Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Likelihood-of-harm/help of microsurgery compared to radiosurgery in large vestibular schwannoma.

PURPOSE: It has been shown that in large vestibular schwannomas (VS), radiosurgery (SRS) is inferior with respect to tumor control compared to microsurgical resection (SURGERY). However, SURGERY poses a significantly higher risk of facial-function deterioration (FFD). The aim of this study was to illustrate the effectiveness in terms of number-needed-to-treat/operate (NNO), number-needed-to-harm (NNH), and likelihood-of-harm/help (LHH) by comparing both treatment modalities in large VS. METHODS: This was a retrospective, dual-center cohort study. Tumor size was classified by Hannover Classification. Absolute risk reduction and risk increase were used to derive additional estimates of treatment effectiveness, namely NNO and NNH. LHH was then calculated by a quotient of NNH/NNO to illustrate the risk-benefit-ratio of SURGERY. RESULTS: Four hundred and forty-nine patients treated met the inclusion criteria. The incidence of tumor recurrence was significantly higher in SRS (14%), compared to SURGERY (3%) resulting in ARR of 11% and NNO of 10. At the same time, SURGERY was related to a significant risk of FFD resulting in an NNH of 12. Overall, the LHH calculated at 1.20 was favored SURGERY, especially in patients under the age of 40 years (LHH = 2.40), cystic VS (LHH = 4.33), and Hannover T3a (LHH = 1.83) and T3b (LHH = 1.80). CONCLUSIONS: Due to a poorer response of large VS to SRS, SURGERY is superior with respect to tumor control. One tumor recurrence can be prevented, when 10 patients are treated by SURGERY instead of SRS. Thus, LHH portrays the benefit of SURGERY in large VS even when taking raised FFD into account.

Cystic vestibular schwannoma - a subgroup analysis from a comparative study between radiosurgery and microsurgery.

Some vestibular schwannoma (VS) show cystic morphology. It is known that these cystic VS bear different risk profiles compared to solid VS in surgical treatment. Still, there has not been a direct comparative study comparing both SRS and SURGERY effectiveness in cystic VS. This retrospective bi-center cohort study aims to analyze the management of cystic VS compared to solid VS in a dual center study with both microsurgery (SURGERY) and stereotactic radiosurgery (SRS). Cystic morphology was defined as presence of any T2-hyperintense and Gadolinium-contrast-negative cyst of any size in the pre-interventional MRI. A matched subgroup analysis was carried out by determining a subgroup of matched SURGERY-treated solid VS and SRS-treated solid VS. Functional status, and post-interventional tumor volume size was then compared. From 2005 to 2011, N = 901 patients with primary and solitary VS were treated in both study sites. Of these, 6% showed cystic morphology. The incidence of cystic VS increased with tumor size: 1.75% in Koos I, 4.07% in Koos II, 4.84% in Koos III, and the highest incidence with 15.43% in Koos IV. Shunt-Dependency was significantly more often in cystic VS compared to solid VS (p = 0.024) and patients with cystic VS presented with significantly worse Charlson Comorbidity Index (CCI) compared to solid VS (p < 0.001). The rate of GTR was 87% in cystic VS and therefore significantly lower, compared to 96% in solid VS (p = 0.037). The incidence of dynamic volume change (decrease and increase) after SRS was significantly more common in cystic VS compared to the matched solid VS (p = 0.042). The incidence of tumor progression with SRS in cystic VS was 25%. When comparing EOR in the SURGERY-treated cystic to solid VS, the rate for tumor recurrence was significantly lower in GTR with 4% compared to STR with 50% (p = 0.042). Tumor control in cystic VS is superior in SURGERY, when treated with a high extent of resection grade, compared to SRS. Therapeutic response of SRS was worse in cystic compared to solid VS. However, when cystic VS was treated surgically, the rate of GTR is lower compared to the overall, and solid VS cohort. The significantly higher number of patients with relevant post-operative facial palsy in cystic VS is accredited to the increased tumor size not its sole cystic morphology. Cystic VS should be surgically treated in specialized centers.

Intermittend pneumatic venous thrombembolism (VTE) prophylaxis during neurosurgical procedures.

BACKGROUND: The management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main issue in debate are the dose and initiation time of pharmacologic VTE prevention to balance the risk of VTE-based morbidity and potentially life-threatening bleeding. Mechanical VTE prophylaxis with intermittend pneumatic compression (IPC), however, is established in only a few neurosurgical hospitals, and its efficacy has not yet been demonstrated. The objective of the present study was to analyze the risk of VTE before and after the implementation of IPC devices during elective neurosurgical procedures. METHODS: All elective surgeries performed at our neurosurgical department between 01/2018-08/2022 were investigated regarding the occurrence of VTE. The VTE risk and associated mortality were compared between groups: (1) only chemoprophylaxis (CHEMO; surgeries 01/2018-04/2020) and (2) IPC and chemoprophylaxis (IPC; surgeries 04/2020-08/2022). Furthermore, general patient and disease characteristics as well as duration of hospitalization were evaluated and compared to the VTE risk. RESULTS: VTE occurred after 38 elective procedures among > 12.000 surgeries. The number of VTEs significantly differed between groups with an incidence of 31/6663 (0.47%) in the CHEMO group and 7/6688 (0.1%) events in the IPC group. In both groups, patients with malignant brain tumors represented the largest proportion of patients, while VTEs in benign tumors occurred only in the CHEMO group. CONCLUSION: The use of combined mechanical and pharmacologic VTE prophylaxis can significantly reduce the risk of postoperative thromboembolism after neurosurgical procedures and, therefore, reduce mortality and morbidity.

Predictive value of facial motor-evoked potential and electromyography for facial motor function in vestibular schwannoma surgery.

PURPOSE: Intraoperative neuromonitoring (IONM) aims to preserve facial nerve (FN) function during vestibular schwannoma (VS) surgery. However, current techniques such as facial nerve motor evoked potentials (FNMEP) or electromyography (fEMG) alone are limited in predicting postoperative facial palsy (FP). The objective of this study was to analyze a compound fEMG/FNMEP approach. METHODS: Intraoperative FNMEP amplitude and the occurrence of fEMG-based A-trains were prospectively determined for the orbicularis oris (ORI) and oculi (OCU) muscle in 322 VS patients. Sensitivity and specificity of techniques to predict postoperative FN function were calculated. Confounding factors as tumor size, volume of intracranial air, or IONM duration were analyzed. RESULTS: A relevant immediate postoperative FP was captured in 105/322 patients with a significant higher risk in large VS. While fEMG demonstrated a high sensitivity (77% and 86% immediately and 15 month postoperative, respectively) for identifying relevant FP, specificity was low. In contrast, FNMEP have a significantly higher specificity of 80.8% for predicting postoperative FP, whereas the sensitivity is low. A retrospective combination of techniques demonstrated still an incorrect prediction of FP in ~ 1/3 of patients. CONCLUSIONS: FNMEP and fEMG differ in sensitivity and specificity to predict postoperative FP. Although a combination of IONM techniques during VS surgery may improve prediction of FN function, current techniques are still inaccurate. Further development is necessary to improve IONM approaches for FP prediction.

Rewiring cortico-muscular control in the healthy and post-stroke human brain with proprioceptive beta-band neurofeedback.

In severely affected stroke survivors, cortico-muscular control is disturbed and volitional upper limb movements often absent. Mental rehearsal of the impaired movement in conjunction with sensory feedback provision are suggested as promising rehabilitation exercises. Knowledge about the underlying neural processes, however, remains vague. In male and female chronic stroke patients with hand paralysis, a brain-computer interface controlled a robotic orthosis and turned sensorimotor beta-band desynchronization during motor imagery (MI) of finger extension into contingent hand opening. Healthy control subjects performed the same task and received the same proprioceptive feedback with a robotic orthosis or visual feedback only. Only when proprioceptive feedback was provided, cortico-muscular coherence (CMC) increased with a predominant information flow from the sensorimotor cortex to the finger extensors. This effect (i) was specific to the beta frequency-band, (ii) transferred to a motor task, (iii) was proportional to subsequent corticospinal excitability and correlated with behavioral changes in the (iv) healthy and (v) post-stroke condition; notably, MI-related enhancement of beta-band CMC in the ipsilesional premotor cortex correlated with motor improvements after the intervention.In the healthy and injured human nervous system, synchronized activation of motor-related cortical and spinal neural pools facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible.Significance statement:This study provides insights into the neural processes that transfer effects of brain-computer interface neurofeedback to subsequent motor behavior. Specifically, volitional control of cortical oscillations and proprioceptive feedback enhances both cortical activity and behaviorally relevant connectivity to the periphery in a topographically circumscribed and frequency-specific way. This enhanced cortico-muscular control can be induced in the healthy and post-stroke brain. Thereby, activating the motor cortex with mental rehearsal of the impaired movement and closing the loop by robot-assisted feedback synchronizes ipsilesional premotor cortex and spinal neural pools in the beta-frequency band. This facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible.

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.

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.

Brain State-dependent Gain Modulation of Corticospinal Output in the Active Motor System.

The communication through coherence hypothesis suggests that only coherently oscillating neuronal groups can interact effectively and predicts an intrinsic response modulation along the oscillatory rhythm. For the motor cortex (MC) at rest, the oscillatory cycle has been shown to determine the brain's responsiveness to external stimuli. For the active MC, however, the demonstration of such a phase-specific modulation of corticospinal excitability (CSE) along the rhythm cycle is still missing. Motor evoked potentials in response to transcranial magnetic stimulation (TMS) over the MC were used to probe the effect of cortical oscillations on CSE during several motor conditions. A brain-machine interface (BMI) with a robotic hand orthosis allowed investigating effects of cortical activity on CSE without the confounding effects of voluntary muscle activation. Only this BMI approach (and not active or passive hand opening alone) revealed a frequency- and phase-specific cortical modulation of CSE by sensorimotor beta-band activity that peaked once per oscillatory cycle and was independent of muscle activity. The active MC follows an intrinsic response modulation in accordance with the communication through coherence hypothesis. Furthermore, the BMI approach may facilitate and strengthen effective corticospinal communication in a therapeutic context, for example, when voluntary hand opening is no longer possible after stroke.

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.

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.

Desynchronization of temporal lobe theta-band activity during effective anterior thalamus deep brain stimulation in epilepsy.

BACKGROUND: Bilateral cyclic high frequency deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) reduces the seizure count in a subset of patients with epilepsy. Detecting stimulation-induced alterations of pathological brain networks may help to unravel the underlying physiological mechanisms related to effective stimulation delivery and optimize target engagement. METHODS: We acquired 64-channel electroencephalography during ten ANT-DBS cycles (145 â€‹Hz, 90 â€‹µs, 3-5 â€‹V) of 1-min ON followed by 5-min OFF stimulation to detect changes in cortical activity related to seizure reduction. The study included 14 subjects (three responders, four non-responders, and seven healthy controls). Mixed-model ANOVA tests were used to compare differences in cortical activity between subgroups both ON and OFF stimulation, while investigating frequency-specific effects for the seizure onset zones. RESULTS: ANT-DBS had a widespread desynchronization effect on cortical theta and alpha band activity in responders, but not in non-responders. Time domain analysis showed that the stimulation induced reduction in theta-band activity was temporally linked to the stimulation period. Moreover, stimulation induced theta-band desynchronization in the temporal lobe channels correlated significantly with the therapeutic response. Responders to ANT-DBS and healthy-controls had an overall lower level of theta-band activity compared to non-responders. CONCLUSION: This study demonstrated that temporal lobe channel theta-band desynchronization may be a predictive physiological hallmark of therapeutic response to ANT-DBS and may be used to improve the functional precision of this intervention by verifying implantation sites, calibrating stimulation contacts, and possibly identifying treatment responders prior to implantation.

Online Mapping With the Deep Brain Stimulation Lead: A Novel Targeting Tool in Parkinson's Disease.

BACKGROUND: Beta-frequency oscillations (13-30 Hz) are a subthalamic hallmark in patients with Parkinson's disease, and there is increased interest in their utility as an intraoperative marker. OBJECTIVES: The objectives of this study were to assess whether beta activity measured directly from macrocontacts of deep brain stimulation leads could be used (a) as an intraoperative electrophysiological approach for guiding lead placements and (b) for physiologically informed stimulation delivery. METHODS: Every millimeter along the surgical trajectory, local field-potential data were collected from each macrocontact, and power spectral densities were calculated and visualized (n = 39 patients). This was done for online intraoperative functional mapping and post hoc statistical analyses using 2 methods: generating distributions of spectral activity along surgical trajectories and direct delineation (presence versus lack) of beta peaks. In a subset of patients, this approach was corroborated by microelectrode recordings. Furthermore, the match rate between beta peaks at the final target position and the clinically determined best stimulation site were assessed. RESULTS: Subthalamic recording sites were delineated by both methods of reconstructing functional topographies of spectral activity along surgical trajectories at the group level (P < 0.0001). Beta peaks were detected when any portion of the 1.5 mm macrocontact was within the microelectrode-defined subthalamic border. The highest beta peak at the final implantation site corresponded to the site of active stimulation in 73.3% of hemispheres (P < 0.0001). In 93.3% of hemispheres, active stimulation corresponded to the first-highest or second-highest beta peak. CONCLUSIONS: Online measures of beta activity with the deep brain stimulation macroelectrode can be used to inform surgical lead placement and contribute to optimization of stimulation programming procedures. © 2020 International Parkinson and Movement Disorder Society.

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.

Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation.

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the ß-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during ß-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract.SIGNIFICANCE STATEMENT The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional ß-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract.

Ki-67 labeling index and expression of p53 are non-predictive for invasiveness and tumor size in functional and nonfunctional pituitary adenomas.

BACKGROUND: It is still controversial whether an increased proliferation index is correlated with the tumor invasiveness of pituitary adenomas. A homogeneous large monocentric series of pituitary adenomas was retrospectively analyzed. The correlation between the proliferation indices (Ki-67 and p53 expression levels) and invasiveness and size of pituitary adenomas was investigated in primary operated and recurrent adenomas. METHOD: Four hundred thirty-nine patients after resection of pituitary adenomas were retrospectively included (43 recurrent tumors, 196 null cell adenomas, 86 somatotroph adenomas, 55 corticotroph adenomas, 55 prolactinomas, 4 thyreotroph adenomas). The maximum tumor diameter and tumor invasiveness in Knosp grading were assessed and Ki-67 and p53 immunostaining was performed. The role of invasiveness was evaluated using a cumulative odds ordinal logistic regression. For calculating the effect of tumor size, a one-way analysis of variance (ANOVA) was conducted. RESULTS: Overall and in the subgroups, no significant correlation between proliferation indices and mean tumor diameter was found. No significant predictive expression value of Ki-67 and p53 on tumor invasiveness and in recurrent tumors could be demonstrated. There was a tendency that Ki-67 LI and p53 LI are higher in recurrent corticotroph adenomas and lactotroph adenomas but values did not reach the significant level. CONCLUSION: Invasive character of pituitary adenomas is neither correlated with increased Ki-67 LI nor with increased p53 expression. Proliferation parameters are independent from adenoma size at initial presentation. The partly elevated expression of Ki-67 in recurrent tumors underlines the clinical importance of the marker.

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.

Brain-robot interface driven plasticity: Distributed modulation of corticospinal excitability.

Brain-robot interfaces (BRI) are studied as novel interventions to facilitate functional restoration in patients with severe and persistent motor deficits following stroke. They bridge the impaired connection in the sensorimotor loop by providing brain-state dependent proprioceptive feedback with orthotic devices attached to the hand or arm of the patients. The underlying neurophysiology of this BRI neuromodulation is still largely unknown. We investigated changes of corticospinal excitability with transcranial magnetic stimulation in thirteen right-handed healthy subjects who performed 40min of kinesthetic motor imagery receiving proprioceptive feedback with a robotic orthosis attached to the left hand contingent to event-related desynchronization of the right sensorimotor cortex in the ß-band (16-22Hz). Neural correlates of this BRI intervention were probed by acquiring the stimulus-response curve (SRC) of both motor evoked potential (MEP) peak-to-peak amplitudes and areas under the curve. In addition, a motor mapping was obtained. The specificity of the effects was studied by comparing two neighboring hand muscles, one BRI-trained and one control muscle. Robust changes of MEP amplitude but not MEP area occurred following the BRI intervention, but only in the BRI-trained muscle. The steep part of the SRC showed an MEP increase, while the plateau of the SRC showed an MEP decrease. MEP mapping revealed a distributed pattern with a decrease of excitability in the hand area of the primary motor cortex, which controlled the BRI, but an increase of excitability in the surrounding somatosensory and premotor cortex. In conclusion, the BRI intervention induced a complex pattern of modulated corticospinal excitability, which may boost subsequent motor learning during physiotherapy.

Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson's disease.

Dynamic modulations of large-scale network activity and synchronization are inherent to a broad spectrum of cognitive processes and are disturbed in neuropsychiatric conditions including Parkinson's disease. Here, we set out to address the motor network activity and synchronization in Parkinson's disease and its modulation with subthalamic stimulation. To this end, 20 patients with idiopathic Parkinson's disease with subthalamic nucleus stimulation were analysed on externally cued right hand finger movements with 1.5-s interstimulus interval. Simultaneous recordings were obtained from electromyography on antagonistic muscles (right flexor digitorum and extensor digitorum) together with 64-channel electroencephalography. Time-frequency event-related spectral perturbations were assessed to determine cortical and muscular activity. Next, cross-spectra in the time-frequency domain were analysed to explore the cortico-cortical synchronization. The time-frequency modulations enabled us to select a time-frequency range relevant for motor processing. On these time-frequency windows, we developed an extension of the phase synchronization index to quantify the global cortico-cortical synchronization and to obtain topographic differentiations of distinct electrode sites with respect to their contributions to the global phase synchronization index. The spectral measures were used to predict clinical and reaction time outcome using regression analysis. We found that movement-related desynchronization of cortical activity in the upper alpha and beta range was significantly facilitated with 'stimulation on' compared to 'stimulation off' on electrodes over the bilateral parietal, sensorimotor, premotor, supplementary-motor, and prefrontal areas, including the bilateral inferior prefrontal areas. These spectral modulations enabled us to predict both clinical and reaction time improvement from subthalamic stimulation. With 'stimulation on', interhemispheric cortico-cortical coherence in the beta band was significantly attenuated over the bilateral sensorimotor areas. Similarly, the global cortico-cortical phase synchronization was attenuated, and the topographic differentiation revealed stronger desynchronization over the (ipsilateral) right-hemispheric prefrontal, premotor and sensorimotor areas compared to 'stimulation off'. We further demonstrated that the cortico-cortical phase synchronization was largely dominated by genuine neuronal coupling. The clinical improvement with 'stimulation on' compared to 'stimulation off' could be predicted from this cortical decoupling with multiple regressions, and the reduction of synchronization over the right prefrontal area showed a linear univariate correlation with clinical improvement. Our study demonstrates wide-spread activity and synchronization modulations of the cortical motor network, and highlights subthalamic stimulation as a network-modulating therapy. Accordingly, subthalamic stimulation may release bilateral cortical computational resources by facilitating movement-related desynchronization. Moreover, the subthalamic nucleus is critical to balance inhibitory and facilitatory cortical players within the motor program.

Lateralized alpha-band cortical networks regulate volitional modulation of beta-band sensorimotor oscillations.

Sensorimotor rhythms (SMRs) are oscillatory brain activities in the α- and ß-bands across the sensorimotor regions of the brain. Each frequency band has its own specific function. The α-band oscillations are closely related to intrinsic cortical networks, whereas oscillations in the ß-band are relevant for the information transfer between the cortex and periphery, as well as for visual and proprioceptive feedback. This study aimed to investigate the interaction between these two frequency bands, under the premise that the regional modulation of ß-band power is linked to a cortical network in the α-band. We therefore designed a procedure to maximize the modulation of ß-band activity over the sensorimotor cortex by combining kinesthetic motor-imagery with closed-loop haptic feedback. The cortical network activity during this procedure was estimated via the phase slope index in electroencephalographic recordings. Analysis of effective connectivity within the α-band network revealed an information flow between the precentral (premotor and primary motor), postcentral (primary somatosensory) and parietal cortical areas. The range of ß-modulation was connected to a reduction of an ipsilateral sensorimotor and parietal α-network and, consequently, to a lateralization of this network to the contralateral side. These results showed that regional sensorimotor oscillatory activity in the ß-band was regulated by cortical coupling of distant areas in the α-band.