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.

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.

[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.

Neurofibromatosis Type 1 Gene Alterations Define Specific Features of a Subset of Glioblastomas.

Neurofibromatosis type 1 (NF1) gene mutations or alterations occur within neurofibromatosis type 1 as well as in many different malignant tumours on the somatic level. In glioblastoma, NF1 loss of function plays a major role in inducing the mesenchymal (MES) subtype and, therefore defining the most aggressive glioblastoma. This is associated with an immune signature and mediated via the NF1-MAPK-FOSL1 axis. Specifically, increased invasion seems to be regulated via mutations in the leucine-rich domain (LRD) of the NF1 gene product neurofibromin. Novel targets for therapy may arise from neurofibromin deficiency-associated cellular mechanisms that are summarised in this review.

Variants of Oxidized Regenerated Cellulose and Their Distinct Effects on Neuronal Tissue.

Based on oxidized regenerated cellulose (ORC), several hemostyptic materials, such as Tabotamp®, Equicel® and Equitamp®, have been developed to approach challenging hemostasis in neurosurgery. The present study compares ORC that differ in terms of compositions and properties, regarding their structure, solubility, pH values and effects on neuronal tissue. Cytotoxicity was detected via DNA-binding fluorescence dye in Schwann cells, astrocytes, and neuronal cells. Additionally, organotypic hippocampal slice cultures (OHSC) were analyzed, using propidium iodide, hematoxylin-eosin, and isolectin B4 staining to investigate the cellular damage, cytoarchitecture, and microglia activation. Whereas Equicel® led to a neutral pH, Tabotamp® (pH 2.8) and Equitamp® (pH 4.8) caused a significant reduction of pH (p < 0.001). Equicel® and Tabotamp® increased cytotoxicity significantly in several cell lines (p < 0.01). On OHSC, Tabotamp® and Equicel® led to a stronger and deeper damage to the neuronal tissue than Equitamp® or gauze (p < 0.01). Equicel® increased strongly the number of microglia cells after 24 h (p < 0.001). Microglia cells were not detectable after Tabotamp® treatment, presumably due to an artifact caused by strong pH reduction. In summary, our data imply the use of Equicel®, Tabotamp® or Equitamp® for specific applications in distinct clinical settings depending on their localization or tissue properties.

Correction to: Is the new ASNM intraoperative neuromonitoring supervision "guideline" a trustworthy guideline? A commentary.

The article Is the new ASNM intraoperative neuromonitoring supervision "guideline" a trustworthy guideline? A commentary, written by Stanley A. Skinner, Elif Ilgaz Aydinlar, Lawrence F. Borges, Bob S. Carter, Bradford L. Currier, Vedran Deletis, Charles Dong, John Paul Dormans, Gea Drost, Isabel Fernandez­Conejero, E. Matthew Hoffman, Robert N. Holdefer, Paulo Andre Teixeira Kimaid, Antoun Koht, Karl F. Kothbauer, David B. MacDonald, John J. McAuliffe III, David E. Morledge, Susan H. Morris, Jonathan Norton, Klaus Novak, Kyung Seok Park, Joseph H. Perra, Julian Prell, David M. Rippe, Francesco Sala, Daniel M. Schwartz, Martín J. Segura, Kathleen Seidel, Christoph Seubert, Mirela V. Simon, Francisco Soto, Jeffrey A. Strommen, Andrea Szelenyi, Armando Tello, Sedat Ulkatan, Javier Urriza and Marshall Wilkinson, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 05 January 2019 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 30 January 2019 to © The Author(s) 2019 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article has been corrected.

Nimodipine-Dependent Protection of Schwann Cells, Astrocytes and Neuronal Cells from Osmotic, Oxidative and Heat Stress Is Associated with the Activation of AKT and CREB.

Clinical and experimental data assumed a neuroprotective effect of the calcium channel blocker nimodipine. However, it has not been proven which neuronal or glial cell types are affected by nimodipine and which mechanisms underlie these neuroprotective effects. Therefore, the aim of this study was to investigate the influence of nimodipine treatment on the in vitro neurotoxicity of different cell types in various stress models and to identify the associated molecular mechanisms. Therefore, cell lines from Schwann cells, neuronal cells and astrocytes were pretreated for 24 h with nimodipine and incubated under stress conditions such as osmotic, oxidative and heat stress. The cytotoxicity was measured via the lactate dehydrogenase (LDH) activity of cell culture supernatant. As a result, the nimodipine treatment led to a statistically significantly reduced cytotoxicity in Schwann cells and neurons during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (p ≤ 0.05), when compared to the vehicle. The cytotoxicity of astrocytes was nimodipine-dependently reduced during osmotic (p ≤ 0.01), oxidative (p ≤ 0.001) and heat stress (not significant). Moreover, a decreased caspase activity as well as an increased proteinkinase B (AKT) and cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation could be observed after the nimodipine treatment under different stress conditions. These results demonstrate a cell type-independent neuroprotective effect of the prophylactic nimodipine treatment, which is associated with the prevention of stress-dependent apoptosis through the activation of CREB and AKT signaling pathways and the reduction of caspase 3 activity.

Increased rate of ventriculostomy-related hemorrhage following endovascular treatment of ruptured aneurysms compared to clipping.

OBJECTIVE: Acutely ruptured aneurysms can be treated by endovascular intervention or via surgery (clipping). After endovascular treatment, the risk of thromboembolic complications is reduced by the use of anticoagulative agents, which is not required after clipping. The aim of the study is to investigate the rate of ventriculostomy-related hemorrhage after endovascular treatment and clipping. METHODS: A consecutive series of 99 patients treated for a ruptured aneurysm which required an external ventricular drainage between 2010 and 2015 were included. Their CT scans were investigated retrospectively for ventriculostomy-related hemorrhage. Furthermore, the extent of bleeding, the rate of revision surgery, and the rate of bacterial ventriculitis have been analyzed. RESULTS: Ventriculostomy-related hemorrhage was observed in 20 of 45 patients after endovascular treatment compared to 7 of 54 patients after clipping (chi-squared test, p < 0.001). Revision surgery was indicated in 75%. In 50% of these patients, revision surgery was required more than once and nearly 50% developed additional cerebral infections. Intraventricular or intracerebral extension of the bleeding was observed only in the endovascular treatment group (chi-squared test, p = 0.003). Glasgow outcome scale showed a significant better outcome in the surgical group (t test, p = 0.005). CONCLUSIONS: Ventriculostomy-related hemorrhage is an underestimated complication after endovascular treatment leading to revision surgeries, bacterial infections, and may have a negative impact on long-term outcome. The probability of occurrence is increased when anticoagulation is performed by heparin in combination with antiplatelet drugs as compared to heparin alone. Lumbar drainage should be considered as an alternative for treatment of acute hydrocephalus in patients with Hunt and Hess grade 1-3.

Interobserver variability of the House-Brackmann facial nerve grading system for the analysis of a randomized multi-center phase III trial.

BACKGROUND: Evidence of a high interobserver variability of the subjective House-Brackmann facial nerve grading system (HBGS) would justify cost- and time-consuming technological enhancements of objective classifications for facial nerve paresis. METHOD: A total of 112 patients were recruited for a randomized multi-center trial to investigate the efficacy of prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery. For the present investigation both treatment groups were pooled for the assessment of facial nerve function preoperatively, in the early postoperative course and 1 year after the surgery. Facial nerve function was documented photographically at rest and in motion and classified according to the HBGS by three independent observers (neurosurgeon, neurologist, ENT) and by the investigator of each center. RESULTS: Interobserver variability was considerably different with respect to the three time points depending upon the severity of facial nerve paresis. Preoperative facial nerve function was normal or only mildly impaired (HB grade I or II) and was assessed consistently in 97%. Facial nerve function deteriorated during the early postoperative course and was subsequently documented without dissent in only 36%, with one grade difference in 45%, two grade difference in 17% and three grade difference in 2%. One year after surgery, facial nerve function predominantly improved resulting in a consistent assessment in 66%. Differing ratings were observed in 34% with one grade deviation in 88% and of two grades in 12%. Patients with differing ratings of two or more grades exhibited considerably worse facial nerve function (p < 0.001). CONCLUSIONS: The HBGS produced comparable results between different observers in patients with normal or only mildly impaired facial nerve function. Interobserver variability increased depending on the severity of facial nerve paresis. The results suggest that the HBGS does not promote uniformity of reporting and comparison of outcomes in patients with moderate or severe facial nerve paresis.

Towards an optimal paradigm for intraoperative auditory nerve monitoring with auditory steady state responses.

Auditory steady state responses (ASSR) may offer an alternative to brainstem auditory evoked potentials for monitoring of the auditory nerve during surgical procedures. In the current study, we evaluated the influence of noise on ASSR characteristics in total intravenous anesthesia (TIVA). Simulated ASSR in real noise recorded during surgery under TIVA were constructed with known parameters. Influence of amplitude, modulation frequency, averaging sweeps and detection threshold on ASSR were evaluated. High amplitude, more sweeps and a liberal threshold facilitated detection. High amplitude ASSR (80 nV) were detected in up to 45 % with 16 s of data, in 80-90 % with 112 s. Near-threshold ASSR were detected in 0.8-25 %. False positives ranged between 0.3 and 10.3 %. Number of sweeps did not influence false positives. Amplitude errors varied between -61 and +39 % and improved with more averages but not with different thresholds. Modulation rate demonstrated the strongest influence on all parameters. 110 Hz yielded best, 90 Hz the worst results. Choice of parameters strongly influences detection and characteristics of ASSR. Optimal parameters enabled detection after 16 s in 45 %. Due to specific noise characteristics, modulation has a critical impact, which is currently not sufficiently recognized in ASSR studies.

The relationship between nervus intermedius anatomy, ultrastructure, electrophysiology, and clinical function. Usefulness in cerebellopontine microsurgery.

BACKGROUND: Although previous studies have described the clinical features of the nervus intermedius (NI), no attempt has yet been made to describe the relationship between the ultrastructural and electrophysiological characteristics of the nervus intermedius and its motor competence. OBJECTIVE: In this study, we analyzed the intraoperative electrophysiological response obtained during vestibular schwannoma surgery. The ultrastructure was studied using electron microscopy. MATERIALS AND METHODS: Thirty-six consecutive patients underwent microsurgery for vestibular schwannoma with cerebellopontine angle tumors. The patients were extensively monitored intraoperatively. Selective stimulation of the nervus intermedius was attempted in all cases. The patients were then examined postoperatively and followed for a minimum of 1 year. Forty-three isolated human brainstems were analyzed to collect the ultrastructural NI data. RESULTS: We found a correlation between the NI motor responses in the perinasal and perioral regions and the ultrastructure characteristics, with few (0.5 %) but large myelinated motor fibers (diameters >12 µm). Both characteristics are consistent with the clinical observation of transient weakness of the levator anguli oris muscle. These observations indicate a relationship between the intraoperative electrophysiological identification of the NI nervus intermedius and its clinical and ultrastructural characteristics. CONCLUSIONS: Identifying the NI in the deformed anatomy of tumors could provide a fixed landmark during cerebellopontine surgery and help prevent damage of the facial nerve.

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.

Reorganization and Plasticity of the Language Network in Patients with Cerebral Gliomas.

Language is organized in large-scale networks in the human brain that show a strong potential for flexible interactions and adaptation. Neuroplasticity is the central mechanism that allows such dynamic modulation to changing conditions across the life span and is particularly important for network reorganization after brain lesions. Most studies on language reorganization focused on language recovery after stroke. Yet, a strong degree of adaptive neuroplasticity can also be observed in patients with brain tumors in language-eloquent brain areas. This review discusses key mechanisms for neural reorganization in patients with brain tumors. Our main aim is to elucidate the underlying mechanisms for intra- and interhemispheric plasticity in the language network in these patients. The following reorganization patterns are discussed: 1) Persisting function within the tumor; 2) Reorganization in perilesional regions; 3) Reorganization in a distributed network of the affected hemisphere; 4) Reorganization to the contralesional hemisphere. In this context, we shed light on language-related reorganization patterns in frontal and temporo-parietal areas and discuss their functional relevance. We also address tumor-related changes in structural and functional connectivity between eloquent brain regions. Thereby, we aim to expand the general understanding of the plastic potential of the neural language network and facilitate clinical decision-making processes for effective, function-preserving tumor treatment.

A toolbox to analyze collective cell migration, proliferation and cellular organization simultaneously.

BACKGROUND: Analyses of collective cell migration and orientation phenomena are needed to assess the behavior of multicellular clusters. While some tools to the authors' knowledge none is capable to analyze collective migration, cellular orientation and proliferation in phase contrast images simultaneously. METHODS: We provide a tool based to analyze phase contrast images of dense cell layers. PIV is used to calculatevelocity fields, while the structure tensor provides cellular orientation. An artificial neural network is used to identify cell division events, allowing to correlate migratory and organizational phenomena with cell density. CONCLUSION: The presented tool allows the simultaneous analysis of collective cell behavior from phase contrast images in terms of migration, (self-)organization and proliferation.

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.

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.

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.

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.