A novel theory for rapid localization of the transverse-sigmoid sinus junction and "keyhole" in the retrosigmoid keyhole approach: micro-anatomical study, technique nuances, and clinical application.

To determine a rapid and accurate method for locating the keypoint and "keyhole" in the suboccipital retrosigmoid keyhole approach. (1) Twelve adult skull specimens were selected to locate the anatomical landmarks on the external surface of the skull.The line between the infraorbital margin and superior margin of the external acoustic meatus was named the baseline. A coordinate system was established using the baseline and its perpendicular line through the top point of diagastric groove.The perpendicular distance (x), and the horizontal distance (y) between the central point of the "keyhole" and the top point of the digastric groove in that coordinate system were measured. The method was applied to fresh cadaveric specimens and 53 clinical cases to evaluate its application value. (1) x and y were 14.20 ± 2.63 mm and 6.54 ± 1.83 mm, respectively (left) and 14.95 ± 2.53 mm and 6.65 ± 1.61 mm, respectively (right). There was no significant difference between the left and right sides of the skull (P > 0.05). (2) The operative area was satisfactorily exposed in the fresh cadaveric specimens, and no venous sinus injury was observed. (3) In clinical practice, drilling did not cause injury to venous sinuses, the mean diameter of the bone windows was 2.0-2.5 cm, the mean craniotomy time was 26.01 ± 3.46 min, and the transverse and sigmoid sinuses of 47 patients were well-exposed. We propose a "one point, two lines, and two distances" for "keyhole" localization theory, that is we use the baseline between the infraorbital margin and superior margin of the external acoustic meatus and the perpendicular line to the baseline through the top point of the digastric groove to establish a coordinate system. And the drilling point was 14.0 mm above and 6.5 mm behind the top point of the digastric groove in the coordinate system.

Research progress of hydrogels as delivery systems and scaffolds in the treatment of secondary spinal cord injury.

Secondary spinal cord injury (SSCI) is the second stage of spinal cord injury (SCI) and involves vasculature derangement, immune response, inflammatory response, and glial scar formation. Bioactive additives, such as drugs and cells, have been widely used to inhibit the progression of secondary spinal cord injury. However, the delivery and long-term retention of these additives remain a problem to be solved. In recent years, hydrogels have attracted much attention as a popular delivery system for loading cells and drugs for secondary spinal cord injury therapy. After implantation into the site of spinal cord injury, hydrogels can deliver bioactive additives in situ and induce the unidirectional growth of nerve cells as scaffolds. In addition, physical and chemical methods can endow hydrogels with new functions. In this review, we summarize the current state of various hydrogel delivery systems for secondary spinal cord injury treatment. Moreover, functional modifications of these hydrogels for better therapeutic effects are also discussed to provide a comprehensive insight into the application of hydrogels in the treatment of secondary spinal cord injury.

Combination of Preoperative Multimodal Image Fusion and Intraoperative Dyna CT in Percutaneous Balloon Compression of Trigeminal Ganglion for Primary Trigeminal Neuralgia: Experience in 24 Patients.

Objective: We retrospectively assessed the surgical results of PBC with preoperative multimodal image fusion and intraoperative Dyna Computed Tomography (CT) in 24 patients with primary trigeminal neuralgia (PTN) to explore a valuable aid for Percutaneous balloon compression (PBC). Methods: We studied the data of 24 patients with PTN. All patients underwent PBC and were assessed with preoperative multimodal image fusion [computed tomography (CT) and magnetic resonance imaging (MRI)] and intraoperative Dyna CT in the Department of Neurosurgery of Zhuhai People's Hospital between October 2020 and September 2021. Multimodal image fusion-three-dimensional (3D) reconstruction of CT and MRI data-was performed using 3D-Slicer software, and preoperative evaluation was performed according to the results of image fusion. Dyna CT was used to dynamically observe the position and shape of the metallic hollow introducer and Fogarty catheter and balloon during the operation to guide the operation in real time. We performed follow-up assessments each month and summarized the clinical characteristics, surgical effects, and complications in all patients. Results: Surgery was successful for all patients; the patients reported immediate pain relief. Surgical complications included facial numbness in 24 patients (100%), mild masseter weakness in three (12.5%), herpes zoster in three (12.5%), and balloon rupture in one (4.2%). None of the patients had serious surgical complications. The mean follow-up time was 9.6 ± 2.7 months. During the follow-up period, 22 patients (91.7%) experienced no recurrence of pain, and two patients (8.3%) experienced recurrence of pain, of which one underwent secondary PBC surgery. Conclusions: Preoperative multimodal image reconstruction can help fully evaluate PBC surgery, clarify the etiology, and predict the volume of contrast medium required during the operation. It provided important assistance for PBC treatment of trigeminal neuralgia patients when preoperative multimodal image fusion is combined with intraoperative Dyna CT.

Precise Localization in Craniotomy With a Retrosigmoid Keyhole Approach: Microsurgical Anatomy and Clinical Study.

Objective: We aimed to explore a method of precise localization within craniotomy based on skull anatomical landmarks via the suboccipital retrosigmoid approach. Method: Craniometric measurements were taken from 15 adult dry skulls and eight cadaver head specimens. In the anatomical study, the keypoint corresponded to the transverse-sigmoid sinus junction's corresponding point on the external surface of the temporal mastoid process, eight cadaveric heads underwent a simulated craniotomy using the suboccipital retrosigmoid approach. The center of the burr hole is precisely oriented 12 mm vertically above the top point of the mastoid groove based on the line between the infraorbital margin and the upper edge of the external auditory canal. Clinical application was verified in clinical surgery by evaluating the accuracy, safety, rapidity, and minimal invasiveness of the procedure in 29 patients. Result: No venous sinus injuries were observed. Within clinical application, 29 patients underwent craniotomy using the suboccipital retrosigmoid approach. The operative area was clearly exposed in all patients and the microsurgical anatomy of the intracranial region after the dura mater incision was satisfactory. No venous sinus ruptures were observed. The average craniectomy time was 27.02 ± 0.86 min. The diameter of the bone window was 1.7-2.9 cm. Conclusion: We conclude that the method can ensure safe, accurate, and rapid craniotomy with good vision while avoiding injury to the venous sinus.

Developing a Method to Precisely Locate the Keypoint During Craniotomy Using the Retrosigmoid Keyhole Approach: Surgical Anatomy and Technical Nuances.

Objective: To explore the precise location of the keypoint during craniotomy using the retrosigmoid keyhole approach. Methods: This study included 20 dry skulls and 10 wet cadaveric specimens. On the inner surface of dry skulls, the junction between the inferior margin of the transverse sinus (ITS) and the posterior margin of the sigmoid sinus (TSJ) was marked. The keypoint (D) was identified as the TSJ's corresponding point on the external surface of the temporal mastoid process (MP). The distance from the keypoint to the top point of the digastric groove, mastoidale, and asterion were noted (AD, BD, CD, respectively). A method to accurately locate the keypoint was developed based on these relationships. The developed method was used on the wet cadaveric specimens to evaluate its accuracy, safety, rapidity, and minimal invasion. Results: No significant difference was found between the AD, BD, and CD of the left and right sides. The drilling point was oriented on a straight line 12 mm above the top point of digastric groove, perpendicular to the Frankfort horizontal plane (FHP). In the cadaveric specimens, the operative area was clearly exposed. No venous sinus rupture occurred. The average craniotomy time was 28.74 ± 3.89 min. Conclusions: A potentially safe, accurate, and rapid craniotomy procedure was developed with the added advantage of preserving the visibility of the operating field and preventing venous sinus injury.

A reproduceable in situ xenograft model of spinal glioma.

BACKGROUND: Spinal glioma is a nervous system tumor that tends to relapse and has no specific prognostic molecular biomarkers. Thus, a stable and reproduceable animal research model of spinal glioma is urgently needed. NEW METHOD: We established a new in situ tumor xenograft model of spinal glioma using nude mice. In this study, we implanted tumors into the cervical spinal cord of nude mice to mimic the pathological characteristics of the original tumors. RESULTS: Through anatomical experiments, we found that the cervical lamina of mice was thinner, the intervertebral space was much wider, and the adhesion muscles were more easily separated. According to the examination of spinal cord sections, the best puncture point we identified was located 0.9 mm lateral to the posterior median line at the level of the line between the midpoints of the scapulae and at a depth of 0.9 mm. In the nude mouse xenograft experiment, the implanted tumor tissue retained the pathological characteristics of the original tumor. COMPARISON WITH EXISTING METHOD(S): This model used the cervical spinal cord as the puncture site and patient-derived primary tumor cells, which has never been performed before. Tumor cells could be injected directly without damaging the lamina. Thus, we could reduce the risk of man-made spinal cord injury and infection and avoid destroying the stability and integrity of the spine. CONCLUSIONS: This study established a stable and reliable animal model of spinal glioma for further molecular research and targeted therapy development.

A Novel Classification and Its Clinical Significance in Spinal Schwannoma Based on the Membranous Hierarchy.

BACKGROUND: Spinal schwannoma is a common benign tumor. However, the high recurrence rate and incidence of surgical complications are unsolved problems. OBJECTIVE: To propose a morphological classification of spinal schwannoma based on tumor-membrane relationships to increase the gross total resection (GTR) rate and to decrease the incidence of surgical complications. METHODS: Histological techniques were used to study 7 adult cadavers. Following picrosirius staining, the membranes around the nerve root were observed under a microscope. Data from 101 patients with spinal schwannoma were also collected for clinical analysis. RESULTS: The sleeve around the spinal nerve root consisted of dura and arachnoid tissues. The space between them gradually narrowed and fused at the proximal pole of the nerve root ganglion. Spinal schwannomas were divided into 4 types based on membranous structure: intrapial (type I), subarachnoidal (type II), intra- and extradural (type III), and extradural growth (type IV). Types II and III were further subdivided into 2 subtypes. GTR was achieved in all patients (100%), with no tumor recurrence during follow-up. Overall functional status significantly improved postoperatively. A total of 59 patients (92%) showed improvement or significant improvement postoperatively. There was no difference in surgical outcomes among the tumor classifications (P = .618). No intraoperative vertebral artery injuries or postoperative cerebrospinal fluid fistula occurred. CONCLUSION: Spinal schwannoma classification based on a membranous hierarchy provides an intuitive platform for preoperative planning and intraoperative safety. This classification scheme may help surgeons better define surgical goals and anticipate or even avoid complications from resection.

HMGB1-Induced p62 Overexpression Promotes Snail-Mediated Epithelial-Mesenchymal Transition in Glioblastoma Cells via the Degradation of GSK-3ß.

Rationale: Glioblastoma (GBM) is the most common and aggressive brain tumor, characterized by its propensity to invade the surrounding brain parenchyma. The effect of extracellular high-mobility group box 1 (HMGB1) protein on glioblastoma (GBM) progression is still controversial. p62 is overexpressed in glioma cells, and has been associated with the malignant features and poor prognosis of GBM patients. Hence, this study aimed to clarify the role of p62 in HMGB1-induced epithelial-mesenchymal transition (EMT) of GBM both in vitro and in vivo. Methods: Immunoblotting, immunofluorescence and qRT-PCR were performed to evaluate EMT progression in both human GBM cell line and primary GBM cells. Transwell and wound healing assays were used to assess the invasion and migration of GBM cells. shRNA technique was used to investigate the role of p62 in HMGB1-induced EMT both in vitro and in vivo orthotopic tumor model. Co-immunoprecipitation assay was used to reveal the interaction between p62 and GSK-3ß (glycogen synthase kinase 3 beta). Immunohistochemistry was performed to detect the expression levels of proteins in human GBM tissues. Results: In this study, GBM cells treated with recombinant human HMGB1 (rhHMGB1) underwent spontaneous EMT through GSK-3ß/Snail signaling pathway. In addition, our study revealed that rhHMGB1-induced EMT of GBM cells was accompanied by p62 overexpression, which was mediated by the activation of TLR4-p38-Nrf2 signaling pathway. Moreover, the results demonstrated that p62 knockdown impaired rhHMGB1-induced EMT both in vitro and in vivo. Subsequent mechanistic investigations showed that p62 served as a shuttling factor for the interaction of GSK-3ß with proteasome, and ultimately activated GSK-3ß/Snail signaling pathway by augmenting the degradation of GSK-3ß. Furthermore, immunohistochemistry analysis revealed a significant inverse correlation between p62 and GSK-3ß, and a combination of the both might serve as a more powerful predictor of poor survival in GBM patients. Conclusions: This study suggests that p62 is an effector for HMGB1-induced EMT, and may represent a novel therapeutic target in GBM.

HERC3-Mediated SMAD7 Ubiquitination Degradation Promotes Autophagy-Induced EMT and Chemoresistance in Glioblastoma.

PURPOSE: Glioblastoma, a common malignant intracranial tumor, has the most dismal prognosis. Autophagy was reported to act as a survival-promoting mechanism in gliomas by inducing epithelial-to-mesenchymal transition (EMT). Here, we determined the critical molecules involved in autophagy-induced EMT and elucidated the possible mechanism of chemoradiotherapy resistance and tumor recurrence. EXPERIMENTAL DESIGN: We used isobaric tags for relative and absolute quantitation to identify the critical proteins and pathway mediating EMT via autophagy inducer treatment, and tested the expression of these proteins using tissue microarray of gliomas and clinical glioblastoma samples as well as tissues and cells separated from the core lesion and tumor-peripheral region. Analysis of the Cancer Genome Atlas database and 110 glioblastoma cases revealed the prognostic value of these molecules. The functional role of these critical molecules was further confirmed by in vitro experiments and intracranial xenograft in nude mice. RESULTS: Autophagy inducers significantly upregulated the expression of HERC3, which promotes ubiquitination-mediated degradation of SMAD7 in an autolysosome-dependent manner. The corresponding increase in p-SMAD2/3 level and TGFß pathway activation finally induced EMT in cell lines and primary glioblastoma cells. Moreover, HERC3 overexpression was observed in pseudo-palisade cells surrounding tumor necrosis and in tumor-adjacent tissue; high HERC3 and low SMAD7 levels predicted poor clinical outcome in glioblastoma; xenograft of nude mice and in vitro experiments confirmed these findings. CONCLUSIONS: Together, our findings reveal the indispensable role of HERC3 in regulating canonical SMAD2/3-dependent TGFß pathway involvement in autophagy-induced EMT, providing insights toward a better understanding of the mechanism of resistance to temozolomide and peripheral recurrence of glioblastoma.