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Purpose: Currently available grading and classification systems for hemifacial spasm either rely on subjective assessments or are excessively intricate. Here, we make use of facial recognition and facial tracking technologies towards accurately grouping patients according to severity and characteristics of the spasms., Methods: A retrospective review of our prospectively maintained preoperative videos database for hemifacial spasm was done. Videos were analyzed using an Apple AR kit-based App. A facial mesh is automatically allocated to specific biometric facial points. Videos are analyzed using Blender software for measuring the amplitude and frequency of the spasms. Classification of the patients into groups was done using both divisive k-means and agglomerative hierarchical clustering. Correlation-Analysis with preoperative quality of Life (Qol) using SF-36 questionnaire and HFS-8 score was performed. Additionally, correlation with postoperative outcome was calculated., Results: 79 preoperative videos were included. Both up-bottom and bottom-up clustering approaches grouped the patients into 3 different clusters according to 4 variables (eye closure, mouth distance change, rate, and repetition of the spasms). Correlation of the groups with the Qol was done for 46/79 patients (58.2%). Spasms could be classified into mild, moderate clonic and severe tonic spasms. Patients with mild spasms showed better Qol scores. Moderate clonic spasms experienced best outcomes following microvascular decompression., Conclusion: This novel classification using facial-tracking and augmented-reality is easy to use and apply. It quantifies the severity and type of the spasms and relates it to the quality of life of patients, postoperative outcome, and could guide our management strategy., Competing Interests: Declarations. Ethics approval: All procedures performed in this study involving human participants were in accordance with the ethical standards of the local institutional research committee (Ethical committee of the University Medicine Greifswald) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethical committee approval number BB 101/16. Informed consent was obtained from all patients including using their videos for research purposes. Consent for publication: “The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in all forms, formats and media (whether known now or created in the future), to i) publish, reproduce, distribute, display and store the Contribution, ii) translate the Contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or, abstracts of the Contribution, iii) create any other derivative work(s) based on the Contribution, iv) to exploit all subsidiary rights in the Contribution, v) the inclusion of electronic links from the Contribution to third party material where—ever it may be located; and, vi) licence any third party to do any or all of the above.” Consent to participate: Although no data in this study could lead to public identification of the patients, all the participating patients signed consent to publication of their data. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Human glioblastoma multiforme (GBM) is a highly aggressive tumor with insufficient therapies available. Especially, novel concepts of immune therapies fail due to a complex immunosuppressive microenvironment, high mutational rates, and inter-patient variations. The intratumoral heterogeneity is currently not sufficiently investigated., Methods: Biopsies from six different locations were taken in a cohort of 16 GBM patients who underwent surgery. The tissue slides were analyzed utilizing high-content imaging microscopy and algorithm-based image quantification. Several immune markers for macrophage and microglia subpopulations were investigated. Flow cytometry was used to validate key results. Besides the surface marker, cytokines were measured and categorized based on their heterogenicity and overall expression., Results: M2-like antigens, including CD204, CD163, Arg1, and CSF1R, showed comparatively higher expression, with GFAP displaying the least intratumoral heterogeneity. In contrast, anti-tumor-macrophage-like antigens, such as PSGL-1, CD16, CD68, and MHC-II, exhibited low overall expression and concurrent high intratumoral heterogeneity. CD16 and PSGL-1 were the most heterogeneous antigens. High expression levels were observed for cytokines IL-6, VEGF, and CCL-2. VILIP-a was revealed to differentiate most in principle component analysis. Cytokines with the lowest overall expression, such as TGF-β1, β-NGF, TNF-α, and TREM1, showed low intratumoral heterogeneity, in contrast to βNGF, TNF-α, and IL-18, which displayed high heterogeneity despite low expression., Conclusion: The study showed high intratumoral heterogeneity in GBM, emphasizing the need for a more detailed understanding of the tumor microenvironment. The described findings could be essential for future personalized treatment strategies and the implementation of reliable diagnostics in GBM.

Background: Colloid cysts (CCs) are benign lesions commonly located in the third ventricle, near the foramen of Monro. They constitute about 0.5%-1% of all intracranial tumors. As benign lesions, CCs can be found incidentally, but they can also present with neurological deterioration and are even associated with sudden death, which might be explained as a result of obstructive hydrocephalus. Thus, larger and symptomatic CCs are often considered for surgery., Observations: The following case presents a rare and curious instance of a spontaneously regressing CC. This represents the 11th case ever reported about an extremely rare occurrence: the spontaneous regression of a previously diagnosed CC in the third ventricle., Lessons: Carefully selected asymptomatic CCs can be monitored through regular imaging studies and neurological examinations. If regression of the cyst is observed, physicians should not be surprised, as this event, although rare, has been documented and published in 11 cases, including this one. https://thejns.org/doi/10.3171/CASE24498.

Purpose: Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus. Secondary stoma closure may be life threatening and is the most common reason for late ETV failure, mostly secondary to local scarring. Local stents intended to maintain patency are rarely used. In this study, we summarize our experience using stented ETV (sETV), efficacy, and safety., Material and Methods: Data was retrospectively collected from all consecutive patients who underwent ETV with stenting at four centers. Collected data included indications for using sETV, hydrocephalic history, surgical technique, outcomes, and complications., Results: Sixty-seven cases were included. Forty had a primary sETV, and 27 had a secondary sETV (following a prior shunt, ETV, or both). The average age during surgery was 22 years. Main indications for sETV included an adjacent tumor (n = 15), thick or redundant tuber cinereum (n = 24), and prior ETV failure (n = 16). Fifty-nine patients (88%) had a successful sETV. Eight patients failed 11 ± 8 months following surgery. Reasons for failure included obstruction of the stent, reabsorption insufficiency, and CSF leak (n = 2 each), and massive hygroma and tumor spread (n = 1 each). Complications included subdural hygroma (n = 4), CSF leak (n = 2), and stent malposition (n = 1). There were no complications associated with two stent removals., Conclusion: Stented ETV appears to be feasible and safe. It may be indicated in selected cases such as patients with prior ETV failure, or as a primary treatment in cases with anatomical alterations caused by tumors or thickened tuber cinereum. Future investigations are needed to further elucidate its role in non-communicating hydrocephalus., (© 2024. The Author(s).)

Introduction: Advances in spine surgery enable safe interventions in elderly patients, but perioperative neurocognitive disorders (pNCD), such as post-operative delirium (POD) and cognitive dysfunction (POCD), remain a serious concern. Pre-operative cognitive impairment is a major risk factor for pNCD. Comprehensive pre-operative cognitive assessments are not feasible in clinical practice, making effective screening methods desirable. This study investigates whether pre-operative cerebrovascular duplex sonography can assess subcortical (vascular) cognitive impairment and the risk for POD., Methods: This prospective single-center study recruited patients aged ≥60 years scheduled for elective spine surgery at a German university hospital. Patients underwent pre-operative assessments including cognitive abilities (CERAD test battery), structural MRI, and cerebrovascular duplex sonography. POD screening was conducted three times daily for at least 3 days. The primary hypothesis, that the mean pulsatility index (PI) of both internal carotid arteries (ICA) predicts POD risk, was tested using logistic regression. Secondary analyses examined the association between POD risk and ICA flow (time-averaged peak velocities, TAPV) and correlations with cognitive profiles and MRI characteristics., Results: POD occurred in 22% of patients ( n  = 22/99) within three postoperative days. Patients with POD were significantly older (75.9 ± 5.4 vs. 70.0 ± 6.9 years, p  < 0.01) but did not differ by gender ( p  = 0.51). ICA PI significantly predicted POD risk (OR = 5.46 [95%CI: 1.81-16.49], p  = 0.003), which remained significant after adjustment for age and duration of surgery (OR adj  = 6.38 [95% CI: 1.77-23.03], p  = 0.005). TAPV did not inform the POD risk ( p  = 0.68). ICA PI Pre-operative cognitive scores were significantly associated with ICA PI (mean CERAD score: r  = -0.32, p  < 0.001). ICA PI was also significantly associated with total white matter lesion volume ( τ  = 0.19, p  = 0.012) and periventricular white matter lesion volume ( τ  = 0.21, p  = 0.007)., Discussion: This is the first study to demonstrate that cerebrovascular duplex sonography can assess the risk for POD in elderly spine surgery patients. Increased ICA PI may indicate subcortical impairment, larger white matter lesion load, and lower white matter volume, predisposing factors for POD. Pre-operative cerebrovascular duplex sonography of the ICA is widely available, easy-to-use, and efficient, offering a promising screening method for POD risk. Increased ICA PI could supplement established predictors like age to adjust surgical and peri-operative procedures to individual risk profiles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saar, Müller, Veser, Behr, Rathmann, Schroeder, Flöel, Müller, von Sarnowski and Fleischmann.)

Introduction: Intraoperative fluorescence guidance is a well-established surgical adjunct in high-grade glioma surgery. In contrast, the clinical use of such dyes and technology has been scarcely reported in skull base surgery., Research Question: We aimed to systematically review the clinical applications of different fluorophores in both open and endonasal skull base surgery., Material and Methods: We performed a systematic review and discussed the current literature on fluorescence guidance in skull base surgery., Results: After a comprehensive literature search, 77 articles on skull base fluorescence guidance were evaluated. A qualitative analysis of the articles is presented, discussing clinical indications and current controversies. The use of intrathecal fluorescein was the most frequently reported in the literature. Beyond that, 5-ALA and ICG were two other fluorescent dyes most extensively discussed, with some experimental fluorophore applications in skull base surgery., Discussion and Conclusion: Intraoperative fluorescence imaging can serve as an adjunct technology in skull base surgery. The scope of initial indications of these fluorophores has expanded beyond malignant glioma resection alone. We discuss current use and controversies and present an extensive overview of additional indications for fluorescence imaging in skull base pathologies. Further quantitative studies will be needed in the future, focusing on tissue selectivity and time-dependency of the different fluorophores currently commercially available, as well as the development of new compounds to expand applications and facilitate skull base surgeries., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eric Suero Molina reports a relationship with Carl Zeiss Meditec AG that includes: funding grants. Walter Stummer has received speaker and consultant fees from Medac, Carl Zeiss Meditec AG, Leica Microsystems, Photonamic, and NXDC and funding grants from Carl Zeiss Meditec AG. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Objectives: Surgery of posterior fossa meningiomas is extremely challenging even for experienced skull base surgeons because of the close proximity to cranial nerves and tight spaces. Endoscope-assisted surgery for posterior fossa meningiomas can enable a high degree of tumor resection even when using small approaches. This study describes the advantage of endoscope-assisted microneurosurgery in resection of posterior fossa skull base meningiomas and the clinical outcome., Methods: All endoscope-assisted surgeries for resection of posterior fossa meningiomas performed between 2002 and 2016 in our department were retrospectively analyzed. For data acquisition, the patient files were used. Tumor size and extent of resection were evaluated on pre- and postoperative magnetic resonance imaging. The value of endoscope assistance was assessed according to the intraoperative videos and the surgical notes. Complications and long-term outcomes were evaluated., Results: We identified 39 female and 10 male patients. The mean age of the patients at the time of surgery was 55 years, ranging from 25 to 78 years. The mean follow-up was 93.8 months. A total of 41% of the tumors were large to giant. The retrosigmoid approach was used in most patients (45). A gross total resection could be achieved in 38 patients (78%). In 11 patients (22%), a near total resection was performed. In 27 patients (55%), a hidden residual tumor, which could not been visualized with the operating microscope, was identified with the endoscope. In 6 patients (22.2%), the internal auditory canal was visualized, in 9 patients (33.3%), the Meckel's cave was visualized, and in 5 patients (18.5%), both were visualized under endoscope assistance. In 26 of those patients (96.3%), the residual tumor was resected under endoscopic view., Conclusion: Endoscope-assisted surgery for posterior fossa skull base meningiomas enables a high degree of tumor resection, avoids more invasive skull base approaches, and reduces the amount of cerebellar retraction., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objectives: Despite a 90% success rate, microvascular decompression occasionally fails to resolve hemifacial spasm (HFS), necessitating revision surgery. We investigated recurrent cases to identify underlying causes., Methods: We evaluated patients at our institution who underwent revision microvascular decompression because of recurrent or persistent HFS, assessing recurrence causes, decompression techniques, complications, and outcomes. Data considered included demographics, preoperative symptoms, disease duration, offending vessel, and magnetic resonance findings. Surgical notes and intraoperative videos were reviewed, and telephone interviews were conducted for recent outcomes., Results: Out of our ongoing series of 493 patients, 43 patients (8.7%) required revision surgery with a patient cohort of 33 females and 10 males. The average symptom duration was 10 years. The median time between primary and revision surgery was 14 months. Thirteen patients (30.2%) underwent initial surgery elsewhere. Adhesions of Teflon pledgets to the facial nerve were the primary cause of nonresolution in 23 patients (53.5%), while in 13 (30.2%), a missed vascular compression was identified. Sixteen patients (37.2%) had sufficient decompression by removing the conflicting pledgets. During 10 revisions (23.3%), additional Teflon pledgets were necessary. After a median follow-up of 67 months after revision surgery, 27 patients (62.8%) reported complete spasm resolution. Six patients (14.0%) had a good outcome with over 90% reduction of their spasms, 3 patients (7.0%) stated a fair outcome (50% improvement), while 7 patients (16.3%) had no improvement., Conclusion: According to our results, adhesions of Teflon to the facial nerve may cause HFS recurrence. Therefore, whenever possible, Teflon should be placed without nerve contact between the brainstem and the offending vessel. Using a sling or bridge technique seems to be beneficial because it leaves the facial nerve completely free. Persistent symptoms often result from missed offending vessels in the pontomedullary sulcus indicating the benefit of endoscopic inspection of this area with an endoscope., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: The surgical anatomy of the nervus intermedius (NI) is highly variable. The aim of this study was to describe the anatomy of the NI during endoscope-assisted microvascular decompression (MVD) in hemifacial spasm (HFS), and the involvement of the nerve in the vascular conflict., Methods: The authors reviewed a prospectively maintained database for MVDs performed between 2002 and 2022 and extracted clinical data including patient demographics, symptoms, and offending vessel(s). Operative videos and photographs were analyzed retrospectively in an attempt to identify the NI., Results: Endoscopic identification of the NI was possible in 139 of 435 MVDs. The anatomy is very variable. In 79 (56.8%) patients, a single-bundle pattern was detected, whereas a multiple-bundle pattern was identified in 60 (43.2%) patients. Overall the most common pattern was a single-bundle type A (49.7%). In 20.1%, a multiple-bundles type A was identified. In 4.3%, a single-bundle type B was detected. In 2.9% a single-bundle type C was found, and in just 0.7% a multiple-bundles type C was detected. A multiple-origin pattern (type D) was found in 31 patients (22.3%). The NI was frequently involved in the neurovascular conflict (approximately 85%). The type of NI or vascular compression pattern did not affect the results regarding the outcome or recurrence of HFS., Conclusions: The anatomy of the NI is for the first time evaluated endoscopically in MVD for HFS. The nerve had various anatomical patterns that were clearly identified. Further studies to evaluate the compression patterns in relation to NI neuralgia are warranted.

Background: Microvascular conflicts in hemifacial spasm typically occur at the facial nerve's root exit zone. While a pure microsurgical approach offers only limited orientation, added endoscopy enhances visibility of the relevant structures without the necessity of cerebellar retraction., Methods: After a retrosigmoid craniotomy, a microsurgical decompression of the facial nerve is performed with a Teflon bridge. Endoscopic inspection prior and after decompression facilitates optimal Teflon bridge positioning., Conclusions: Endoscope-assisted microsurgery allows a clear visualization and safe manipulation on the facial nerve at its root exit zone., (© 2024. The Author(s).)

Pineal cysts are typically detected in around 1.3% to 4.3% of patients during routine magnetic resonance imaging (MRI) scans. 1 , 2 The vast majority of pineal cysts are benign, asymptomatic, and typically do not necessitate surgical intervention. Large pineal cysts are known to cause hydrocephalus with its associated symptoms and thus can require in rare cases surgical resection. Even in the absence of hydrocephalus, selected patients with large pineal cysts causing headaches and visual disturbances can find relief after surgical resection. 3 , 4 The supracerebellar infratentorial (SCIT) approach is widely used and represents an extraparenchymatous approach through a natural corridor to the pineal region. 5 Performing this approach in a semisitting position allows for an optimal retraction of the cerebellum by gravity. We employ a minimally invasive paramedian SCIT approach for the resection of pineal cysts. In our experience, the paramedian SCIT approach allows for a less steep operating angle and a smaller craniotomy compared with the midline SCIT approach. We present a 24-year-old female complaining of headache. The initial MRI was conducted 2 years before surgery. Following the initial evaluation, the patient experienced progressive headaches without neurologic deficits. A subsequent MRI revealed enlargement of the pineal cyst, leading to the indication for surgical resection. The surgery was performed mainly under the operating microscope with endoscopic visualization in suitable situations as our small approach restricts bimanual dissection with an endoscope. In our experience, this approach provides a versatile and minimally invasive access to the pineal region, making it optimally suitable for pineal cysts requiring surgical resection., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Primary hemifacial spasm (HFS) is usually caused by arterial compression of the facial nerve at the root exit zone at the brainstem. Rarely, a purely venous compression is seen. However, arachnoid bands strangulating the facial nerve have not been recognized as a cause of hemifacial spasm., Observations: The authors present a case of a 24-year-old female who had experienced HFS for 9 years. Endoscopic inspection of the root exit zone revealed no vascular compression but an arachnoid band strangulating the facial nerve. After cutting the band, the lateral spread response disappeared, and the patient was immediately spasm free after the surgery. Two years later, she was still doing well without any spasms., Lessons: This is the third patient in the authors' series of 535 patients who had no vascular conflict but rather a strangulation of the nerve by arachnoid bands. All patients have remained spasm free. To the authors' knowledge, no other group has reported arachnoid bands as an etiological factor of HFS so far.

The development of brain metastases hallmarks disease progression in 20-40% of melanoma patients and is a serious obstacle to therapy. Understanding the processes involved in the development and maintenance of melanoma brain metastases (MBM) is critical for the discovery of novel therapeutic strategies. Here, we generated transcriptome and methylome profiles of MBM showing high or low abundance of infiltrated Iba1 high tumor-associated microglia and macrophages (TAMs). Our survey identified potential prognostic markers of favorable disease course and response to immune checkpoint inhibitor (ICi) therapy, among them APBB1IP and the interferon-responsive gene ITGB7. In MBM with high ITGB7/APBB1IP levels, the accumulation of TAMs correlated significantly with the immune score. Signature-based deconvolution of MBM via single sample GSEA revealed enrichment of interferon-response and immune signatures and revealed inflammation, stress and MET receptor signaling. MET receptor phosphorylation/activation maybe elicited by inflammatory processes in brain metastatic melanoma cells via stroma cell-released HGF. We found phospho-MET Y1234/1235 in a subset of MBM and observed a marked response of brain metastasis-derived cell lines (BMCs) that lacked druggable BRAF mutations or developed resistance to BRAF inhibitors (BRAFi) in vivo to MET inhibitors PHA-665752 and ARQ197 (tivantinib). In summary, the activation of MET receptor in brain colonizing melanoma cells by stromal cell-released HGF may promote tumor self-maintenance and expansion and might counteract ICi therapy. Therefore, therapeutic targeting of MET possibly serves as a promising strategy to control intracranial progressive disease and improve patient survival., (© 2024. The Author(s).)

Purpose: Endoscopic transaqueductal stenting has become a well-accepted treatment option for a selected small subset of aqueductal stenosis-related obstructive hydrocephalus. However, transaqueductal stenting poses unique challenges and risks which requires critical consideration. This report discusses the clinical experiences with transaqueductal stenting for periaqueductal tumor-related aqueductal stenosis focusing on pediatric patients., Methods: A retrospective analysis of all patients undergoing endoscopic TAS from 01/1993 to 01/2022 in the author's departments was performed. Demographic, clinical, radiological, and intraoperative endoscopic data were evaluated. All patients with AS-related occlusive hydrocephalus that was treated with TAS were analyzed and prospectively followed. Special attention has been given to providing insights into indications, surgical technique, and limitations., Results: Out of 28 endoscopic transaqueductal endoscopis stenting procedures, five procedures were performed on periaqueductal tumor-related obstructive hydrocephalus, two children and three adult patients. CSF pathway was obstructed by tumor located in the aqueduct in 2, by tumor in the thalamus/mesencephalon in 1, by a tumor within the third ventricle in 1, and by a tumor of the lamina tecti in 1. Simultaneously with transaqueductal stenting, 2 endoscopic third ventriculostomies (ETV), 3 tumor biopsies, and 1 tumor resection were performed. Postoperative complications included the following: CSF fistula (1 case), and asymptomatic fornix contusion (1 case). A working aqueductal stent was achieved in all cases based on clinical follow-up evaluation. Postoperatively, all patients showed improvement or resolution of their symptoms. The mean follow-up period was 25.2 months (range, 1-108 months). One patient died due to tumor progression during early follow-up. No stent migration was seen., Conclusion: Endoscopic third ventriculostomy remains the gold standard for treatment of CSF circulation obstructions with lesions in the posterior third ventricle and aqueduct. Transaqueductal stenting for periaqueductal tumor-related aqueductal compression is technically feasible. However, because of the potential high risks and subtle advantages compared with ETV transaqueductal stenting, it might be indicated in a small subset of well-selected patients if alternative treatment options are not at hand., (© 2023. The Author(s).)

Background: Lag screw osteosynthesis for odontoid fractures has a high rate of pseudoarthrosis, especially in elderly patients. Besides biomechanical properties of the different screw types, insufficient fragment compression or unnoticed screw stripping may be the main causing factors for this adverse event. The aim of the study was to compare two screws in clinical use with different design principles in terms of compression force and stability against screw stripping., Methods: Twelve human cadaveric C2 vertebral bodies were considered. Bone density was determined. The specimens were matched according to bone density and randomly assigned to two experimental groups. An odontoid fracture was induced, which were fixed either with a 3.5 mm standard compression screw or with a 5 mm sleeve nut screw. Both screws are certified for the treatment of odontoid fractures. The bone samples were fixed in a measuring device. The screwdriver was driven mechanically. The tests were analyzed for peak interfragmentary compression and screw-in torque with a frequency of 20 Hz., Findings: The maximum fragment compression was significantly higher with screw with sleeve nut at 346.13(SD ±72.35) N compared with classic compression screw at 162.68(SD ±114.13) N (p = 0.025). Screw stripping occurred significantly earlier in classic compression screw at 255.5(SD ±192.0)° rotation after reaching maximum compression than in screw with sleeve nut at 1005.2(SD ±341.1)° (p = 0.0039)., Interpretation: Screw with sleeve nut achieves greater fragment compression and is more robust to screw stripping compared to classic compression screw. Whether the better biomechanical properties lead to a reduction of pseudoarthrosis has to be proven in clinical studies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan-Uwe Mueller reports financial support was provided by SIGNUS Medizintechnik GmbH., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Reaching a tumor within the third ventricle is challenging, and planning an accessible trajectory is crucial without injuring the surrounding structures. We report a 5-year-old boy presented with headache and a seizure where sequential MRI brain studies in a short time period revealed a rapid growing immature teratoma within the third ventricle with hydrocephalic changes. Several management procedures were performed for CSF diversion and medical treatment of the tumor with chemotherapy and stem cell therapy. The tumor was rapidly growing, and surgical excision was decided. Total resection was achieved via endoscope-assisted microsurgical transcallosal approach. Seven years after surgery, the patient experienced no recurrence of the tumor with a favorable clinical condition., Conclusion: We report a rare case of posterior third ventricular immature teratoma where the endoscope-assisted microsurgical technique was implemented with favorable long-term postoperative outcome., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers., Methods: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included., Results: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients., Conclusions: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Early and chronic stress was reported to alter the hypothalamic-pituitary-adrenal axis functioning which regulates the secretion of cortisol. Nevertheless, few studies mainly focused on specific study populations (e.g. adolescents, pregnant women, and psychiatric patients), and researched interactive associations of pituitary volumes and single stress markers. The present study used pituitary volumes of two adult general-population cohorts of the Study of Health in Pomerania (SHIP-START-2: N = 1026, 54% Men, 30-90 years; SHIP-TREND-0: N = 1868, 53% Men, 21-82 years). In linear regression models, main effects of the pituitary volumes as well as interaction effects with childhood abuse and neglect (Childhood Trauma Questionnaire) were estimated using depressive symptoms (Beck Depression Inventory-II), and serum cortisol concentrations as outcome variables. The results of both cohorts were integrated via meta-analyses. No main effect between pituitary volumes and depressive symptoms was observed (START-2: β = -0.004 [-0.082; 0.075], p = .929; TREND-0: β = 0.020 [-0.033; 0.073], p = .466; Meta-analysis: β = 0.012 [-0.031; 0.056], p = .580). However, larger pituitary volumes were associated with more depressive symptoms in participants with more severe childhood neglect (START-2: β = 0.051 [-0.024; 0.126], p = .183; TREND-0: β = 0.083 [0.006; 0.159], p = .034; Meta-analysis: β = 0.066 [0.013; 0.120], p = .015). Further, larger pituitary volumes were associated with lower serum cortisol concentrations in participants with more severe depressive symptoms (START-2: β = -0.087 [-0.145; -0.030], p = .003; TREND-0: β = -0.053 [-0.091; -0.015], p = .006; Meta-analysis: β = -0.063 [-0.095; -0.032], p = 8.39e-05). Summarizing, larger pituitary volumes were associated with more severe psychopathological symptoms, particularly in participants reporting early life stress. This was supported by stronger associations between pituitary volumes and cortisol concentrations in participants with more severe depressive symptoms. Future studies are needed to transfer these results into developmental stages of high hormonal changes and patient samples., Competing Interests: Declaration of competing interest HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen Cilag. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: The pathogenesis of different narcolepsy phenotypes remains unclear. In rare cases, narcolepsy can be attributable to secondary brain pathologies affecting the midbrain. These cases may elucidate the pathological background and the treatment of narcolepsy, but are often limited by poor objective symptom characterization and effects of therapeutic intervention, especially by modern diagnostic standards., Methods: A young adult presented with excessive daytime sleepiness (EDS) that was refractory to classic narcolepsy medication. Diagnosis of narcolepsy was made based on the pathologically shortened sleep latencies in polysomnography and Multiple Sleep Latency Test (MSLT), together with confirmed sleep-onset REM-sleep (SOREM). Preserved hypocretin levels in cerebrospinal fluid, together with the absence of cataplectic events confirmed the diagnosis of narcolepsy type II. MRI revealed a large arachnoid cyst with compression of the midbrain., Results: Six months after fenestration of the cyst, the patient's EDS had vastly improved. No further SOREM was observed, and polysomnographic and MSLT sleep latencies normalized. No further drug treatment was required., Conclusion: Symptomatic narcolepsy due to space-occupying lesions in the mesencephalon comprises a unique curative treatment option. Here, surgical intervention offers an effective curative therapeutic approach. However, differential diagnosis of symptomatic narcolepsy requires special consideration., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Künstler et al.)

Background and Objectives: There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery., Methods: To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed., Results: Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (β = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach., Conclusion: Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Introduction: Endoscopy was first employed in the surgical treatment of neurosurgical diseases early in the twentieth century, but did not become an established practice for a long time, mainly because of poor technology and clinical results. After a slow re-appearance in the 1980s, the 1990s saw an explosion of techniques and instrumentation. Continuing technological improvement has led to further expansion of surgical techniques and indications for use of neuroendoscopy., Discussion: The expansion of ventricular endoscopy has led to significant understanding of CSF disorders. Aqueduct stenosis as cause of hydrocephalus and arachnoid cysts are an example of pathologies, the concept and understanding of which now is considerably enhanced, due to the application of neuroendoscopy in their treatment. Management of loculated hydrocephalus has been facilitated considerably with the use of the endoscope. The concepts of aqueductoplasty, septostomy, and foraminoplasty of the foramina of Monro and Magendie emerged, which were previously unknown. Skull base surgery, especially surgery for craniopharyngioma, has seen dramatic improvement in results with the use of the endoscope. Coupling of the endoscope with neuronavigation has expanded technical capabilities even further. Overall, we can do a lot more with the endoscope now in comparison to 30 years ago., Conclusion: We should always remember that the endoscope is only a tool. Its use has indications and limitations related to its design and our ability to extract the maximum, in the context of its shortcomings. Further technological advances will push surgical frontiers even more in years to come., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available., Objective: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas., Design: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed., Setting: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values., Results: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%., Conclusions: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Glioblastoma (GBM) is still a deadly tumor due to its highly infiltrative growth behavior and its resistance to therapy. Evidence is accumulating that sphingosine-1-phosphate (S1P) acts as an important tumor-promoting molecule that is involved in the activation of the S1P receptor subtype 1 (S1PR1). Therefore, we investigated the effect of ACT-209905 (a putative S1PR1 modulator) on the growth of human (primary cells, LN-18) and murine (GL261) GBM cells. The viability and migration of GBM cells were both reduced by ACT-209905. Furthermore, co-culture with monocytic THP-1 cells or conditioned medium enhanced the viability and migration of GBM cells, suggesting that THP-1 cells secrete factors which stimulate GBM cell growth. ACT-209905 inhibited the THP-1-induced enhancement of GBM cell growth and migration. Immunoblot analyses showed that ACT-209905 reduced the activation of growth-promoting kinases (p38, AKT1 and ERK1/2), whereas THP-1 cells and conditioned medium caused an activation of these kinases. In addition, ACT-209905 diminished the surface expression of pro-migratory molecules and reduced CD62P-positive GBM cells. In contrast, THP-1 cells increased the ICAM-1 and P-Selectin content of GBM cells which was reversed by ACT-209905. In conclusion, our study suggests the role of S1PR1 signaling in the growth of GBM cells and gives a partial explanation for the pro-tumorigenic effects that macrophages might have on GBM cells.

Study Design: Prospective quasi-experimental observational study., Objective: The objective of this study was to evaluate whether duration of surgery is a modifiable risk factor for postoperative delirium (POD) after spine surgery and explore further modifiable risk factors. In addition, we sought to investigate the association between POD and postoperative cognitive dysfunction and persistent neurocognitive disorders., Summary of Background Data: Advances in spine surgery enable technically safe interventions in elderly patients with disabling spine disease. The occurrence of POD and delayed neurocognitive complications ( e.g. postoperative cognitive dysfunction/persistent neurocognitive disorder) remain a concern since these contribute to inferior functional outcomes and long-term care dependency after spine surgery., Materials and Methods: This prospective single-center study recruited patients aged 60 years or above and scheduled for elective spine surgery between February 2018 and March 2020. Functional (Barthel Index, BI) and cognitive outcomes [Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery; telephone Montréal Cognitive Assessment] were assessed at baseline, three (V3), and 12 months postoperatively. The primary hypothesis was that the duration of surgery predicts POD. Multivariable predictive models of POD included surgical and anesthesiological parameters., Results: Twenty-two percent of patients developed POD (n=22/99). In a multivariable model, duration of surgery [OR adj =1.61/h (95% CI, 1.20-2.30)], age [OR adj =1.22/yr (95% CI, 1.10-1.36)], and baseline deviations of intraoperative systolic blood pressure [25th percentile: OR adj =0.94/mm Hg (95% CI, 0.89-0.99); 90th percentile: OR adj =1.07/mm Hg (95% CI, 1.01-1.14)] were significantly associated with POD. Postoperative cognitive scores generally improved (V3, ΔCERAD total z -score: 0.22±0.63). However, this positive group effect was counteracted by POD [beta: -0.87 (95% CI, -1.31 to 0.42)], older age [beta: -0.03/yr (95% CI, -0.05 to 0.01)], and lack of functional improvement [ΔBI; beta: -0.04/point (95% CI, -0.06 to 0.02)]. Cognitive scores at twelve months remained inferior in the POD group, adjusted for baseline cognition/age., Conclusions: This study identified distinct neurocognitive effects after spine surgery, which are influenced by perioperative risk factors. Potential cognitive benefits are counteracted by POD, rendering its prevention critical in an aging population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Indications Corridor and Limits of Exposure: This video demonstrates our endoscope-assisted microvascular decompression (MVD) technique in hemifacial spasm. A 2-cm lower retrosigmoid approach is used to reach the facial nerve exit zone. The additional use of endoscopy serves to overcome the microscopes linear axis of view on the compression site., Anatomic Essentials Need for Preoperative Planning and Assessment: A neurovascular conflict in the facial nerve exit zone is to be identified on CISS-MRI. A CT scan helps assessing the approach. Acoustic evoked potentials and facial nerve neuromonitoring including lateral spreads are required. 1., Essential Steps of the Procedure: The patient is positioned supine with 45° head rotation to the contralateral side. In addition, the operating table is tilted 30° to facilitate optimal cerebellar retraction by gravity avoiding the need for cerebellar spatula. The dura is incised parallel to the sigmoid sinus. With the operating microscope, the arachnoid is dissected exposing the vestibulocochlear nerve and the lower cranial nerves. The lower cranial nerve group is exposed up to the exit from the brain stem, enabling a subfloccular approach to the facial nerve exit zone. The endoscope is used to inspect the facial nerve and to identify the compressing vessel. Microscopically, the vessel is mobilized and the nerve decompressed by shredded Teflon. 2., Pitfalls/avoidance of Complications: Jugular vein compression by excessive head rotation must be avoided. Teflon placed directly onto the nerve can cause spasms itself. Opened mastoid cells are carefully sealed., Variants and Indications for Their Use: Transposition is favored over interposition. Besides shredded Teflon, a Teflon-Bridge or Teflon-Sling can be placed. 3-5The patient consented to the procedure and to the publication of her image., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Importance: After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome., Objective: To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage., Design, Setting, and Participants: The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours., Intervention: A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage., Main Outcomes and Measures: Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage., Results: Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04)., Conclusion and Relevance: In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage., Trial Registration: ClinicalTrials.gov Identifier: NCT01258257.

Objective: Microvascular decompression (MVD) is the only curative treatment modality for hemifacial spasm (HFS). Although generally considered to be safe, this surgical procedure is surrounded by many risks and possible complications. The authors present the spectrum of complications that they met in their case series, the possible causes, and the strategies recommended to minimize them., Methods: The authors reviewed a prospectively maintained database for MVDs performed from 2005 until 2021 and extracted relevant data including patient demographics, offending vessel(s), operative technique, outcome, and different complications. Descriptive statistics with uni- and multivariable analyses for the factors that may influence the seventh, eighth, and lower cranial nerves were performed., Results: Data from 420 patients were obtained. Three hundred seventeen of 344 patients (92.2%) with a minimum follow-up of 12 months had a favorable outcome. The mean follow-up (standard deviation) was 51.3 ± 38.7 months. Immediate complications reached 18.8% (79/420). Complications persisted in only 7.14% of patients (30/420) including persistent hearing deficits (5.95%) and residual facial palsy (0.95%). Temporary complications included CSF leakage (3.10%), lower cranial nerve deficits (3.57%), meningitis (0.71%), and brainstem ischemia (0.24%). One patient died because of herpes encephalitis. Statistical analyses showed that the immediate postoperative disappearance of spasms and male gender are correlated with postoperative facial palsy, whereas combined vessel compressions involving the vertebral artery (VA) and anterior inferior cerebellar artery can predict postoperative hearing deterioration. VA compressions could predict postoperative lower cranial nerve deficits., Conclusions: MVD is safe and effective for treating HFS with a low rate of permanent morbidity. Proper patient positioning, sharp arachnoid dissection, and endoscopic visualization under facial and auditory neurophysiological monitoring are the key points to minimize the rate of complications in MVD for HFS.

Background: Eosinophilic granuloma (EG) belongs to the family of Langerhans cell histiocytosis (LCH) and is considered to be a benign disease typically found in children younger than 15 years of age. Here, the authors describe an EG of unusual localization and clinical presentation., Observations: The authors report a 9-year-old girl with an EG presenting as an osteolytic lesion of the clivus. After transsphenoidal resection and histological confirmation, adjuvant chemotherapy was initiated. Presenting signs and symptoms were weight loss, episodic grimacing, and moderate ballism-like movements. After a follow-up-period of 32 months, the patient presented with a total resolution of initial symptoms and no further tumor growth., Lessons: Although these lesions are rare, one should consider EG as a differential diagnosis when confronted with osteolytic lesions of the clivus.

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD ( n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD ( n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00-1.03], p = 0.05), moderated by IL-6 (Wald-χ 2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

Introduction: and Research Question: Invasive growth of meningiomas into CNS tissue is rare but of prognostic significance. While it has entered the WHO classification as a stand-alone criterion for atypia, its true prognostic impact remains controversial. Retrospective analyses, on which the current evidence is based, show conflicting results. Discordant findings might be explained by different intraoperative sampling methodologies., Material and Methods: To assess the applied sampling methods in the light of the novel prognostic impact of CNS invasion, an anonymous survey was designed and distributed via the EANS website and newsletter. The survey was open from June 5th until July 15th, 2022., Results: After exclusion of 13 incomplete responses, 142 (91.6%) datasets were used for statistical analysis. Only 47.2% of participants' institutions utilize a standardized sampling method, and 54.9% pursue a complete sampling of the area of contact between the meningioma surface and CNS tissue. Most respondents (77.5%) did not change their sampling practice after introduction of the new grading criteria to the WHO classification of 2016. Intraoperative suspicion of CNS invasion changes the sampling for half of the participants (49.3%). Additional sampling of suspicious areas of interest is reported in 53.5%. Dural attachment and adjacent bone are more readily sampled separately if tumor invasion is suspected (72.5% and 74.6%, respectively), compared to meningioma tissue with signs of CNS invasion (59.9%)., Discussion and Conclusions: Intraoperative sampling methods during meningioma resection vary among neurosurgical departments. There is need for a structured sampling to optimize the diagnostic yield of CNS invasion., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

This video demonstrates the purely endoscopic gross-total resection of a third ventricle colloid cyst that is partially covered by a large thalamostriate vein. To gain an ideal approach, the initial trajectory pointed to the interventricular septum above the cyst. After the head of the caudate nucleus is passed, it is retracted laterally by the endoscopic sheath for the ideal far lateral approach to the cyst. Using a pneumatic endoscope holder enables the surgeon to perform the procedure bimanually. After complete removal of the cyst, postoperative inspection confirms the intact fornix, veins, and caudate nucleus without signs of pressure-related damage. The video can be found here: https://stream.cadmore.media/r10.3171/2023.1.FOCVID22140., Competing Interests: Disclosures Dr. Schroeder reported personal fees from Karl Storz SE & Co. KG, Tuttlingen, Germany, during the conduct of the study.Dr. Schroeder reported personal fees from Karl Storz SE & Co. KG, Tuttlingen, Germany, during the conduct of the study., (© 2023, The Authors.)

Background: Epilepsy is common in patients harboring cavernous malformation, and surgery is reported to be an effective treatment. However, few patients still experience seizures after surgery. We analyzed the outcome and predictive factors after cavernoma-related epilepsy (CRE) surgery., Methods: A database was created for all patients with CRE treated surgically from 2003 to 2020 at a university hospital. A chart review, perioperative epilepsy workup, surgical strategies, and postoperative and follow-up notes were analyzed. Postoperative seizure outcome was evaluated according to the Engel classification., Results: Thirty-seven patients (40.5% women; mean age 39.1 ± 14.5 years) were studied. The mean follow-up time was 5.6 ± 3.9 years. Among 37 patients, 32 (86.5%) achieved Engel class I at the last follow-up. Engel class II was found in 1 (2.7%), Engel class III in 1 (2.7%), and Engel class IV in 3 (8.1%) cases. Engel class Ia was observed in 23 patients (62.2%). None of the patients had a worse seizure outcome after the operation (Engel class IVc). Univariate and multivariate analysis showed that short-standing, sporadic, or low-frequent (≤3) seizures were the only variables significantly associated with seizure freedom, whereas longstanding, drug-resistant, or high-frequent seizure history were associated with worse seizure outcomes., Conclusions: Surgical treatment results in favorable seizure control in most patients after CRE surgery. Long duration of epilepsy before surgery, high seizure frequency, and drug-resistant epilepsy could have a negative effect on seizure outcome (Engel class II-IV). Therefore, early surgical resection of the cavernoma after careful presurgical planning is recommended to achieve an optimal result., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Despite being rarely reported, ischemic insults resulting from compromising small brainstem perforators following microvascular decompression (MVD) remain a potential devastating complication. To avoid this complication, we have been using indocyanine green (ICG) angiography intraoperatively to check the flow within the small brainstem perforators. We aim to evaluate the safety and usefulness of ICG videoangiography in MVD., Methods: We extracted retrospective data of patients who received ICG videoangiography from our prospectively maintained database for microvascular decompression. We noted relevant data including demographics, offending vessels, operative technique, outcome, and complications., Results: Out of the 438 patients, 15 patients with a mean age (SD) of 53 ± 10.5 years underwent intraoperative ICG angiography. Male:female was 1:1.14. The mean disease duration prior to surgery was 7.7 ± 5.3 years. The mean follow-up (SD) was 50.7 ± 42.0 months. In 14 patients, the offending vessel was an artery, and in one patient, a vein. Intraoperative readjustment of the Teflon pledget or sling was required in 20% (3/15) of the cases. No patient had any sort of brainstem ischemia. Eighty percent of the patients (12/15) experienced complete resolution of the spasms. 86.7% (13/15) of the patients reported a satisfactory outcome with marked improvement of the spasms. Three patients experienced slight hearing affection after surgery, which improved in two patients later. There was no facial or lower cranial nerve affection., Conclusion: Intraoperative ICG is a safe tool for evaluating the flow within the brain stem perforators and avoiding brainstem ischemia in MVD for hemifacial spasm., (© 2022. The Author(s).)

Objective: Hydrocephalus is the most common brain disorder in children and is more common in low- and middle-income countries. Research output on hydrocephalus remains sparse and of lower quality in low- and middle-income countries compared with high-income countries. Most studies addressing hydrocephalus epidemiology are retrospective registry studies entailing their inherent limitations and biases. This study aimed to investigate child-related, parental, and socioeconomic risk factors of congenital hydrocephalus (CH) in a lower-middle-income country., Methods: An investigator-administered questionnaire was used to query parents of patients with CH and controls who visited the authors' institution from 2017 until 2021. Patients with secondary hydrocephalus and children older than 2 years of age at diagnosis were excluded. Uni- and multivariable logistic regression was performed to identify the factors affecting CH development., Results: Seven hundred forty-one respondents (312 cases and 429 controls) were included in this study. The authors showed that maternal diseases during pregnancy (OR 3.12, 95% CI 1.96-5.03), a lack of periconceptional folic acid intake (OR 1.92, 95% CI 1.32-2.81), being a housewife (OR 2.66, 95% CI 1.51-4.87), paternal illiteracy (OR 1.65, 95% CI 1.02-2.69), parental consanguinity (OR 3.67, 95% CI 2.40-5.69), a history of other CNS conditions in the family (OR 2.93, 95% CI 1.24-7.34), conceiving a child via assisted fertilization techniques (OR 3.93, 95% CI 1.57-10.52), and the presence of other congenital anomalies (OR 2.57, 95% CI 1.38-4.87) were associated with an independent higher odds of a child having CH. Conversely, maternal hypertension (OR 0.22, 95% CI 0.09-0.48), older maternal age at delivery (OR 0.93, 95% CI 0.89-0.97), and having more abortions (OR 0.80, 95% CI 0.67-0.95) were negatively correlated with CH., Conclusions: Multiple parental, socioeconomic, and child-related factors were associated with higher odds for developing CH. These results can be utilized to guide parental counseling and management, and direct social education and prevention programs.

Aim: Peripheral nerve tumors (PNT) are rare lesions. To date, no systematic multicenter studies on epidemiology, clinical symptoms, treatment strategies and outcomes, genetic and histopathologic features, as well as imaging characteristics of PNT were published. The main goal of our PNT Registry is the systematic multicenter investigation to improve our understanding of PNT and to assist future interventional studies in establishing hypotheses, determining potential endpoints, and assessing treatment efficacy., Methods: Aims of the PNT registry were set at the 2015 Meeting of the Section of Peripheral Nerve Surgery of the German Society of Neurosurgery. A study protocol was developed by specialists in PNT care. A minimal data set on clinical status, treatment types and outcomes is reported by each participating center at initial contact with the patient and after 1 year, 2 years, and 5 years. Since the study is coordinated by the Charité Berlin, the PNR Registry was approved by the Charité ethics committee (EA4/058/17) and registered with the German Trials Registry (www.drks.de). On a national level, patient inclusion began in June 2016. The registry was rolled out across Europe at the 2019 meeting of the European Association of Neurosurgery in Dublin., Results: Patient recruitment has been initiated at 10 centers throughout Europe and 14 additional centers are currently applying for local ethics approval., Conclusion: To date, the PNT registry has grown into an international study group with regular scientific and clinical exchange awaiting the first results of the retrospective study arm.

Background/aim: Glioblastoma (GBM) is the most common and most lethal type of cancer of the central nervous system in adults. Despite aggressive treatment, which is based on surgical resection, if possible, followed by radiation and chemotherapy, a high recurrence rate and therapy resistance is observed. Thus, additional innovative therapies are urgently needed to improve the poor median survival of only 15 months. Treatment of solid tumours with non-invasive physical plasma (NIPP) represents such a novel and innovative anticancer procedure., Materials and Methods: In this study, we investigated the effect of NIPP, an ionized argon gas, on the in vitro growth of human GBM cell lines, LN-18 and U-87 MG. Proliferation was measured by live cell count. Subsequently, proliferative factors were analysed at the level of nucleic acids (polymerase chain reaction) and proteins (western blotting)., Results: For both GBM lines, a treatment time-dependent decrease in growth was observed compared to controls. Additionally, NIPP treatment resulted in reduced rates of AKT serine/threonine kinase 1 (AKT1) and extracellular-regulated kinase 1/2 ERK1/2 expression, whereas expression of p21, proliferating cell nuclear antigen, and heat-shock proteins 90α and 90β was not affected. In both cell lines, a strong increase in expression of tumour-suppressive microRNA-1 (miR-1) was detected after exposure to NIPP., Conclusion: Our results demonstrated that NIPP is able to efficiently attenuate growth of GBM cells and suggest AKT1, ERK1/2 and miR-1 to be pivotal factors of NIPP-modulated cellular signalling. Translated into the clinical setting, NIPP may represent a promising option for the treatment of GBM., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62L low /CD45RO high ) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future.

•OGM surgery is much more complex than a simple debate of "from above or from below" (transcranial vs endoscopic).•Lateral Sub-frontal and Superior Interhemispheric seem the most effective, superior and versatile approaches for OGM.•Minimally Invasive Transcranial approaches showed no inferiority in OGM sized <4 ​cm.•Endoscopic Endonasal Approaches showed inferior results in surgical and in functional outcomes for OGM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Image 2, (© 2022 The Author(s).)

Background:  In recent years, a correlation of thrombocytosis and a worse prognosis was shown for many solid cancers, including glioblastoma multiforme (GBM)., Methods:  A retrospective review was performed for all patients with a histologically proven and first-diagnosed GBM between 2005 and 2015 in our department. Clinical and paraclinical parameters were acquired from patient documentation and structured for subsequent data analysis. The association of potential risk factors with overall survival was assessed using the Kaplan-Meier survival analysis and Cox regression., Results:  The present study includes 309 patients first diagnosed with primary GBM. Our analyses validate well-known risk factors of a decreased overall survival such as higher patient age, a larger preoperative tumor volume, Karnofsky performance status, extent of resection, tumor localization, and adjuvant treatment. However, no correlation was observed between a preoperative thrombocytosis, the mean platelet volume, leucocyte count, activated partial thromboplastin time (apTT), fibrinogen level, and acetylsalicylic acid 100 co-medication. Patients with preoperative hemoglobin below 7.5 mmol/L had decreased overall survival., Conclusion:  The present study, enrolling the largest numbers of patients assessing this topic to date, did not find any association between a preoperative thrombocytosis and overall survival in 309 patients with GBM., Competing Interests: None declared., (Thieme. All rights reserved.)

Indications for surgery of pineal cysts without ventriculomegaly are still under debate. In view of the limited data for pineal cyst resection in the absence of hydrocephalus, and the potential risk of this approach, we have analyzed our patient cohort focusing on strategies to avoid complications according to our experience in a series of 73 pineal cyst patients. From 2003 to 2015, we reviewed our database retrospectively for all patients operated on a pineal cyst. Furthermore, we prospectively collected patients from 2016 to 2020. In summary, 73 patients with a pineal cyst were treated surgically between 2003 and 2020. All patients were operated on via a microscopic supracerebellar-infratentorial (SCIT) approach. The mean follow-up period was 26.6 months (range: 6-139 months). Seventy-three patients underwent surgery for a pineal cyst. An absence of enlarged ventricles was documented in 62 patients (51 female, 11 male, mean age 28.1 (range 4-59) years). Main presenting symptoms included headache, visual disturbances, dizziness/vertigo, nausea/emesis, and sleep disturbances. Complete cyst resection was achieved in 59/62 patients. Fifty-five of 62 (89%) patients improved after surgery with good or even excellent results according to the Chicago Chiari Outcome Scale, with complete or partial resolution of the leading symptoms. Pineal cysts resection might be an indication in certain patients for surgery even in the absence of ventriculomegaly. The high percentage of postoperative resolution of quality-of-life impairing symptoms in our series seems to justify surgery. Preoperatively, other causes of the leading symptoms have to be excluded., (© 2022. The Author(s).)

Purpose: Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting are well-established treatments of obstructive hydrocephalus (HCP) in adult and pediatric patients. However, there is a lack of data with regard to the quality of life (QoL) of these patients during long-term follow-up METHODS: Inclusion criteria were pediatric patients with endoscopic treatment of hydrocephalus at the University Medicine Greifswald between 1993 and 2016. Patients older than 14 years at present were assessed with the Short Form-12 (SF-12) questionnaire. Patients younger than 14 years of age were assessed with the KINDL-R questionnaire that was completed by their parents. Patients' values were compared with the scores of a corresponding age-matched group of the healthy population and with patients who received later shunt treatment. Information about comorbidities, current symptoms, and educational level were gained by an additional part. Comparative analysis between patients with ETV success and failure (defined as shunt implantation after ETV) was performed., Results: A total of 107 patients (53 m, 54f) were included. Fifty-seven/107 patients (53.3%) were considered as ETV success. Mean age at ETV was 6.9 ± 5.9 years. Fifty-four statements of 89 patients that are still alive were gained (response rate 63%). Of these, 49 questionnaires were complete and evaluable (23 m, 26f; mean age 19.8 ± 10.0 years with an average follow-up period of 13.7 ± 7.2 years). Twenty-six/49 patients (53.1%) are considered ETV success. No statistically significant differences could be obtained between patients with ETV success and ETV failure. Patients older 14 years show QoL within normal range, patients younger than 14 years show significantly lower result regarding their environment of peers and social contacts. Patients younger than 6 months at the time of ETV and patients with posthemorrhagic HCP show significantly lower physical QoL. Gait disturbance, fatigue, and seizures are associated with a lower QoL, and educational level is lower than in the normal population., Conclusions: Patients who underwent ETV in childhood do not have a lower health-related QoL in general. Subsequent insertions of ventriculoperitoneal (vp) shunts do not lower QoL. Certain subgroups of the patients show lower results compared to the healthy population., (© 2022. The Author(s).)

Introduction: Cushing's disease is a state of chronic and excessive cortisol levels caused by a pituitary adenoma., Research Question: CD is a complex entity and often entails difficulties in its diagnosis and management. For that reason, there are still controversial points to that respect. The aim of this consensus paper of the skull base section of the EANS is to review the main aspects of the disease a neurosurgeon has to know and also to offer updated recommendations on the controversial aspects of its management., Material and Methods: PUBMED database was used to search the most pertinent articles published on the last 5 years related with the management of CD. A summary of literature evidence was proposed for discussion within the EANS skull base section and other international experts., Results: This article represents the consensual opinion of the task force regarding optimal management and surgical strategy in CD., Discussion and Conclusion: After discussion in the group several recommendations and suggestions were elaborated. Patients should be treated by an experienced multidisciplinary team. Accurate clinical, biochemical and radiological diagnosis is mandatory. The goal of treatment is the complete adenoma resection to achieve permanent remission. If this is not possible, the treatment aims to achieving eucortisolism. Radiation therapy is recommended to patients with CD when surgical options have been exhausted. All patients in remission should be tested all life-long., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

Endoscopic visualization during microvascular decompression for hemifacial spasm enables better identification of compression areas along the facial nerve, which is especially important in cases with complex compression and enlarged vessels obscuring the compression site. A 40-year-old man presented with a 10-year history of left hemifacial spasm. Magnetic resonance imaging showed a deep compression site with multiple vessels. Within the narrow space, the compression area was clearly visualized using an angled endoscope. Arterial transposition was performed using a polytetrafluoroethylene (Teflon) sling, which was fixed to the nearby dura using an aneurysm clip. Decompression was visually confirmed using the angled endoscope. The patient was free of spasms directly after surgery with no further complications and no recurrence of spasm during 6-month follow-up (Video 1)., (Copyright © 2022 Elsevier Inc. All rights reserved.)