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.

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.

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.

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.

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.

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.

Nimodipine Treatment Protects Auditory Hair Cells from Cisplatin-Induced Cell Death Accompanied by Upregulation of LMO4.

Ototoxicity is one of the main dose-limiting side effects of cisplatin chemotherapy and impairs the quality of life of tumor patients dramatically. Since there is currently no established standard therapy targeting hearing loss in cisplatin treatment, the aim of this study was to investigate the effect of nimodipine and its role in cell survival in cisplatin-associated hearing cell damage. To determine the cytotoxic effect, the cell death rate was measured using undifferentiated and differentiated UB/OC-1 and UB/OC-2 cells, after nimodipine pre-treatment and stress induction by cisplatin. Furthermore, immunoblot analysis and intracellular calcium measurement were performed to investigate anti-apoptotic signaling, which was associated with a reduced cytotoxic effect after nimodipine pre-treatment. Cisplatin's cytotoxic effect was significantly attenuated by nimodipine up to 61%. In addition, nimodipine pre-treatment counteracted the reduction in LIM Domain Only 4 (LMO4) by cisplatin, which was associated with increased activation of Ak strain transforming/protein kinase B (Akt), cAMP response element-binding protein (CREB), and signal transducers and activators of transcription 3 (Stat3). Thus, nimodipine presents a potentially well-tolerated substance against the ototoxicity of cisplatin, which could result in a significant improvement in patients' quality of life.

Learning from EMG: semi-automated grading of facial nerve function.

The current grading of facial nerve function is based on subjective impression with the established assessment scale of House and Brackmann (HB). Especially for research a more objective method is needed to lower the interobserver variability to a minimum. We developed a semi-automated grading system based on (facial) surface EMG-data measuring the facial nerve function of 28 patients with vestibular schwannoma surgery. The sEMG was recorded preoperatively, postoperatively and after 3-12 months. In addition, the HB grade was determined. After manual selection and preprocessing, the data were subjected to machine learning classificators (Logistic regression, SVM and KNN). Lateralization indices were calculated and multivariant machine learning analysis was performed according to three scenarios [differentiation of normal (1) and slight (2) vs. impaired facial nerve function and classification of HB 1-3 (3)]. The calculated AUC for each scenario showed overall good differentiation capability with a median AUC of 0.72 for scenario 1, 0.91 for scenario 2 and multiclass AUC of 0.74 for scenario 3. This study approach using sEMG and machine learning shows feasibility regarding facial nerve grading in perioperative VS-surgery setting. sEMG may be a viable alternative to House Brackmann regarding objective evaluation of facial function especially for research purposes.

Epithelioid Hemangioendothelioma in the Area of the Neurovascular Bundle of the Upper Arm Mimicking a Schwannoma of the Ulnar Nerve.

Epithelioid hemangioendothelioma (EH) is a rare vascular malignant sarcoma. To date, there are only two published case reports of EH mimicking nerve sheath tumors of a peripheral nerve. A 41-year-old woman presented with a painful node on the inside of the upper arm and motor deficits of the ulnar nerve. Magnetic resonance imaging (MRI) follow-up and neurosonography revealed a slowly progressive, contrast-enhancing tumor in the area of the neurovascular bundle. A schwannoma of the ulnar nerve was suspected. At surgery, the tumor was adherent to the brachial artery, but not to nerves. Pathology revealed an EH. EH may mimic a nerve sheath tumor and should be taken into consideration, especially because of its potential for metastasis and fatal progression.

[Macroscopic and microscopic changes of the vestibulocochlear nerve after Gamma Knife treatment]. / Makroskopische und mikroskopische Veränderungen des N. vestibulocochlearis nach Gamma-Knife-Therapie.

We report on a case in which macroscopic and microscopic changes of the vestibulocochlear nerve could be observed after radiosurgery of an intrameatal vestibular schwannoma. This case shows for the first time a morphological correlate for undesirable effects after radiosurgical treatment of a vestibular schwannoma and indicates that despite a certain distance to the actual tumor, degenerative changes in neural structures can be expected.

Volumetry and Surgical Grading Systems for Vestibular Schwannoma Size Assessment and their Relationship to Postoperative Facial Nerve Function.

BACKGROUND AND STUDY AIMS: Treatment modalities in vestibular schwannoma (VS) are difficult to compare since different techniques for size measurements are used. The purpose of this study was to evaluate the relation between different tumor size grading systems regarding their compatibility as well as the relationship to facial nerve outcome facilitating comparisons of different studies. MATERIAL AND METHODS: In this retrospective study, preoperative magnetic resonance imaging of 100 patients with surgically treated VS was evaluated regarding total tumor volume and anatomical extension based on the Koos and Samii classification, as well as volumetric and maximal diameter measures. Three-dimensional constructive interference in steady state (3D-CISS) and T1 postcontrast volumetric interpolated breath-hold examination (VIBE) sequences were used. Facial nerve function was evaluated according to the House-Brackmann (HB) scale 6 months following complete tumor removal via the retrosigmoid approach. RESULTS: Tumor size showed a moderate influence on postsurgical facial nerve function with correlations not exceeding 0.4. Severe palsy was observed mainly in patients with large tumors with Koos grade 4, Samii grade 4b, respectively a volume of at least 6 cm3 or a maximum diameter of 2.4 cm for HB ≥ 3 and a volume of 7.5 cm3 and maximum diameter of 3.2 cm for HB ≥ 4. In regard to volumetry, the Koos and Samii grading systems were highly comparable, whereas the maximal diameter showed consistently lower correlation values. CONCLUSIONS: The results of our study allow direct comparison of studies on surgery versus radiotherapy of VS. The data allow for translation of tumor sizes based on different grading systems. Comparison of microsurgical, radiotherapeutic and radiosurgical approaches should concentrate on patients with large tumors. Whereas smaller tumors were rarely associated with severe facial palsy, large tumors did not exclude the possibility of weak or no palsy 6 months after surgery.

Variability in the distance from the end of the gray matter to the end of the conus medullaris: a case-triggered histological investigation.

OBJECTIVE: The background for this investigation was the dramatic course of a 14-year-old girl with a spontaneous hemorrhage in the area of the conus medullaris resulting in a complete cross-sectional syndrome with bladder and bowel dysfunction. Despite immediate surgical treatment, the patient showed close to no postoperative improvement. Subsequent histopathological examination of the removed masses revealed a cavernoma. To better understand the link between the site and symptoms of conus medullaris lesions, the authors performed a literature search and then histological examination of the conus medullaris of 18 cadaveric specimens from body donors. METHODS: After a literature search regarding the histological features of the structure of the conus medullaris did not lead to satisfying results, the authors performed histological examination of the conus medullaris in 18 cadaveric specimens from body donors. The largest (a) and smallest (b) diameters of the conus medullaris were measured, noting individual variations in the distance from the caudal ending of the gray matter to the macroscopically visible end of the conus medullaris. Correlations of these differences with sex, body height, gray matter transverse diameter, and cross-sectional area at the end of the gray matter were analyzed. RESULTS: Gray matter displayed in the form of a butterfly figure was found along almost the entire length of the conus medullaris. The specific slide containing the end of the gray matter was noted. The distance between the caudal ending of the gray matter in the conus and the macroscopical end of the conus medullaris was defined as the gray matter to cone termination (GMCT) distance. There were great individual variations in the distance from the caudal ending of the gray matter to the macroscopically visible end of the conus medullaris. Analysis of the correlations of these differences with sex, body height, gray matter transverse diameter, and cross-sectional area at the end of the gray matter showed no significant sex-specific differences in the GMCT distance. Patient body height and transverse diameter at the end of the gray matter were found to be correlated positively with the GMCT distance. Moreover, greater height also correlated positively with the cross-sectional area at the end of the gray matter. CONCLUSIONS: This report is, to the authors' knowledge, the first published description of the histological structure of the conus medullaris and can serve as the basis for a better understanding of neurological deficits in patients with a conus medullaris syndrome. Findings that gray matter can be detected far into the conus medullaris, with large individual differences in the endpoint of the gray matter, are important for operative care of intramedullary masses and vascular malformations in this area. It is therefore important to use electrophysiological monitoring during these operations.

Frequency of actionable molecular drivers in lung cancer patients with precocious brain metastases.

Brain metastases frequently occur during the course of disease in patients suffering from lung cancer. Occasionally, neurological symptoms caused by brain metastases (BM) might represent the first sign of systemic tumor disease (so called precocious metastases), leading to the detection of the primary lung tumor. The biological basis of precocious BM is largely unknown, and treatment options are not well established for this subgroup of patients. Therefore, we retrospectively analyzed 33 patients (24 non-small cell lung cancer (NSCLC)), 9 small cell lung cancer (SCLC)) presenting with precocious BM focusing on molecular alterations potentially relevant for the tumor's biology and treatment. We found five FGFR1 amplifications (4 adenocarcinoma, 1 SCLC) among 31 analyzed patients (16.1%), eight MET amplifications among 30 analyzed tumors (7 NSCLC, 1 SCLC; 26.7%), three EGFR mutations within 33 patients (all adenocarcinomas, 9.1%), and five KRAS mutations among 32 patients (all adenocarcinomas; 15.6%). No ALK, ROS1 or RET gene rearrangements were detected. Our findings suggest that patients with precocious BM of lung cancer harbor EGFR mutations, MET amplifications or FGFR1 amplifications as potential targeted treatment options.

Prophylactic nimodipine treatment for hearing preservation after vestibular schwannoma surgery: study protocol of a randomized multi-center phase III trial-AkniPro 2.

BACKGROUND: A previously performed phase III trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, though it should be considered that protection of facial nerve function was the primary outcome. However, the risk for postoperative hearing loss was halved in the nimodipine group compared to the control group (OR 0.49; 95% CI 0.18-1.30; p = 0.15). Accordingly, this phase III extension trial investigates the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery. METHODS: This is a randomized, multi-center, two-armed, open-label phase III trial with blinded expert review and two-stage with interim analysis. Three hundred thirty-six adults with the indication for microsurgical removal of VS (Koos I-IV) and serviceable preoperative hearing (Gardner-Robertson scale (GR) 1-3) are assigned to either the therapy (intravenous nimodipine 1-2 mg/h from the day before surgery until the fifth postoperative day and standard of care) or the control group (surgery only and standard of care). The primary endpoint of the trial is postoperative cochlear nerve function measured before discharge according to GR 1-3 versus GR 4-5 (binary). Hearing function will be determined by pre- and postoperative audiometry with speech discrimination, which will be evaluated by a blinded expert reviewer. Furthermore, patient-reported outcomes using standardized questionnaires will be analyzed. DISCUSSION: Prophylactic parenteral nimodipine treatment may have a positive effect on hearing preservation in VS surgery and would improve patient's quality of life. Further secondary analyses are planned. Except for dose-depending hypotension, nimodipine is known as a safe drug. In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery. VS can be considered as an ideal model for clinical evaluation of neuroprotection, since hearing outcome can be classified by well-recognized criteria. The beneficial effect of nimodipine may be transferable to other surgical procedures with nerves at risk and may have impact on basic research. TRIAL REGISTRATION: EudraCT 2019-002317-19, DRKS00019107 . 8th May 2020.

Facial Nerve EMG: Low-Tech Monitoring with a Stopwatch.

OBJECTIVE: The quantity of A-trains, a high-frequency pattern of free-running facial nerve electromyography, is correlated with the risk for postoperative high-grade facial nerve paresis. This correlation has been confirmed by automated analysis with dedicated algorithms and by visual offline analysis but not by audiovisual real-time analysis. METHODS: An investigator was presented with 29 complete data sets measured during actual surgeries in real time and without breaks in a random order. Data were presented either strictly via loudspeaker (audio) or simultaneously by loudspeaker and computer screen (audiovisual). Visible and/or audible A-train activity was then quantified by the investigator with the computerized equivalent of a stopwatch. The same data were also analyzed with quantification of A-trains by automated algorithms. RESULTS: Automated (auto) traintime (TT), known to be a small, yet highly representative fraction of overall A-train activity, ranged from 0.01 to 10.86 s (median: 0.58 s). In contrast, audio-TT ranged from 0 to 1,357.44 s (median: 29.69 s), and audiovisual-TT ranged from 0 to 786.57 s (median: 46.19 s). All three modalities were correlated to each other in a highly significant way. Likewise, all three modalities correlated significantly with the extent of postoperative facial paresis. As a rule of thumb, patients with visible/audible A-train activity < 1 minute presented with a more favorable clinical outcome than patients with > 1 minute of A-train activity. CONCLUSION: Detection and even quantification of A-trains is technically possible not only with intraoperative automated real-time calculation or postoperative visual offline analysis, but also with very basic monitoring equipment and real-time good quality audiovisual analysis. However, the investigator found audiovisual real-time-analysis to be very demanding; thus tools for automated quantification can be very helpful in this respect.

Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial.

A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1-4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1-3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1-4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine's efficacy.