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.

Impaired phase synchronization of motor-evoked potentials reflects the degree of motor dysfunction in the lesioned human brain.

The functional corticospinal integrity (CSI) can be indexed by motor-evoked potentials (MEP) following transcranial magnetic stimulation of the motor cortex. Glial brain tumors in motor-eloquent areas are frequently disturbing CSI resulting in different degrees of motor dysfunction. However, this is unreliably mirrored by MEP characteristics. In 59 consecutive patients with diffuse glial tumors and 21 healthy controls (CTRL), we investigated the conventional MEP features, that is, resting motor threshold (RMT), amplitudes and latencies. In addition, frequency-domain MEP features were analyzed to estimate the event-related spectral perturbation (ERSP), and the induced phase synchronization by intertrial coherence (ITC). The clinical motor status was captured including the Medical Research Council Scale (MRCS), the Grooved Pegboard Test (GPT), and the intake of antiepileptic drugs (AED). Motor function was classified according to MRCS and GPT as no motor deficit (NMD), fine motor deficits (FMD) and gross motor deficits (GMD). CSI was assessed by diffusion-tensor imaging (DTI). Motor competent subjects (CTRL and NMD) had similar ERSP and ITC values. The presence of a motor deficit (FMD and GMD) was associated with an impairment of high-frequency ITC (150-300 Hz). GMD and damage to the CSI demonstrated an additional reduction of high-frequency ERSP (150-300 Hz). GABAergic AED increased ERSP but not ITC. Notably, groups were indistinguishable based on conventional MEP features. Estimating MEP phase synchronization provides information about the corticospinal transmission after transcranial magnetic stimulation and reflects the degree of motor impairment that is not captured by conventional measures.

The Contribution of Subthalamic Nucleus Deep Brain Stimulation to the Improvement in Motor Functions and Quality of Life.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. OBJECTIVES: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study. METHODS: Sixty-nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. RESULTS: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ-39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = -13.1, z = -6.3) and the PDQ-39 differed (x = 14.8, y = -12.4, z = -4.3) ~3.8 mm. CONCLUSIONS: The main influence of DBS on QoL is likely mediated through the sensory-motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Interhemispheric differences in time-frequency representation of motor evoked potentials in brain tumor patients.

OBJECTIVE: Conventional time-series parameters are unreliable descriptors of motor-evoked potentials (MEPs) in brain tumor patients. Frequency domain analysis is suggested to provide additional information about the status of the cortico-spinal motor system. Aim of the present study was to describe the time-frequency representation of MEPs and its relation to the motor performance. METHODS: This study enrolled 17 consecutive brain tumor patients with impaired dexterity. After brain mapping of the affected (AH) and non-affected (NAH) hemisphere, TMS was applied to the hotspots of the abductor pollicis brevis muscles (APB). Using a Morlet wavelet approach, event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) of the MEPs were calculated and compared to the Grooved Pegboard Test (GPT). Additionally, inter- and intra-subject reliability was assessed by the intraclass correlation coefficient (ICC). RESULTS: MEPs were projecting to a frequency band between 30 and 400 Hz with a local maximum between 100 and 150 Hz. There was a significant ERSP and ITC reduction of the AH in comparison to the NAH. In contrast, no interhemispheric differences were depicted in the conventional time-series analysis. ERSP and ITC values correlated significantly with GPT results (r = 0.35 and r = 0.50). Time-frequency MEP description had good inter-and intra-subject reliability (ICC = 0.63). CONCLUSIONS: Brain tumors affect corticospinal transmission resulting in a reduction of temporal and spectral MEP synchronization correlating with the dexterity performance. SIGNIFICANCE: Time-frequency representation of MEPs provide additional information beyond conventional time-domain features.

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.

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.

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.

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

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

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.

Quality of Life After Vestibular Schwannoma Surgery: A Question of Perspective.

OBJECTIVE: Health-related quality of life (HRQoL) and self-reported outcome measures have a relevant impact on the medical decision-making process. They capture either the current status and allow for multiple prospective evaluations in the course of a treatment or rely on the retrospective comparison of health of patients before and after an intervention to assess its benefit. Importantly, these patient-assessed measures may be influenced by psychological factors. We compared HRQoL and perceived benefit in the course of surgical vestibular schwannoma (VS) treatment, as assessed by the patients from a prospective and retrospective point-of-view, and evaluated the influence of co-morbid depression. METHODS: Within a prospective observational single-center study, forty-three patients with VS were investigated before and after retrosigmoid tumor resection. SF-36, Beck Depression Inventory and patient-assessed clinical symptoms were acquired before surgery and at follow-up. At follow-up, the Glasgow Benefit Inventory (GBI) was acquired as well. RESULTS: SF-36 scores were significantly lower than the age and sex matched normative data in six and three out of eight categories before and after surgery, respectively. Three categories improved significantly after vs. before surgery; one of them (global health) reached a minimal clinical important difference. In contrast, patients reported predominantly a deterioration, when asked for a retrospective evaluation of the benefit (i.e., GBI). Depression correlated with both SF-36 and GBI, determined dissatisfaction, improved significantly after surgery and was the measure that had the largest impact on HRQoL. CONCLUSION: Prospective and retrospective HRQoL measures may lead to different findings and can be confounded by psychological factors.

Clinical and Kinematic Correlates of Favorable Gait Outcomes From Subthalamic Stimulation.

Objective: Gait and freezing of gait (FoG) are highly relevant to the outcomes of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). Previous studies pointed to variable response to combined dopaminergic and STN-DBS treatment. Here, we performed a prospective exploratory study on associations of preoperative clinical and kinematic gait measures with quantitative gait and FoG outcomes after STN-DBS implantation. Methods: We characterized 18 consecutive PD patients (13 freezers) before and after STN-DBS implantation. The patients received preoperative levodopa challenges (MedOff vs. MedOn) and a postoperative reassessment at 6 months from surgery in MedOn/StimOn condition. We correlated the FoG outcome, calculated as improvement of Freezing of Gait Assessment Course (FoG-AC) from baseline MedOff to 6-month follow-up MedOn/StimOn, with the levodopa response of preoperative clinical and kinematic gait measures. We considered measures with significant correlations for a multiple regression model. Results: We found that the postoperative gait and FoG outcomes were associated with the preoperative levodopa response of clinical and kinematic gait measures. In particular, preoperative levodopa sensitivity of FoG showed high correlation with a favorable quantitative FoG outcome. Among kinematic measures, preoperative levodopa response of stride length and range of motion showed high correlation with favorable FoG outcome. In addition, the preoperative levodopa sensitivity of FoG predicted postoperative FoG outcome with high accuracy (R 2 = 0.952; 95% CI: 0.95-1.29; P < 0.001). Conclusions: Preoperative clinical and kinematic measures correlated with favorable postoperative gait and FoG outcomes. The findings should be reproduced in larger and independent cohorts to verify their predictive value.

Time-Frequency Representation of Motor Evoked Potentials in Brain Tumor Patients.

Background: The integrity of the motor system can be examined by applying navigated transcranial magnetic stimulation (nTMS) to the cortex. The corresponding motor-evoked potentials (MEPs) in the target muscles are mirroring the status of the human motor system, far beyond corticospinal integrity. Commonly used time domain features of MEPs (e.g., peak-to-peak amplitudes and onset latencies) exert a high inter-subject and intra-subject variability. Frequency domain analysis might help to resolve or quantify disease-related MEP changes, e.g., in brain tumor patients. The aim of the present study was to describe the time-frequency representation of MEPs in brain tumor patients, its relation to clinical and imaging findings, and the differences to healthy subject. Methods: This prospective study compared 12 healthy subjects with 12 consecutive brain tumor patients (with and without a paresis) applying nTMS mapping. Resulting MEPs were evaluated in the time series domain (i.e., amplitudes and latencies). After transformation into the frequency domain using a Morlet wavelet approach, event-related spectral perturbation (ERSP), and inter-trial coherence (ITC) were calculated and compared to diffusion tensor imaging (DTI) results. Results: There were no significant differences in the time series characteristics between groups. MEPs were projecting to a frequency band between 30 and 300 Hz with a local maximum around 100 Hz for both healthy subjects and patients. However, there was ERSP reduction for higher frequencies (>100 Hz) in patients in contrast to healthy subjects. This deceleration was mirrored in an increase of the inter-peak MEP latencies. Patients with a paresis showed an additional disturbance in ITC in these frequencies. There was no correlation between the CST integrity (as measured by DTI) and the MEP parameters. Conclusion: Time-frequency analysis may provide additional information above and beyond classical MEP time domain features and the status of the corticospinal system in brain tumor patients. This first evaluation indicates that brain tumors might affect cortical physiology and the responsiveness of the cortex to TMS resulting in a temporal dispersion of the corticospinal transmission.

A critical comparison between the semisitting and the supine positioning in vestibular schwannoma surgery: subgroup analysis of a randomized, multicenter trial.

OBJECTIVE: Patient positioning in vestibular schwannoma (VS) surgery is a matter of ongoing discussion. Factors to consider include preservation of cranial nerve functions, extent of tumor resection, and complications. The objective of this study was to determine the optimal patient positioning in VS surgery. METHODS: A subgroup analysis of a randomized, multicenter trial that investigated the efficacy of prophylactic nimodipine in VS surgery was performed to investigate the impact of positioning (semisitting or supine) on extent of resection, functional outcomes, and complications. The data of 97 patients were collected prospectively. All procedures were performed via a retrosigmoid approach. The semisitting position was chosen in 56 patients, whereas 41 patients were treated while supine. RESULTS: Complete resection was obtained at a higher percentage in the semisitting as compared to the supine position (93% vs 73%, p = 0.002). Logistic regression analysis revealed significantly better facial nerve function in the early postoperative course in the semisitting group (p = 0.004), particularly concerning severe facial nerve paresis (House-Brackmann grade IV or worse; p = 0.002). One year after surgery, facial nerve function recovered. However, there was still a tendency for better facial nerve function in the semisitting group (p = 0.091). There were no significant differences between groups regarding hearing preservation rates. Venous air embolism with the necessity to terminate surgery occurred in 2 patients in the semisitting position (3.6%). Supplementary analysis with a 2-tailed permutation randomization with 10,000 permutations of treatment choice and a propensity score matching showed either a tendency or significant results for better facial nerve outcomes in the early postoperative course and extent of resection in the semisitting group. CONCLUSIONS: Although the results of the various statistical analyses are not uniform, the data indicate better results concerning both a higher rate of complete removal (according to the intraoperative impression of the surgeon) and facial nerve function after a semisitting as compared to the supine position. These advantages may justify the potential higher risk for severe complications of the semisitting position in VS surgery. The choice of positioning has to consider all individual patient parameters and risks carefully.

Intraoperative localization of spatially and spectrally distinct resting-state networks in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for symptomatic Parkinson's disease (PD); the clinical benefit may not only mirror modulation of local STN activity but also reflect consecutive network effects on cortical oscillatory activity. Moreover, STN-DBS selectively suppresses spatially and spectrally distinct patterns of synchronous oscillatory activity within cortical-subcortical loops. These STN-cortical circuits have been described in PD patients using magnetoencephalography after surgery. This network information, however, is currently not available during surgery to inform the implantation strategy.The authors recorded spontaneous brain activity in 3 awake patients with PD (mean age 67 ± 14 years; mean disease duration 13 ± 7 years) during implantation of DBS electrodes into the STN after overnight withdrawal of dopaminergic medication. Intraoperative propofol was discontinued at least 30 minutes prior to the electrophysiological recordings. The authors used a novel approach for performing simultaneous recordings of STN local field potentials (LFPs) and multichannel electroencephalography (EEG) at rest. Coherent oscillations between LFP and EEG sensors were computed, and subsequent dynamic imaging of coherent sources was performed.The authors identified coherent activity in the upper beta range (21-35 Hz) between the STN and the ipsilateral mesial (pre)motor area. Coherence in the theta range (4-6 Hz) was detected in the ipsilateral prefrontal area.These findings demonstrate the feasibility of detecting frequency-specific and spatially distinct synchronization between the STN and cortex during DBS surgery. Mapping the STN with this technique may disentangle different functional loops relevant for refined targeting during DBS implantation.

Directional communication during movement execution interferes with tremor in Parkinson's disease.

BACKGROUND: Both the cerebello-thalamo-cortical circuit and the basal ganglia/cortical motor loop have been postulated to be generators of tremor in PD. The recent suggestion that the basal ganglia trigger tremor episodes and the cerebello-thalamo-cortical circuitry modulates tremor amplitude combines both competing hypotheses. However, the role of the STN in tremor generation and the impact of proprioceptive feedback on tremor suppression during voluntary movements have not been considered in this model yet. OBJECTIVES: The objective of this study was to evaluate the role of the STN and proprioceptive feedback in PD tremor generation during movement execution. METHODS: Local-field potentials of the STN as well as electromyographical and electroencephalographical rhythms were recorded in tremor-dominant and nontremor PD patients while performing voluntary movements of the contralateral hand during DBS surgery. Effective connectivity between these electrophysiological signals were analyzed and compared to electromyographical tremor activity. RESULTS: There was an intensified information flow between the STN and the muscle in the tremor frequencies (5-8 Hz) for tremor-dominant, in comparison to nontremor, patients. In both subtypes, active movement was associated with an increase of afferent interaction between the muscle and the cortex in the ß- and γ-frequencies. The γ-frequency (30-40 Hz) of this communication between muscle and cortex correlated inversely with electromyographical tremor activity. CONCLUSIONS: Our results indicate an involvement of the STN in propagation of tremor-related activity to the muscle. Furthermore, we provide evidence that increased proprioceptive information flow during voluntary movement interferes with central tremor generation. © 2018 International Parkinson and Movement Disorder Society.

Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: a combined analysis of a randomized, multicenter, Phase III trial and its pilot study.

OBJECTIVE In clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled. METHODS The patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1-2 mg/hour) and HES (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery. RESULTS Pooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22-0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17-0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09-0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated. CONCLUSIONS Prophylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept. Clinical trial registration no.: DRKS 00000328 ( https://drks-neu.uniklinik-freiburg.de/drks_web/ ).

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.

Stability of hearing preservation and regeneration capacity of the cochlear nerve following vestibular schwannoma surgery via a retrosigmoid approach.

OBJECTIVE The purpose of this research was to examine the stability of long-term hearing preservation and the regeneration capacity of the cochlear nerve following vestibular schwannoma (VS) surgery in a prospective study. METHODS A total of 112 patients were recruited for a randomized multicenter trial between January 2010 and April 2012 to investigate the efficacy of prophylactic nimodipine treatment versus no prophylactic nimodipine treatment in VS surgery. For the present investigation, both groups were pooled to compare hearing abilities in the early postoperative course and 1 year after the surgery. Hearing was examined using pure-tone audiometry with speech discrimination, which was performed preoperatively, in the early postoperative course, and 12 months after surgery and was subsequently classified by an independent otorhinolaryngologist using the Gardner-Robertson classification system. RESULTS Hearing abilities at 2 time points were compared by evaluation in the early postoperative course and 1 year after surgery in 102 patients. The chi-square test showed a very strong association between the 2 measurements in all 102 patients (p < 0.001) and in the subgroup of 66 patients with a preserved cochlear nerve (p < 0.001). CONCLUSIONS There is no significant change in cochlear nerve function between the early postoperative course and 1 year after VS surgery. The result of hearing performance, as evaluated by early postoperative audiometry after VS surgery, seems to be a reliable prognosticator for future hearing ability. Clinical trial registration nos.: 2009-012088-32 ( clinicaltrialsregister.eu ) and DRKS 00000328 ("AkNiPro," drks-neu.uniklinik-freiburg.de/drks_web/ ).

Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial.

OBJECTIVE: A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS: An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS: Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34-3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS: There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.