Susceptibility-Weighted MRI for Predicting NF-2 Mutations and S100 Protein Expression in Meningiomas.

S100 protein expression levels and neurofibromatosis type 2 (NF-2) mutations result in different disease courses in meningiomas. This study aimed to investigate non-invasive biomarkers of NF-2 copy number loss and S100 protein expression in meningiomas using morphological, radiomics, and deep learning-based features of susceptibility-weighted MRI (SWI). This retrospective study included 99 patients with S100 protein expression data and 92 patients with NF-2 copy number loss information. Preoperative cranial MRI was conducted using a 3T clinical MR scanner. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and subsequent registration of FLAIR to high-resolution SWI was performed. First-order textural features of SWI were extracted and assessed using Pyradiomics. Morphological features, including the tumor growth pattern, peritumoral edema, sinus invasion, hyperostosis, bone destruction, and intratumoral calcification, were semi-quantitatively assessed. Mann-Whitney U tests were utilized to assess the differences in the SWI features of meningiomas with and without S100 protein expression or NF-2 copy number loss. A logistic regression analysis was used to examine the relationship between these features and the respective subgroups. Additionally, a convolutional neural network (CNN) was used to extract hierarchical features of SWI, which were subsequently employed in a light gradient boosting machine classifier to predict the NF-2 copy number loss and S100 protein expression. NF-2 copy number loss was associated with a higher risk of developing high-grade tumors. Additionally, elevated signal intensity and a decrease in entropy within the tumoral region on SWI were observed in meningiomas with S100 protein expression. On the other hand, NF-2 copy number loss was associated with lower SWI signal intensity, a growth pattern described as "en plaque", and the presence of calcification within the tumor. The logistic regression model achieved an accuracy of 0.59 for predicting NF-2 copy number loss and an accuracy of 0.70 for identifying S100 protein expression. Deep learning features demonstrated a strong predictive capability for S100 protein expression (AUC = 0.85 ± 0.06) and had reasonable success in identifying NF-2 copy number loss (AUC = 0.74 ± 0.05). In conclusion, SWI showed promise in identifying NF-2 copy number loss and S100 protein expression by revealing neovascularization and microcalcification characteristics in meningiomas.

Identification of IDH and TERTp mutations using dynamic susceptibility contrast MRI with deep learning in 162 gliomas.

PURPOSE: Isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutations play crucial roles in glioma biology. Such genetic information is typically obtained invasively from excised tumor tissue; however, these mutations need to be identified preoperatively for better treatment planning. The relative cerebral blood volume (rCBV) information derived from dynamic susceptibility contrast MRI (DSC-MRI) has been demonstrated to correlate with tumor vascularity, functionality, and biology, and might provide some information about the genetic alterations in gliomas before surgery. Therefore, this study aims to predict IDH and TERTp mutational subgroups in gliomas using deep learning applied to rCBV images. METHOD: After the generation of rCBV images from DSC-MRI data, classical machine learning algorithms were applied to the features obtained from the segmented tumor volumes to classify IDH and TERTp mutation subgroups. Furthermore, pre-trained convolutional neural networks (CNNs) and CNNs enhanced with attention gates were trained using rCBV images or a combination of rCBV and anatomical images to classify the mutational subgroups. RESULTS: The best accuracies obtained with classical machine learning algorithms were 83 %, 68 %, and 76 % for the identification of IDH mutational, TERTp mutational, and TERTp-only subgroups, respectively. On the other hand, the best-performing CNN model achieved 88 % accuracy (86 % sensitivity, 91 % specificity) for the IDH-mutational subgroups, 70 % accuracy (73 % sensitivity and 67 % specificity) for the TERTp-mutational subgroups, and 84 % accuracy (86 % sensitivity, 81 % specificity) for the TERTp-only subgroup using attention gates. CONCLUSIONS: DSC-MRI can be utilized to noninvasively classify IDH- and TERTp-based molecular subgroups of gliomas, facilitating preoperative identification of these genetic alterations.

Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway  in neoplasia.

Magnetic resonance spectroscopic correlates of progression free and overall survival in "glioblastoma, IDH-wildtype, WHO grade-4".

Background: The 2021 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification has suggested that isocitrate dehydrogenase wildtype (IDH-wt) WHO grade-2/3 astrocytomas with molecular features of glioblastoma should be designated as "Glioblastoma, IDH-wildtype, WHO grade-4." This study analyzed the metabolic correlates of progression free and overall survival in "Glioblastoma, IDH-wildtype, WHO grade-4" patients using short echo time single voxel 1H-MRS. Methods: Fifty-seven adult patients with hemispheric glioma fulfilling the 2021 WHO CNS Tumor Classification criteria for "Glioblastoma, IDH-wildtype, WHO grade-4" at presurgery time point were included. All patients were IDH1/2-wt and TERTp-mut. 1H-MRS was performed on a 3 T MR scanner and post-processed using LCModel. A Mann-Whitney U test was used to assess the metabolic differences between gliomas with or without contrast enhancement and necrosis. Cox regression analysis was used to assess the effects of age, extent of resection, presence of contrast enhancement and necrosis, and metabolic intensities on progression-free survival (PFS) and overall survival (OS). Machine learning algorithms were employed to discern possible metabolic patterns attributable to higher PFS or OS. Results: Contrast enhancement (p = 0.015), necrosis (p = 0.012); and higher levels of Glu/tCr (p = 0.007), GSH/tCr (p = 0.019), tCho/tCr (p = 0.032), and Glx/tCr (p = 0.010) were significantly associated with shorter PFS. Additionally, necrosis (p = 0.049), higher Glu/tCr (p = 0.039), and Glx/tCr (p = 0.047) were significantly associated with worse OS. Machine learning models differentiated the patients having longer than 12 months OS with 81.71% accuracy and the patients having longer than 6 months PFS with 77.41% accuracy. Conclusion: Glx and GSH have been identified as important metabolic correlates of patient survival among "IDH-wt, TERT-mut diffuse gliomas" using single-voxel 1H-MRS on a clinical 3 T MRI scanner.

Arterial Supply of the Basal Ganglia: A Fiber Dissection Study.

BACKGROUND: The basal ganglia, a group of subcortical nuclei located deep in the insular cortex, are responsible for many functions such as motor learning, emotion, and behavior control. Nowadays, because it has been shown that deep brain stimulation and insular tumor surgery can be performed by endovascular treatment, the importance of the vascular anatomy of the basal ganglia is being increasingly recognized. OBJECTIVE: To explain the arterial blood supply of the basal ganglia using white matter dissection. METHODS: The Klingler protocol was used to prepare 12 silicone-injected human hemispheres. The dissections were performed from lateral to medial with the fiber dissection technique to preserve arteries. RESULTS: The globus pallidus blood supply came from the medial lenticulostriate, lateral lenticulostriate, and anterior choroidal arteries; the substantia nigra and subthalamic nucleus were supplied by the branches of posterior cerebral artery; the putamen was supplied by the lateral and medial lenticulostriate arteries; and the caudate nucleus was supplied by the lateral lenticulostriate and medial lenticulostriate arteries and the recurrent artery of Heubner. CONCLUSION: Knowledge of the detailed anatomy of the basal ganglia and its vascular supply is essential for avoiding postoperative ischemic complications in surgeries related to the insula. In addition, knowledge of this anatomy and vascular relationship opens the doors to endovascular deep brain stimulation treatment. This study provides a 3-dimensional understanding of the blood supply to the basal ganglia by examining it using the fiber dissection technique. Further studies could use advanced imaging modalities to explore the vascular relationships with critical structures in the brain.

The effect of tumor shape irregularity on Gamma Knife treatment plan quality and treatment outcome: an analysis of 234 vestibular schwannomas.

The primary aim of Gamma Knife (GK) radiosurgery is to deliver high-dose radiation precisely to a target while conforming to the target shape. In this study, the effects of tumor shape irregularity (TSI) on GK dose-plan quality and treatment outcomes were analyzed in 234 vestibular schwannomas. TSI was quantified using seven different metrics including volumetric index of sphericity (VioS). GK treatment plans were created on a single GK-Perfexion/ICON platform. The plan quality was measured using selectivity index (SI), gradient index (GI), Paddick's conformity index (PCI), and efficiency index (EI). Correlation and linear regression analyses were conducted between shape irregularity features and dose plan indices. Machine learning was employed to identify the shape feature that predicted dose plan quality most effectively. The treatment outcome analysis including tumor growth control and serviceable hearing preservation at 2 years, were conducted using Cox regression analyses. All TSI features correlated significantly with the dose plan indices (P < 0.0012). With increasing tumor volume, vestibular schwannomas became more spherical (P < 0.05) and the dose plan indices varied significantly between tumor volume subgroups (P < 0.001 and P < 0.01). VioS was the most effective predictor of GK indices (P < 0.001) and we obtained 89.36% accuracy (79.17% sensitivity and 100% specificity) for predicting PCI. Our results indicated that TSI had significant effects on the plan quality however did not adversely affect treatment outcomes.

MEOX2 homeobox gene promotes growth of malignant gliomas.

BACKGROUND: Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss of chromosome 10, and aberrantly activated receptor tyrosine kinase signaling pathways. Previously, we identified Mesenchyme Homeobox 2 (MEOX2), a gene located on chromosome 7, as an upregulated transcription factor in GBM. Overexpressed transcription factors can be involved in driving GBM. Here, we aimed to address the role of MEOX2 in GBM. METHODS: Patient-derived GBM tumorspheres were used to constitutively knockdown or overexpress MEOX2 and subjected to in vitro assays including western blot to assess ERK phosphorylation. Cerebral organoid models were used to investigate the role of MEOX2 in growth initiation. Intracranial mouse implantation models were used to assess the tumorigenic potential of MEOX2. RNA-sequencing, ACT-seq, and CUT&Tag were used to identify MEOX2 target genes. RESULTS: MEOX2 enhanced ERK signaling through a feed-forward mechanism. We identified Ser155 as a putative ERK-dependent phosphorylation site upstream of the homeobox-domain of MEOX2. S155A substitution had a major effect on MEOX2 protein levels and altered its subnuclear localization. MEOX2 overexpression cooperated with p53 and PTEN loss in cerebral organoid models of human malignant gliomas to induce cell proliferation. Using high-throughput genomics, we identified putative transcriptional target genes of MEOX2 in patient-derived GBM tumorsphere models and a fresh frozen GBM tumor. CONCLUSIONS: We identified MEOX2 as an oncogenic transcription regulator in GBM. MEOX2 increases proliferation in cerebral organoid models of GBM and feeds into ERK signaling that represents a core signaling pathway in GBM.

Information theory approaches to improve glioma diagnostic workflows in surgical neuropathology.

AIMS: Resource-strained healthcare ecosystems often struggle with the adoption of the World Health Organization (WHO) recommendations for the classification of central nervous system (CNS) tumors. The generation of robust clinical diagnostic aids and the advancement of simple solutions to inform investment strategies in surgical neuropathology would improve patient care in these settings. METHODS: We used simple information theory calculations on a brain cancer simulation model and real-world data sets to compare contributions of clinical, histologic, immunohistochemical, and molecular information. An image noise assay was generated to compare the efficiencies of different image segmentation methods in H&E and Olig2 stained images obtained from digital slides. An auto-adjustable image analysis workflow was generated and compared with neuropathologists for p53 positivity quantification. Finally, the density of extracted features of the nuclei, p53 positivity quantification, and combined ATRX/age feature was used to generate a predictive model for 1p/19q codeletion in IDH-mutant tumors. RESULTS: Information theory calculations can be performed on open access platforms and provide significant insight into linear and nonlinear associations between diagnostic biomarkers. Age, p53, and ATRX status have significant information for the diagnosis of IDH-mutant tumors. The predictive models may facilitate the reduction of false-positive 1p/19q codeletion by fluorescence in situ hybridization (FISH) testing. CONCLUSIONS: We posit that this approach provides an improvement on the cIMPACT-NOW workflow recommendations for IDH-mutant tumors and a framework for future resource and testing allocation.

Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system.

OBJECTIVE: Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort. METHODS: Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21-71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters). RESULTS: The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2 ± 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator. CONCLUSIONS: The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.

Lumbar intervertebral disc degeneration, end-plates and paraspinal muscle changes in children and adolescents with low-back pain.

The prevalence of low-back pain (LBP) in adolescents ranges from 7 to 72%. We aimed to define the radiologic characteristics of the lumbar spine in children and adolescents with LBP with/without leg pain. Two hundred and fourteen children and adolescents, who were born between 2001 and 2009 and had lumbar spine MRI for LBP with/without leg pain, were evaluated in terms of intervertebral disc degeneration (IVDD), end-plates and paraspinal muscle changes on lumbar spine MRIs. Severe IVDD was detected at all lumbar levels except for L2-L3. Modic changes were present in 4.2% of the patients. Modic changes were more common in patients with severe IVDD than in those with mild-to-moderate IVDD. Severe IVDD was significantly associated with Modic changes at the corresponding L1-L2 and L3-L4 disc levels. Girls had significantly more fatty infiltration in the paraspinal muscles when compared to boys. The risk of having severe IVDD concomitant with Modic changes was high [odds ratio (OR), 8.6]. The OR was 20.7 for predicting the presence of severe IVDD at any level if Modic changes presented particularly at the L3-L4 level. The ORs of Modic changes presented at any lumbar level at the background of fat-infiltrated multifidus at L3-L4 and L4-L5 levels were 8.3 and 9.1, respectively. Fatty infiltration in the paraspinal muscles and IVDD were closely associated with Modic changes in children and adolescents with LBP. Lumbar IVDD in children and adolescents could be the result of a mechanical pathology.

Intradiscal vacuum phenomenon and spinal degeneration: a cross-sectional analysis of 219 subjects.

INTRODUCTION: Intradiscal vacuum phenomenon (IVP) is the collection of gas within the intervertebral discs. It has been reported with various spinal disorders. The exact role of IVP in spinal degeneration leading to low back pain (LBP) is unclear. We aimed to obtain the prevalence of IVP in patients with LBP. Our second aim was to understand whether IVP was associated with intervertebral disc degeneration (IVDD), Modic changes, and subchondral sclerosis (SS). METHODS: A total of 12.450 consecutive patients with chronic LBP were evaluated in terms of having abdominal computed tomography (CT) scan concomitant with lumbar spine magnetic resonance imaging (MRI) using radiological database of three spine centers. We excluded the patients with a history of malignancy, metabolic disease, spinal infection, traumatic or osteoporotic spine fracture, and spine surgery. All lumbar levels were evaluated in terms of IVDD and Modic changes on MRI, while they were evaluated in terms of IVP and SS on CT scans. RESULTS: We included 219 patients. Severe IVDD, Modic changes, IVP, and SS were seen in 53.9% (n: 118), 38.8% (n: 85), 26.5% (n: 58), and 16% (n: 35) of the patients, respectively. Intradiscal vacuum phenomenon was closely associated with severe IVDD (OR: 8.204), Modic changes (OR: 3.547) and SS (OR: 4.231). DISCUSSION: Intradiscal vacuum phenomenon was closely associated with severe IVDD, Modic changes, and SS. Further prospective clinical and laboratory studies are necessary to better delineate the pathogenesis of IVP.

The reliability and interobserver reproducibility of T2/FLAIR mismatch in the diagnosis of IDH-mutant astrocytomas.

PURPOSE: The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate dehydrogenase (IDH) mutant astrocytoma between WHO grade II and III diffuse hemispheric gliomas. METHODS: WHO grade II and grade III diffuse hemispheric gliomas (n=133) treated in our institute were included in the study. Pathological findings and molecular markers of the cases were reviewed with the criteria of WHO 2016. The finding of mismatch between T2-weighted and FLAIR images in preoperative magnetic resonance imaging (MRI) of the cases was evaluated by two different radiologists. The readers reviewed MRIs independently, blinded to the histopathologic diagnosis or molecular subset of tumors. The cases were classified as IDH-mutant astrocytoma, oligodendroglioma and IDH-wildtype (IDH-wt) astrocytoma according to molecular and genetic features. RESULTS: T2/FLAIR mismatch positivity was observed in 46 patients (34.6%). T2/FLAIR mismatch positivity was observed in 42 of 75 IDH-mutant astrocytomas (56%) and 4 of 43 oligodendrogliomas (9.30%), while it was not seen among IDH-wt astrocytomas (0/15, 0%). The T2/FLAIR mismatch ratio was significantly different between IDH-mutant astrocytomas (WHO grade II and grade III) and oligodendrogliomas (chi-square, p <0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T2/FLAIR mismatch in predicting IDH-mutant astrocytomas were 58.7%, 90.7%, 91.7%, 61.4%, and 70.3% respectively. Radiologist 1 diagnosed T2/FLAIR mismatch in 48 of 133 cases (36.1%) and Radiologist 2 in 66 of 133 cases (49.6%). The interrater agreement for the T2/FLAIR mismatch sign was 0.61 (p <0.05), 95% CI (0.55, 0.67). CONCLUSION: T2/FLAIR mismatch appears to be an important MRI finding in distinguishing IDH-mutant astrocytomas from other diffuse hemispheric gliomas. However, it should be kept in mind that T2/FLAIR mismatch sign can be seen in a minority of oligodendrogliomas besides IDH-mutant astrocytomas.

Neurosurgical follow-up and treatment of a series of 26 WHO grade III meningiomas.

Meningiomas are the most common primary intracranial tumors. They have three pathologic grades. Surgical resection aiming Simpson I resection is the standard treatment for meningiomas. Radiotherapy and Gamma Knife radiosurgery are the main adjuvant and salvage treatments. Chemotherapy has limited use. Grade II, and III meningiomas have a higher recurrence rate, and adjuvant radiotherapy is usually the standard treatment for grade III meningiomas. In this paper, we analyzed our meningioma series of 1401 patients and presented the treatment and follow-up results of 26 grade III meningioma cases. Median follow-up of grade III meningiomas was 40.5 (range, 1-154) months. The mean age of patients was 51.7 ± 15.7 years; 12 of them were female and 14 were male (female/male ratio = 0.9). The median progression-free survival (PFS) of them was 22 months, and overall survival (OS) was 62 months. Meningiomas with gross total resection (GTR), non-skull base meningiomas, and primary grade III meningiomas had longer PFS, while meningiomas with GTR, non-skull base meningiomas, and primary meningiomas had longer OS with a statistical significance.

Treatment and follow-up results of WHO grade II meningiomas.

Meningiomas are the most common primary intracranial tumors. They have three pathologic grades. Surgical resection aiming Simpson I resection is the standard treatment for meningiomas. Radiotherapy and Gamma Knife radiosurgery are the main adjuvant and salvage treatments. Chemotherapy has limited use. Grade II, and III meningiomas have a higher recurrence rate, and adjuvant radiotherapy is usually the standard treatment for grade III meningiomas but there is not a consensus regarding grade II meningiomas. In this paper, we analyzed our meningioma series of 1401 patients and presented the treatment and follow-up results of 170 grade II meningioma cases. The median follow-up of grade II meningiomas was 61 (range = 1-231) months. The mean age of patients was 52.5 ± 15.0 years, 102 of them were female and 68 were male (female/male ratio = 1.5). The median progression-free survival (PFS) of them was 109 months, and the cumulative overall survival (OS) rate was 85% at 10 years. Meningiomas with gross total resection, non-skull base meningiomas, and primary grade II meningiomas had longer PFS with statistical significance, while non-skull base meningiomas, younger group of patients, and primary grade II meningiomas had longer OS with a statistical significance.

Analysis of Mitochondrial DNA Control Region D-Loop in Gliomas: Result of 52 Patients.

AIM: To investigate the effect of mitochondrial DNA (mtDNA) variants mainly in D-loop on glioma biology. MATERIAL AND METHODS: Sanger sequencing of D-loop (15971?16451 bp) for 52 glioma patients was performed and the variations were statistically analyzed for gender, WHO classification, morphological grade, IDH/TERT status. RESULTS: Total of 122 variations (51 unique) were identified in 52 patients. C16223T, T16189C, T16311C and T16126C variants were frequently detected. The total variation number was statistically non-significant among the analyzed categories. When individual variants were considered, T16311C and T16224C were statistically significant for WHO classification (p=0.033), morphological grade (p=0.036) and gender (p=0.039), respectively. CONCLUSION: Total variation number in D-loop was not found to be related with clinical variables. Our data suggests that individual variants may play a critical role in glioma biology.

Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma.

BACKGROUND: In the clinical setting, workflows for analyzing individual genomics data should be both comprehensive and convenient for clinical interpretation. In an effort for comprehensiveness and practicality, we attempted to create a clinical individual whole exome sequencing (WES) analysis workflow, allowing identification of genomic alterations and presentation of neurooncologically-relevant findings. METHODS: The analysis workflow detects germline and somatic variants and presents: (1) germline variants, (2) somatic short variants, (3) tumor mutational burden (TMB), (4) microsatellite instability (MSI), (5) somatic copy number alterations (SCNA), (6) SCNA burden, (7) loss of heterozygosity, (8) genes with double-hit, (9) mutational signatures, and (10) pathway enrichment analyses. Using the workflow, 58 WES analyses from matched blood and tumor samples of 52 patients were analyzed: 47 primary and 11 recurrent diffuse gliomas. RESULTS: The median mean read depths were 199.88 for tumor and 110.955 for normal samples. For germline variants, a median of 22 (14-33) variants per patient was reported. There was a median of 6 (0-590) reported somatic short variants per tumor. A median of 19 (0-94) broad SCNAs and a median of 6 (0-12) gene-level SCNAs were reported per tumor. The gene with the most frequent somatic short variants was TP53 (41.38%). The most frequent chromosome-/arm-level SCNA events were chr7 amplification, chr22q loss, and chr10 loss. TMB in primary gliomas were significantly lower than in recurrent tumors (p = 0.002). MSI incidence was low (6.9%). CONCLUSIONS: We demonstrate that WES can be practically and efficiently utilized for clinical analysis of individual brain tumors. The results display that NOTATES produces clinically relevant results in a concise but exhaustive manner.

Associations of meningioma molecular subgroup and tumor recurrence.

BACKGROUND: We and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients. METHODS: We analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent of resection, postoperative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan-Meier analyses to compare progression-free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling. RESULTS: Meningioma molecular subgroups exhibited divergent clinical courses at 2 years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, tumor necrosis factor receptor-associated factor 7 [TRAF7]) recurring at an average rate of 22 times higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared with other subgroups. Recurrence of NF2 tumors was associated with male sex, high grade, and elevated Ki-67. Multivariate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence. CONCLUSION: We describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide postoperative management decisions for meningiomas.

Location of Central Sulcus According to Coronal Suture.

BACKGROUND: It is essential to localize the central sulcus in patients with lesions within or nearby the sensorial and/or motor cortex. The coronal suture is a valuable bony landmark in neurosurgical practice; it could be used to localize the central sulcus. There are scarce amount of literature about normal values of the distance between the central sulcus and the coronal suture. In the present study, the authors aimed to learn normative values of the distance between the central sulcus and the coronal suture in a patient sample representing Turkish population. The authors also aimed to look for any difference in values according to sex and age. METHODS: The authors retrospectively reviewed a prospectively collected database. Patients were evaluated on cranial computed tomography (CT) reformatted in 3 planes (axial, coronal, and sagittal). Intracranial and extracranial pathologies were scanned. If there was no pathology, the reviewed CT scan was added up to the database. The coronal suture and the central sulcus were identified at the midline location on axial and sagittal view CT images. Vertical distance between coronal suture and central sulcus was measured. RESULTS: Mean distance of the central sulcus to the coronal suture was 47.5 ±â€Š7.6 mm (range = 26.2-67.3 mm). CONCLUSIONS: Identifying the central sulcus relative to the coronal suture is essential to preserve the primary motor and/or sensory cortices in neurosurgical procedures. The distance of the central sulcus to the coronal suture is approximately 4.7 cm in adult patients from Turkey, which did not differ according to age or sex.

Reciprocal relationship between multifidus and psoas at L4-L5 level in women with low back pain.

Background Low back pain (LBP) may originate from different sources such as intervertebral disc degeneration (IVDD), end-plate and paraspinal muscle changes. Our aim is to explore the relevance of paraspinal muscles' fat-infiltration in women with LBP and its association with IVDD and Modic changes.Methods Consecutive female patients presenting with chronic LBP to the outpatient clinics were included. Patients were evaluated in terms of IVDD, vertebral end-plate changes, and fatty infiltration in the paraspinal muscles at all lumbar levels on lumbar spine magnetic resonance imaging (MRI). Visual Analogue Scale (VAS) scores were recorded using our prospectively collected database.Results Patients with higher VAS scores were significantly more likely to have more fatty infiltration in the multifidus and less fatty infiltration in the psoas at L4-L5 level when compared to those with lower VAS scores (69.1 vs. 31.8%, p = 0.003). To predict LBP, fatty infiltration in the multifidus and psoas had odds ratio (OR) of 4 (p = 0.010), and 0.3 (p = 0.013), respectively; whereas disc degeneration had an OR of 0.5 (p = 0.028).Conclusion This is the first clinical cross-sectional study suggested that women with chronic low back pain could have less fat-infiltrated psoas to compensate more fat-infiltrated multifidus at L4-L5 disc level.