Unilateral Multifocal Inner Ear and Internal Auditory Canal or Cerebellopontine Angle Cochleovestibular Schwannomas-Genetic Analysis and Management by Surgical Resection and Cochlear Implantation.

OBJECTIVE: To describe the genetic characteristics and the management of two very rare cases of unilateral multifocal inner ear and internal auditory canal or cerebellopontine angle cochleovestibular schwannomas not being associated to full neurofibromatosis type 2-related schwannomatosis. PATIENTS: In a 29-year-old man and a 55-year-old woman with single-sided deafness multifocal unilateral cochleovestibular schwannomas were surgically resected, and hearing was rehabilitated with a cochlear implant (CI). Unaffected tissue was analyzed using next generation sequencing of the NF2 gene. Tumor tissue was analyzed using a 340-parallel sequencing gene panel. MAIN OUTCOME MEASURES: Mutations in the NF2 gene, word recognition score for monosyllables at 65 dB SPL (WRS 65 ) with CI. RESULTS: No disease-causing mutation was detected in the examined sequences in blood leucokytes. All tumor samples revealed, among others, somatic pathogenic NF2 mutations. While the anatomically separate tumors in case 1 were likely molecular identical, the tumors in case 2 showed different genetic patterns. WRS 65 was 55% at 6 years of follow-up and 60% at 4.5 years of follow-up, respectively. CONCLUSIONS: The occurrence of multifocal unilateral cochleovestibular schwannomas without pathogenic variants in NF2 in non-affected blood leucocytes can be associated with mosaic NF2 -related schwannomatosis (case 1), or with likely sporadic mutations (case 2) and may be overlooked due to their extreme rarity. Although challenging, successful hearing rehabilitation could be achieved through surgical resection of the tumors and cochlear implantation.

Perceived Health Benefits in Vestibular Schwannoma Patients with Long-Term Postoperative Headache: Insights from Personality Traits and Pain Coping-A Cross-Sectional Study.

Postoperative headaches (POHs) following retrosigmoid microsurgery for vestibular schwannoma (VS) can significantly impact patients' perceived health benefits (PHBs). In this cross-sectional observational study, 101 VS patients were investigated. For the assessment of pain, the Rostock Headache Compendium (RoKoKo) and the German pain processing questionnaire (FESV) were used. The perceived health benefits (PHBs) were assessed by the Glasgow Benefit Inventory (GBI) and Big Five personality traits were measured using the Ten-Item Personality Inventory (TIPI-G). We showed that 55% of the participants experienced POHs, leading to a marked reduction in overall PHBs compared to those without POHs. The correlation analysis revealed an association between decreased PHBs and elevated levels of pain-related helplessness, depression, anxiety, and anger. Positive correlations were identified between PHBs and action-planning competence, cognitive restructuring, and the experience of competence. Low emotional stability and openness yielded associations with pain-related psychological impairment. Hearing loss and facial paresis did not exert a significant impact on PHBs. The study highlights the influence of pain-related coping strategies on PHBs in long-term POH patients. Thus, coping mechanisms and personality traits should be assessed even before surgery for post-surgery pain prevention. The limitations of this study include a relatively small sample size, potential biases introduced by the overrepresentation of female patients, and the use of an online survey methodology. In conclusion, this research highlights that the interplay between headaches, PHBs, and psychological factors is also relevant in VS patients undergoing microsurgery. Short-term psychological interventions should therefore be taken into account to improve post-surgery adaptive coping strategies.

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery.

BACKGROUND: Vasoplegia is common after cardiac surgery, is associated with hyperreninemia, and can lead to acute kidney stress. We aimed to conduct a pilot study to test the hypothesis that, in vasoplegic cardiac surgery patients, angiotensin-II (AT-II) may not increase kidney stress (measured by [TIMP-2]*[IGFBP7]). METHODS: We randomly assigned patients with vasoplegia (cardiac index [CI] > 2.1l/min, postoperative hypotension requiring vasopressors) and Δ-renin (4-hour postoperative-preoperative value) ≥3.7 µU/mL, to AT-II or placebo targeting a mean arterial pressure ≥65 mm Hg for 12 hours. The primary end point was the incidence of kidney stress defined as the difference between baseline and 12 hours [TIMP-2]*[IGFBP7] levels. Secondary end points included serious adverse events (SAEs). RESULTS: We randomized 64 patients. With 1 being excluded, 31 patients received AT-II, and 32 received placebo. No significant difference was observed between AT-II and placebo groups for kidney stress (Δ-[TIMP-2]*[IGFBP7] 0.06 [ng/mL]2/1000 [Q1-Q3, -0.24 to 0.28] vs -0.08 [ng/mL]2/1000 [Q1-Q3, -0.35 to 0.14]; P = .19; Hodges-Lehmann estimation of the location shift of 0.12 [ng/mL]2/1000 [95% confidence interval, CI, -0.1 to 0.36]). AT-II patients received less fluid during treatment than placebo patients (2946 vs 3341 mL, P = .03), and required lower doses of norepinephrine equivalent (0.19 mg vs 4.18mg, P < .001). SAEs were reported in 38.7% of patients in the AT-II group and in 46.9% of patients in the placebo group. CONCLUSIONS: The infusion of AT-II for 12 hours appears feasible and did not lead to an increase in kidney stress in a high-risk cohort of cardiac surgery patients. These findings support the cautious continued investigation of AT-II as a vasopressor in hyperreninemic cardiac surgery patients.

Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial.

PURPOSE: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. METHODS: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. RESULTS: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21-3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. CONCLUSION: One in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors.

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells.

Glioblastoma (GBM) is a highly aggressive brain tumor that often utilizes aerobic glycolysis for energy production (Warburg effect), resulting in increased methylglyoxal (MGO) production. MGO, a reactive dicarbonyl compound, causes protein alterations and cellular dysfunction via glycation. In this study, we investigated the effect of glycation on sialylation, a common post-translational modification implicated in cancer. Our experiments using glioma cell lines, human astrocytes (hA), and primary glioma samples revealed different gene expressions of sialyltransferases among cells, highlighting the complexity of the system. Glycation has a differential effect on sialyltransferase expression, upregulating ST8SIA4 in the LN229 and U251 cell lines and decreasing the expression in normal hA. Subsequently, polysialylation increased in the LN229 and U251 cell lines and decreased in hA. This increase in polysialylation could lead to a more aggressive phenotype due to its involvement in cancer hallmark processes such as immune evasion, resistance to apoptosis, and enhancing invasion. Our findings provide insights into the mechanisms underlying GBM aggressiveness and suggest that targeting glycation and sialylation could be a potential therapeutic strategy.

Elucidation of GPR55-Associated Signaling behind THC and LPI Reducing Effects on Ki67-Immunoreactive Nuclei in Patient-Derived Glioblastoma Cells.

GPR55 is involved in many physiological and pathological processes. In cancer, GPR55 has been described to show accelerating and decelerating effects in tumor progression resulting from distinct intracellular signaling pathways. GPR55 becomes activated by LPI and various plant-derived, endogenous, and synthetic cannabinoids. Cannabinoids such as THC exerted antitumor effects by inhibiting tumor cell proliferation or inducing apoptosis. Besides its effects through CB1 and CB2 receptors, THC modulates cellular responses among others via GPR55. Previously, we reported a reduction in Ki67-immunoreactive nuclei of human glioblastoma cells after GPR55 activation in general by THC and in particular by LPI. In the present study, we investigated intracellular mechanisms leading to an altered number of Ki67+ nuclei after stimulation of GPR55 by LPI and THC. Pharmacological analyses revealed a strongly involved PLC-IP3 signaling and cell-type-specific differences in Gα-, Gßγ-, RhoA-ROCK, and calcineurin signaling. Furthermore, immunochemical visualization of the calcineurin-dependent transcription factor NFAT revealed an unchanged subcellular localization after THC or LPI treatment. The data underline the cell-type-specific diversity of GPR55-associated signaling pathways in coupling to intracellular G proteins. Furthermore, this diversity might determine the outcome and the individual responsiveness of tumor cells to GPR55 stimulation by cannabin oids.

Personalized acute kidney injury treatment.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a complex syndrome that might be induced by different causes and is associated with an increased morbidity and mortality. Therefore, it is a very heterogeneous syndrome and establishing a "one size fits all" treatment approach might not work. This review aims to examine the potential of personalized treatment strategies for AKI. RECENT FINDINGS: The traditional diagnosis of AKI is based on changes of serum creatinine and urine output, but these two functional biomarkers have several limitations. Recent research identified different AKI phenotypes based on clinical features, biomarkers, and pathophysiological pathways. Biomarkers, such as Cystatin C, NGAL, TIMP2∗IGFBP7, CCL14, and DKK-3, have shown promise in predicting AKI development, renal recovery, and prognosis. Biomarker-guided interventions, such as the implementation of the KDIGO bundle, have demonstrated an improvement in renal outcomes in specific patient groups. SUMMARY: A personalized approach to AKI treatment as well as research is becoming increasingly important as it allows the identification of distinct AKI phenotypes and the potential for targeted interventions. By utilizing biomarkers and clinical features, physicians might be able to stratify patients into subphenotypes, enabling more individualized treatment strategies. This review highlights the potential of personalized AKI treatment, emphasizing the need for further research and large-scale clinical trials to validate the efficacy of these approaches.

Plasma ß-synuclein, GFAP, and neurofilaments in patients with malignant gliomas undergoing surgical and adjuvant therapy.

We analyzed the longitudinal concentrations and prognostic roles of plasma ß-synuclein (ß-syn), glial fibrillary acidic protein (GFAP), and neurofilament proteins (NfL and NfH) in 33 patients with malignant gliomas, who underwent surgical and adjuvant therapy. GFAP and NfL levels were increased in patients with glioblastoma compared to cases with other tumors. ß-syn, NfL and NfH increased after surgery, whereas GFAP decreased at long-term follow-up. ß-syn and neurofilament concentrations were influenced by surgery and/or radiotherapy regimens. GFAP and neurofilament levels were significantly associated with survival. Plasma neuronal and astrocytic biomarkers are differentially altered in malignant glioma types and displayed distinct trajectories after surgical and adjuvant therapy.

Premorbid Psychological Factors Associated with Long-Term Postoperative Headache after Microsurgery in Vestibular Schwannoma-A Retrospective Pilot Study.

Associations between premorbid psychological factors and postoperative headache (POH) after microsurgical treatment via the retrosigmoid approach for vestibular schwannoma (VS) were investigated in this retrospective single-center study. A total of 101 VS patients completed the Rostock headache questionnaire (RoKoKo), the hospital and anxiety scale (HADS-D), and the screening for somatoform disorders (SOMS-2), all of which were used as short self-assessed questionnaires. Fifty-four patients with POH were compared with 47 non-POH patients in terms of premorbid psychological factors, somatization tendencies, and psychological burden using the chi2-test and Mann-Whitney U-test. Regression analyses were conducted to assess the weighted contribution of psychological and procedural factors to POH. In individuals with POH, mental ailments, preexisting headaches, premorbid chronic pain syndromes, and higher somatization tendencies were found to be significantly more common. POH was predicted by the number of premorbid psychosomatic symptoms, preexisting mental ailments, and premorbid chronic pain syndromes. Depression and anxiety were predicted by low emotional stability. Additionally, the number of premorbid psychosomatic symptoms predicted depression, anxiety, and overall psychological burden. It was observed that the reported symptoms of headache might fit into the classification of chronic postsurgical pain (CPSP) rather than being classified as secondary headaches after craniotomy. Premorbid psychological factors were found to play an important role in the emergence of POH in VS, particularly after microsurgery via the retrosigmoid approach. Therefore, it is suggested that psychological screening be incorporated into the treatment process.

Establishment of vestibular schwannoma primary cell cultures obtained from cavitron ultrasonic surgical aspirator tissue material.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor arising from the Schwann cells of the eighth cranial nerve. The complexity in treatment is associated with unpredictable progression of this tumor. Some of the VS do not alter for years, while others rapidly increase in size. The mechanisms behind size progression are not well studied. Furthermore, despite several studies, there is no pharmacological treatment available for sporadic VS. Therefore, in vitro models are essential tools to study the cellular and molecular processes of VS. In addition, patient-derived cell cultures are important for substance screening to investigate pharmacological approaches in vitro. NEW METHOD: This study presents a simple and fast method for culturing VS cells from patient tissue material obtained using a cavitron ultrasonic surgical aspirator (CUSA). In addition, the cells were characterized based on the expression of schwannoma markers, growth properties and screened for fibroblast contamination. RESULT: We could show that CUSA obtained material is a suitable resource for isolation of VS primary cultures and enables real time analysis on living cells. COMPARISON WITH EXISTING METHODS: To date, only a few protocols are available for culturing VS cells from patient tissue material. A disadvantage of these methods is the relatively large amount of tissue needed to obtain the primary cells, which can be difficult, especially in small VS. By obtaining the cells from the CUSA, there is the possibility to establish a primary culture even with limited material. CONCLUSION: This approach could be particularly useful for testing substances that represent candidates for drug therapy of vestibular schwannoma.

Surgical Site Infections in Glioblastoma Patients-A Retrospective Analysis.

Surgical site infections (SSIs) after craniotomy lead to additional morbidity and mortality for patients, which are related to higher costs for the healthcare system. Furthermore, SSIs are associated with a longer hospital stay for the patient, which is particularly detrimental in glioblastoma patients due to their limited life expectancy. Risk factors for SSIs have already been described for craniotomies in general. However, there is limited data available for glioblastoma patients. As postoperative radiation influences wound healing, very early radiation is suspected to be a risk factor for SSI. Nevertheless, there are no data on the optimal timing of radiotherapy. To define risk factors for these patients, we analyzed our collective. We performed a retrospective analysis of all operations with histological evidence of a glioblastoma between 2012 and 2021. Open biopsy and tumor removal (gross total resection, subtotal resection) were included. Stereotactic biopsies were excluded. Demographic data such as age and gender, as well as duration of surgery, diameter of the trepanation, postoperative radiation with interval, postoperative chemotherapy, highest blood glucose level, previous surgery, ASA score, foreign material introduced, subgaleal suction drainage, ventricle opening and length of hospital stay, were recorded. The need for surgical revision due to infection was registered as an SSI. A total of 177 patients were included, of which 14 patients (7.9%) suffered an SSI. These occurred after a median of 45 days. The group with SSIs tended to include more men (57.1%, p = 0.163) and more pre-operated patients (50%, p = 0.125). In addition, foreign material and subgaleal suction drains had been implanted more frequently and the ventricles had been opened more frequently, without reaching statistical significance. Surprisingly, significantly more patients without SSIs had been irradiated (80.3%, p = 0.03). The results enable a better risk assessment of SSIs in glioblastoma patients. Patients with previous surgery, introduced foreign material, subgaleal suction drain and opening of the ventricle may have a slightly higher for SSIs. However, because none of these factors were significant, we should not call them risk factors. A less radical approach to surgery potentially involving these factors is not justified. The postulated negative role of irradiation was not confirmed, hence a rapid chemoradiation should be induced to achieve the best possible oncologic outcome.

Recurrences and progression following microsurgery of vestibular schwannoma.

Background: The treatment approach of vestibular schwannoma (VS) has seen a change in recent years, with a trend away from radical surgery towards preservation of cranial nerve function. A recent study reported recurrences as long as 20 years after complete removal of VS. Objective: To report the risk of recurrence and progression in our patient population the authors retrospectively reviewed outcomes of patients. Methods: Cases with unilateral VS who had undergone primary microsurgery via retrosigmoidal approach between 1995 and 2021 were investigated. Complete tumor removal was defined as gross total resection (GTR), a capsular remnant was categorized as near total resection (NTR) and residual tumor was designated as subtotal resection (STR). The primary endpoint was radiological recurrence-free survival. Results: 386 patients fulfilled the inclusion criteria of the study and were evaluated. GTR was achieved in 284 patients (73.6%), NTR was achieved in 63 patients (10.1%) and STR was present in 39 patients (16.3%). A total of 28 patients experienced recurrences with significant differences in the three subgroups. The strongest predictor of recurrence was the extent of resection, with patients who underwent STR having an almost 10-fold higher risk of recurrence and patients who had undergone NTR having an almost 3-fold higher risk than those treated with GTR. More than 20% of recurrences (6/28) occured after more than 5 years. Conclusion: The degree of resection is an important guide to the interval of follow-up, but long-term follow-up should be considered also in the case of GTR. The majority of recurrences occurs after 3-5 years. Nevertheless, a follow-up of at least 10 years should be carried out.

Glycation Leads to Increased Invasion of Glioblastoma Cells.

Glioblastoma (GBM) is a highly aggressive and invasive brain tumor with a poor prognosis despite extensive treatment. The switch to aerobic glycolysis, known as the Warburg effect, in cancer cells leads to an increased production of methylglyoxal (MGO), a potent glycation agent with pro-tumorigenic characteristics. MGO non-enzymatically reacts with proteins, DNA, and lipids, leading to alterations in the signaling pathways, genomic instability, and cellular dysfunction. In this study, we investigated the impact of MGO on the LN229 and U251 (WHO grade IV, GBM) cell lines and the U343 (WHO grade III) glioma cell line, along with primary human astrocytes (hA). The results showed that increasing concentrations of MGO led to glycation, the accumulation of advanced glycation end-products, and decreasing cell viability in all cell lines. The invasiveness of the GBM cell lines increased under the influence of physiological MGO concentrations (0.3 mmol/L), resulting in a more aggressive phenotype, whereas glycation decreased the invasion potential of hA. In addition, glycation had differential effects on the ECM components that are involved in the invasion progress, upregulating TGFß, brevican, and tenascin C in the GBM cell lines LN229 and U251. These findings highlight the importance of further studies on the prevention of glycation through MGO scavengers or glyoxalase 1 activators as a potential therapeutic strategy against glioma and GBM.

Subarachnoid Hemorrhage with Negative Initial Digital Subtraction Angiography: Subsequent Detection of Aneurysms and Complication Rates of Repeated Angiography.

BACKGROUND: The data on handling of spontaneous, nontraumatic subarachnoid hemorrhage (SAH) with negative initial digital subtraction angiography (DSA) are still inconclusive. The intention of this study was to evaluate the requirement of repeat DSA in patients with negative initial DSA and to compare the clinical outcomes of these cases. METHODS: In a retrospective study, we reviewed patients with SAH and negative initial DSA treated in our department from January 2006 until December 2017. The patients were divided according to an established radiographic classification into perimesencephalic (pm) and nonperimesencephalic (npm) SAH. An interventional neuroradiologist and a neurosurgeon reviewed all DSA scans. RESULTS: In all, 52 patients with negative initial DSA, comprising 36 (69.2%) patients with pm and 16 (30.8%) patients with npm bleeding pattern, were included. All patients underwent a second and 23 of these patients underwent a third DSA. In these 23 patients, subarachnoid blood distribution in the initial computed tomography (CT) scan was suspicious for the presence of aneurysm. In total, two aneurysms were detected during the second DSA (diagnostic yield: 3.85%). Both were in the pm group (diagnostic yield: 5.6%). The second repeat DSA did not show any causative vascular lesion. Complications after the DSA occurred in only 2 of 127 patients (1.6%). The rate of complications concerning vasospasm (pm 52.8%, npm 56.3%), hydrocephalus (pm 47.2%, npm 50%), and the need for temporary or permanent shunt (pm 44.4%, npm 50%) was similar in both groups and there was no statistically significant difference. CONCLUSION: Repeat DSA after negative initial DSA in pm SAH had a diagnostic yield of 5.6%. However, a second repeat DSA cannot be recommended in case of SAH with initial negative DSA. The pm SAH should not be underrated concerning the occurrence of complications and cared with a high level of surveillance.

Neural networks for estimation of facial palsy after vestibular schwannoma surgery.

PURPOSE: Facial nerve damage in vestibular schwannoma surgery is associated with A-train patterns in free-running EMG, correlating with the degree of postoperative facial palsy. However, anatomy, preoperative functional status, tumor size and occurrence of A-trains clusters, i.e., sudden A-trains in most channels may further contribute. In the presented study, we examine neural networks to estimate postoperative facial function based on such features. METHODS: Data from 200 consecutive patients were used to train neural feed-forward networks (NN). Estimated and clinical postoperative House and Brackmann (HB) grades were compared. Different input sets were evaluated. RESULTS: Networks based on traintime, preoperative HB grade and tumor size achieved good estimation of postoperative HB grades (chi2 = 54.8), compared to using tumor size or mean traintime alone (chi2 = 30.6 and 31.9). Separate intermediate nerve or detection of A-train clusters did not improve performance. Removal of A-train cluster traintime improved results (chi2 = 54.8 vs. 51.3) in patients without separate intermediate nerve. CONCLUSION: NN based on preoperative HB, traintime and tumor size provide good estimations of postoperative HB. The method is amenable to real-time implementation and supports integration of information from different sources. NN could enable multimodal facial nerve monitoring and improve postoperative outcomes.

Cranial and Spinal Metastasis of a Nonfunctioning Pituitary Adenoma: Report of a Case.

Pituitary carcinoma is a rare disease with surgical, radiotherapeutic, and chemotherapeutic treatment options. We present the case of a female patient diagnosed with a nonfunctioning pituitary adenoma who underwent several surgical procedures, radiations, and chemotherapeutic treatments with various substances. Sixteen years after the first diagnosis, a cranial and spinal metastatic spread of the tumor occurred. We opted for an individual therapy based on anecdotal evidence. Unfortunately, the recommended off-label treatment with a somatostatin analog substance was never given due to bureaucratic delays. This case report is about the challenging aspects of individual decision-making in rare neurosurgical diseases.

Rationale and design of the peripheral nerve tumor registry: an observational cohort study.

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.

Vestibular Schwannoma Volume and Tumor Growth Correlates with Macrophage Marker Expression.

Vestibular schwannoma is the most common benign tumor of the cerebellopontine angle and originates from Schwann cells surrounding the vestibulocochlear nerve. Since the size of the VS varies widely, affected patients suffer from symptoms of varying severity. It is often difficult to determine the optimal time for therapy, due to the unpredictability of the growth rate. Despite many investigations on influencing factors, no mechanism responsible for the increase in the growth rate of certain VS has been identified so far. Therefore, the present study investigates the influence of the seven markers: Ki-67, cyclooxygenase 2 (COX2), vascular endothelial growth factor (VEGF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), CD163, and CD68 on tumor progression and tumor size in a cohort of 173 VS. The markers were determined by quantitative PCR and correlated with tumor volume and VS growth rate. The analysis showed a significantly negative correlation of the Ki-67, COX2, and VEGF on tumor volume. Moreover, with a higher volume of VS, the expression of the macrophage markers CD68, CD163, and GM-CSF increased significantly. Our results suggest that the increase in VS size is not primarily due to Schwann cell growth but to an infiltration of macrophages. This may have an impact on non-invasive therapy to preserve the hearing function of affected patients.

Insufficient Closing Forces of Yasargil Titanium Clips in Two Small Aneurysms Detected with Intraoperative Indocyanine Green Videoangiography.

BACKGROUND AND STUDY AIMS: Aneurysm clips must have adequate closing forces because residual blood flow in clipped aneurysms may result in aneurysm recurrence. Such flow can be intraoperatively detected by visual inspection, microvascular Doppler sonography, indocyanine green videoangiography (ICG-V), angiography, and puncture. PATIENTS: We present two patients with ruptured very small middle cerebral artery aneurysms (3 and 2.9 mm). The necks of both aneurysms were microsurgically clipped with Yasargil aneurysm clips without any complications. RESULTS: In both aneurysms, visual inspection suggested complete occlusion, but ICG-V showed persistent residual blood flow between the middle parts of the clip blades.The first patient was treated with a 5.4-mm FT744T clip (closing force of 1.47 N). After the ICG-V finding, a second 3.9-mm FT714T clip (closing force of 1.08 N) was placed on the tips of the already implanted clip to increase the closing forces. Subsequent ICG-V did not show any further residual blood flow. In the second patient, the aneurysm was clipped with an 8.0-mm FE764K clip (closing force of 1.77 N). Intraoperative ICG-V showed persistent residual blood flow within the aneurysmal dome despite complete closure of the clip. The clip was repositioned closer to the parent vessel. Consecutive ICG-V did not show any residual blood flow. CONCLUSION: Visually undetected incomplete aneurysm occlusion can be revealed with ICG-V. In very small aneurysms, standard closing forces of clips may not be sufficient and complete closure of the clip branches should be intraoperatively validated with ICG-V.