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.

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.

Identification of IDH and TERTp mutation status using 1 H-MRS in 112 hemispheric diffuse gliomas.

BACKGROUND: There is a growing interest in noninvasively defining molecular subsets of hemispheric diffuse gliomas based on the isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase gene promoter (TERTp) mutation status, which correspond to distinct tumor entities, and differ in demographics, natural history, treatment response, recurrence, and survival patterns. PURPOSE: To investigate whether metabolite levels detected with short echo time (TE) proton MR spectroscopy (1 H-MRS) at 3T can be used for noninvasive molecular classification of IDH and TERTp mutation-based subsets of gliomas. STUDY TYPE: Retrospective. SUBJECTS: In all, 112 hemispheric diffuse gliomas (70 males/42 females, mean age: 42.1 ± 13.9 years). FIELD STRENGTH/SEQUENCE: Short-TE 1 H-MRS (repetition time (TR) = 2000 msec, TE = 30 msec, number of signal averages = 192) and routine clinical brain tumor MR protocols were acquired at 3T. ASSESSMENT: 1 H-MRS data were quantified using LCModel software. TERTp and IDH1 or IDH2 (IDH1/2) mutations in the tissue were determined by either minisequencing or Sanger sequencing. STATISTICAL TESTS: Metabolic differences between IDH mutant and IDH wildtype gliomas were assessed by a Mann-Whitney U-test. A Kruskal-Wallis test followed by a Tukey-Kramer test was used to analyze metabolic differences between IDH and TERTp mutational molecular subsets of gliomas. A Spearman rank correlation coefficient was used to assess the correlations of metabolite intensities with the Ki-67 index. Furthermore, machine learning was employed to classify the IDH and TERTp mutational status of gliomas, and the accuracy, sensitivity, and specificity values were estimated. RESULTS: Short-TE 1 H-MRS classified the presence of an IDH mutation with 88.39% accuracy, 76.92% sensitivity, and 94.52% specificity, and a TERTp mutation within primary IDH wildtype gliomas with 92.59% accuracy, 83.33% sensitivity, and 95.24% specificity. DATA CONCLUSION: Short-TE 1 H-MRS could be used to identify molecular subsets of hemispheric diffuse gliomas corresponding to IDH and TERTp mutations. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1799-1809.

Association between facet joint orientation/tropism and lumbar intervertebral disc degeneration.

Background: The aim of this study was to understand how facet joint orientation (FJO) and facet joint tropism (FJT) affected severe intervertebral disc degeneration (IVDD) process at lower lumbar levels in patients with LBP.Methods: This study is a cross-sectional analysis of a retrospective database. Patients were evaluated in terms of IVDD, FJO, and FJT at all lumbar levels on magnetic resonance imaging.Results: In this study (n: 123) facet joints were aligned more coronal in men than in women at upper lumbar levels. Men had less FJT compared to women, significantly at L2-L3 and L3-L4 levels. Severe IVDD at L4-L5 was associated with more coronal aligned L1-L2 (29.0 ± 2.5° vs. 23.3 ± 2.3°, p = 0.006) and misaligned L5-S1 (8.3 ± 1.9° vs. 4.5 ± 1.7°, p = 0.008). Besides, severe IVDD at L3-L4 was associated with more coronal aligned L4-L5 (49.1 ± 3.2° vs. 41.4 ± 2.8°, p = 0.014).Conclusion: There is a close association between FJO/FJT with lumbar IVDD. Facet joint orientation and FJT do not affect the disc at only the corresponding level; the lumbar spine should be evaluated as a whole.

Is diabetes mellitus a risk factor for modic changes?: A novel model to understand the association between intervertebral disc degeneration and end-plate changes.

OBJECTIVE: Mechanical failure and inflammatory response are two mechanisms proposed for the development of Modic changes, even though they have not been clearly demonstrated, yet. Diabetes mellitus (DM) harbors micro- and macroangiopathy due to the irreversible glycation of proteins, increased oxidative stress, and inflammation. In this study, we aimed to identify whether DM was associated with Modic changes in terms of inflammatory process. METHODS: We conducted a cross-sectional study using our prospectively collected retrospective database of patients with DM who had visited the outpatient clinics at a university hospital. In 3999 patients with DM, 266 had spinal MRI due to cervical, thoracic or low back pain. We included patients, who had lumbar spine MRIs due to low back and/or leg pain and blood draw for HbA1c simultaneously. We analyzed 48 symptomatic patients with DM. We had also symptomatic patients without DM as control group. RESULTS: Severe intervertebral disc degeneration was significantly associated with Modic changes. Severe intervertebral disc degeneration had no significant association with serum HbA1c percentage and DM duration. Patients with Modic changes at any lumbar level had significantly higher HbA1c percentages, and longer duration of DM than those without Modic changes. Symptomatic patients with DM had higher rates of Modic changes compared to symptomatic ones without DM. CONCLUSIONS: Severity and duration of DM were both closely associated with Modic changes, whereas the association of severity and duration of DM with severe intervertebral disc degeneration remained unclear.

Clinical proton MR spectroscopy in central nervous system disorders.

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

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.

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.

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.

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.

Asymptomatic remote cerebellar hemorrhage: CT and MRI findings.

The aim of this study was to evaluate the computed tomography (CT) and magnetic resonance imaging findings (MRI) of asymptomatic remote cerebellar hemorrhage (RCH) at the preoperative, early postoperative, and postoperative period. A total of 983 consecutive adult patients who underwent supratentorial craniotomies were included in the study. The ethics committee approved the study. The patient's clinical records and radiological examinations were retrospectively analyzed. All patients had preoperative CT and MRI examinations, immediate postoperative CT, and postoperative MRI within 24 h. The patients with the radiological diagnosis of RCH were followed up to 5 years. Eight asymptomatic RCH cases were recruited. The prevalence of asymptomatic RCH was 0.8% in our series. RCH was unilateral in two patients and bilateral in six patients. The postoperative CT was positive in two cases. The hemorrhage presented on MRI as folial linear hypointensities in six cases. In three cases (including one mixed case), punctate hypointense spots were identified at the superior cerebellar folia. Diffuse hemorrhage in the cerebellar tonsil, subarachnoid hemorrhage, and hemorrhage in the cerebellar vermis and the ventricles were also seen. The MRI findings were stable up to 5 years. The prevalence of asymptomatic RCH is higher than previously reported. Immediate postoperative CT is usually unremarkable; however, MRI demonstrates various hemorrhagic patterns at the cerebellum other than classical "zebra sign". This condition is self-limiting and no further investigation or follow-up study is required. In the proper clinical setting, the awareness of different hemorrhagic patterns in patients with RCH would prevent unnecessary investigations.

Gamma knife radiosurgery for jugular foramen schwannomas.

Jugular foramen schwannomas are very rare tumors. Advances in skull base surgery have led to more aggressive resection of these tumors, but surgery may associate with development of new neurological deficits. In this report, we analyze the long-term results for 17 patients with newly diagnosed or residual/recurrent jugular foramen schwannoma who underwent gamma-knife treatment. During a mean 64 months of follow-up, magnetic resonance imaging revealed reduced tumor size in 13 cases and no size change in four cases. The tumor growth control rate was 100% and only one patient had transient hoarseness. For patients who have small- to moderate-sized jugular foramen schwannomas, gamma-knife radiosurgery is associated with good tumor control and carries minimal risk of adverse radiation effects.

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.

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.

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.