Rare simultaneous fetal posterior cerebral artery and conventional posterior cerebral artery duplication in a patient with a ruptured posterior communicating artery aneurysm: illustrative case.

BACKGROUND: The fetal-type posterior cerebral artery (PCA) is defined as a variant anatomy in which the posterior communicating artery (PCOM) is larger than the hypoplastic or aplastic P1 segment of the PCA. The authors present the novel case of a patient with a duplicated right PCA in parallel with fetal-type and conventional PCAs supplying adjacent components of the PCA cerebral territory. OBSERVATIONS: A 59-year-old woman presented with a modified Fisher Scale score 4 subarachnoid hemorrhage. A right irregular PCOM aneurysm that measured 9.5 mm × 4.5 mm × 4.5 mm arose from the base of a variant branch supplying a portion of the PCA, rather than a conventional PCOM, and was found on digital subtraction angiography. Following endovascular coil embolization, the patient was discharged home. LESSONS: The fetal-type variant has implications for thromboembolic events. If an embolism occludes the anterior circulation in a patient with a fetal-type PCA, it may result in an infarct in the PCA territory. Awareness of cerebral arterial anatomy, including an atypical collateral supply, informs a treating team's latitude in tolerance of which sites must be preserved and which can be safely sacrificed. https://thejns.org/doi/10.3171/CASE23735.

Nighttime Treatment of Ruptured Intracranial Aneurysms Are Associated With Poor Outcomes.

BACKGROUND AND OBJECTIVES: Rebleeding of ruptured intracranial aneurysms (RIA) is associated with poor outcomes. Although immediate treatment of RIAs is preferred, optimal treatment timing is multifactorial and may be a complicating factor for achieving the best outcomes. The objective of this study was to compare outcomes for patients with RIAs as a function of treatment time of day. To the best of our knowledge, this is the first study that examines how treatment time of day influences treatment outcomes. METHODS: This retrospective single-center study included all patients who were treated, either surgically or endovascularly, for RIAs within 24 hours after admission. Exclusion criteria were blister, mycotic or giant aneurysms, or incomplete records. The modified Rankin Scale was used to evaluate treatment outcomes using multivariate analysis. Nighttime treatment was defined when greater than 50% of the procedure was performed between 10 pm and 7 am, with other times classified as daytime treatment. Off-hours treatment was defined when more than 50% of the procedure was performed between 7 pm and 7 am, with other times classified as on-hours. RESULTS: This study included 493 patients, with 84.2% (415) treated during the daytime, 15.8% (78) during the nighttime, 67.5% (333) during on-hours, and 32.5% (160) during off-hours. These groups did not differ according to age, sex, World Federation of Neurosurgical Societies and Fisher scales, aneurysm size, location, and surgical or endovascular treatment. Outcomes were favorable (modified Rankin Scale 0-2) for 72.0% (299) of patients treated during the daytime and 60.0% (46) of patients treated during the nighttime. Aneurysm treatment during the nighttime (OR: 0.50 [95% CI: 0.28-0.91], P = .023) but not during off-hours (OR: 0.76 [0.50-1.14], P = .18) was independently associated with unfavorable outcomes. CONCLUSION: Nighttime treatment was associated with poorer outcomes. Further studies are needed to evaluate outcomes if treatment is postponed to daytime hours.

Microsurgical posterior fossa re-exploration for recurrent trigeminal neuralgia after previous microvascular decompression: common grounds-scarring, deformation, and the "piston effect".

OBJECTIVE: Microvascular decompression (MVD) is a well-accepted treatment modality for trigeminal neuralgia (TN) with high initial success rates. The causes for recurrence of TN after previously successful MVD have not been fully clarified, and its treatment is still a matter of debate. Here, we present the surgical findings and the clinical outcome of patients with recurrent TN after MVD who underwent posterior fossa re-exploration. METHODS: Microsurgical posterior fossa re-exploration was performed in 26 patients with recurrent TN (mean age 59.1 years) who underwent MVD over a period of 10 years. The trigeminal nerve was exposed, and possible factors for recurrent TN were identified. Arachnoid scars and Teflon granulomas were dissected meticulously without manipulating the trigeminal nerve. Outcome of posterior fossa re-exploration was graded according to the Barrow Neurological Institute (BNI) pain intensity score. Follow-up was analyzed postoperatively at 3, 12, and 24 months and at the latest available time point for long-term outcome. RESULTS: The mean duration of recurrent TN after the first MVD was 20 months. Pain relief was achieved in all patients with recurrent TN on the first postoperative day. Intraoperative findings were as follows: arachnoid scar tissue in 22/26 (84.6%) patients, arterial compression in 1/26 (3.8%), venous contact in 8/26 (30.8%), Teflon granuloma in 14/26 (53.8%), compression by an electrode in Meckel's cave used for treatment of neuropathic pain in 1/26 (3.8%), evidence of pulsations transmitted to the trigeminal nerve through the Teflon inserted previously/scar tissue ("piston effect") in 15/26 (57.7%), and combination of findings in 18/26 (69.2%). At long-term follow-up (mean 79.5 months; range, 29-184 months), 21/26 (80.8%) patients had favorable outcome (BNI I-IIIa). New hypaesthesia secondary to microsurgical posterior fossa re-exploration occurred in 5/26 (19.2%) patients. CONCLUSIONS: Posterior fossa re-exploration avoiding manipulation to the trigeminal nerve, such as pinching or combing, may be a useful treatment option for recurrent TN after previously successful MVD providing pain relief in the majority of patients with a low rate of new hypaesthesia.

Parenthood and neurosurgery in Europe a white paper from the European Association of Neurosurgical Societies' Diversity in Neurosurgery Committee Part I - Family Planning and Practice during Pregnancy.

Introduction: Family and work have immensely changed and become intertwined over the past half century for both men and women. Additionally, alongside to traditional family structures prevalent, other forms of families such as single parents, LGBTQ + parents, and bonus families are becoming more common. Previous studies have shown that surgical trainees regularly leave residency when considering becoming a parent due to the negative stigma associated with pregnancy during training, dissatisfaction with parental leave options, inadequate lactation and childcare support, and desire for greater mentorship on work-life integration. Indeed, parenthood is one of the factors contributing to attrition in surgical specialities, neurosurgery not being an exception. Research question: The Diversity in Neurosurgery Committee (DC) of the European Association of Neurosurgical Societies (EANS) recognizes the challenges individuals face in parenthood with neurosurgery and wishes to address them in this white paper. Materials and methods: In the following sections, the authors will focus on the issues pertaining to family planning and neurosurgical practice during pregnancy in itemized fashion based on an exhaustive literature search and will make recommendations to address the matters raised. Results: Potential solutions would be to further improve the work-family time ration as well as improving working conditions in the hospital. Discussion and conclusion: While many obstacles have been quoted in the literature pertaining to parenthood in medicine, and in neurosurgery specifically, initiatives can and should be undertaken to ensure not only retention of colleagues, but also to increase productivity and job satisfaction of those seeking to combine neurosurgery and a family life, regardless of their sexual identity and orientation.

Women in leadership positions in European neurosurgery - Have we broken the glass ceiling?

Introduction: The proportion of male neurosurgeons has historically been higher than of women, although at least equal numbers of women have been entering European medical schools. The Diversity Committee (DC) of the European Association of Neurosurgical Societies (EANS) was founded recently to address this phenomenon. Research question: In this cross-sectional study, we aimed to characterize the status quo of female leadership by assessing the proportion of women heading European neurosurgical departments. Material and methods: European neurosurgical departments were retrieved from the EANS repository. The gender of all department chairs was determined via departmental websites or by personal contact. The proportion of females was stratified by region and by type of hospital (university versus non-university). Results: A total of 41 (4.3%) female department chairs were identified in 961 neurosurgery departments in 41 European countries. Two thirds (68.3%) of European countries do not have a female neurosurgery chair. The highest proportion of female chairs was found in Northern Europe (11.1%), owing to four female chairs in a relatively small number of departments (n = 36). The proportions were considerably smaller in Western Europe (n = 17/312 (5.5%)), Southern Europe (n = 14/353 (4.0%)) and Central and Eastern Europe (n = 6/260 (2.3%)) (p = 0.06). The distribution of female chairs in university (n = 19 (46.3%)) versus non-university departments (n = 22 (53.7%)) was even. Discussion and Conclusion: There is a significant gender imbalance with 4% of all European neurosurgery departments headed by women. The DC intends to develop strategies to support equal chances and normalize the presence of female leaders in European neurosurgery.

Severity Assessment of Complex and Repeated Intracranial Surgery in Rats.

INTRODUCTION: Evidence-based grading of the impact of intracranial surgery on rat's well-being is important for ethical and legal reasons. We assessed the severity of complex and repeated intracranial surgery in a 6-hydroxydopamine (6-OHDA) Parkinson's rat model with subsequent intracranial electrode implantation and in an intracranial tumor model with subsequent resection. METHODS: Stereotactic surgery was performed in adult male rats with the same general anesthesia and perioperative pain management. In Parkinson's model, Sprague Dawley rats received unilateral injection of 6-OHDA (n = 11) or vehicle (n = 7) into the medial forebrain bundle as first operation (1st OP). After four weeks, neural electrodes were implanted in all rats as second operation (2nd OP). For tumor formation, BDIX/UlmHanZtm rats (n = 8) received frontocortical injection of BT4Ca cells as 1st OP, followed by tumor resection as 2nd OP after one week. Multiple measures severity assessment was done two days before and four days after surgery in all rats, comprising clinical scoring, body weight, and detailed behavioral screening. To include a condition with a known burden, rats with intracranial tumors were additionally assessed up to a predefined humane endpoint that has previously been classified as "moderate". RESULTS: After the 1st OP, only 6-OHDA injection resulted in transient elevated clinical scores, a mild long-lasting weight reduction, and motor disturbances. After the second surgery, body weight was transiently reduced in all groups. All other parameters showed variable results. Principal component analysis showed a separation from the preoperative state driven by motor-related parameters after 6-OHDA injection, while separation after electrode implantation and more clearly after tumor resection was driven by pain-related parameters, although not reaching the level of the humane endpoint of our tumor model. CONCLUSION: Overall, cranial surgery of different complexity only transiently and rather mildly affects rat's well-being. Multiple measures assessment allows the differentiation of model-related motor disturbances in Parkinson's model from potentially pain-related conditions after tumor resection and electrode implantation.

Resection of posterior fossa tumors in the semi-sitting position in children younger than 4 years of age.

PURPOSE: The semi-sitting position for resection of posterior fossa tumors is a matter of ongoing debate. Here we report about our experience with this approach in children younger than 4 years of age. METHODS: We retrospectively analyzed data of children younger than 4 years of age operated on in our institution in the semi-sitting position over a 15-year period. Patients were intraoperatively monitored for venous air embolism (VAE) by transthoracic Doppler (TTD) or transesophageal echocardiography (TEE). The severity of VAE was classified according to the Tübingen grading scale. Intraoperative incidents of VAE were recorded and the patients' course was followed postoperatively with a special focus on possible complications. RESULTS: Twenty-four children (18 boys, 6 girls) were operated on in the semi-sitting position (26 operations). Mean age was 2.2 years (± 1.0), range between 0.4 and 3.9 years. External ventricular drains were inserted in 18 children with hydrocephalus preoperatively. VAE was detected in 6 instances during surgery (6/26 (23.1%)). In 3 patients with grade 1 VAE, no additional treatment was necessary. In one patient with grade 2 VAE, intracardiac air suction via the central venous catheter was performed, and in two patients with grade 4 VAE, additional cathecholamine-infusion was administered. No major intraoperative complications occurred. Postoperative CT images showed pneumocephalus in all children. In two children, small asymptomatic impression skull fractures at the site of the Mayfield pin occurred. Revision surgery was necessary in one child with a suboccipital CSF fistula. CONCLUSION: The semi-sitting position for resection of tumors in the posterior fossa in children younger than 4 years of age can be safely performed in experienced centers taking special caution to detect and treat potential complications in an interdisciplinary setting.

Routine postoperative admission to the neurocritical intensive care unit after microvascular decompression: necessary or can it be abandoned?

Postoperative neurocritical intensive care unit (NICU) admission of patients who underwent craniotomy for close observation is common practice. In this study, we performed a comparative analysis to determine if there is a real need for NICU admission after microvascular decompression (MVD) for cranial nerve disorders or whether it may be abandoned. The present study evaluates a consecutive series of 236 MVD surgeries performed for treatment of trigeminal neuralgia (213), hemifacial spasm (17), vagoglossopharyngeal neuralgia (2), paroxysmal vertigo (2), and pulsatile tinnitus (2). All patients were operated by the senior surgeon according to a standard protocol over a period of 12 years. Patients were admitted routinely to NICU during the first phase of the study (phase I), while in the second phase (phase II), only patients with specific indications would go to NICU. While 105 patients (44%) were admitted to NICU postoperatively (phase I), 131 patients (56%) returned to the ward after a short stay in a postanaesthesia care unit (PACU) (phase II). Specific indications for NICU admission in phase I were pneumothorax secondary to central venous catheter insertion (4 patients), AV block during surgery, low blood oxygen levels after extubation, and postoperative dysphagia and dysphonia (1 patient, respectively). There were no significant differences in the distribution of ASA scores or the presence of cardiac and pulmonary comorbidities like congestive heart failure, arterial hypertension, or chronic obstructive pulmonary disease between groups. There were no secondary referrals from PACU to NICU. Our study shows that routine admission of patients after eventless MVD to NICU does not provide additional value. NICU admission can be restricted to patients with specific indications. When MVD surgery is performed in experienced hands according to a standard anaesthesia protocol, clinical observation on a neurosurgical ward is sufficient to monitor the postoperative course. Such a policy results in substantial savings of costs and human resources.

Operative findings and outcome of microvascular decompression/adhesiolysis for trigeminal neuralgia in multiple sclerosis without demyelinating brain stem lesions.

OBJECTIVE: Trigeminal neuralgia (TN) in multiple sclerosis (MS) poses several challenges for treatment. Although these patients often have typical attacks, they may not be considered as candidates for microvascular decompression (MVD). Here we report on surgical findings and long term follow-up of MVD/ adhesiolysis in a series of patients with multiple sclerosis but without demyelinating brain stem lesions. METHODS: Fifteen patients with MS-related TN underwent MVD/ adhesiolysis. Demyelinating brain stem lesions were excluded radiologically. Outcome of the intervention was assessed according to the Barrow Neurological Institute (BNI) pain intensity score at 3, 12, 24 months follow-up and at the last available follow-up (mean 88.2 months, range 38-146). RESULTS: All 15 patients benefited from MVD/adhesiolysis and were pain free on the first day of surgery. Intraoperative findings included arterial contact in 7/15 (47 %) patients, venous contact in 9/15 (60 %), and prominent arachnoid thickening in 12/15 (80 %). The distribution of the BNI pain intensity scores showed marked improvement at all follow-up evaluations. Five patients underwent repeat MVD/adhesiolysis for pain recurrence at a mean of 43 months after the first surgery. Long term evaluation at the last available follow-up demonstrated favorable outcome in 13/15 patients (BNI I-IIIa) (87 %), while 2/15 patients had limited benefit (BNI IV). CONCLUSIONS: MS-related TN in patients without demyelinating brain stem lesions may be related either to vascular conflicts or to focal arachnoiditis at the trigeminal nerve entry zone. MVD/ adhesiolysis may be considered as a useful treatment option in this subgroup of patients with regard to long term outcome.

Microvascular decompression: is routine postoperative CT imaging necessary?

BACKGROUND: Postoperative head CT imaging is routinely performed for detection of postoperative complications following intracranial procedures. However, it remains unclear whether with regard to radiation exposure, costs, and possibly lack of consequences this practice is truly justified in various operative procedures. The objective of this study was to analyze whether routine postoperative CT imaging after microvascular decompression (MVD) is necessary or whether it may be abandoned. METHODS: A series of 202 MVD surgeries for trigeminal neuralgia (179), hemifacial spasm (17), vagoglossopharyngeal neuralgia (2), paroxysmal vertigo (2), and pulsatile tinnitus (2) operated by the senior surgeon (JKK) and who had postoperative routine CT imaging was analyzed. RESULTS: Routine postoperative CT imaging detected small circumscribed postoperative hemorrhage in 9/202 (4.4%) instances. Hemorrhage was localized at the site of the Teflon felt (1/9), the cerebellum (4/9), in the frontal subdural space (3/9), and in the frontal subarachnoid space (1/9). In two patients, asymptomatic hemorrhage was accompanied by mild cerebellar edema (1%), and another patient had mild transient hydrocephalus (0.5%). Furthermore, there were small accumulations of intracranial air in 86/202 instances. No other complications such as infarction or skull fracture secondary to fixation with the Mayfield clamp were detected. MVD had been performed for trigeminal neuralgia in 6/9 patients, for hemifacial spasm in 2/9, and in one patient with both. No patient underwent a second surgery. Hemorrhage was symptomatic at the time of imaging in only one instance who had mild postoperative gait ataxia. Two patients with hemorrhage developed delayed facial palsy most likely unrelated to hemorrhage which remitted with corticosteroid treatment. At 3-month follow-up and at long-term follow-up, they had no neurological deficits. CONCLUSION: Routine postoperative CT imaging is not necessary after MVD in a standard setting in patients who do not have postoperative neurological deficits.

Tumour-treating fields (TTFields): Investigations on the mechanism of action by electromagnetic exposure of cells in telophase/cytokinesis.

Tumour-treating fields (TTFields) use alternating electric fields which interfere with dividing cells, thereby reducing tumour growth. Previous reports suggest that electrical forces on cell structure proteins interfered with the chromosome separation during mitosis and induced apoptosis. In the present report we evaluate electromagnetic exposure of cells in telophase/cytokinesis in order to further analyse the mechanism of action on cells. We performed numerical electromagnetic simulations to analyse the field distribution in a cell during different mitotic phases. Based thereon, we developed an electric lumped element model of the mitotic cell. Both the electromagnetic simulation and the lumped element model predict a local increase of the specific absorption rate (SAR) as a measure of the electromagnetically induced power absorption density at the mitotic furrow which may help to explain the anti-proliferative effect. In accordance with other reports, cell culture experiments confirmed that TTFields reduce the proliferation of different glioma cell lines in a field strength- and frequency-dependent manner. Furthermore, we found an additional dependence on the commutation time of the electrical fields. The report gives new insights into TTFields' anti-proliferative effect on tumours, which could help to improve future TTFields application systems.

The Role of Neurosurgery in the Treatment of Intracranial Tumor-Like Inflammatory Lesions.

BACKGROUND: Different inflammatory diseases can manifest as intracranial lesions. They may be indistinguishable from intracranial neoplasms in the clinical setting, imaging studies, or laboratory studies. The value of surgery in the diagnosis and the treatment of such lesions is still unclear. METHODS: A total of 3066 reports of histopathologic examinations over a 10-year period were reviewed. Forty patients with an inflammatory intracranial lesion were identified. Clinical, radiologic, and follow-up data were analyzed and the diagnostic and therapeutic value of surgery was assessed. RESULTS: We identified 24 women and 16 men (mean age, 47 years). The diameter of the lesion varied between 1 and 5.5 cm (mean, 2.6 cm). The location of the inflammatory lesion was intracerebral supratentorial (n = 18, 45%), intrasellar/suprasellar (n = 5, 12.5%), cerebellar (n = 5, 12.5%), in the brainstem (n = 4, 10%), in the cerebellopontine angle (n = 3, 7.5%), meningeal (n = 3, 7.5%), and at other locations (n = 6, 15%). Seventeen patients underwent surgical removal of the mass lesion, whereas in 23 patients a biopsy was taken. The lesions were classified into 7 groups: specific (infectious) granuloma (n = 10, 25%), unspecific granuloma (n = 7, 17.5%), idiopathic inflammatory pseudotumor (n = 5, 12.5%), demyelinating lesions (n = 5, 12.5%) encapsulated hematoma (n = 4, 10%), organized cerebral infarction (n = 3, 7.5%), and vasculitis (n = 4, 10%). Surgery was judged as valuable in 35 patients (87.5%). CONCLUSIONS: The differential diagnosis of intracranial inflammatory lesions involves a wide spectrum. Surgery has a diagnostic and/or therapeutic value in most entities and clinical circumstances. However, attention must be taken to avoid surgery without a therapeutic or diagnostic value for the patient.

Intracranial foreign material granulomas after cranial surgery.

BACKGROUND: Various synthetic materials are used in neurosurgery and left in place intentionally during surgery for several purposes such as hemostasis, dural closure, or cranioplasty. Although leaving such substances in surgical sites is considered safe, in general, foreign body granuloma may occur months or years after intracranial surgery. Thus, far relatively little is known about treatment and outcome of such lesions. METHODS: A systematic review of 3466 histopathological examinations after cranial surgeries achieved over a 13-year period was performed. After excluding patients with Teflon granulomas or infection, a total of 12 patients with foreign body granulomas induced by synthetic material used in a prior surgery were identified. Patient records, imaging studies, and histopathological data were analyzed. Furthermore, postoperative outcome was assessed. RESULTS: Mean age at the second surgery was 51 years (range, 11-68 years). The median time between the primary and the secondary surgery was 13 months (range, 1-545 months). Eight patients (75%) presented with signs and symptoms related to the foreign body granulomas. Total resection of the foreign body granulomas was performed in all patients. The granulomas were induced by oxidized cellulose polymer (n = 6), suture material (n = 3), Gelfoam (n = 1), methylmethacrylate (n = 1), and bone wax (n = 1). The mean postoperative follow-up time was 54 months (range 1-137 months). There was symptomatic improvement in all instances. Imaging studies did not demonstrate any recurrence. CONCLUSION: Despite its rarity, foreign body granuloma should be taken into consideration in the differential diagnosis of intracranial mass lesions especially in cases of suspected tumor recurrence after prior surgery. The pathogenesis of foreign body granuloma still needs further clarification. Our study demonstrates that they have good prognosis after surgical removal.

Severe Subarachnoid Hemorrhage Due to Fusiform Lateral Anterior (A1) Artery Perforator Aneurysm with "Spontaneous Resolution".

Perforating arteries are thin and long vessels which originate from the main cerebral arteries. Subarachnoidal hemorrhage from a perforator aneurysm is rare. Here, we report on a 70-year-old woman who presented with severe subarachnoid hemorrhage from a fusiform lateral anterior (A1) artery perforator aneurysm. Unexpectedly, digital subtraction angiography was non-diagnostic. MR imaging, however, demonstrated occlusion of the aneurysm secondary to thrombosis. Surgery was performed to remove the associated hematoma, and histopathological examination verified intraaneurysmal thrombosis.

Severe Cerebral Complications Secondary to Perforation Injury of the Anterior Skull Base During Sinonasal Surgery: An Underappreciated Problem?

OBJECTIVE: Functional endonasal sinus surgery (FESS) is widely practiced and is considered a generally safe procedure. Skull base injuries occur in <1% of procedures and are typically associated with cerebrospinal fluid leaks. Rarely, skull base injuries might result in cerebral lesions. Here we present a series of 4 patients with iatrogenic perforating injuries of the anterior skull base and cerebral lesions after routine FESS. METHODS: Four patients with iatrogenic perforating cerebral lesions after routine FESS, performed at other institutions, were referred to a tertiary neurosurgery department. Within a 10-year period these procedures were performed in 3 patients as endoscopic FESS and as a microscopic FESS in 1 patient. RESULTS: There were 3 men and 1 woman. Mean age at the time of surgery was 50 years. In 3 instances (in which an endoscope was used), the ear, nose, and throat physician had noted perforation of the skull base during surgery, but it went unnoticed in 1 patient operated with the microscope. Frontal lobe hematoma occurred in all patients, and in 3 of them cerebral infarction developed secondary to injury of branches of the anterior cerebral artery. Three patients developed acute hydrocephalus. Two had rapid global brain swelling and they succumbed within days. The other 2 patients survived without apparent neurological deficits. CONCLUSIONS: Cerebral lesions during FESS still occur in contemporary surgery and they are possibly underreported. Even with prompt conservative and surgical measures, these lesions may result in catastrophic outcome. Associated vascular injuries have a worse prognosis. The only risk factor associated with lethal outcome in our series was younger age.

Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis.

Taxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. Cabazitaxel (XRP-6258, Jevtana®) is a second generation semisynthetic taxane with high chemotherapeutic potential in prostate cancer. There, cabazitaxel can overcome docetaxel-resistant prostate cancer. Here, we tested the effects of cabazitaxel on glioma cells, and non-transformed cells such as neurons and astrocytes. Cabazitaxel operates highly toxic in various human glioma cells at nanomolar concentrations. In contrast, primary astrocytes and neurons are not affected by this agent. Cabazitaxel disrupts cytoskeletal F-actin fibers and induces apoptotic cell death in gliomas. Moreover, cabazitaxel displayed highest efficacy in inhibiting glioma cell migration and invasion. Here we demonstrate that cabazitaxel inhibited tumor migration already at 1 nM. We also tested cabazitaxel in the ex vivo VOGiM assay. Cabazitaxel stalled glioma growth and at the same time inhibited tumor-induced angiogenesis. In summary, we found that cabazitaxel operates as an apoptosis-inducing gliomatoxic agent with strongest effects on migration and invasive growth. Thus, our report uncovered cabazitaxel actions on gliomas and on the brain tumor microenvironment. These data reveal novel aspects for adjuvant approaches when applied to brain tumor patients.

PRG3 induces Ras-dependent oncogenic cooperation in gliomas.

Malignant gliomas are one of the most devastating cancers in humans. One characteristic hallmark of malignant gliomas is their cellular heterogeneity with frequent genetic lesions and disturbed gene expression levels conferring selective growth advantage. Here, we report on the neuronal-associated growth promoting gene PRG3 executing oncogenic cooperation in gliomas. We have identified perturbed PRG3 levels in human malignant brain tumors displaying either elevated or down-regulated PRG3 levels compared to non-transformed specimens. Further, imbalanced PRG3 levels in gliomas foster Ras-driven oncogenic amplification with increased proliferation and cell migration although angiogenesis was unaffected. Hence, PRG3 interacts with RasGEF1 (RasGRF1/CDC25), undergoes Ras-induced challenges, whereas deletion of the C-terminal domain of PRG3 (PRG3ΔCT) inhibits Ras. Moreover PRG3 silencing makes gliomas resistant to Ras inhibition. In vivo disequilibrated PRG3 gliomas show aggravated proliferation, invasion, and deteriorate clinical outcome. Thus, our data show that the interference with PRG3 homeostasis amplifies oncogenic properties and foster the malignancy potential in gliomas.