Falcotentorial Meningiomas: Insights from Surgical Strategies and Clinical Outcomes.

Background: Falcotentorial meningiomas are exceptionally uncommon tumors, presenting a challenge for neurosurgeons due to their close proximity to vital structures. Gross total resection represents the standard of treatment for these tumors. However, care must be taken when surgically approaching these lesions, since damaging neurovascular structures may cause unacceptable morbidity. Selecting the optimal surgical approach for each tumor is of paramount importance when treating these patients. Methods: The authors reviewed medical records to identify all patients with falcotentorial meningiomas who underwent resection at the University Hospital of Freiburg between January 2001 and December 2021. Clinical and imaging data, surgical management, and clinical outcomes were analyzed. Results: Falcotentorial meningiomas occurred in 0.7% (15 of 2124 patients) of patients with intracranial meningiomas. Of these 15 patients, 8 were female and 7 male. The occipital interhemispheric approach was used in nine patients, the supracerebellar infratentorial approach in five patients, and the retrosigmoidal approach in one patient. Three patients developed visual field deficits after surgical resection. Incomplete resection was significantly associated with tumor progression (p < 0.05). Conclusions: Individualized surgical strategies, guided by preoperative imaging and classification systems, play a crucial role in optimizing patient care. Among the available approaches, the occipital interhemispheric and supracerebellar infratentorial approaches are frequently employed and considered among the safest options for these tumors.

Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older-Retrospective International Multicenter Study.

BACKGROUND AND OBJECTIVES: Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool. METHODS: Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm 3 ), medium (10-50 cm 3 ), and large (>50 cm 3 ). RESULTS: The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm 3 and 27.3 cm 3 ; large PTBE volume correlated with poor preoperative KPS status ( P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery. CONCLUSION: Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.

Multiomic spatial landscape of innate immune cells at human central nervous system borders.

The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system.

Management of Medial Sphenoid Wing Meningioma Involving the Cavernous Sinus: A Single-Center Series of 105 Cases.

OBJECTIVE: Medial sphenoid wing meningiomas are among the three most common intracranial meningiomas. These tumors pose a challenge to neurosurgeons in terms of surgical treatment, as they may involve critical neurovascular structures and invade the cavernous sinus. In case of the latter, a complete resection may not be achievable. The purpose of this study was to investigate prognostic features affecting recurrence and progression-free survival (PFS) of medial sphenoid wing meningiomas involving the cavernous sinus, focusing on the contribution of surgery and postoperative radiotherapy. METHODS: A retrospective analysis was conducted of the database of our institution, and 105 cases of medial sphenoid wing meningioma with invasion of the cavernous sinus, which were treated between 1998 and 2019, were included. Surgical treatment only was performed in 64 cases, and surgical treatment plus postoperative radiotherapy was performed in 41 cases. Kaplan-Meier analysis was conducted to estimate median survival and PFS rates, and Cox regression analysis was applied to determine significant factors that were associated with each therapeutic modality. RESULTS: The risk of recurrence was significantly reduced after near-total resection (NTR) (p-value = 0.0011) compared to subtotal resection. Progression-free survival was also significantly prolonged after postoperative radiotherapy (p-value = 0.0002). CONCLUSIONS: Maximal safe resection and postoperative stereotactic radiotherapy significantly reduced the recurrence rate of medial sphenoid wing meningiomas with infiltration of the cavernous sinus.

Basic Surveillance Parameters Improve the Prediction of Delayed Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Background: To establish a practical risk chart for prediction of delayed cerebral infarction (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) by using information that is available until day 5 after ictus. Methods: We assessed all consecutive patients with aSAH admitted to our service between September 2008 and September 2015 (n = 417). The data set was randomly split into thirds. Two-thirds were used for model development and one-third was used for validation. Characteristics that were present between the bleeding event and day 5 (i.e., prior to >95% of DCI diagnoses) were assessed to predict DCI by using logistic regression models. A simple risk chart was established and validated. Results: The amount of cisternal and ventricular blood on admission CT (Hijdra sum score), early sonographic vasospasm (i.e., mean flow velocity of either intracranial artery >160 cm/s until day 5), and a simplified binary level of consciousness score until day 5 were the strongest predictors of DCI. A model combining these predictors delivered a high predictive accuracy [the area under the receiver operating characteristic (AUC) curve of 0.82, Nagelkerke's R 2 0.34 in the development cohort]. Validation of the model demonstrated a high discriminative capacity with the AUC of 0.82, Nagelkerke's R 2 0.30 in the validation cohort. Conclusion: Adding level of consciousness and sonographic vasospasm between admission and postbleed day 5 to the initial blood amount allows for simple and precise prediction of DCI. The suggested risk chart may prove useful for selection of appropriate candidates for interventions to prevent DCI.

Early cisternal fibrinolysis is more effective than rescue spasmolysis for the prevention of delayed infarction after subarachnoid haemorrhage.

BACKGROUND: To compare the efficacy of two different concepts of cisternal therapy-PREVENTIVE fibrinolysis plus on-demand spasmolysis versus RESCUE spasmolysis-for the prevention of cerebral vasospasm (CVS) and delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid haemorrhage (aSAH). METHODS: Retrospective analysis of 84 aSAH patients selected for cisternal therapy for DCI prevention. 66 high-risk patients received PREVENTIVE cisternal therapy to enhance blood clearance. Either stereotactic catheter ventriculocisternostomy (STX-VCS) or intraoperative placement of a cisterno-ventriculostomy catheter (CVC), followed by fibrinolytic cisternal lavage using urokinase was performed. In case of vasospasm, nimodipine was applied intrathecally. 22 low-risk patients who developed CVS against expectations were selected for STX-VCS as RESCUE intervention for cisternal spasmolysis with nimodipine. Rates of DCI and mean flow velocities of daily transcranial Doppler (TCD) ultrasonographies were evaluated. RESULTS: Despite a higher prespecified DCI risk, patients selected for PREVENTIVE intervention primarily aiming at blood clearance had a lower DCI rate compared with patients selected for intrathecal spasmolysis as a RESCUE therapy (11.3% vs 18.2%). After intrathecal treatment onset, CVS (TCD>160 cm/s) occurred in 45% of patients with PREVENTIVE and 77% of patients with RESCUE therapy (p=0.013). A stronger response of CVS to intrathecal nimodipine was observed in patients with PREVENTIVE intervention as the mean CVS duration after start of intrathecal nimodipine was 3.2 days compared with 5.8 days in patients with RESCUE therapy (p=0.026). CONCLUSIONS: PREVENTIVE cisternal therapy directed at blood clearance is more effective for the prevention of CVS and delayed infarction compared with cisternal RESCUE spasmolysis. TRIAL REGISTRATION NUMBER: DRKS00016532.

Progression-Free Survival, Prognostic Factors, and Surgical Outcome of Spheno-Orbital Meningiomas.

OBJECTIVE: Spheno-orbital meningiomas (SOM) are rare intracranial tumors that arise at the sphenoid wing. These tumors can invade important neurovascular structures making radical resection difficult, while residual tumors often lead to recurrence. The purpose of this study was to evaluate prognostic factors influencing the recurrence and progression-free survival (PFS) rates of spheno-orbital meningiomas, with a particular focus on the role of surgery and postoperative radiotherapy. METHODS: Between 2000 and March 2020, 65 cases of spheno-orbital meningioma were included, of which 50 cases underwent surgical treatment alone, and 15 cases underwent resection and radiotherapy. A Kaplan-Meier analysis was performed to provide median point estimates and PFS rates; further, Cox regression analysis was used to identify significant factors associated with treatment. RESULTS: Gross total resection significantly reduced the risk of recurrence (p-value = 0.0062). There was no significant benefit for progression-free survival after postoperative radiotherapy (p-value = 0.42). Additionally, spheno-orbital meningiomas with an invasion of the cavernous sinus and intraconal invasion showed significantly worse PFS compared to other locations (p-value = 0.017). CONCLUSION: The maximal safe resection remains the most important prognostic factor associated with lower recurrence rates and longer PFS in patients with spheno-orbital meningioma. The invasion of the cavernous sinus and intraconal invasion was an independent factor associated with worse PFS. Patients with postoperative high-precision radiotherapy did not show significantly better PFS due to the small number of patients.

Patterns of intracerebral hemorrhage that result in unfavorable outcomes in patients with subarachnoid hemorrhage.

OBJECTIVE(S): Intracerebral hemorrhage (ICH) contributes considerably to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH). Specific patterns of aSAH-associated ICH that are not compatible with favorable outcome remain unknown. The main objective of this study is to report patterns of aSAH-associated ICH that result in unfavorable outcomes. METHODS: This is a retrospective analysis of 1036 consecutive aSAH patients admitted to an academic neurosurgical center in a 15-year period (01/2005-12/2019). Admission imaging was investigated for presence, location and size of intracerebral hemorrhage. The rates of favorable outcome at 6 months (modified Rankin Scale) relative to ICH location and volume were analyzed to identify patterns of ICH which were incompatible with favorable outcome. RESULTS: 284 of 1036 patients (27.4%) suffered from aSAH-related ICH. The median ICH volume was 14.0 ml. Outcome of patients with ICH < 10 ml was comparable to patients without ICH. ICH volumes > 10 ml were associated with worse outcomes. We identified the fronto-basal brain to tolerate even larger ICH without compromise of neurological outcomes. ICH located in the frontal, fronto-insular, temporo-insular and temporal regions were associated with intermediate prognoses as outcome declined with larger ICH volumes. ICH located in the basal ganglia, cerebellum, corpus callosum and bifrontal ICH were associated with particularly poor outcomes irrespective of ICH volumes. CONCLUSION: aSAH-associated ICH of the basal ganglia, cerebellum, corpus callosum and bifrontal brain are associated with exceptionally poor outcomes. ICH volume alone is insufficient for prognostic considerations.

Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial.

BACKGROUND: Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer's solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH. METHODS: This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0-3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints. DISCUSSION: New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer's solution. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645 . Registered on 8 May 2019.

[Orbital decompression in Graves' orbitopathy-Experiences and results]. / Orbitadekompression bei endokriner Orbitopathie ­ Erfahrungen und Ergebnisse.

BACKGROUND: Graves' orbitopathy is the most frequent extrathyroidal manifestation of Graves' disease, affecting approximately 25-50% of patients. It leads to inflammation and swelling of orbital soft tissues. The treatment is mostly conservative. Surgical orbital decompression is indicated in severe cases with disfiguring exophthalmos or an acute steroid-refractive threat to vision, facilitating visual and cosmetic recovery. An important aspect in the quality of care is the avoidance of postoperative diplopia. OBJECTIVE: To report experiences and results from 100 cases of orbital decompression surgery performed on 62 patients at a multidisciplinary orbit center. Patients with signs of apical crowding were treated by pterional decompression. Patients without signs of apical crowding were treated either by deep lateral wall resection or pterional decompression. METHODS: A retrospective data analysis was carried out. RESULTS: The mean reduction in exophthalmos was 2.9 mm. Visual acuity improved by a mean of 2.2 lines in eyes with sight-threatening disease. In moderate to severe disease, visual acuity remained stable. The complication rate was 4%. New postoperative diplopia occurred after two interventions and one patient experienced a deterioration in visual acuity from 0.8 to 0.1. In nine cases, surgery led to a complete regression of previously reported double vision. CONCLUSION: Visual acuity gain, reduction of exophthalmos and complications in this collective are comparable to previously published results. The results of this study confirm the role of orbital decompression in the treatment of sight-threatening and severely disfiguring endocrine orbitopathy.

Impact of Stereotactic Ventriculocisternostomy on Delayed Cerebral Infarction and Outcome After Subarachnoid Hemorrhage.

Background and Purpose- Delayed cerebral infarction (DCI) is an important cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Stereotactic catheter ventriculocisternostomy (STX-VCS) and fibrinolytic/spasmolytic lavage is a new method for DCI prevention. Here, we assess the effects of implementing STX-VCS in an unselected aSAH patient population of a tertiary referral center. Methods- Retrospective cohort study of all consecutive aSAH patients admitted to a neurosurgical referral center during a 7-year period (April 2012 to April 2019). Midterm STX-VCS was introduced and offered to patients at high risk for DCI. We compared the incidence and burden of DCI, neurological outcome, and the use of induced hypertension and endovascular rescue therapy in this consecutive aSAH population 3.5 years before versus 3.5 years after STX-VCS became available. Results- Four hundred thirty-six consecutive patients were included: 222 BEFORE and 214 AFTER. Fifty-seven of 214 (27%) patients received STX-VCS. Stereotactic procedures resulted in one (2%) subdural hematoma. Favorable neurological outcome at 6 months occurred in 118 (53%) patients BEFORE and 139 (65%) patients AFTER (relative risk, 0.79 [95% CI, 0.66-0.95]). DCI occurred in 40 (18.0%) patients BEFORE and 17 (7.9%) patients AFTER (relative risk, 0.68 [95% CI, 0.57-0.86]), and total DCI volumes were 8933 (100%) and 3329 mL (36%), respectively. Induced hypertension was used in 97 (44%) and 30 (15%) patients, respectively (relative risk, 0.55 [95% CI, 0.46-0.65]). Thirty (13.5%) patients BEFORE versus 5 (2.3%) patients AFTER underwent endovascular rescue therapies (relative risk, 0.17 [95% CI, 0.07-0.42]). Conclusions- Selecting high-risk patients for STX-VCS reduced the DCI incidence, burden, and related mortality in a consecutive aSAH patient population. This was associated with an improved neurological outcome.

Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma.

Reactive astrocytes evolve after brain injury, inflammatory and degenerative diseases, whereby they undergo transcriptomic re-programming. In malignant brain tumors, their function and crosstalk to other components of the environment is poorly understood. Here we report a distinct transcriptional phenotype of reactive astrocytes from glioblastoma linked to JAK/STAT pathway activation. Subsequently, we investigate the origin of astrocytic transformation by a microglia loss-of-function model in a human organotypic slice model with injected tumor cells. RNA-seq based gene expression analysis of astrocytes reveals a distinct astrocytic phenotype caused by the coexistence of microglia and astrocytes in the tumor environment, which leads to a large release of anti-inflammatory cytokines such as TGFß, IL10 and G-CSF. Inhibition of the JAK/STAT pathway shifts the balance of pro- and anti-inflammatory cytokines towards a pro-inflammatory environment. The complex interaction of astrocytes and microglia cells promotes an immunosuppressive environment, suggesting that tumor-associated astrocytes contribute to anti-inflammatory responses.

Cisternal lavage via third ventriculostomy through the fenestrated lamina terminalis after aneurysm clipping: Technical note.

Delayed cerebral infarction (DCI) contributes to the burden of morbidity and mortality acquired by patients with aneurysmal subarachnoid hemorrhage (SAH). Cisternal lavage may prevent DCI. Delivery of lavage therapy to the basal cisterns, however, is challenging. Here, we report a novel method for the delivery of cisternal lavage using a cisterno-ventricular catheter (CVC) inserted via the fenestrated lamina terminalis during aneurysm clipping. In two high-risk aSAH patients a CVC was inserted into the third ventricle through the fenestrated lamina terminalis during aneurysm clipping. Post-operatively, continuous cisternal lavage using Urokinase or Nimodipine was applied using an external ventricular drain (EVD) as inflow tract and the CVC as outflow tract. Neurological outcome at 6 months was assessed by modified Rankin scale. Catheter placement into the third ventricle through the fenestrated lamina terminalis was performed without complications. Application of a free-running electrolyte solution containing Urokinase or Nimodipine via the EVD and drainage via the CVC was feasible. Cisternal Nimodipine application normalized sonographic vasospasm in both cases. DCI did not occur. CVC placement for ventriculo-cisternal lavage may represent a useful method for DCI prevention. It can be considered in aSAH patients at risk for DCI if the chiasmatic region is accessed during aneurysm clipping.

MR-spectroscopic imaging of glial tumors in the spotlight of the 2016 WHO classification.

BACKGROUND: The purpose of this study is to map spatial metabolite differences across three molecular subgroups of glial tumors, defined by the IDH1/2 mutation and 1p19q-co-deletion, using magnetic resonance spectroscopy. This work reports a new MR spectroscopy based classification algorithm by applying a radiomics analytics pipeline. MATERIALS: 65 patients received anatomical and chemical shift imaging (5 × 5 × 20 mm voxel size). Tumor regions were segmented and registered to corresponding spectroscopic voxels. Spectroscopic features were computed (n = 860) in a radiomic approach and selected by a classification algorithm. Finally, a random forest machine-learning model was trained to predict the molecular subtypes. RESULTS: A cluster analysis identified three robust spectroscopic clusters based on the mean silhouette widths. Molecular subgroups were significantly associated with the computed spectroscopic clusters (Fisher's Exact test p < 0.01). A machine-learning model was trained and validated by public available MRS data (n = 19). The analysis showed an accuracy rate in the Random Forest model by 93.8%. CONCLUSIONS: MR spectroscopy is a robust tool for predicting the molecular subtype in gliomas and adds important diagnostic information to the preoperative diagnostic work-up of glial tumor patients. MR-spectroscopy could improve radiological diagnostics in the future and potentially influence clinical and surgical decisions to improve individual tumor treatment.

Expression differences of programmed death ligand 1 in de-novo and recurrent glioblastoma multiforme.

The biology of recurrent glioblastoma multiforme (GBM) is a dynamic process influenced by selection pressure induced by different antitumoural therapies. The poor clinical outcome of tumours in the recurrent stage necessitates the development of effective therapeutic strategies. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy being investigated in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo and recurrent glioblastoma multiforme and to explore associated genetic alterations and clinical traits. We show that PD-L1 expression was reduced in recurrent GBM in comparison to de-novo GBM. Additionally, patients who received an extended dose of temozolomide (TMZ) chemotherapy showed a significantly reduced level of PD-L1 expression in the recurrence stage compared to the corresponding de-novo tumour. Our findings may provide an explanation for potentially lower response to immunotherapy in the recurrent stage due to the reduced expression of the therapeutic target PD-L1.

Malignant Transformation of a Dysembryoplastic Neuroepithelial Tumor (DNET) Characterized by Genome-Wide Methylation Analysis.

Dysembryoplastic neuroepithelial tumors (DNET) are considered to be rare, benign, and associated with chronic epilepsy. We present the case of a 28-year-old man with a history of epilepsy since age 12. Surgery of an occipital cortical lesion in 2009 revealed a DNET. Five years later, a recurrent tumor at the edge of the resection cavity was removed, and the tissue underwent an intensive diagnostic workup. The first tumor was unequivocally characterized as a DNET, but neuropathological diagnostics of the recurrent tumor revealed a glioblastoma. After 6 months, another recurrent tumor was detected next to the location of the original tumor, and this was also resected. An Illumina 450 K beadchip methylation array was performed to characterize all of the tumors. The methylation profile of these tumors significantly differed from other glioblastoma and epilepsy-associated tumor profiles and revealed a DNET-like methylation profile. Thus, molecular characterization of these recurrent tumors suggests malignant transformation of a previously benign DNET. We found increased copy number changes in the recurrent DNET tumors after malignant transformation. Modern high-throughput analysis adds essential molecular information in addition to standard histopathology for proper identification of rare brain tumors that present with an unusual clinical course.