Neuroprotective Effects of Genome-Edited Human iPS Cell-Derived Neural Stem/Progenitor Cells on Traumatic Brain Injury.

Despite developing neurosurgical procedures, few treatment options have achieved functional recovery from traumatic brain injury (TBI). Neural stem/progenitor cells (NS/PCs) may produce a long-term effect on neurological recovery. Although induced pluripotent stem cells (iPSCs) can overcome ethical and practical issues of human embryonic or fetal-derived tissues in clinical applications, the tumorigenicity of iPSC-derived populations remains an obstacle to their safe use in regenerative medicine. We herein established a novel treatment strategy for TBI using iPSCs expressing the enzyme-prodrug gene yeast cytosine deaminase-uracil phosphoribosyl transferase (yCD-UPRT). NS/PCs derived from human iPSCs displayed stable and high transgene expression of yCD-UPRT following CRISPR/Cas9-mediated genome editing. In vivo bioluminescent imaging and histopathological analysis demonstrated that NS/PCs concentrated around the damaged cortex of the TBI mouse model. During the subacute phase, performances in both beam walking test and accelerating rotarod test were significantly improved in the treatment group transplanted with genome-edited iPSC-derived NS/PCs compared with the control group. The injury area visualized by extravasation of Evans blue was smaller in the treatment group compared with the control group, suggesting the prevention of secondary brain injury. During the chronic phase, cerebral atrophy and ventricle enlargement were significantly less evident in the treatment group. Furthermore, after 5-fluorocytosine (5-FC) administration, 5-fluorouracil converted from 5-FC selectively eliminated undifferentiated NS/PCs while preserving the adjacent neuronal structures. NS/PCs expressing yCD-UPRT can be applied for safe regenerative medicine without the concern for tumorigenesis.

Bridging veins at the craniocervical junction: from anatomy to clinical significance in dural arteriovenous shunts.

PURPOSE: Bridging veins (BVs) serve as a route of pial venous reflux, and its anatomy is essential to understand the pathophysiology of dural arteriovenous shunts (dAVSs) around the craniocervical junction (CCJ) (from the jugular foramen level to the atlantal level). However, the anatomical variations of the BVs and their proximal connections remained poorly elucidated. This study aimed to radiologically investigate the anatomy of the bridging veins around CCJ and discuss the clinical significance of these BVs in the dAVS. METHODS: We investigated normal venous anatomy of the BVs from the jugular foramen level to the atlantal level using preoperative computed tomography digital subtraction venography in patients undergoing elective neurosurgery. BVs affected by the dAVSs in the same region were also evaluated. The three types of dAVS, craniocervical junction, anterior condylar, and proximal sigmoid sinus, were investigated. RESULTS: We identified six BV groups: superolateral, anterolateral, lateral, posterior, inferolateral, and inferoposterior. The superolateral and inferolateral groups, connected with the proximal sigmoid sinus and suboccipital cavernous sinus, respectively, were the largest groups. Each group has a specific downstream venous connection. The association with dVASs was observed only in the inferolateral group, which was typically the sole venous drainage in most dAVSs at the CCJ. CONCLUSION: We reported detailed anatomy of BVs from the jugular level to the atlantal level, which enhanced our understanding of the pathophysiology of dAVSs in the corresponding region.

Exploration of postural effects on the external jugular and diploic venous system using upright computed tomography scanning.

PURPOSE: Few studies have investigated the influence of posture on the external jugular and diploic venous systems in the head and cranial region. In this study, we aimed to investigate the effects of posture on these systems using upright computed tomography (CT) scanning. METHODS: This study retrospectively analysed an upright CT dataset from a previous prospective study. In each patient, the diameters of the vessels in three external jugular tributaries and four diploic veins were measured using CT digital subtraction venography in both supine and sitting positions. RESULTS: Amongst the 20 cases in the original dataset, we eventually investigated 19 cases due to motion artifacts in 1 case. Compared with the supine position, most of the external jugular tributaries collapsed, and the average size significantly decreased in the sitting position (decreased by 22-49% on average). In contrast, most of the diploic veins, except the occipital diploic veins, tended to increase or remain unchanged (increased by 12-101% on average) in size in the sitting position compared with the supine position. However, the changes in the veins associated with this positional shift were not uniform; in approximately 5-30% of the cases, depending on each vein, an opposite trend was observed. CONCLUSION: Compared to the supine position, the contribution of external jugular tributaries to head venous drainage decreased in the sitting position, whilst most diploic veins maintained their contribution. These results could enhance our understanding of the physiology and pathophysiology of the head region in upright and sitting positions.

Effect of rehabilitation on renal outcomes after acute kidney injury associated with cardiovascular disease: a retrospective analysis.

BACKGROUND: Acute kidney injury (AKI) incidence is extremely high worldwide, and patients who develop AKI are at increased risk of developing chronic kidney disease (CKD), CKD progression, and end-stage kidney disease (ESKD). However, there is no established treatment strategy for AKI. Based on the idea that exercise has a stabilizing effect on hemodynamics, we hypothesized that rehabilitation would have beneficial renal outcomes in patients with AKI associated with cardiovascular disease. Therefore, the purpose of this study was to determine whether rehabilitation can stabilize hemodynamics and positively impact renal outcomes in patients with AKI associated with cardiovascular disease. METHODS: In total, 107 patients with AKI associated with cardiovascular disease were enrolled in this single-center retrospective study and were either assigned to the exposure group (n = 36), which received rehabilitation at least once a week for at least 8 consecutive weeks, or to the control group (n = 71). Estimated glomerular filtration rate was assessed at baseline before admission, at the lowest value during hospitalization, and at 3, 12, and 24 months after enrolment. Trends over time (group × time) between the two groups were compared using generalized estimating equations. Moreover, congestive status was assessed by amino-terminal pro-B-type natriuretic peptide (NT-proBNP), and the effect of rehabilitation on congestion improvement was investigated using logistical regression analysis. RESULTS: The time course of renal function after AKI, from baseline to each of the three timepoints suggested significant differences between the two groups (p < 0.01). However, there was no significant difference between the two groups at any time point in terms of percentage of patients who experienced a 40% estimated glomerular filtration rate reduction from that at baseline. The proportion of patients with improved congestion was significantly higher in the exposure group compared with that in the control group (p = 0.018). Logistic regression analysis showed that rehabilitation was significantly associated with improved congestion (p = 0.021, OR: 0.260, 95%CI: 0.083-0.815). CONCLUSION: Our results suggest that rehabilitation in patients with AKI associated with cardiovascular disease correlates with an improvement in congestion and may have a positive effect on the course of renal function.

Usefulness of STA ultrasonography parameters after STA-MCA bypass in patients with moyamoya disease: A short review.

STA bypass assessment by ultrasonography after bypass surgery in patients with moyamoya disease is minimally invasive and can be performed repeatedly. With STA bypass assessment by ultrasonography, it was shown that in the short term, blood flow that passes through the STA peaks approximately 5 days after the bypass surgery and then gradually decreases over 7 days. In the medium and long terms, it has been shown that the blood flow through the bypass decreases, compared with that during the first postoperative week, and continues for approximately half a year. The ultrasonographic STA parameters can also clearly indicate bypass patency, but there remains some discussion regarding bypass function. Although some reports have tried to show that these parameters are also useful for predicting acute-phase TNEs and predicting the future of bypass function, no studies have yet examined these parameters in detail in relation to the state of cerebral circulation or degree of residual antegrade flow, and additional studies are needed in the future.

Natural history of hearing and tumor growth in vestibular schwannoma in neurofibromatosis type 2-related schwannomatosis.

OBJECTIVES: To determine the natural history of hearing loss and tumor volume in patients with untreated neurofibromatosis type 2 (NF2)-related schwannomatosis. Moreover, we statistically examined the factors affecting hearing prognosis. METHODS: This retrospective cohort study was conducted on 37 ears of 24 patients with NF2-related vestibular schwannomatosis followed up without treatment for more than 1 year. We obtained detailed chronological changes in the PTA and tumor volume in each case over time, and the rate of change per year was obtained. Multivariate analysis was also conducted to investigate factors associated with changes in hearing. RESULTS: The average follow-up period was approximately 9 years, and hearing deteriorated at an average rate of approximately 4 dB/year. The rate of maintaining effective hearing decreased from 30 ears (81%) at the first visit to 19 ears (51%) at the final follow-up. The average rate of change in tumor growth for volume was approximately 686.0 mm3/year. This study revealed that most patients with NF2 experienced deterioration in hearing acuity and tumor growth during the natural course. A correlation was observed between an increase in tumor volume and hearing loss (r = 0.686; p < 0.001). CONCLUSIONS: Although the hearing preservation rate in NF2 cases is poor with the current treatment methods, many cases exist in which hearing acuity deteriorates, even during the natural course. Patients with an increased tumor volume during the follow-up period were more likely to experience hearing deterioration. Trial registration number 20140242 (date of registration: 27 October 2014).

The Long-Term Natural History of Fibrous Dysplasia.

Fibrous dysplasia (FD), a developmental, nonfamilial, benign anomaly of bone development, is characterized by the replacement of normal bone by proliferating fibro-osseous tissue. Marked craniofacial deformities, functional disturbances, and emotional stress are major indications for treatment, and various surgical procedures have been performed; however, excision and regrowth issues have also been reported. While several treatment options are available, no studies have reported the natural history of untreated FD. Here, we report 2 patients, aged 73 and 50 years, respectively, who had not received treatment. Both patients presented to the hospital complaining of noise when moving their heads. Computed tomography scans showed niveau with honeycomb cavities in both patients, indicating abscess formation, and resection was performed. Relatively large cranial FD leads to the development of central necrosis over time. In such cases, surgical intervention should be performed at an early disease stage.

Aneurysmal subarachnoid hemorrhage occurring during sleep: Clinical characteristics and risk factors.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is known to be triggered by several specific human activities. Sleep, by contrast, has not been considered a triggering activity for aSAH, and clinical characteristics of patients who sustain aSAH during sleep have rarely been reported in the literature. METHODS: This is a retrospective analysis on the data acquired through a multicenter aSAH registry. Between January 2019 and December 2021, a total of 732 aSAH patients had been registered into our database. After excluding 109 patients whose activities at aSAH onset had been unidentifiable, the remaining 623 aSAH patients were dichotomized to 59 patients who sustained aSAH during sleep (Sleep group) and 564 patients who sustained aSAH during daytime activities (Awake group). Two-group comparison of demographic variables and multivariate logistic regression analysis were performed to clarify their clinical characteristics and identify potential risk factors. RESULTS: The Sleep group exhibited significantly higher frequencies of diabetes (15.5 % vs. 6.4 %, p = 0.01) and antiplatelet use (13.8 % vs. 4.6 %, p=0.004) than the Awake group. Furthermore, multivariate logistic regression analysis showed that diabetes (OR, 3.051; 95 % CI, 1.281-7.268; p = 0.012) and antiplatelet use (OR, 3.640; 95 % CI, 1.422-9.316; p = 0.007) were correlated with aSAH occurring during sleep. There were no significant inter-group differences in the patient outcomes evaluated at discharge. CONCLUSION: The current results indicate that risk factors may exist for aSAH occurring during sleep. Further investigations on how comorbidities such as diabetes, antiplatelet use and sleep apnea affect human hemodynamic and hemostatic parameters during sleep is warranted to better understand those relationships.

"Missing-piece" sign with dural arteriovenous fistula at craniocervical junction: A case report.

OBJECTIVES: Spinal dural arteriovenous fistula (sDAVF) is a rare and often underdiagnosed spinal disease. Early diagnosis is required because the deficits are reversible and delays in treatment cause permanent morbidity. Although the abnormal vascular flow void is a critical radiographic feature of sDAVF, they are not always present. A characteristic enhancement pattern of sDAVF has been recently reported as the "missing-piece" sign which can lead to the early and correct diagnosis. METHODS: We presented imaging findings, treatment decisions, and the outcome of a rare case of sDAVF, in which the "missing-piece" sign appeared atypical. RESULTS: A 60-year-old woman developed numbness and weakness in her extremities. Spinal MRI revealed longitudinal hyperintensity in the T2-weighted image, extending from the thoracic level to medulla oblongata. At first, myelopathy with inflammation or tumor was suspected because of the lack of flow voids and vascular abnormalities in CT-angiography and MR-DSA. However, we administered intravenous methylprednisolone and her symptom got worse with the appearance of the "missing-piece" sign. Then, we successfully diagnosed sDAVF by angiography. The "missing-piece" sign was considered to derive from inconsistency of the intrinsic venous system of spinal cord, with the abrupt segments without enhancement. The same etiology was considered in our case. CONCLUSIONS: Detecting the "missing-piece" sign can lead to the correct diagnosis of sDAVF, even if the sign appeared atypical.

Role of endovascular treatment for ruptured aneurysms involving the anterior spinal artery at the craniocervical junction.

Ruptured aneurysms at the craniocervical junction (CCJ) involving the anterior spinal artery (ASA) are rare and consist of heterogenous lesions with variable clinical entities. However, the standard therapeutic strategy for the lesions has not been well-established. Moreover, despite advances in modern neurointervention, reports describing endovascular treatment for this specific lesion have been few. Here, we report three cases of ruptured aneurysms on the pial tributary of the ASA at the CCJ, which were subsequently treated by transarterial glue injection or coil embolization. Endovascular treatment can be a therapeutic option, particularly for these ruptured aneurysms. Either transarterial glue injection or coil embolization can be effective depending on the type of etiology and the surrounding vasculature anatomy.

[Molecular Mechanisms of Pituitary Tumorigenesis].

Scientific advances have improved our understanding of the molecular pathological mechanisms underlying pituitary tumorigenesis, allowing us to analyze tumors in a more precise manner and to identify the tumors that have a greater risk of aggressive behavior at an earlier stage. Based on these molecular pathological findings, the classification of pituitary tumors has been revised over the last two decades to better describe their biological and clinical behavior and to identify prognostic markers of aggressiveness and poor prognosis. Understanding pituitary tumors at the molecular level has enabled increasingly targeted treatments with safety and efficacy validated in randomized trials. This paper reviews recent advances in the study of pituitary tumors, particularly pituitary endocrine tumors, and craniopharyngiomas, and describes potential therapies for pituitary tumors.

TPT1 Supports Proliferation of Neural Stem/Progenitor Cells and Brain Tumor Initiating Cells Regulated by Macrophage Migration Inhibitory Factor (MIF).

One of the key areas in stem cell research is the identification of factors capable of promoting the expansion of Neural Stem Cell/Progenitor Cells (NSPCs) and understanding their molecular mechanisms for future use in clinical settings. We previously identified Macrophage Migration Inhibitory Factor (MIF) as a novel factor that can support the proliferation and/or survival of NSPCs based on in vitro functional cloning strategy and revealed that MIF can support the proliferation of human brain tumor-initiating cells (BTICs). However, the detailed downstream signaling for the functions has largely remained unknown. Thus, in the present study, we newly identified translationally-controlled tumor protein-1 (TPT1), which is expressed in the ventricular zone of mouse embryonic brain, as a downstream target of MIF signaling in mouse and human NSPCs and human BTICs. Using gene manipulation (over or downregulation of TPT1) techniques including CRISPR/Cas9-mediated heterozygous gene disruption showed that TPT1 contributed to the regulation of cell proliferation/survival in mouse NSPCs, human embryonic stem cell (hESC) derived-NSPCs, human-induced pluripotent stem cells (hiPSCs) derived-NSPCs and BTICs. Furthermore, gene silencing of TPT1 caused defects in neuronal differentiation in the NSPCs in vitro. We also identified the MIF-CHD7-TPT1-SMO signaling axis in regulating hESC-NSPCs and BTICs proliferation. Intriguingly, TPT1suppressed the miR-338 gene, which targets SMO in hESC-NSPCs and BTICs. Finally, mice with implanted BTICs infected with lentivirus-TPT1 shRNA showed a longer overall survival than control. These results also open up new avenues for the development of glioma therapies based on the TPT1 signaling pathway.

Extracranial prevertebral venous network of the craniocervical junction: CT-digital subtraction venography analysis.

PURPOSE: Although the craniocervical junction has a complex anatomical structure associated with clinical diseases, its ventral venous network has not been well studied. This study aimed to clarify the extracranial ventral venous structure at the craniocervical junction. METHODS: Head computed tomography digital subtraction venography (CT-DSV) images of 273 patients (age 6 months to 93 years) taken at our department were retrospectively analyzed. We analyzed the frequency and anatomical features of the venous channels, as well as their upstream and downstream connections with the surrounding channels at the ventral craniocervical junction, from the level of the hypoglossal canal to the second cervical vertebra. RESULTS: In 54% of the cases, the vein descended from the anterior condylar confluence, running medially along the basioccipital and fusing with its counterpart in the midline at the level of the atlanto-occipital membrane. Furthermore, 24% of this vein was connected caudally to the anterior external vertebral venous plexus. We also identified venous channels, either as a sole vein or venous plexus, on the tip of the odontoid process (10%), which has not been well described previously. The vein around the odontoid process was connected to several veins, including the aforementioned vein anterior to the condyle and the anterior internal vertebral venous plexus. CONCLUSIONS: CT-DSV analysis revealed a detailed venous architecture ventral to the craniocervical junction. Venous structures identified in this study may be involved in diseases in this area.

Imaging of the venous plexus of Rektorzik using CT-digital subtraction venography: a retrospective study.

PURPOSE: The venous plexus of Rektorzik (VPR), first described by Rektorzik in 1858, is a venous plexus around the internal carotid artery in the carotid canal. However, the VPR has never been investigated using the recently developed imaging modalities. In this study, we analyzed the VPR using computed tomography-digital subtraction venography (CT-DSV). METHODS: This study included 253 patients who had undergone head CT-DSV. The presence or absence of the right and left VPRs and their connecting veins were visually examined by two researchers. RESULTS: The VPR was observed in 60 patients (24%), 39 of which showed VPR only on the right side, 10 only on the left side, and 11 on both sides. VPR was significantly more common on the right side (p = 0.0002) and was observed more frequently around the horizontal segment of the internal carotid artery than around the vertical segment. The most common veins identified as distal and proximal VPR connections were the cavernous sinus (63/71, 89%) and the anterior condylar confluence (27/71, 38%), respectively. The mean age was significantly lower in patients with the VPR than in those without (53 vs. 57 years, p = 0.02). CONCLUSION: The VPR was significantly more frequent on the right side and in younger patients but was not a radiographically constant structure. In most cases, the VPR connected the cavernous sinus and anterior condylar confluence. Preoperative evaluation of VPR may lead to refined surgical procedures.

Discharge disposition and 1-year readmission in acute-phase hospitalized patients with heart failure: a retrospective observational multi-center study.

Patients hospitalized for acute heart failure (HF) tend to experience declines in physical function and activities of daily living (ADL) due to bed rest and restricted mobilization. This could result in some patients being transferred to rehabilitation hospitals. This study aims to examine the relationship between discharge disposition and 1-year readmission and mortality rates in HF patients. Nine hundred fifty six consecutive HF patients who were hospitalized for acute decompensated HF and underwent rehabilitation were divided into two groups: home (returned home) or transfer (transferred to rehabilitative or long-term care hospital units due to decline in physical function and/or ADL) groups. The primary and secondary outcomes were 1-year readmission and mortality rates after discharge, respectively. Of the 956 patients, 8.6% (n = 82) were transferred to rehabilitative or long-term care hospital units. Over a 1-year follow-up period, all-cause and HF readmission rates were 50.1% (n = 479) and 27.2% (n = 260), respectively. The transfer group had significantly lower readmission rates compared to home group after adjusting for the pre-existing risk factors (hazard ratio for all-cause and HF readmission: 0.600 and 0.552, 95% CI 0.401-0.897 and 0.314-0.969; P = 0.013 and P = 0.038, respectively). There was no significant relationship between discharge disposition and all-cause mortality rate. Low ADL defined as Barthel index < 60 points was identified as a predictor of all-cause and HF readmission among the home group (odds ratio for all-cause and HF readmission rates: 2.156 and 1.847, 95% CI 1.026-4.531 and 1.036-2.931; P = 0.043 and P = 0.037, respectively). This multi-center study demonstrated that HF patients transferred to rehabilitative or long-term care hospital units after an acute hospitalization had a significantly decreased 1-year all-cause and HF readmission rates compared to patients who returned to their home. These findings may help in selecting a discharge disposition for older HF patients with ADL decline.

Application of Deep Learning Techniques for Automated Diagnosis of Non-Syndromic Craniosynostosis Using Skull.

ABSTRACT: Non-syndromic craniosynostosis (NSCS) is a disease, in which a single cranial bone suture is prematurely fused. The early intervention of the disease is associated with a favorable outcome at a later age, so appropriate screening of NSCS is essential for its clinical management. The present study aims to develop a classification and detection system of NSCS using skull X-ray images and a convolutional neural network (CNN) deep learning framework. A total of 56 NSCS cases (scaphocephaly [ n = 17], trigonocephaly [n = 28], anterior plagiocephaly [n = 8], and posterior plagiocephaly [n = 3]) and 25 healthy control infants were included in the study. All the cases underwent skull X-rays and computed tomography scan for diagnosis in our institution. The lateral views obtained from the patients were retrospectively examined using a CNN framework. Our CNN model classified the 4 NSCS types and control with high accuracy (100%). All the cases were correctly classified. The proposed CNN model may offer a safe and high-sensitivity screening of NSCS and facilitate early diagnosis of the disease and better neurocognitive outcome for patients.

Endoscopic Endonasal Reconstruction Using a Pedicled Middle Turbinate Flap for Spontaneous Cerebrospinal Fluid Rhinorrhea.

ABSTRACT: Although endoscopic skull-base reconstruction protocols to reduce cerebrospinal fluid (CSF) leakage are reported, the most effective management strategies have not been determined. We describe the successful repair of a spontaneous CSF leak using a vascularized middle turbinate flap (MTF) via an endonasal endoscopic approach and also discuss the effective reconstruction with other available pedicled flaps. An 11-year-old girl had a 5-month history of intermittent CSF rhinorrhea. Endoscopic endonasal skull base reconstruction was performed using the pedicled MTF technique, which sufficiently covered the unilateral cribriform plate and ethmoidal fovea including suspicious leakage site. Middle turbinate flaps may be good for repairing spontaneous CSF leaks, which commonly have small, low-flow CSF fistulas around a cribriform plate. As spontaneous CSF leaks are known to have a higher recurrence rate, MTF may be advantageous because more of the normal structures are retained.

A Critical Overview of Targeted Therapies for Vestibular Schwannoma.

Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.

[Schwannoma:Update on Molecular Profiling and Therapeutic Advances].

Schwannoma is a tumor that develops from the Schwann cells in the peripheral nervous system or cranial nerves. Gamma Knife radiosurgery has become an accepted treatment for schwannoma, with a high rate of tumor control. For sporadic or neurofibromatosis type 2-associated schwannoma resistant to radiotherapy, vascular endothelial growth factor(VEGF)-A/VEGF receptor(VEGFR)-targeted therapy(e.g., bevacizumab)may become the first-line therapy. However, some aspects of treatment with bevacizumab are problematic, such as the need for frequent parenteral administration, side effects, apparent drug resistance, and rebound tumor progression after cessation. In these situations, the gene product of the SH3PXD2A-HTRA1 fusion and several protein tyrosine kinase inhibitors may be supportive in preventing tumor progression because merlin inhibits signaling by tyrosine receptor kinases and there is activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Although the tumor-microenvironment(TME)plays a key role in tumor growth, this physiological state is unclear in schwannoma. Tumor-associated macrophages may be a major component of the immunosuppressive cells in the TME of schwannoma. To impede tumor growth, the TME is also explored as a potential therapeutic target. Multimodal therapy is required to manage patients with refractory schwannoma. Furthermore, basic scientific research may be essential in achieving a novel treatment strategy.

Angio-anatomical study of the pterygovaginal artery based on cone-beam computed tomography.

PURPOSE: To investigate the anatomical characteristics and clinical implications of the pterygovaginal artery (PtVA), a recurrent branch from the distal internal maxillary artery (IMA), which courses through the pterygovaginal canal that connects the pterygopalatine fossa and nasopharynx. METHODS: Eighty-two patients with 90 sides of cone-beam computed tomography (CBCT) reconstructed from rotational angiography of the external or common carotid artery with a field of view covering the pterygopalatine fossa were retrospectively reviewed. The origin from the IMA, branching type, distribution, and anastomoses was evaluated. The underlying lesions were 36 hypervascular lesions with possible supply from PtVA (17 cavernous sinus arteriovenous fistulas (AVFs), 6 anterior condylar AVFs, and 13 nasopharyngeal, parasellar, or paraclival tumors) and 46 other diseases. RESULTS: PtVA was identified in 75 sides (83%). It originated from the pterygopalatine segment of the IMA in 45 sides (60%) and from the pterygoid segment in 30 sides (40%). It arose independently (77%), sharing the common trunk with the Vidian artery (15%) or with other branches. It ran posteromedially through the pterygovaginal canal to supply the mucosa over the nasopharyngeal roof, the choanae, and the pharyngeal ostium of the eustachian tube. It anastomosed with the ascending pharyngeal artery (n=37), the accessory meningeal artery (n=7), and the mandibular artery from the petrous internal carotid artery (n=2). It served as a feeder of osseous AVFs and skull base tumors. CONCLUSION: PtVA was often identified by CBCT even in normal anatomy. Its detailed angio-anatomy could be evaluated in the presence of parasellar or paraclival hypervascular lesions.