Click Chemistry with Cell-Permeable Fluorophores Expands the Choice of Bioorthogonal Markers for Two-Color Live-Cell STED Nanoscopy.

STED nanoscopy allows for the direct observation of dynamic processes in living cells and tissues with diffraction-unlimited resolution. Although fluorescent proteins can be used for STED imaging, these labels are often outperformed in photostability by organic fluorescent dyes. This feature is especially crucial for time-lapse imaging. Unlike fluorescent proteins, organic fluorophores cannot be genetically fused to a target protein but require different labeling strategies. To achieve simultaneous imaging of more than one protein in the interior of the cell with organic fluorophores, bioorthogonal labeling techniques and cell-permeable dyes are needed. In addition, the fluorophores should preferentially emit in the red spectral range to reduce the potential phototoxic effects that can be induced by the STED light, which further restricts the choice of suitable markers. In this work, we selected five different cell-permeable organic dyes that fulfill all of the above requirements and applied them for SPIEDAC click labeling inside living cells. By combining click-chemistry-based protein labeling with other orthogonal and highly specific labeling methods, we demonstrate two-color STED imaging of different target structures in living specimens using different dye pairs. The excellent photostability of the dyes enables STED imaging for up to 60 frames, allowing the observation of dynamic processes in living cells over extended time periods at super-resolution.

Robot-assisted stereoencephalography vs subdural electrodes in the evaluation of temporal lobe epilepsy.

OBJECTIVE: Invasive video-electroencephalography (iVEEG) is the gold standard for evaluation of refractory temporal lobe epilepsy before second stage resective surgery (SSRS). Traditionally, the presumed seizure onset zone (SOZ) has been covered with subdural electrodes (SDE), a very invasive procedure prone to complications. Temporal stereoelectroencephalography (SEEG) with conventional frame-based stereotaxy is time-consuming and impeded by the geometry of the frame. The introduction of robotic assistance promised a simplification of temporal SEEG implantation. However, the efficacy of temporal SEEG in iVEEG remains unclear. The aim of this study was therefore to describe the efficiency and efficacy of SEEG in iVEEG of temporal lobe epilepsy. METHODS: This retrospective study enrolled 60 consecutive patients with medically intractable epilepsy who underwent iVEEG of a potential temporal SOZ by SDE (n = 40) or SEEG (n = 20). Surgical time efficiency was analyzed by the skin-to-skin time (STS) and the total procedure time (TPT) and compared between groups (SDE vs SEEG). Surgical risk was depicted by the 90-day complication rate. Temporal SOZ were treated by SSRS. Favorable outcome (Engel°1) was assessed after 1 year of follow-up. RESULTS: Robot-assisted SEEG significantly reduced the duration of surgery (STS and TPT) compared to SDE implantations. There was no significant difference in complication rates. Notably, all surgical revisions in this study were attributed to SDE. Unilateral temporal SOZ was detected in 34/60 cases. Of the 34 patients, 30 underwent second stage SSRS. Both SDE and SEEG had a good predictive value for the outcome of temporal SSRS with no significant group difference. SIGNIFICANCE: Robot-assisted SEEG improves the accessibility of the temporal lobe for iVEEG by increasing surgical time efficiency and by simplifying trajectory selection without losing its predictive value for SSRS.

Polarization-resolved mode evolution in TMI-limited Yb-doped fiber amplifiers using a novel high-speed Stokes polarimeter.

In this work we have developed a high-speed Stokes polarimeter method based on simultaneous 4-channel imaging with a high-speed camera. Thus, current speed limitations of imaging polarimeters for wavelengths around 1 µm can be overcome, allowing a sub-ms polarization-resolved characterization of transverse mode instability (TMI). Additionally, the Stokes parameters of each individual mode are calculated by a simultaneous 4-beam mode reconstruction algorithm during post-processing and can be analyzed with unprecedented temporal resolution. We demonstrate the measurement capabilities of this polarimeter setup by characterizing TMI of a large-mode-area Yb-doped polarization maintaining (PM) fiber amplifier with 30 kHz video frame rate. Upon thorough characterization, we have found for the first time that at the onset of TMI in a PM fiber, the modal polarization states begin to oscillate on circular and elliptical trajectories at the same frequencies as the modal energy transfer occurs. The ability to measure the modal polarization states with sub-ms temporal resolution is key to developing a fundamental understanding and subsequently possible mitigation strategies of TMI in PM-fiber lasers.

Surgical Treatment of Craniopharyngiomas in Adults: Comparison between Primary Surgery and Surgery for Recurrence.

OBJECTIVE: Few studies have investigated the differences in outcomes between primary and repeat surgery for a craniopharyngioma in adults. As a result, a treatment concept for adult patients with a craniopharyngioma has not yet been established. The present study aimed to retrospectively analyze adult patients with craniopharyngioma to compare surgical outcomes between primary surgery and surgery for recurrence. METHODS: The demographic and clinical data of 68 adult patients with craniopharyngioma who had primary surgery (n=50) or surgery for recurrence (n=18) were retrospectively analyzed. In addition, the patients were followed up for an average of 38.6 months (range: 1-133 months). RESULTS: The cohorts of patients undergoing primary surgery or repeat surgery did not differ preoperatively in terms of demographic data, or radiological tumor features. However, patients with recurrent craniopharyngioma had significantly more pituitary hormone deficits and hypothalamo-pituitary disorders before surgery compared with patients with newly diagnosed craniopharyngioma. The success rate of complete resection in primary surgery was 53.2%. Even after repeat surgery, a satisfactory rate of complete resection of 35.7% was achieved. Operative morbidity was increased neither in patients with repeat surgery compared with those with primary surgery (postoperative bleeding P=0.560; meningitis P=1.000; CSF leak P=0.666; visual disturbance P=0.717) nor in patients with complete resection compared with those with partial resection. We found no difference in recurrence-free survival between initial surgery and repeat surgery (P=0.733). The recurrence rate was significantly lower after complete resection (6.9%) than after partial resection (47.8%; P<0.001). CONCLUSION: Attempting complete resection is justified for not only those with newly diagnosed craniopharyngioma but also for those with recurrent craniopharyngioma. However, the surgeon must settle for less than total resection if postoperative morbidity is anticipated.

The importance of MRI quality and reader's experience for detecting an adenoma in Cushing's disease.

Objective: In Cushing's disease (CD), detection of an adenoma by MRI is challenging. The aim of this study is to compare real-life MRI in the initial diagnostic workup of CD with high-quality MRI performed in a tertiary center for pituitary diseases. Design and methods: We retrospectively analyzed 139 patients with CD who underwent primary transsphenoidal surgery (TSS) in our department and had both an MRI conducted at a different institution (external MRI; extMRI) and an MRI conducted at our institution (internal MRI; intMRI). Preoperative interpretation of MRI was performed independently by an external radiologist (extRAD), an internal neuroradiologist (intRAD) and a pituitary surgeon (SURG). Intraoperative detection of an adenoma and endocrinological remission provided proof of the true adenoma localization in 105 patients. Results: Interpretation of extMRI by extRAD and SURG was concordant in only 64% (89/139) of cases, while 74.1% (103/139) concordance was observed for interpretation of intMRI by intRAD and SURG. Based on extMRI, the true localization of the adenoma was correctly predicted in only 46.7% of the patients by extRAD and in 65.7% by SURG. In contrast, the sensitivity to correctly identify the adenoma on intMRI was 80.0% for intRAD and 94.3% for SURG. Conclusion: Both the quality of MRI and the reader's experience are paramount for detection of microadenomas in CD. Every effort should be made to perform high-quality initial MRI according to current standards and to ensure rating by an expert in pituitary imaging.

Management of neurofibromatosis type 2 and schwannomatosis associated peripheral and intraspinal schwannomas: influence of surgery, genetics, and localization.

INTRODUCTION: Peripheral and intraspinal schwannomas are common and clinically complex pathologies in patients with Neurofibromatosis Type 2 (NF2) and Schwannomatosis (SWNT). Functional preservation and pain relief are the major goals in treating these tumors. METHODS: This retrospective observational study investigates the clinical and functional outcome of 205 operated peripheral (n = 148, 72%) and intraspinal (n = 57, 28%) schwannomas in 85 patients (53 NF2, 32 SWNT) treated at our department between 2006 and 2017. Associated factors such as genetics, age, and location were evaluated. RESULTS: Persisting drug-resistant pain was the most common symptom (84%, n = 173) and indication for surgery (54%, n = 110). Improvement in pain intensity was postoperatively seen in 81%. Peripheral nerve schwannomas exhibited worse pain intensity preoperatively compared to intraspinal lesions (p = 0.017 NF2, p = 0.029 SWNT). More total resections could be achieved in 93% of SWNT vs. 82% of NF2-associated tumors, p = 0.030). NF2 patients with intraspinal lesions were more neurologically affected (p < 0.05). Perioperative comparison of both tumor syndromes showed more neurological deficits (p = 0.027), and less pain (p = 0.024) in NF2-associated tumors. Mosaic NF2 patients had worse pain levels before surgery, and SWNT patients had a worse neurological function and more pain compared to non-mosaic or non-mutated cases. CONCLUSIONS: Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity. The influence of mutations needs to be further investigated in larger cohorts.

Design and Evaluation of a Custom-Made Electromyographic Biofeedback System for Facial Rehabilitation.

Background: In the rehabilitation of postoperative facial palsy, physical therapy is of paramount importance. However, in the early rehabilitation phase, voluntary movements are often limited, and thus, the motivation of patients is impacted. In these situations, biofeedback of facial electromyographic (EMG) signals enables the visual representation of the rehabilitation progress, even without apparent facial movements. In the present study, we designed and evaluated a custom-made EMG biofeedback system enabling cost-effective facial rehabilitation. Methods: This prospective study describes a custom-made EMG system, consisting of a microcontroller board and muscle sensors, which was used to record the EMG of frontal and zygomatic facial muscles during frowning and smiling. First, the mean EMG amplitudes and movement onset detection rates (ACC) achieved with the custom-made EMG system were compared with a commercial EMG device in 12 healthy subjects. Subsequently, the custom-made device was applied to 12 patients with and without postoperative facial paresis after neurosurgical intervention. Here, the ratio [laterality index (LI)] between the mean EMG amplitude of the healthy and affected side was calculated and related to the facial function as measured by the House and Brackmann scale (H&B) ranging from 1 (normal) to 6 (total paralysis). Results: In healthy subjects, a good correlation was measured between the mean EMG amplitudes of the custom-made and commercial EMG device for both frontal (r = 0.84, p = 0.001) and zygomatic muscles (r = 0.8, p = 0.002). In patients, the LI of the frontal and zygomatic muscles correlated significantly with the H&B (r = -0.83, p = 0.001 and r = -0.65, p = 0.023). The ACC of the custom-made EMG system varied between 65 and 79% depending on the recorded muscle and cohort. Conclusion: The present study demonstrates a good application potential of our custom-made EMG biofeedback device to detect facial EMG activity in healthy subjects as well as patients with facial palsies. There is a correlation between the electrophysiological measurements and the clinical outcome. Such a device might enable cost-efficient home-based facial EMG biofeedback. However, movement detection accuracy should be improved in future studies to reach ranges of commercial devices.

Rediscovery of the transcerebellar approach: improving the risk-benefit ratio in robot-assisted brainstem biopsies.

OBJECTIVE: Conventional frame-based stereotaxy through a transfrontal approach (TFA) is the gold standard in brainstem biopsies. Because of the high surgical morbidity and limited impact on therapy, brainstem biopsies are controversial. The introduction of robot-assisted stereotaxy potentially improves the risk-benefit ratio by simplifying a transcerebellar approach (TCA). The aim of this single-center cohort study was to evaluate the risk-benefit ratio of transcerebellar brainstem biopsies performed by 2 different robotic systems. In addition to standard quality indicators, a special focus was set on trajectory selection for reducing surgical morbidity. METHODS: This study included 25 pediatric (n = 7) and adult (n = 18) patients who underwent 26 robot-assisted biopsies via a TCA. The diagnostic yield, complication rate, trajectory characteristics (i.e., length, anatomical entry, and target-point location), and skin-to-skin (STS) time were evaluated. Transcerebellar and hypothetical transfrontal trajectories were reconstructed and transferred into a common MR space for further comparison with anatomical atlases. RESULTS: Robot-assisted, transcerebellar biopsies demonstrated a high diagnostic yield (96.2%) while exerting no surgical mortality and no permanent morbidity in both pediatric and adult patients. Only 3.8% of cases involved a transient neurological deterioration. Transcerebellar trajectories had a length of 48.4 ± 7.3 mm using a wide stereotactic corridor via crus I or II of the cerebellum and the middle cerebellar peduncle. The mean STS time was 49.5 ± 23.7 minutes and differed significantly between the robotic systems (p = 0.017). The TFA was characterized by longer trajectories (107.4 ± 11.8 mm, p < 0.001) and affected multiple eloquent structures. Transfrontal target points were located significantly more medial (-3.4 ± 7.2 mm, p = 0.042) and anterior (-3.9 ± 8.4 mm, p = 0.048) in comparison with the transcerebellar trajectories. CONCLUSIONS: Robot-assisted, transcerebellar stereotaxy can improve the risk-benefit ratio of brainstem biopsies by avoiding the restrictions of a TFA and conventional frame-based stereotaxy. Profound registration and anatomical-functional trajectory selection were essential to reduce mortality and morbidity.

Clinical validation of kinematic assessments of post-stroke upper limb movements with a multi-joint arm exoskeleton.

BACKGROUND: The clinical evaluation of the upper limb of severely impaired stroke patient is challenging. Sensor-based assessments may allow for an objective evaluation of this patient population. This study investigated the validity of a device-assisted approach in comparison to the clinical outcome that it is supposed to reflect. METHODS: In nineteen severely impaired chronic stroke patients, we applied a gravity-compensating, multi-joint arm exoskeleton (Armeo Spring) and compared this sensor-based assessment with the clinical outcome measure Upper Extremity Fugl-Meyer Assessment (UE-FMA) scale. Specifically, we assessed separately and subsequently the range of motion in joint space for four single joints (i.e., wrist, elbow and shoulder flexion/extension (FE), and shoulder internal/external rotation (IER)), and the closing and opening of the hand with a pressure sensor placed in the handle. RESULTS: Within the kinematic parameters, a strong correlation was observed between wrist and elbow FE (r > 0.7, p < 0.003; Bonferroni corrected). The UE-FMA was significantly predicted by a multiple regression model (F (5, 13) = 12.22, p < 0.0005, adj. R2 = 0.83). Both shoulder IER and grip pressure added significantly (p < 0.05) to the prediction with the standardized coefficients ß of 0.55 and 0.38, respectively. CONCLUSIONS: By applying an exoskeleton-based self-contained evaluation of single-joint movements, a clinically valid assessment of the upper limb range of motion in severely impaired stroke patients is feasible. Shoulder IER contributed most relevantly to the prediction of the clinical status. These findings need to be confirmed in a large, independent patient cohort.

Patient-to-robot registration: The fate of robot-assisted stereotaxy.

BACKGROUND: Robot-assisted stereotaxy (RAS) promises higher stereotactic accuracy (SA) and time efficiency (TE) than frame-based stereotaxy. However, both aspects are attributed to the problem of patient-to-robot registration. OBJECTIVE: To examine different registration techniques regarding their SA and TE. METHODS: This study enrolled 57 patients undergoing RAS with bone fiducial registration (BFR) or laser surface registration (LSR). SA was measured by the entry point error (EPE). Additionally, predictors of SA (registration error [RegE], distance-to-registration plane [DTC]) and TE (imaging, skin-to-skin) were assessed. RESULTS: The mean SA was 1.0 ± 0.8 mm. BFR increased SA by reducing RegE and DTC. In LSR, EPE depended on DTC (face and forehead) with highest accuracy for DTC ≤100 mm. CT-based LSR exerted a higher SA than MR-based LSR. In BFR, TE was confined by the additional imaging. CONCLUSION: Every registration technique counteracts one of the promises of RAS. New solutions are needed to increase the acceptance of RAS in neurosurgery.

Framed and non-framed robotics in neurosurgery: A 10-year single-center experience.

BACKGROUND: Safety, efficacy and efficiency of neurosurgical robots are defined by their design (i.e., framed and non-framed) and procedural workflow (PW) (from image to surgery). The present study describes the quality indicators of three different robots in brain and spine surgery. METHODS: This single-centre study enrolled 252 patients over a 10-year period. Safety (complication rate) and efficacy (diagnostic yield, pedicle screw placement) were determined. Predictors of workflow efficiency (e.g., skin-to-skin) were evaluated and compared to conventional techniques (neuronavigation, stereotaxy). RESULTS: All robots showed excellent reliability (97.5%-100%) with low complication rates (4.5%-5.3%) and high efficacy (94.7%-97.7%). Robotics demonstrated a better time-efficiency than neuronavigation. However, there was no shortening of surgery time compared to conventional stereotaxy. Time-efficiency differed significantly between framed and non-framed workflows. CONCLUSION: While all neurosurgical robots were reliable, safe and efficacious, there were significant differences in time-efficiency. PWs should be improved to increase the acceptance of robotics in neurosurgery.

Frame-based and robot-assisted insular stereo-electroencephalography via an anterior or posterior oblique approach.

OBJECTIVE: There is an increasing interest in stereo-electroencephalography (SEEG) for invasive evaluation of insular epilepsy. The implantation of insular SEEG electrodes, however, is still challenging due to the anatomical location and complex functional segmentation in both an anteroposterior and ventrodorsal (i.e., superoinferior) direction. While the orthogonal approach (OA) is the shortest trajectory to the insula, it might insufficiently cover these networks. In contrast, the anterior approach (AOA) or posterior oblique approach (POA) has the potential for full insular coverage, with fewer electrodes bearing a risk of being more inaccurate due to the longer trajectory. Here, the authors evaluated the implantation accuracy and the detection of epilepsy-related SEEG activity with AOA and POA insular trajectories. METHODS: This retrospective study evaluated the accuracy of 220 SEEG electrodes in 27 patients. Twelve patients underwent a stereotactic frame-based procedure (frame group), and 15 patients underwent a frameless robot-assisted surgery (robot group). In total, 55 insular electrodes were implanted using the AOA or POA considering the insular anteroposterior and ventrodorsal functional organization. The entry point error (EPE) and target point error (TPE) were related to the implantation technique (frame vs robot), the length of the trajectory, and the location of the target (insular vs noninsular). Finally, the spatial distribution of epilepsy-related SEEG activity within the insula is described. RESULTS: There were no significant differences in EPE (mean 0.9 ± 0.6 for the nonsinsular electrodes and 1.1 ± 0.7 mm for the insular electrodes) and TPE (1.5 ± 0.8 and 1.6 ± 0.9 mm, respectively), although the length of trajectories differed significantly (34.1 ± 10.9 and 70.1 ± 9.0 mm, repsectively). There was a significantly larger EPE in the frame group than in the robot group (1.5 ± 0.6 vs 0.7 ± 0.5 mm). However, there was no group difference in the TPE (1.5 ± 0.8 vs 1.6 ± 0.8 mm). Epilepsy-related SEEG activity was detected in 42% (23/55) of the insular electrodes. Spatial distribution of this activity showed a clustering in both anteroposterior and ventrodorsal directions. In purely insular onset cases, subsequent insular lesionectomy resulted in a good seizure outcome. CONCLUSIONS: The implantation of insular electrodes via the AOA or POA is safe and efficient for SEEG implantation covering both anteroposterior and ventrodorsal functional organization with few electrodes. In this series, there was no decrease in accuracy due to the longer trajectory of insular SEEG electrodes in comparison with noninsular SEEG electrodes. The results of frame-based and robot-assisted implantations were comparable.

Risk Stratification for Immediate Postoperative Hearing Loss by Preoperative BAER (Brainstem Auditory Evoked Response) and Audiometry in NF2-Associated Vestibular Schwannomas.

Both brainstem auditory evoked potentials (BAEP) and audiometry play a crucial role in neuro-oncological treatment decisions in Neurofibromatosis Type 2 associated (NF2) vestibular schwannoma (VS) as hearing preservation is the major goal. In this study, we investigated the risk of immediate postoperative hearing deterioration (>15 dB and/or 15% loss in pure-tone average [PTA]/ speech discrimination score [SDS] in a cohort of 100 operated VS (ears) in 72 NF2 patients by retrospective analysis of pre- and postoperative hearing data (PTA, SDS, American Association of Otolaryngology-Head and Neck Surgery [AAO-HNS], and brainstem auditory evoked potential [BAEP] class) taking into account relevant influencing factors, particularly preoperative audiometry and BAEP status and the extent of resection. Immediately after surgery, the hearing was preserved in 73% of ears and approximately ~60% of ears kept their hearing classes. Preoperative BAEP (p = 0.015) and resection amount (p = 0.048) significantly influenced postoperative hearing outcome. The prediction model for postoperative hearing deterioration/loss between preoperative BAEP and AAO-HNS class showed increased risk by increasing BAEP class. Twenty-one tumors/ears were identified with large BAEP and AAO-HNS class discrepancies (≥2 points) and were associated with a high (48-100%) risk of deafness after surgery in ears with preoperative available hearing. Overall, the results were heterogeneous but the better both BAEP and audiometry class before surgery, the higher the chance of hearing maintenance afterwards. Large resection amounts (e.g., 100% risk in near-total resections) exhibit a significant (p < 0.05) higher risk compared to smaller amounts (e.g., 10/20% in laser-coagulated/partially resected tumors). Our results emphasized the indispensable role of both hearing monitoring in form of audiometry and neurophysiology (BAEP) in the pre-and perioperative monitoring of NF2-associated VS. Both BAEP and audiometry are good prognostic markers for the postoperative hearing outcome. The extent of resection should be strictly guided by and adjusted to the intraoperative neurophysiological monitoring.

Predicting the membrane permeability of organic fluorescent probes by the deep neural network based lipophilicity descriptor DeepFl-LogP.

Light microscopy has become an indispensable tool for the life sciences, as it enables the rapid acquisition of three-dimensional images from the interior of living cells/tissues. Over the last decades, super-resolution light microscopy techniques have been developed, which allow a resolution up to an order of magnitude higher than that of conventional light microscopy. Those techniques require labelling of cellular structures with fluorescent probes exhibiting specific properties, which are supplied from outside and therefore have to surpass cell membranes. Currently, major efforts are undertaken to develop probes which can surpass cell membranes and exhibit the photophysical properties required for super-resolution imaging. However, the process of probe development is still based on a tedious and time consuming manual screening. An accurate computer based model that enables the prediction of the cell permeability based on their chemical structure would therefore be an invaluable asset for the development of fluorescent probes. Unfortunately, current models, which are based on multiple molecular descriptors, are not well suited for this task as they require high effort in the usage and exhibit moderate accuracy in their prediction. Here, we present a novel fragment based lipophilicity descriptor DeepFL-LogP, which was developed on the basis of a deep neural network. DeepFL-LogP exhibits excellent correlation with the experimental partition coefficient reference data (R2 = 0.892 and MSE = 0.359) of drug-like substances. Further a simple threshold permeability model on the basis of this descriptor allows to categorize the permeability of fluorescent probes with 96% accuracy. This novel descriptor is expected to largely simplify and speed up the development process for novel cell permeable fluorophores.

Rhodamines with a Chloronicotinic Acid Fragment for Live Cell Superresolution STED Microscopy*.

Formylation of 2,6-dichloro-5-R-nicotinic acids at C-4 followed by condensation with 3-hydroxy-N,N-dimethylaniline gave analogs of the popular TAMRA fluorescent dye with a 2,6-dichloro-5-R-nicotinic acid residues (R=H, F). The following reaction with thioglycolic acid is selective, involves only one chlorine atom at the carbon between pyridine nitrogen and the carboxylic acid group and affords new rhodamine dyes absorbing at 564/ 573 nm and emitting at 584/ 597 nm (R=H/ F, in aq. PBS). Conjugates of the dyes with "small molecules" provided specific labeling (covalent and non-covalent) of organelles as well as of components of the cytoskeleton in living cells and were combined with fluorescent probes prepared from 610CP and SiR dyes and applied in two-color STED microscopy with a 775 nm STED laser.

Time Efficiency in Stereotactic Robot-Assisted Surgery: An Appraisal of the Surgical Procedure and Surgeon's Learning Curve.

BACKGROUND: Frame-based stereotactic procedures are still the gold standard in neurosurgery. However, there is an increasing interest in robot-assisted technologies. Introducing these increasingly complex tools in the clinical setting raises the question about the time efficiency of the system and the essential learning curve of the surgeon. METHODS: This retrospective study enrolled a consecutive series of patients undergoing a robot-assisted procedure after first system installation at one institution. All procedures were performed by the same neurosurgeon to capture the learning curve. The objective read-out were the surgical procedure time (SPT), the skin-to-skin time, and the intraoperative registration time (IRT) after laser surface registration (LSR), bone fiducial registration (BFR), and skin fiducial registration (SFR), as well as the quality of the registration (as measured by the fiducial registration error [FRE]). The time measures were compared to those for a patient group undergoing classic frame-based stereotaxy. RESULTS: In the first 7 months, we performed 31 robot-assisted surgeries (26 biopsies, 3 stereotactic electroencephalography [SEEG] implantations, and 2 endoscopic procedures). The SPT was depending on the actual type of surgery (biopsies: 85.0 ± 36.1 min; SEEG: 154.9 ± 75.9 min; endoscopy: 105.5 ± 1.1 min; p = 0.036). For the robot-assisted biopsies, there was a significant reduction in SPT within the evaluation period, reaching the level of frame-based surgeries (58.1 ± 17.9 min; p < 0.001). The IRT was depending on the applied registration method (LSR: 16.7 ± 2.3 min; BFR: 3.5 ± 1.1 min; SFR: 3.5 ± 1.6 min; p < 0.001). In contrast to BFR and SFR, there was a significant reduction in LSR time during that period (p = 0.038). The FRE differed between the applied registration methods (LSR: 0.60 ± 0.17 mm; BFR: 0.42 ± 0.15 mm; SFR: 2.17 ± 0.78 mm; p < 0.001). There was a significant improvement in LSR quality during the evaluation period (p = 0.035). CONCLUSION: Introducing stereotactic, robot-assisted surgery in an established clinical setting initially necessitates a prolonged intraoperative preparation time. However, there is a steep learning curve during the first cases, reaching the time level of classic frame-based stereotaxy. Thus, a stereotactic robot can be integrated into daily routine within a decent period of time, thereby expanding the neurosurgeons' armamentarium, especially for procedures with multiple trajectories.

Prestress and Area Compressibility of Actin Cortices Determine the Viscoelastic Response of Living Cells.

Shape, dynamics, and viscoelastic properties of eukaryotic cells are primarily governed by a thin, reversibly cross-linked actomyosin cortex located directly beneath the plasma membrane. We obtain time-dependent rheological responses of fibroblasts and MDCK II cells from deformation-relaxation curves using an atomic force microscope to access the dependence of cortex fluidity on prestress. We introduce a viscoelastic model that treats the cell as a composite shell and assumes that relaxation of the cortex follows a power law giving access to cortical prestress, area-compressibility modulus, and the power law exponent (fluidity). Cortex fluidity is modulated by interfering with myosin activity. We find that the power law exponent of the cell cortex decreases with increasing intrinsic prestress and area-compressibility modulus, in accordance with previous finding for isolated actin networks subject to external stress. Extrapolation to zero tension returns the theoretically predicted power law exponent for transiently cross-linked polymer networks. In contrast to the widely used Hertzian mechanics, our model provides viscoelastic parameters independent of indenter geometry and compression velocity.

Age at Onset and Presenting Symptoms of Neurofibromatosis Type 2 as Prognostic Factors for Clinical Course of Vestibular Schwannomas.

The presenting symptoms of the tumor suppressor gene syndrome neurofibromatosis type 2 (NF2) are often non-specific and unrelated to the disease hallmark bilateral vestibular schwannomas (VS). However, age at onset and presenting symptoms may have predictive values for the clinical course of VS. In this retrospective single-center study, we addressed this issue by reviewing 106 patients with 194 VS. Presenting symptoms attributable to VS commonly occur in 87% of adults and 31% of children. Age at onset significantly correlates with tumor volumes at presentation (p = 0.034). In addition, age at onset significantly correlates with pure-tone average (p = 0.0001), speech discrimination scores (p = 0.001), age at beginning of hearing loss (p = 0.0001), age at deafness (p = 0.0001), and age at first surgery (p = 0.0001). Patients presenting with VS related symptoms had significantly (p < 0.05) worse hearing values at presentation and after surgery. These patients also exhibited higher growth rates and tumor volumes compared to patients with non-VS related presenting symptoms, but this difference did not reach the significance level of p < 0.05. Due to the late appearance of these symptoms, the time of beginning hearing loss, surgery and deafness is significantly delayed (p < 0.05) compared to patients not presenting with VS. In summary, age at onset and type of presenting symptom provide excellent prognostic parameters for predicting VS- and hearing-related clinical course.

Occurrence and management of postoperative pneumocephalus using the semi-sitting position in vestibular schwannoma surgery.

BACKGROUND: The semi-sitting position in neurosurgical procedures is still under debate due to possible complications such as venous air embolism (VAE) or postoperative pneumocephalus (PP). Studies reporting a high frequency of the latter raise the question about the clinical relevance (i.e., the incidence of tension pneumocephalus) and the efficacy of a treatment by an air replacement procedure. METHODS: This retrospective study enrolled 540 patients harboring vestibular schwannomas who underwent posterior fossa surgery in a supine (n = 111) or semi-sitting (n = 429) position. The extent of the PP was evaluated by voxel-based volumetry (VBV) and related to clinical predictive factors (i.e., age, gender, position, duration of surgery, and tumor size). RESULTS: PP with a mean volume of 32 ± 33 ml (range: 0-179.1 ml) was detected in 517/540 (96%) patients. The semi-sitting position was associated with a significantly higher PP volume than the supine position (40.3 ± 33.0 ml [0-179.1] and 0.8 ± 1.4 [0-10.2], p < 0.001). Tension pneumocephalus was observed in only 14/429 (3.3%) of the semi-sitting cases, while no tension pneumocephalus occurred in the supine position. Positive predictors for PP were higher age, male gender, and longer surgery duration, while large (T4) tumor size was established as a negative predictor. Air exchange via a twist-drill was only necessary in 14 cases with an intracranial air volume > 60 ml. Air replacement procedures did not add any complications or prolong the ICU stay. CONCLUSION: Although pneumocephalus is frequently observed following posterior fossa surgery in semi-sitting position, relevant clinical symptoms (i.e., a tension pneumocephalus) occur in only very few cases. These cases are well-treated by an air evacuation procedure. This study indicates that the risk of postoperative pneumocephalus is not a contraindication for semi-sitting positioning.