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.

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.

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.

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.

Investigation of the neuroprotective impact of nimodipine on Neuro2a cells by means of a surgery-like stress model.

Nimodipine is well characterized for the management of SAH (subarachnoid hemorrhage) and has been shown to promote a better outcome and less DIND (delayed ischemic neurological deficits). In rat experiments, enhanced axonal sprouting and higher survival of motoneurons was demonstrated after cutting or crushing the facial nerve by nimodipine. These results were confirmed in clinical trials following vestibular Schwannoma surgery. The mechanism of the protective competence of nimodipine is unknown. Therefore, in this study, we established an in vitro model to examine the survival of Neuro2a cells after different stress stimuli occurring during surgery with or without nimodipine. Nimodipine significantly decreased ethanol-induced cell death of cells up to approximately 9% in all tested concentrations. Heat-induced cell death was diminished by approximately 2.5% by nimodipine. Cell death induced by mechanical treatment was reduced up to 15% by nimodipine. Our findings indicate that nimodipine rescues Neuro2a cells faintly, but significantly, from ethanol-, heat- and mechanically-induced cell death to different extents in a dosage-dependent manner. This model seems suitable for further investigation of the molecular mechanisms involved in the neuroprotective signal pathways influenced by nimodipine.

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.

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.

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.

Archery under the (electroencephalography-)hood: Theta-lateralization as a marker for motor learning.

An intrinsic characteristic of the motor system is the preference of one side of the body. Lateralization is found in motor behavior and in the structural and functional correlates of cortical motor networks. While genetic factors have been elucidated as mechanisms leading to such asymmetries, findings in motor learning and experience from clinical experience demonstrate considerable additional plasticity during the lifespan. If and how functional lateralization develops in short timeframes during training of motor skills involving both sides of the body is still largely unclear. In the present exploratory study, we investigate lateralization of theta-, alpha- and beta-band oscillations during training of an ecologically valid skill - archery. We relate lateralization shift to performance improvement and elucidate the underlying cortical areas. To this end, healthy participants without any previous experience in archery underwent intensive training with 100 shots on each of three days. 64-channel electroencephalography was recorded simultaneously during the individual shots. We found that a central-parietal theta lateralization shift to the left immediately before the shot was associated with performance improvement. Lateralization of alpha or beta did not yield a significant association. Importantly, areas of maximum activation were not identical with areas showing the strongest associations with performance improvement. These data suggest that learning a complex bimanual motor skill is associated with a shift of theta-band oscillations to the left in central-parietal areas. The relationship with performance improvement may reflect increased cortical efficiency of task-relevant processing.

Case report of a fulminant non-aneurysmal convexity subarachnoid hemorrhage after COVID-19.

We report on a case of a fulminant non-aneurysmal subarachnoid hemorrhage after COVID-19 in a patient without previous medical history or known previous illness despite a COVID-19 infection one month prior. We saw rarefied vessels in the area of the left middle cerebral artery besides a massive left frontal hemorrhage on cranial imaging. We concluded that these rarefied vessels are the expression of an RCVS, which fits the history of progressive headaches for one month. The RCVS might be caused by the COVID-19 infection and is related to the hemorrhage. Unfortunately, due to preoperative entrapment, brain death occurred a few days later.

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.

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.

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.

Tabotamp®, Respectively, Surgicel®, Increases the Cell Death of Neuronal and Glial Cells In Vitro.

Oxidized regenerated cellulose (ORC) is an approved absorbable hemostat in neurosurgery, and contains 18-21% carboxylic acid groups. This modification leads to a low pH in aqueous solutions. Therefore, the aim of study was to analyze the pH­dependent effects of the ORC Tabotamp® on astrocytes, Schwann cells, and neuronal cells in vitro to investigate whether Tabotamp® is a suitable hemostat in cerebral eloquent areas. The ORC­dependent pH value changes were measured with (i) a pH meter, (ii) electron paramagnetic resonance spectroscopy, using pH­sensitive spin probes, and (iii) with fluorescence microscopy. Cell lines from neurons, astrocytes, and Schwann cells, as well as primary astrocytes were incubated with increasing areas of Tabotamp®. Cytotoxicity was detected using a fluorescence labeled DNA­binding dye. In addition, the wounding extent was analyzed via crystal violet staining of cell layers. The strongest pH reduction (to 2.2) was shown in phosphate buffered saline, whereas culture medium and cerebrospinal fluid demonstrated a higher buffer capacity during Tabotamp® incubation. In addition, we could detect a distance­dependent pH gradient by fluorescence microscopy. Incubation of Tabotamp® on cell monolayers led to detachment of covered cells and showed increased cytotoxicity in all tested cell lines and primary cells depending on the covered area. These in vitro results indicate that Tabotamp® may not be a suitable hemostat in cerebral eloquent areas.

MSI1 Promotes the Expression of the GBM Stem Cell Marker CD44 by Impairing miRNA-Dependent Degradation.

The stem cell marker Musashi1 (MSI1) is highly expressed during neurogenesis and in glioblastoma (GBM). MSI1 promotes self-renewal and impairs differentiation in cancer and non-malignant progenitor cells. However, a comprehensive understanding of its role in promoting GBM-driving networks remains to be deciphered. We demonstrate that MSI1 is highly expressed in GBM recurrences, an oncologist's major defiance. For the first time, we provide evidence that MSI1 promotes the expression of stem cell markers like CD44, co-expressed with MSI1 within recurrence-promoting cells at the migrating front of primary GBM samples. With GBM cell models of pediatric and adult origin, including isolated primary tumorspheres, we show that MSI1 promotes stem cell-like characteristics. Importantly, it impairs CD44 downregulation in a 3'UTR- and miRNA-dependent manner by controlling mRNA turnover. This regulation is disturbed by the previously reported MSI1 inhibitor luteolin, providing further evidence for a therapeutic target potential of MSI1 in GBM treatment.

Intraoperative auditory steady-state monitoring during surgery in the cerebellopontine angle for estimation of postoperative hearing classes.

OBJECTIVE Brainstem auditory evoked potentials (BAEPs) have been used for intraoperative monitoring of the auditory nerve for many years. However, BAEPs yield limited information about the expected postoperative hearing quality and speech perception. The auditory steady-state response (ASSR) enables objective audiograms to be obtained in patients under anesthesia. These ASSRs could be used for intraoperative estimation of hearing classes to improve the postoperative outcome and quality of life. Studies investigating the clinical use of ASSRs during total intravenous anesthesia are currently lacking. The work presented in this article therefore investigates the application of ASSRs for intraoperative estimation of hearing classes. METHODS In 43 patients undergoing surgery for vestibular schwannoma, ASSR measurements were performed at the beginning and end of the surgical procedure. ASSR stimuli consisted of 80-dB hearing level amplitude-modulated tones with 5-minute duration, 90-Hz modulation, and 3 different carrier frequencies: 500, 1000, and 2000 Hz. Stimulation was performed unilaterally with and without contralateral masking, using single and combined carriers. Evoked responses were recorded and analyzed in the frequency domain. ASSRs were compared with extraoperative hearing classes and BAEPs using ANOVA, correlation, and receiver operating characteristic statistics. RESULTS ASSRs yielded high and consistent area under the curve (AUC) values (mean 0.83) and correlation values (mean -0.63), indicating reliable prediction of hearing classes. Analysis of BAEP amplitude changes showed lower AUC (mean 0.79) and correlation values (0.63, 0.37, and 0.50 for Waves I, III, and V, respectively). Latencies showed low AUC values (mean 0.6) and no significant correlation. Combination of several carriers for simultaneous evaluation reduced ASSR amplitudes and respective AUC values. Contralateral masking did not show a significant effect. CONCLUSIONS ASSRs robustly estimate hearing class in patients under total intravenous anesthesia, even when using short measurement durations. The method provides a diagnostic performance that exceeds conventional BAEP monitoring and enables objective and automated evaluation. On the basis of these findings, continuous intraoperative auditory monitoring could become a promising alternative or adjunct to BAEPs.

Viability of intraoperative auditory steady state responses during intracranial surgery.

BACKGROUND: For intraoperative monitoring of auditory nerve function, the auditory steady-state response (ASSR) analysis may be an alternative to brain stem auditory evoked potentials, offering frequency specificity and short detection times. Clinical studies investigating the viability of ASSR under total intravenous anesthesia have not been performed. METHODS: During craniotomy under total intravenous anesthesia with propofol and remifentanil in 20 patients, ASSR were recorded. An additional control patient undergoing cerebellopontine angle surgery was included, in whom the auditory nerve could not be preserved. One-minute sinus tones (500, 1,000, 2,000 Hz) were applied with 60-, 70-, and 80-decibel hearing level. Stimuli were amplitude modulated with 40, 90, or 110 Hz and applied monaurally to the left and right ears. Time to detect a significant response and response amplitudes at 40, 90, or 110 Hz in the evoked EEG spectra was evaluated. RESULTS: Overall, 90-Hz ASSR were successfully detected in all 20 patients, 110 Hz in 18 patients, and 40 Hz in 14 patients after a median of 10 seconds. No ASSR could be detected in the control patient at the end of the surgical procedure. Time-to-significance and ASSR amplitudes were influenced by stimulus intensity, carrier, and modulation frequency (Scheirer-Ray-Hare test, P < 0.005). Ipsilateral responses were higher than contralateral (P < 0.0001). CONCLUSIONS: In conclusion, 90- and 110-Hz ASSR can be reliably detected under total intravenous anesthesia. Our results are in line with those from previous studies in awake patients. Auditory steady-state response during anesthesia may enable intraoperative frequency-specific audiometry and monitoring of the auditory nerve.