoenzymatic analysis tests using a commercial ELISA kit according to the manufacturer's recommendations. The labeling index Ki-67 was determined by immunohistochemical analysis using a monoclonal antibody (clone SP6; Spring Bioscience Corporation). Statistical data analysis was performed using the programs "IMB SPSS Statistics 29.0". RESULTS: We found significant differences in TRAF2 (rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% (p < 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%, p < 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA (p < 0.001). In the dominant model, GG and AG genotypes reduced PA odds by 3.07-fold, while in the recessive model, the GG genotype reduced PA odds by 8.33-fold (p < 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model (p < 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% (p < 0.001), with the G allele being less frequent (9.4% vs. 34.2%, p < 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% (p < 0.001), and the G allele was less common (13.7% vs. 34.2%, p < 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold (p = 0.001), and each G allele reduced microadenoma odds by 3.1-fold (p < 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model (p < 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA (p < 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold (p < 0.001), and each G allele reduced odds by 2.2-fold in the additive model (p < 0.001). CONCLUSIONS: The TRAF2 (rs867186) G allele and GG genotype are significantly associated with reduced odds of pituitary adenomas, including both microadenomas and macroadenomas, compared to the AA genotype. These findings suggest a protective role of the G allele against the occurrence of these tumors.

The Influence of Telomere-Related Gene Variants, Serum Levels, and Relative Leukocyte Telomere Length in Pituitary Adenoma Occurrence and Recurrence.

In this study, we examined 130 patients with pituitary adenomas (PAs) and 320 healthy subjects, using DNA samples from peripheral blood leukocytes purified through the DNA salting-out method. Real-time polymerase chain reaction (RT-PCR) was used to assess single nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (RLTLs), while enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of TERF1, TERF2, TNKS2, CTC1, and ZNF676 in blood serum. Our findings reveal several significant associations. Genetic associations with pituitary adenoma occurrence: the TERF1 rs1545827 CT + TT genotypes were linked to 2.9-fold decreased odds of PA occurrence. Conversely, the TNKS2 rs10509637 GG genotype showed 6.5-fold increased odds of PA occurrence. Gender-specific genetic associations with PA occurrence: in females, the TERF1 rs1545827 CC + TT genotypes indicated 3.1-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was associated with 4.6-fold increased odds. In males, the presence of the TERF1 rs1545827 T allele was associated with 2.2-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was linked to a substantial 10.6-fold increase in odds. Associations with pituitary adenoma recurrence: the TNKS2 rs10509637 AA genotype was associated with 4.2-fold increased odds of PA recurrence. On the other hand, the TERF1 rs1545827 CT + TT genotypes were linked to 3.5-fold decreased odds of PA without recurrence, while the TNKS2 rs10509637 AA genotype was associated with 6.4-fold increased odds of PA without recurrence. Serum TERF2 and TERF1 levels: patients with PA exhibited elevated serum TERF2 levels compared to the reference group. Conversely, patients with PA had decreased TERF1 serum levels compared to the reference group. Relative leukocyte telomere length (RLTL): a significant difference in RLTL between the PA group and the reference group was observed, with PA patients having longer telomeres. Genetic associations with telomere shortening: the TERF1 rs1545827 T allele was associated with 1.4-fold decreased odds of telomere shortening. In contrast, the CTC1 rs3027234 TT genotype was linked to 4.8-fold increased odds of telomere shortening. These findings suggest a complex interplay between genetic factors, telomere length, and pituitary adenoma occurrence and recurrence, with potential gender-specific effects. Furthermore, variations in TERF1 and TNKS2 genes may play crucial roles in telomere length regulation and disease susceptibility.

Antisense lncRNA CHROMR is linked to glioma patient survival.

Background: Natural non-coding antisense transcripts (ncNATs) are long non-coding RNAs (lncRNA) transcribed from the opposite strand of a separate protein coding or non-coding gene. As such, ncNATs can increase overlapping mRNA (and the coded protein) levels by stabilizing mRNA, absorbing inhibitory miRNAs and protecting the mRNA from degradation, or conversely decrease mRNA (or protein) levels by directing the mRNA towards degradation or inhibiting protein translation. Recently, growing numbers of ncNATs were shown to be dysregulated in cancerous cells, however, actual impact of ncNATs on cancer progression remains largely unknown. We therefore investigated gene expression levels of natural antisense lncRNA CHROMR (Cholesterol Induced Regulator of Metabolism RNA) and its sense protein coding gene PRKRA (Protein Activator of Interferon Induced Protein Kinase EIF2AK2) in gliomas. Next, we checked CHROMR effect on the survival of glioma patients. Methods: We performed RNA-seq on post-surgical tumor samples from 26 glioma patients, and normal brain tissue. Gene expression in TPM values were extracted for CHROMR and PRKRA genes. These data were validated using the TCGA and GTEx gene expression databases. Results: The gene expression level of ncNAT lncRNA CHROMR in glioma tissue was significantly higher compared to healthy brain tissue, while the expression of its sense counterpart protein coding PRKRA mRNA did not differ between glioma and healthy samples. Survival analysis showed lower survival rates in patients with low mRNA PRKRA/lncRNA CHROMR gene expression ratio compared to high ratio showing a link between lncRNA CHROMR and glioma patient survival prognosis. Conclusion: Here we show that elevated levels of lncRNA CHROMR (i.e., low ratio of mRNA PRKRA/lncRNA CHROMR) is associated with poor prognosis for glioma patients.

Radiomic features of amygdala nuclei and hippocampus subfields help to predict subthalamic deep brain stimulation motor outcomes for Parkinson's disease patients.

Background and purpose: The aim of the study is to predict the subthalamic nucleus (STN) deep brain stimulation (DBS) outcomes for Parkinson's disease (PD) patients using the radiomic features extracted from pre-operative magnetic resonance images (MRI). Methods: The study included 34 PD patients who underwent DBS implantation in the STN. Five patients (15%) showed poor DBS motor outcome. All together 9 amygdalar nuclei and 12 hippocampus subfields were segmented using Freesurfer 7.0 pipeline from pre-operative MRI images. Furthermore, PyRadiomics platform was used to extract 120 radiomic features for each nuclei and subfield resulting in 5,040 features. Minimum Redundancy Maximum Relevance (mRMR) feature selection method was employed to reduce the number of features to 20, and 8 machine learning methods (regularized binary logistic regression (LR), decision tree classifier (DT), linear discriminant analysis (LDA), naive Bayes classifier (NB), kernel support vector machine (SVM), deep feed-forward neural network (DNN), one-class support vector machine (OC-SVM), feed-forward neural network-based autoencoder for anomaly detection (DNN-A)) were applied to build the models for poor vs. good and very good STN-DBS motor outcome prediction. Results: The highest mean prediction accuracy was obtained using regularized LR (96.65 ± 7.24%, AUC 0.98 ± 0.06) and DNN (87.25 ± 14.80%, AUC 0.87 ± 0.18). Conclusion: The results show the potential power of the radiomic features extracted from hippocampus and amygdala MRI in the prediction of STN-DBS motor outcomes for PD patients.

Associations of miR-181a with Health-Related Quality of Life, Cognitive Functioning, and Clinical Data of Patients with Different Grade Glioma Tumors.

Gliomas are central nervous system tumors with a lethal prognosis. Small micro-RNA molecules participate in various biological processes, are tissue-specific, and, therefore, could be promising targets for cancer treatment. Thus, this study aims to examine miR-181a as a potent biomarker for the diagnosis and prognosis of glioma patients and, for the first time, to find associations between the expression level of miR-181a and patient quality of life (QoL) and cognitive functioning. The expression level of miR-181a was analyzed in 78 post-operative II-IV grade gliomas by quantitative real-time polymerase chain reaction. The expression profile was compared with patient clinical data (age, survival time after the operation, tumor grade and location, mutation status of isocitrate dehydrogenase 1 (IDH1), and promoter methylation of O-6-methylguanine methyltransferase). Furthermore, the health-related QoL was assessed using the Karnofsky performance scale and the quality of life questionnaires; while cognitive assessment was assessed by the Hopkins verbal learning test-revised, trail-making test, and phonemic fluency tasks. The expression of miR-181a was significantly lower in tumors of grade III and IV and was associated with IDH1 wild-type gliomas and a worse prognosis of patient overall survival. Additionally, a positive correlation was observed between miR-181a levels and functional status and QoL of glioma patients. Therefore, miR-181a is a unique molecule that plays an important role in gliomagenesis, and is also associated with changes in patients' quality of life.

Feasibility of the optimal cerebral perfusion pressure value identification without a delay that is too long.

Optimal cerebral perfusion pressure (CPPopt)-targeted treatment of traumatic brain injury (TBI) patients requires 2-8 h multi-modal monitoring data accumulation to identify CPPopt value for individual patient. Minimizing the time required for monitoring data accumulation is needed to improve the efficacy of CPPopt-targeted therapy. A retrospective analysis of multimodal physiological monitoring data from 87 severe TBI patients was performed by separately representing cerebrovascular autoregulation (CA) indices in relation to CPP, arterial blood pressure (ABP), and intracranial pressure (ICP) to improve the existing CPPopt identification algorithms. Machine learning (ML)-based algorithms were developed for automatic identification of informative data segments that were used for reliable CPPopt, ABPopt, ICPopt and the lower/upper limits of CA (LLCA/ULCA) identification. The reference datasets of the informative data segments and, artifact-distorted segments, and the datasets of different clinical situations were used for training the ML-based algorithms, allowing us to choose the appropriate individualized CPP-, ABP- or ICP-guided management for 79% of the full monitoring time for the studied population. The developed ML-based algorithms allow us to recognize informative physiological ABP/ICP variations within 24 min intervals with an accuracy up to 79% (compared to the initial accuracy of 74%) and use these segments for timely optimal value identification or CA limits determination in CPP, ABP or ICP data. Prospective clinical studies are needed to prove the efficiency of the developed algorithms.

Transcriptome-wide analysis of glioma stem cell specific m6A modifications in long-non-coding RNAs.

The interest in chemical RNA modifications is rapidly growing in the field of molecular biology. Dynamic and reversible alterations of N6-methyladenosine (m6A) RNA modification are responsible for a platter of structural and functional changes in healthy and cancerous cell states. Although many studies reported the link between tumor initiation/progression and m6A modulators, there are few studies exploring transcriptome-wide m6A profile of non-coding RNAs. The aim of current study was to identify glioma stem cell (GSC) specific m6A landscape of long non-coding RNAs (lncRNAs) applying MeRIP-seq approach. MeRIP-seq analysis assigned 77.9% of m6A peaks to mRNAs and 8.16% to lncRNAs. GSCs and differentiated cells showed 76.4% conservation of m6A peaks, while 19.4% were unique to GSCs. Seven novel GSC-specific m6A modified lncRNAs were identified: HRAT92, SLCO4A1-AS1, CEROX1, PVT1, AGAP2-AS1, MIAT, and novel lncRNA gene ENSG00000262223. Analysis disclosed a strong negative correlation between lncRNAs m6A modification rate and expression. MeRIP-seq analysis revealed m6A modifications on previously reported glioma-associated lncRNAs: LINC000461, HOTTIP, CRNDE, TUG1, and XIST. Moreover, current study disclosed that most highly m6A modified lncRNAs primarily contain m6A modifications close to 3' and 5' ends. Our results provide basis and insight for further studies of m6A modifications in non-coding transcriptome of GSCs.

Application of 3D Gel Dosimetry as a Quality Assurance Tool in Functional Leksell Gamma Knife Radiosurgery.

Highly precise dose delivery to the target (tumor or cancerous tissue) is a key point when brain diseases are treated applying recent stereotactic techniques: intensity-modulated, image-guided radiotherapy, volumetric modulated arc therapy, Gamma knife radiosurgery. The doses in one single shot may vary between tens and hundreds of Gy and cause significant cell/tissue/organ damages. This indicates the need for implementation of quality assurance (QA) measures which are realized performing treatment dose verification with more than one calibrated quality assurance method or tool, especially when functional radiosurgery with a high dose (up to 40 Gy in our case) shall be delivered to the target using small 4 mm collimator. Application of two dosimetry methods: radiochromic film dosimetry using RTQA2 and EBT3 films and dose gel dosimetry using modified nPAG polymer gels for quality assurance purposes in stereotactic radiosurgery treatments using Leksell Gamma Knife© Icon™ facility is discussed in this paper. It is shown that due to their polymerization ability upon irradiation nPAG gels might be potentially used as a quality assurance tool in Gamma knife radiosurgery: they indicate well pronounced linear dose response in hypo-fractionated (up to 10 Gy) dose range and are sensitive enough to irradiation dose changes with a high (at least 0.2 mm) spatial resolution. Dose assessment sensitivity of gels depends on parameters of a dose evaluation method (optical or magnetic resonance imaging), however, is similar to this estimated using film dosimetry, which is set as a standard dosimetry method for dose verification in radiotherapy.

Advanced image analysis-based evaluation of protein antibody microarray chemiluminescence signal improves glioma type identification by blood serum proteins concentrations.

BACKGROUND AND OBJECTIVE: Gliomas are the most common brain tumors usually classified as benign low-grade or aggressive high-grade glioma. One of the promising possibilities of glioma diagnostics and tumor type identification could be based on concentration measurements of glioma secreted proteins in blood. However, several published approaches of quantitative proteomic analysis emphasize limits of one single protein to be used as biomarker of these types of tumors. Simultaneous multi-protein concentrations analysis giving antibody array-based methods suffer from poor measurement accuracy due to technical limitations of imaging systems. METHODS: We applied Principal Component Analysis (PCA) for series of repeated antibody array chemiluminescence images to extract the component representing relative values of protein concentrations, free from zero-mean noise and uneven background illumination - main factors corrupting evaluation result. RESULTS: The proposed method increased accuracy of protein concentration estimates at least 2-fold. Decision tree classifier applied to the relative concentration values of three proteins TIMP-1, PAI-1 and NCAM-1 estimated by proposed image analysis method effectively distinguished between low-grade glioma, high-grade glioma and healthy control subjects showing validation accuracy of 74.9% with the highest positive predictive value of 81.2% for high grade glioma and 57.1% for low grade glioma cases. CONCLUSIONS: PCA-based image processing could be applied in protein antibody microarray and other multitarget detection/evaluation investigations to increase estimation accuracy.

Mesenchymal and Proneural Subtypes of Glioblastoma Disclose Branching Based on GSC Associated Signature.

Glioblastomas (GBM)-the most common, therapy-resistant, and lethal tumors driven by populations of glioma stem cells (GSCs) are still on the list of the most complicated pathologies. Thus, deeper understanding and characterization of GSCs is indispensable to find suitable targets and develop more effective therapies. In the present study, we applied native glioblastoma cells and GSCs sequencing, screened for GSC-specific targets and checked if the signature is related to GBM patient pathological, clinical data as well as molecular subtypes applying TCGA cohort. Data analysis revealed that tumors of proneural and mesenchymal subtypes are branching in separate clusters based on screened gene expression. Samples of the same subtype revealed significantly different patient survival prognosis as well as recurrence chance between the clusters. Recently, different subpopulations of mesenchymal GSC demonstrating different properties were shown, which indicates possible internal heterogeneity of GBM subtypes as well. Current findings also revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations.

Delayed intracerebral hemorrhage associated with placement of a deep brain stimulating electrode over two years prior.

INTRODUCTION AND IMPORTANCE: Most severe complications of DBS appear in the perioperative period. There are no published case reports of delayed ICH occurring more than three months from electrode implantation. The pathogenesis of delayed ICH remains unclear. CASE PRESENTATION: We present a 64-year-old male with essential tremor who sustained a delayed intracerebral hemorrhage (ICH) 2.5 years after implantation of a deep brain stimulating electrode. DISCUSSION: The patient sustained a thalamic-midbrain ICH that may have been related to the positioning of the electrode. An analysis was performed to determine the cause and risk factors that may have contributed. Based on these findings, it is possible that the proximity of the cannula or electrode may have mildly injured the wall of the superior thalamic vein during implantation, or perhaps being in contact with the vein over a longer-term having an effect, which in either of these scenarios can subsequently lead to ICH formation on the sudden rise of intracranial pressure. CONCLUSION: It emphasizes the importance of proper surgical navigation planning, image- guidance, and the use of image verification.

Influence of Decompressive Craniectomy Post Evacuation of Epidural Hematoma in Comatose Patients.

BACKGROUND: Epidural hematoma causing brain herniation is a major cause of mortality and morbidity after severe traumatic brain injury, even if surgical treatment is performed quickly. Decompression may be effective in decreasing intracranial pressure, but its effect on outcomes remains unclear. METHODS: A retrospective analysis of deeply comatose patients (Glasgow Coma Scale score 3-5) who underwent surgical treatment during a 12-year period, either via osteoplastic craniotomy (OC) or decompressive craniectomy, was carried out. Patient groups were compared on the basis of demographics, admission clinical state, head computed tomography imaging characteristics, and discharge outcome. RESULTS: A total of 60 patients were examined. The first group of 31 patients (52%) needed decompression during primary surgery. The second group of 29 patients (48%) underwent OC with evacuation of epidural hematoma without decompression. Both patient groups were similar according to age (40.9 ± 13 vs. 40.6 ± 12.5 years), Glasgow Coma Scale score before surgery (4 [3-5] vs. 4 [3-5]), hematoma thickness (based on computed tomography) (3.44 ± 1 vs. 3.36 ± 1.62 cm), and midline shift (1.42 ± 0.83 vs. 1.36 ± 0.9 cm). Mortality was more evident in the decompression group (45.2% vs. 13.8%; P = 0.008), and the Glasgow Outcome Score was also lower, 2.26 ± 1.5 versus 3.45 ± 1.5 (P = 0.003). CONCLUSIONS: Decompressive craniectomy following the evacuation of an acute epidural hematoma in deeply comatose patients demonstrated inferior outcomes in comparison with OC. Brain injury in the decompressive craniectomy patient group was more severe (concomitant subdural hematoma, early brain ischemia, and early brain herniation), which may have influenced the outcome. Further prospective studies are needed.

Successful management of spinal cord ischemia in a pediatric patient with fibrocartilaginous embolism: illustrative case.

BACKGROUND: Fibrocartilaginous embolism (FCE) is a rare cause of ischemic myelopathy that occurs when the material of the nucleus pulposus migrates into vessels supplying the spinal cord. The authors presented a case of pediatric FCE that was successfully managed by adapting evidence-based recommendations used for spinal cord neuroprotection in aortic surgery. OBSERVATIONS: A 7-year-old boy presented to the emergency department with acute quadriplegia and hemodynamic instability that quickly progressed to cardiac arrest. After stabilization, the patient regained consciousness but remained in a locked-in state with no spontaneous breathing. The patient presented a diagnostic challenge. Traumatic, inflammatory, infectious, and ischemic etiologies were considered. Eventually, the clinical and radiological findings led to the presumed diagnosis of FCE. Treatment with continuous cerebrospinal fluid drainage (CSFD), pulse steroids, and mean arterial pressure augmentation was applied, with subsequent considerable and consistent neurological improvement. LESSONS: The authors proposed consideration of the adaptation of spinal cord neuroprotection principles used routinely in aortic surgery for the management of traumatic spinal cord ischemia (FCE-related in particular), namely, permissive arterial hypertension and CSFD. This is hypothesized to allow for the maintenance of sufficient spinal cord perfusion until adequate physiological blood perfusion is reestablished (remodeling of the collateral arterial network and/or clearing/absorption of the emboli).

Unique Interplay Between Molecular miR-181b/d Biomarkers and Health Related Quality of Life Score in the Predictive Glioma Models.

In the last decade, an increasing amount of research has been conducted analyzing microRNA expression changes in glioma tissue and its expressed exosomes, but there is still sparse information on microRNAs or other biomarkers and their association with patients' functional/psychological outcomes. In this study, we performed a combinational analysis measuring miR-181b and miR-181d expression levels by quantitative polymerase chain reaction (qPCR), evaluating isocitrate dehydrogenase 1 (IDH1) single nucleotide polymorphism (SNP), and O-6-methylguanine methyltransferase (MGMT) promoter methylation status in 92 post-surgical glioma samples and 64 serum exosomes, including patients' quality of life evaluation applying European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-30), EORTC the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), and the Karnofsky performance status (KPS). The tumoral expression of miR-181b was lower in grade III and glioblastoma, compared to grade II glioma patients (p < 0.05). Additionally, for the first time, we demonstrated the association between miR-181 expression levels and patients' quality of life. A positive correlation was observed between tumoral miR-181d levels and glioma patients' functional parameters (p < 0.05), whereas increased exosomal miR-181b levels indicated a worse functional outcome (p < 0.05). Moreover, elevated miR-181b exosomal expression can indicate a significantly shorter post-surgical survival time for glioblastoma multiforme (GBM) patients. In addition, both tumoral and exosomal miR-181 expression levels were related to patients' functioning and tumor-related symptoms. Our study adds to previous findings by demonstrating the unique interplay between molecular miR-181b/d biomarkers and health related quality of life (HRQOL) score as both variables remained significant in the predictive glioma models.

The Role of CASC2 and miR-21 Interplay in Glioma Malignancy and Patient Outcome.

Recently long non-coding RNAs (lncRNAs) were highlighted for their regulatory role in tumor biology. The novel human lncRNA cancer susceptibility candidate 2 (CASC2) has been characterized as a potential tumor suppressor in several tumor types. However, the roles of CASC2 and its interplay with miR-21 in different malignancy grade patient gliomas remain unexplored. Here we screened 99 different malignancy grade astrocytomas for CASC2, and miR-21 gene expression by real-time quantitative polymerase chain reaction (RT-qPCR) in isocitrate dehydrogenase 1 (IDH1) and O-6-methylguanine methyltransferase (MGMT) assessed gliomas. CASC2 expression was significantly downregulated in glioblastomas (p = 0.0003). Gliomas with low CASC2 expression exhibited a high level of miR-21, which was highly associated with the higher glioma grade (p = 0.0001), IDH1 wild type gliomas (p < 0.0001), and poor patient survival (p < 0.001). Taken together, these observations suggest that CASC2 acts as a tumor suppressor and potentially as a competing endogenous RNA (ceRNA) for miR-21, plays important role in IDH1 wild type glioma pathogenesis and patients' outcomes.

A SEMA3 Signaling Pathway-Based Multi-Biomarker for Prediction of Glioma Patient Survival.

Glioma is a lethal central nervous system tumor with poor patient survival prognosis. Because of the molecular heterogeneity, it is a challenge to precisely determine the type of the tumor and to choose the most effective treatment. Therefore, novel biomarkers are essential to improve the diagnosis and prognosis of glioma tumors. Class 3 semaphorin proteins (SEMA3) play an important role in tumor biology. SEMA3 transduce their signals by using neuropilin and plexin receptors, which functionally interact with the vascular endothelial growth factor-mediated signaling pathways. Therefore, the aim of this study was to explore the potential of SEMA3 signaling molecules for prognosis of glioma patient survival. The quantitative real-time PCR method was used to evaluate mRNA expression of SEMA3(A-G), neuropilins (NRP1 and NRP2), plexins (PLXNA2 and PLXND1), cadherins (CDH1 and CDH2), integrins (ITGB1, ITGB3, ITGA5, and ITGAV), VEGFA and KDR genes in 59 II-IV grade glioma tissues. Seven genes significantly associated with patient overall survival were used for multi-biomarker construction, which showed 64%, 75%, and 68% of accuracy of predicting the survival of 1-, 2-, and 3-year glioma patients, respectively. The results suggest that the seven-gene signature could serve as a novel multi-biomarker for more accurate prognosis of a glioma patient's outcome.

Single root multiple spinal schwannomas: Case report, treatment strategy and review of literature.

INTRODUCTION: Schwannomatosis is defined as multiple schwannomas without presence of neurofibromatosis and is a rare pathology. In vast majority of cases the schwannomas grow from different nerve roots or peripheral nerves. PRESENTATION OF CASE: A 52-year-old woman presented with multiple intradural schwannomas arranged in a chain along the spinal canal causing significant compression. The lesions were successfully removed using a left side en-bloc hemilaminectomy technique in order to preserve maximal stability of the posterior column. Back and leg pain resolved completely. Tendon reflexes returned to normal shortly. There was decreased pain sensation in the distribution of the left L3 spinal root. DISCUSSION: The traditional surgical strategy for posterior approach by laminectomy or laminotomy is sometimes complicated with instability or deformation of the vertebral column that requires surgical stabilization. We performed a one side en-bloc hemilaminectomy thus maintaining the integrity of the muscles and ligaments on the opposite side and preserving maximal stability of the vertebral column. Densely adherent tumors required careful sharp dissection and separation under neurosurgical monitoring and stimulation for recognition and preservation of spinal roots. An additional tumor was discovered by exploration of the spinal canal using an endoscope. CONCLUSION: Multiple spinal cord schwannomas that are growing along the same part of the vertebral column can be safely removed by one-sided hemilaminectomy with preservation of the integrity of the muscles and ligaments on the opposite side and thus maintain spinal stability. The 30° endoscope can be a good tool for visual exploration of the spinal canal.

Clinical and Biological Correlates of Preoperative Cognitive Functioning of Glioma and Meningioma Patients.

OBJECTIVES: This study aimed to investigate the association of high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations with cognitive functions of glioma and meningioma patients. METHODS: 177 brain tumor patients awaiting for brain tumor surgery participated in the study. Patients were assessed preoperatively, using neuropsychological tests for verbal memory, psychomotor speed, mental flexibility, and verbal fluency. The functional status of patients was evaluated using the Karnofsky Performance Index. Blood samples were drawn for evaluation of serum hsCRP and NT-proBNP concentrations upon hospital admission. RESULTS: The highest NT-proBNP concentration was observed in meningioma patients. Glioma and meningioma patients did not differ in hsCRB concentration. Patients in the highest hsCRP tertile were older and more frequently reported cardiovascular comorbidity. Patients in the highest NT-proBNP tertile were older, more frequently with cardiovascular comorbidity, females, and diagnosed with a meningioma. hsCRP was significantly related to slower psychomotor speed in high-grade glioma patients (rho = 0.30, p < 0.05). In meningioma sample, NT-proBNP correlated with decreased psychomotor speed (rho = 0.38, p < 0.01), mental flexibility (rho = 0.33, p < 0.01), worse cumulative learning (rho = -0.27, p < 0.05), and delayed recall (rho = 0.30, p < 0.01). However, the relationship between the NT-proBNP and cognitive functions became nonsignificant when demographic and clinical covariates were included into analysis. Higher hsCRP concentration remained significantly related to slower psychomotor speed (p = 0.02) and worse mental flexibility (p = 0.05) in glioma patients, independently from demographic and clinical covariates. Preoperative cognitive functioning was also predicted by older age, gender, side and location of the tumor, and tumor malignancy, and general functional status of a patient. CONCLUSIONS: NT-proBNP was not associated with memory, language, and attention/executive cognitive domains of glioma and meningioma patients. Increased hsCRP was related to slower psychomotor speed and worse mental flexibility in glioma patients, indicating that inflammation processes are important for cognitive functioning in glial tumors.

Neuropsychiatric complications and neuroimaging characteristics after deep brain stimulation surgery for Parkinson's disease.

Psychiatric complications after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease patients are common. The aim of this study was to evaluate a possible role of cortical thickness, cortical and subcortical volume for neuropsychiatric complications after STN-DBS implantation surgery. Twenty-two Parkinson's disease patients underwent STN-DBS. Control group consisted of 18 healthy volunteers who were matched by age and gender. All Parkinson's disease patients and control subjects underwent neuropsychological assessment and brain MRI. Control group subjects had normal MRI and neurocognitive testing results. Seven (31.8%) Parkinson's disease patients developed neuropsychiatric complications (psychosis and delirium) after STN-DBS implantation surgery with full recovery in short follow up. Two Parkinson's disease patients were excluded from further analysis, because they did not match image processing and analysis quality control. Volumetric analysis showed significant differences in cortical thickness between STN-DBS patients with and without postoperative neuropsychiatric complications in 13 gyruses on the right hemisphere (superior frontal, caudal middle frontal, pars triangularis and opercularis, temporal lobe, superior and inferior parietal, supramarginal) and in 7 gyruses on the left hemisphere (caudal middle frontal, inferior and middle temporal, pre and postcentral, superior parietal and supramarginal). White matter volume analysis showed also its reduction in the left caudal middle frontal area. Moreover, white matter volume and surface area reduction implicating that this area can be the most important for postoperative neuropsychiatric complication risk. Study results suggest that neuropsychiatric complications are common in Parkinson's disease patients after STN-DBS implantation and can be associated with excitation of frontal-striatum-thalamus and temporal-parietal circuits.

Identification of Astrocytoma Blood Serum Protein Profile.

High-grade astrocytomas are some of the most common and aggressive brain cancers, whose signs and symptoms are initially non-specific. Up to the present date, there are no diagnostic tools to observe the early onset of the disease. Here, we analyzed the combination of blood serum proteins, which may play key roles in the tumorigenesis and the progression of glial tumors. Fifty-nine astrocytoma patients and 43 control serums were analyzed using Custom Human Protein Antibody Arrays, including ten targets: ANGPT1, AREG, IGF1, IP10, MMP2, NCAM1, OPN, PAI1, TGFß1, and TIMP1. The decision tree analysis indicates that serums ANGPT1, TIMP1, IP10, and TGFß1 are promising combinations of targets for glioma diagnostic applications. The accuracy of the decision tree algorithm was 73.5% (75/102), which correctly classified 79.7% (47/59) astrocytomas and 65.1% (28/43) healthy controls. The analysis revealed that the relative value of osteopontin (OPN) protein level alone predicted the 12-month survival of glioblastoma (GBM) patients with the specificity of 84%, while the inclusion of the IP10 protein increased model predictability to 92.3%. In conclusion, the serum protein profiles of ANGPT1, TIMP1, IP10, and TGFß1 were associated with the presence of astrocytoma independent of its malignancy grade, while OPN and IP10 were associated with GBM patient survival.