Search

Erika CS Künstler,1,2 Matthias Schwab,1,2 Henry WS Schroeder,3 Sven Rupprecht1,2 1Department of Neurology, Jena University Hospital, Jena, Germany; 2Interdisciplinary Centre for Sleep and Ventilatory Medicine, Jena University Hospital, Jena, Germany; 3Department of Neurosurgery, University Medicine Greifswald, Greifswald, GermanyCorrespondence: Erika CS Künstler, Department of Neurology, Jena University Hospital, Am Klinikum 1, Jena, D-07747, Germany, Tel +49 3641 9323525, Email Erika.Kuenstler@med.uni-jena.deObjective: 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.Keywords: symptomatic narcolepsy, arachnoid cyst, excessive daytime sleepiness, remission, case report

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.)

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.

Introduction: Orbital surgery has always been disputed among specialists, mainly neurosurgeons, otorhinolaryngologists, maxillofacial surgeons and ophthalmologists. The orbit is a borderland between intra- and extracranial compartments; Krönlein's lateral orbitotomy and the orbitozygomatic infratemporal approach are the historical milestones of modern orbital-cranial surgery., Research Question: Since its first implementation, endoscopy has significantly impacted neurosurgery, changing perspectives and approaches to the skull base. Since its first application in 2009, transorbital endoscopic surgery opened the way for new surgical scenario, previously feasible only with extensive tissue dissection., Material and Methods: A PRISMA based literature search was performed to select the most relevant papers on the topic., Results: Here, we provide a narrative review on the current state and future trends in endoscopic orbital surgery., Discussion and Conclusion: This manuscript is a joint effort of the EANS frontiers committee in orbital tumors and the EANS skull base section., Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article., (© 2023 The Authors.)

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.

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.)

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).)

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.)

Introduction: The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated., Research Question: The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section., Material and Methods: We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts., Results: 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases., Discussion and Conclusion: After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy., (Crown Copyright © 2022 Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies. Several experimental studies have suggested gas plasma technology, a partially ionized gas that generates a potent mixture of reactive oxygen species (ROS), as a future complement to the existing treatment arsenal. However, aspects such as immunomodulation, inflammatory consequences, and feasibility studies using GBM tissue have not been addressed so far. In vitro, gas plasma generated ROS that oxidized cells and led to a treatment time-dependent metabolic activity decline and G2 cell cycle arrest. In addition, peripheral blood-derived monocytes were co-cultured with glioblastoma cells, and immunomodulatory surface expression markers and cytokine release were screened. Gas plasma treatment of either cell type, for instance, decreased the expression of the M2-macrophage marker CD163 and the tolerogenic molecule SIGLEC1 (CD169). In patient-derived GBM tissue samples exposed to the plasma jet kINPen ex vivo, apoptosis was significantly increased. Quantitative chemokine/cytokine release screening revealed gas plasma exposure to significantly decrease 5 out of 11 tested chemokines and cytokines, namely IL-6, TGF-β, sTREM-2, b-NGF, and TNF-α involved in GBM apoptosis and immunomodulation. In summary, the immuno-modulatory and proapoptotic action shown in this study might be an important step forward to first clinical observational studies on the future discovery of gas plasma technology's potential in neurosurgery and neuro-oncology especially in putative adjuvant or combinatory GBM treatment settings.

Introduction: The evolution of cavernous sinus meningiomas (CSMs) might be unpredictable and the efficacy of their treatments is challenging due to their indolent evolution, variations and fluctuations of symptoms, heterogeneity of classifications and lack of randomized controlled trials. Here, a dedicated task force provides a consensus statement on the overall management of CSMs., Research Question: To determine the best overall management of CSMs, depending on their clinical presentation, size, and evolution as well as patient characteristics., Material and Methods: Using the PRISMA 2020 guidelines, we included literature from January 2000 to December 2020. A total of 400 abstracts and 77 titles were kept for full-paper screening., Results: The task force formulated 8 recommendations (Level C evidence). CSMs should be managed by a highly specialized multidisciplinary team. The initial evaluation of patients includes clinical, ophthalmological, endocrinological and radiological assessment. Treatment of CSM should involve experienced skull-base neurosurgeons or neuro-radiosurgeons, radiation oncologists, radiologists, ophthalmologists, and endocrinologists., Discussion and Conclusion: Radiosurgery is preferred as first-line treatment in small, enclosed, pauci-symptomatic lesions/in elderly patients, while large CSMs not amenable to resection or WHO grade II-III are candidates for radiotherapy. Microsurgery is an option in aggressive/rapidly progressing lesions in young patients presenting with oculomotor/visual/endocrinological impairment. Whenever surgery is offered, open cranial approaches are the current standard. There is limited experience reported about endoscopic endonasal approach for CSMs and the main indication is decompression of the cavernous sinus to improve symptoms. Whenever surgery is indicated, the current trend is to offer decompression followed by radiosurgery., 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.)

Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research. We have previously demonstrated that PIM1 is involved in survival of GBM cells and in GBM growth in a mouse model. However, little is known about the importance of PIM1 in cancer stem cells. Here, we report on the role of PIM1 in GBM stem cell behavior and killing. PIM1 inhibition negatively regulates the protein expression of the stem cell markers CD133 and Nestin in GBM cells (LN-18, U-87 MG). In contrast, CD44 and the astrocytic differentiation marker GFAP were up-regulated. Furthermore, PIM1 expression was increased in neurospheres as a model of GBM stem-like cells. Treatment of neurospheres with PIM1 inhibitors (TCS PIM1-1, Quercetagetin, and LY294002) diminished the cell viability associated with reduced DNA synthesis rate, increased caspase 3 activity, decreased PCNA protein expression, and reduced neurosphere formation. Our results indicate that PIM1 affects the glioblastoma stem cell behavior, and its inhibition kills glioblastoma stem-like cells, pointing to PIM1 targeting as a potential anti-glioblastoma therapy.

The middle turbinate's basal lamella (3BL) is a variable landmark which needs to be understood in endoscopic transnasal skull base surgery. It comprises an anterior frontal and a posterior horizontal part and appears in its simplest depiction to be "L"-shaped, when viewed laterally. In this study we analyzed its 3D morphology and variations focusing on a precise and systematic description of the anatomy. CBCTs of 25 adults, 19 cadavers and 6 skulls (total: 100 sides) were investigated with the 3DSlicer software, creating 3D models of the 3BL. We introduced a novel geometrical classification of the 3BL's shape, based on segments. We analyzed their parameters and relationship to neighboring structures. When viewed laterally, there was no consistent "L"-shaped appearance of the 3BL, as it is frequently quoted. A classification of 9 segment types was used to describe the 3BL. The 3BLs had in average of 2.95 ± 0.70 segments (median: 3), the most frequent was the horizontal plate (23.05% of all segments), next a concave/convex plate (22.71%), then a sigma plate (22.37%). Further types were rare. We identified a horizontal plate in 68% of all lateral views whilst 32% of the 3BLs were vertical. A sigma-concave/convex-horizontal trisegmental 3BL was the most common phenotype (27%). Globally, the sigma-concave/convex pattern was present in 42%. The 3BL adhered the ethmoidal bulla in 87%. The segmenting method is eligible to describe the 3BL's sophisticated morphology., (© 2021. The Author(s).)