More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

Endoscopic and exoscopic surgery for brain tumors.

Nerves and blood vessels must be protected during brain tumor surgery, which has traditionally relied on microscopes. In the 2000s, endoscopes and related equipment were developed for neurosurgery. In this review, we aim to outline the role of endoscopes in brain tumor surgery and discuss the emerging use of exoscopes. The primary use of endoscopes in brain tumor surgery is in endoscopic endonasal surgery for pituitary tumors. By using the space within the sphenoid sinus, surgeons can insert an endoscope and instruments such as forceps or scissors through the nose to access and remove the tumor. Compared to microscopes, endoscopes can get closer to tumors, nerves, and blood vessels. They enable wide-angle observation of the skull base, making them valuable for skull base tumors as well as pituitary tumors. Endoscopes are also used in cases where a brain tumor is associated with hydrocephalus, allowing surgeons to correct obstructive hydrocephalus and perform tumor biopsies simultaneously. Exoscopy, a newer technique introduced in recent years, involves surgeons wearing special glasses and removing the tumor while viewing a three-dimensional monitor. This approach reduces surgeon fatigue and allows for more natural positioning during lengthy brain tumor surgeries. Future brain tumor surgeries will likely involve robotic surgery, which is already used for other organs. This is expected to make brain tumor removal safer and more accurate.

Inferior temporal quadrantanopia associated with pituitary adenomas and a potential mechanism of excessive optic nerve bending.

Background: Pituitary adenomas show typical visual field defects that begin superiorly and progress inferiorly. The cause of atypical visual field defects that start inferiorly remains unclear. This study aimed to understand this phenomenon using magnetic resonance imaging (MRI). Methods: A total of 220 patients with pituitary adenomas underwent a visual field assessment of both eyes. Preoperative visual fields were assessed and classified into two types: superior quadrantanopia (typical) and inferior quadrantanopia (atypical). Several parameters related to tumor characteristics and optic nerve compression were evaluated using MRI. Results: Of the 440 eyes examined, 174 (39.5%) had visual field defects. Of these, 28 (16.1%) had typical and 11 (6.3%) had atypical visual field defects. Patient age, tumor size, degree of cavernous sinus invasion, tumor pathology, and intratumor bleeding were similar between the two groups. The angle formed by the optic nerve in the optic canal and in the intracranial subarachnoid space at the exit of the optic canal (degree of optic nerve bending) was significantly larger in the atypical group than in the typical group (42.6° vs. 23.9°, P = 0.046). Conclusion: In some pituitary adenomas, visual field defects begin inferiorly. This may be caused by optic nerve compression on the superior surface by the bony margin of the optic canal exit. Therefore, pituitary adenomas should be considered in patients with atypical visual field defects.

Determination of Significant Three-Dimensional Hemodynamic Features for Postembolization Recanalization in Cerebral Aneurysms Through Explainable Artificial Intelligence.

BACKGROUND: Recanalization poses challenges after coil embolization in cerebral aneurysms. Establishing predictive models for postembolization recanalization is important for clinical decision making. However, conventional statistical and machine learning (ML) models may overlook critical parameters during the initial selection process. METHODS: In this study, we automated the identification of significant hemodynamic parameters using a PointNet-based deep neural network (DNN), leveraging their three-dimensional spatial features. Further feature analysis was conducted using saliency mapping, an explainable artificial intelligence (XAI) technique. The study encompassed the analysis of velocity, pressure, and wall shear stress in both precoiling and postcoiling models derived from computational fluid dynamics simulations for 58 aneurysms. RESULTS: Velocity was identified as the most pivotal parameter, supported by the lowest P value from statistical analysis and the highest area under the receiver operating characteristic curves/precision-recall curves values from the DNN model. Moreover, visual XAI analysis showed that robust injection flow zones, with notable impingement points in precoiling models, as well as pronounced interplay between flow dynamics and the coiling plane, were important three-dimensional features in identifying the recanalized aneurysms. CONCLUSIONS: The combination of DNN and XAI was found to be an accurate and explainable approach not only at predicting postembolization recanalization but also at discovering unknown features in the future.

Characterization of Maximum Wall Shear Stress Points in Unruptured Cerebral Aneurysms Using Four-dimensional Flow Magnetic Resonance Imaging.

BACKGROUND: Maximum wall shear stress (maxWSS) points of unruptured cerebral aneurysms (UCAs) may cause wall remodeling leading to rupture. We characterized maxWSS points and their inherent intra-aneurysmal flow structures in a sizable cohort of saccular UCAs using four-dimensional (4D) flow magnetic resonance imaging (MRI). METHODS: After contrast administration, 50 saccular UCAs were subjected to 4D flow MRI using a 1.5 T MRI scanner. Post-processing of obtained data was performed using commercially available software. The maxWSS points and maxWSS values were evaluated. The maxWSS values were statistically compared between aneurysm groups. RESULTS: The maxWSS point was located on the aneurysm apex in 9 (18.0%), body in 2 (4.0%), and neck in 39 (78.0%) UCAs. The inherent intra-aneurysmal flow structure of the maxWSS point was an inflow zone in 34 (68.0%) UCAs, an inflow jet in 8 (16.0%), and an impingement zone in 8 (16.0%). The maxWSS point on the neck had significantly higher maxWSS values than those points on the other wall areas (P = 0.008). The maxWSS values of the maxWSS points on the apex and on the impingement zone were not significantly different compared with those of the other maxWSS points. CONCLUSION: The maxWSS points existed preferentially on the aneurysmal neck adjacent to the inflow zone with higher maxWSS values. The maxWSS points existed occasionally on the aneurysmal apex adjacent to the impingement zone. 4D flow MRI may be helpful to discriminate saccular UCAs with higher-risk maxWSS points that can cause wall remodeling leading to rupture.

Correction: Recurrence pattern predicts aneurysm rupture after coil embolization.

[This corrects the article DOI: 10.1371/journal.pone.0261996.].

Fluid dynamic analysis in predicting the recanalization of intracranial aneurysms after coil embolization - A study of spatiotemporal characteristics.

Purpose: Hemodynamics play a key role in the management of cerebral aneurysm recanalization after coil embolization; however, the most reliable hemodynamic parameter remains unknown. Previous studies have explored the use of both spatiotemporally averaged and maximal definitions for hemodynamic parameters, based on computational fluid dynamics (CFD) analysis, to build predictive models for aneurysmal recanalization. In this study, we aimed to assess the influence of different spatiotemporal characteristics of hemodynamic parameters on predictive performance. Methods: Hemodynamics were simulated using CFD for 66 cerebral aneurysms from 65 patients. We evaluated 14 types of spatiotemporal definitions for two hemodynamic parameters in the pre-coiling model and five in virtual post-coiling model (VM) created by cutting the aneurysm from the pre-coiling model. A total of 91 spatiotemporal hemodynamic features were derived and utilized to develop univariate predictor (UP) and multivariate logistic regression (LR) models. The model's performance was assessed using two metrics: the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Results: Different spatiotemporal hemodynamic features exhibited a wide range of AUROC values ranging from 0.224 to 0.747, with 22 feature pairs showing a significant difference in AUROC value (P-value <0.05), despite being derived from the same hemodynamic parameter. PDave,q1 was identified as the strongest UP with AUROC/AUPRC values of 0.747/0.385, yielding sensitivity and specificity value of 0.889 and 0.614 at the optimal cut-off value, respectively. The LR model further improved the prediction performance, having AUROC/AUPRC values of 0.890/0.903. At the optimal cut-off value, the LR model achieved a specificity of 0.877, sensitivity of 0.719, outperforming the UP model. Conclusion: Our research indicated that the characteristics of hemodynamic parameters in terms of space and time had a significant impact on the development of predictive model. Our findings suggest that LR model based on spatiotemporal hemodynamic features could be clinically useful in predicting recanalization after coil embolization in patients, without the need for invasive procedures.

Systemic Candida abscess after hypofractionated radiotherapy with temozolomide for glioblastoma in an older patient: illustrative case.

BACKGROUND: Hypofractionated radiotherapy with temozolomide is recommended for older patients with glioblastoma. Nevertheless, a potential complication of treatment is opportunistic infections with immunosuppression. OBSERVATIONS: An 86-year-old man presented with hemiparesis, prompting an investigation that revealed a right frontotemporal glioblastoma, isocitrate dehydrogenase wildtype. After the diagnostic biopsy, hypofractionated radiotherapy with temozolomide was administered. Lymphocytopenia was observed before the start of chemoradiotherapy and gradually worsened until 2 months later, possibly as a side effect of the treatment. One month after the completion of the initial treatment, the patient developed septic shock, leading to death within 2 days. Postmortem examination with autopsy revealed evidence of an invasive Candida infection possibly originating from the urinary catheter. LESSONS: Immunodeficiency, which is a side effect of radiation therapy with temozolomide, can cause rare and potentially fatal invasive Candida infections, especially in older and frail patients with newly diagnosed glioblastoma, even with short-term hypofractionated chemoradiotherapy. https://thejns.org/doi/10.3171/CASE24175.

Urinary D-asparagine level is decreased by the presence of glioblastoma.

Gliomas, particularly glioblastomas (GBMs), pose significant challenges due to their aggressiveness and poor prognosis. Early detection through biomarkers is critical for improving outcomes. This study aimed to identify novel biomarkers for gliomas, particularly GBMs, using chiral amino acid profiling. We used chiral amino acid analysis to measure amino acid L- and D-isomer levels in resected tissues (tumor and non-tumor), blood, and urine from 33 patients with primary gliomas and 24 healthy volunteers. The levels of D-amino acid oxidase (DAO), a D-amino acid-degrading enzyme, were evaluated to investigate the D-amino acid metabolism in brain tissue. The GBM mouse model was created by transplanting GBM cells into the brain to confirm whether gliomas affect blood and urine chiral amino acid profiles. We also assessed whether D-amino acids produced by GBM cells are involved in cell proliferation. D-asparagine (D-Asn) levels were higher and DAO expression was lower in glioma than in non-glioma tissues. Blood and urinary D-Asn levels were lower in patients with GBM than in healthy volunteers (p < 0.001), increasing after GBM removal (p < 0.05). Urinary D-Asn levels differentiated between healthy volunteers and patients with GBM (area under the curve: 0.93, sensitivity: 0.88, specificity: 0.92). GBM mouse model validated the decrease of urinary D-Asn in GBM. GBM cells used D-Asn for cell proliferation. Gliomas induce alterations in chiral amino acid profiles, affecting blood and urine levels. Urinary D-Asn emerges as a promising diagnostic biomarker for gliomas, reflecting tumor presence and severity.

Recurrence of an extracranial internal carotid artery aneurysm treated with STA-MCA bypass and trapping due to neovascularization from an ascending pharyngeal artery: illustrative case.

BACKGROUND: Extracranial internal carotid artery aneurysms (EICAs) are rare. Although a high mortality risk has been reported in nonoperated cases, the optimal treatment for EICAs remains unknown. OBSERVATIONS: A 79-year-old female presented with painless swelling in the right neck. Imaging revealed a giant EICA with a maximum diameter of 3.2 cm. Superficial temporal artery-middle cerebral artery bypass and internal carotid artery (ICA) trapping were performed. Because the distal aneurysm edge was at the C1 level, the distal portion of the aneurysm was occluded by endovascular coiling, and the proximal portion was surgically ligated. Blood flow into the aneurysm disappeared after the operation. Three years postsurgery, enlargement of the aneurysm with blood flow from the ascending pharyngeal artery (APA) was detected. The EICA was resected after coiling the APA and ligating both ends of the aneurysm. Pathologically, neovascularization within the aneurysm wall was observed. LESSONS: Even if blood flow into an EICA disappears after ICA trapping, the EICAs can enlarge due to neovascularization from the neighboring artery. From the outset, removal of the aneurysm should be considered as a radical treatment strategy for giant EICAs.

Comprehensive genomic analysis reveals clonal origin and subtype-specific evolution in a case of sporadic multiple meningiomas.

Meningioma is the most common primary intracranial tumor in adults, with up to 10% manifesting as multiple tumors. Data on the genomic and molecular changes in sporadic multiple meningiomas are scarce, leading to ongoing debates regarding their evolutionary processes. A comprehensive genetic analysis of a large number of lesions, including precursor lesions, is necessary to explore these two possible origins: clonal and independent. In the present study, we performed whole-exome sequencing and analyzed somatic single-nucleotide variants (SNVs), insertions/deletions (INDELs), and copy number alterations (CNAs) in a patient with sporadic multiple meningiomas. These meningiomas included two mass-forming lesions of different histological subtypes (transitional and chordoid) and two small meningothelial nests. Genetic analysis revealed CNAs on chromosomes 22q and Y as common abnormalities in the two largest tumors. Furthermore, we identified SNV/INDELs unique to each focus, with NF2 mutation prevalent in the transitional meningioma and CREBBP mutation in the chordoid meningioma. Loss of chromosome 22 was detected in two small meningothelial nests. Overall, we elucidated the clonal origin and subtype-specific evolution of multiple meningiomas in this case. CNAs may serve as the initial driving event in meningioma development.

Astrocyte-induced mGluR1 activates human lung cancer brain metastasis via glutamate-dependent stabilization of EGFR.

There are limited methods to stably analyze the interactions between cancer cells and glial cells in vitro, which hinders our molecular understanding. Here, we develop a simple and stable culture method of mouse glial cells, termed mixed-glial culture on/in soft substrate (MGS), which serves well as a platform to study cancer-glia interactions. Using this method, we find that human lung cancer cells become overly dependent on metabotropic glutamate receptor 1 (mGluR1) signaling in the brain microenvironment. Mechanistically, interactions with astrocytes induce mGluR1 in cancer cells through the Wnt-5a/prickle planar cell polarity protein 1 (PRICKLE1)/RE1 silencing transcription factor (REST) axis. Induced mGluR1 directly interacts with and stabilizes the epidermal growth factor receptor (EGFR) in a glutamate-dependent manner, and these cells then become responsive to mGluR1 inhibition. Our results highlight increased dependence on mGluR1 signaling as an adaptive strategy and vulnerability of human lung cancer brain metastasis.

An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy.

Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling the movement of small molecules and macromolecules between the cell nucleus and cytoplasm through their intricate core channel resembling a spiderweb with several layers. Currently, there are few methods available to accurately measure the dynamics of nuclear pores on the nuclear membranes at the nanoscale. The limitation of traditional optical imaging is due to diffraction, which prevents achieving the required resolution for observing a diverse array of organelles and proteins within cells. Super-resolution techniques have effectively addressed this constraint by enabling the observation of subcellular components on the nanoscale. Nevertheless, it is crucial to acknowledge that these methods often need the use of fixed samples. This also raises the question of how closely a static image represents the real intracellular dynamic system. High-speed atomic force microscopy (HS-AFM) is a unique technique used in the field of dynamic structural biology, enabling the study of individual molecules in motion close to their native states. Establishing a reliable and repeatable technique for imaging mammalian tissue at the nanoscale using HS-AFM remains challenging due to inadequate sample preparation. This study presents the rapid strainer microfiltration (RSM) protocol for directly preparing high-quality nuclei from the mouse brain. Subsequently, we promptly utilize HS-AFM real-time imaging and cinematography approaches to record the spatiotemporal of nuclear pore nano-dynamics from the mouse brain.

Mentalizing can be Impaired in Patients with Meningiomas Originating in the Anterior Skull Base.

OBJECTIVE: Mentalizing is an essential function of our social lives. Impairment of mentalizing due to meningiomas has not received attention because most patients return to their social lives after surgical treatment. We investigated the influence of meningiomas and their surgical resection on mentalizing. METHODS: Low- and high-level mentalizing were retrospectively examined in 61 patients with meningiomas and 14 healthy volunteers. Mentalizing was assessed using the facial expression recognition test and picture arrangement test of the Wechsler Adult Intelligence Scale, third edition, before and after surgery. We examined the influence of tumor localization on mentalizing and recovery from mentalizing disorders after tumor resection. Voxel-based lesion-symptom mapping was performed to investigate the relationship between impairments in mentalizing and tumor location. RESULTS: Before surgery, mentalizing was impaired significantly in patients with meningiomas compared to those in the control group (low-level: P = 0.015, high-level: P = 0.011). This impairment was associated with contact between the tumor and frontal lobe (low-level: P = 0.036, high-level: P = 0.047) and was severe in patients with tumors arising in the anterior skull base (low-level: P = 0.0045, high-level: P = 0.043). Voxel-based lesion-symptom mapping revealed that when the basal cortex of the frontal lobe was compressed by the tumor, the risk of impaired mentalizing was high. The region responsible for high-level mentalizing was located deeper than that responsible for low-level mentalizing. After the surgical removal of the tumor, the test scores significantly improved (low-level: P = 0.035, high-level: P = 0.045). CONCLUSIONS: Mentalizing was impaired by meningiomas arising from the anterior skull base, but it can improve after surgical resection of the tumors.