High frequency oscillations in relation to interictal spikes in predicting postsurgical seizure freedom.

We evaluate whether interictal spikes, epileptiform HFOs and their co-occurrence (Spike + HFO) were included in the resection area with respect to seizure outcome. We also characterise the relationship between high frequency oscillations (HFOs) and propagating spikes. We analysed intracranial EEG of 20 patients that underwent resective epilepsy surgery. The co-occurrence of ripples and fast ripples was considered an HFO event; the co-occurrence of an interictal spike and HFO was considered a Spike + HFO event. HFO distribution and spike onset were compared in cases of spike propagation. Accuracy in predicting seizure outcome was 85% for HFO, 60% for Spikes, and 79% for Spike + HFO. Sensitivity was 57% for HFO, 71% for Spikes and 67% for Spikes + HFO. Specificity was 100% for HFO, 54% for Spikes and 85% for Spikes + HFO. In 2/2 patients with spike propagation, the spike onset included the HFO area. Combining interictal spikes with HFO had comparable accuracy to HFO. In patients with propagating spikes, HFO rate was maximal at the onset of spike propagation.

Safety of microneurosurgical interventions for superficial and deep-seated brain metastases: single-center cohort study of 637 consecutive cases.

PURPOSE: Microneurosurgical techniques have greatly improved over the past years due to the introduction of new technology and surgical concepts. To reevaluate the role of micro-neurosurgery in brain metastases (BM) resection in the era of new systemic and local treatment options, its safety profile needs to be reassessed. The aim of this study was to analyze the rate of adverse events (AEs) according to a systematic, comprehensive and reliably reproducible grading system after microneurosurgical BM resection in a large and modern microneurosurgical series with special emphasis on anatomical location. METHODS: Prospectively collected cases of BM resection between 2013 and 2022 were retrospectively analyzed. Number of AEs, defined as any deviations from the expected postoperative course according to Clavien-Dindo-Grade (CDG) were evaluated. Patient, surgical, and lesion characteristics, including exact anatomic tumor locations, were analyzed using uni- and multivariate logistic regression and survival analysis to identify predictive factors for AEs. RESULTS: We identified 664 eligible patients with lung cancer being the most common primary tumor (44%), followed by melanoma (25%) and breast cancer (11%). 29 patients (4%) underwent biopsy only whereas BM were resected in 637 (96%) of cases. The overall rate of AEs was 8% at discharge. However, severe AEs (≥ CDG 3a; requiring surgical intervention under local/general anesthesia or ICU treatment) occurred in only 1.9% (n = 12) of cases with a perioperative mortality of 0.6% (n = 4). Infratentorial tumor location (OR 5.46, 95% 2.31-13.8, p = .001), reoperation (OR 2.31, 95% 1.07-4.81, p = .033) and central region tumor location (OR 3.03, 95% 1.03-8.60) showed to be significant predictors in a multivariate analysis for major AEs (CDG ≥ 2 or new neurological deficits). Neither deep supratentorial nor central region tumors were associated with more major AEs compared to convexity lesions. CONCLUSIONS: Modern microneurosurgical resection can be considered an excellent option in the management of BM in terms of safety, as the overall rate of major AEs are very rare even in eloquent and deep-seated lesions.

Association of perioperative adverse events with subsequent therapy and overall survival in patients with WHO grade III and IV gliomas.

Background: Maximum safe resection followed by chemoradiotherapy as current standard of care for WHO grade III and IV gliomas can be influenced by the occurrence of perioperative adverse events (AE). The aim of this study was to determine the association of AE with the timing and choice of subsequent treatments as well as with overall survival (OS). Methods: Prospectively collected data of 283 adult patients undergoing surgery for WHO grade III and IV gliomas at the University Hospital Zurich between January 2013 and June 2017 were analyzed. We assessed basic patient characteristics, KPS, extent of resection, and WHO grade, and we classified AE as well as modality, timing of subsequent treatment (delay, interruption, or non-initiation), and OS. Results: In 117 patients (41%), an AE was documented between surgery and the 3-month follow-up. There was a significant association of AE with an increased time to initiation of subsequent therapy (p = 0.005) and a higher rate of interruption (p < 0.001) or non-initiation (p < 0.001). AE grades correlated with time to initiation of subsequent therapy (p = 0.038). AEs were associated with shorter OS in univariate analysis (p < 0.001). Conclusion: AEs are associated with delayed and/or altered subsequent therapy and can therefore limit OS. These data emphasize the importance of safety within the maximum-safe-resection concept.

Evaluation of a new cortical strip electrode for intraoperative somatosensory monitoring during perirolandic brain surgery.

OBJECTIVE: During neurosurgical procedures, strip electrodes should have low impedance and sufficient adherence on the brain surface. We evaluated the signal quality, safety, and performance of a novel strip electrode (WISE Cortical Strip, WCS®), with conductive electrode contacts created with platinum nanoparticles embedded in a polymer base. METHODS: In a multicenter interventional, non-inferiority study, we compared WCS to a conventional strip electrode (Ad-Tech). We recorded impedance and somatosensory evoked potentials (SEP) and determined the signal-to-noise ratio (SNR). We performed direct stimulation of the motor cortex. An external clinical event committee rated safety and adverse events and users rated usability. RESULTS: During 32 brain surgeries in the paracentral region, WCS was rated safe and effective in signal transmission. Two seizure events were classified as probably related to the stimulation with WCS. The users rated WCS adhesion to the brain as satisfactory but reported difficulties sliding the WCS under the dura. The median (IQR) impedance of WCS was lower than for Ad-Tech: 2.7 (2.3-3.7) vs 5.30 (4.3-6.6) kΩ (p < 0.005). The SNR of SEP was non-inferior for WCS compared to Ad-Tech. CONCLUSIONS: The impedance of WCS was lower than Ad-Tech without safety limitations. In small craniotomies not exposing the motor cortex its use may be limited. SIGNIFICANCE: Low impedance electrodes facilitate recordings with high SNR.

Sex-related differences in postoperative complications following elective craniotomy for intracranial lesions: An observational study.

INTRODUCTION: The integration of sex-related differences in neurosurgery is crucial for new, possible sex-specific, therapeutic approaches. In neurosurgical emergencies, such as traumatic brain injury and aneurysmal subarachnoid hemorrhage, these differences have been investigated. So far, little is known concerning the impact of sex on frequency of postoperative complications after elective craniotomy. This study investigates whether sex-related differences exist in frequency of postoperative complications in patients who underwent elective craniotomy for intracranial lesion. MATERIAL AND METHODS: All consecutive patients who underwent an elective intracranial procedure over a 2-year period at our center were eligible for inclusion in this retrospective study. Demographic data, comorbidities, frequency of postoperative complications at 24 hours following surgery and at discharge, and hospital length of stay were compared among females and males. RESULTS: Overall, 664 patients were considered for the analysis. Of those, 339 (50.2%) were females. Demographic data were comparable among females and males. More females than males suffered from allergic, muscular, and rheumatic disorders. No differences in frequency of postoperative complications at 24 hours after surgery and at discharge were observed among females and males. Similarly, the hospital length of stay was comparable. CONCLUSIONS: In the present study, no sex-related differences in frequency of early postoperative complications and at discharge following elective craniotomy for intracranial lesions were observed.

Mapping and Monitoring of the Corticospinal Tract by Direct Brainstem Stimulation.

BACKGROUND: Direct stimulation and diffusion tensor imaging/tractography are established techniques that assist in complex surgery for lesions in the eloquent area of the central nervous system. OBJECTIVE: To continuously map the corticospinal tract (CST) by direct stimulation during brainstem surgery and to explore the association between direct brainstem stimulation and the shortest distance from the stimulation point to the CST (DS-to-T). METHODS: We prospectively enrolled 30 consecutive patients for microsurgical resection of lesions within or in proximity to the brainstem between January 2019 and August 2021. Direct stimulation with initially 2 mA was performed for mapping and monitoring the motor fiber tracts. To evaluate CST status and measure DS-to-T, postoperative diffusion tensor imaging/tractography was used. Preoperative and postoperative modified Ranking Scale and motor function were evaluated to assess the clinical outcome. RESULTS: Intraoperative direct brainstem stimulation was successfully performed in all patients with a total of 909 stimulation points. One patient experienced a temporary neurological deficit postoperatively. Mapping of the CST was achieved in 5 patients. DS-to-T was ≤4 mm when motor-evoked potential responses were positive under 2 mA stimulation and ≤2 mm under 1 mA. Overall sensitivity and specificity for this association were 84.7% and 100%, respectively. CONCLUSION: This study further supports the paradigm for continuous CST monitoring and mapping through direct brainstem stimulation. The relationship between stimulation intensity and DS-to-T in brainstem surgery could help surgeon's better estimate the safe edge intraoperatively.

Automatic Detection of High-Frequency Oscillations With Neuromorphic Spiking Neural Networks.

Interictal high-frequency oscillations (HFO) detected in electroencephalography recordings have been proposed as biomarkers of epileptogenesis, seizure propensity, disease severity, and treatment response. Automatic HFO detectors typically analyze the data offline using complex time-consuming algorithms, which limits their clinical application. Neuromorphic circuits offer the possibility of building compact and low-power processing systems that can analyze data on-line and in real time. In this review, we describe a fully automated detection pipeline for HFO that uses, for the first time, spiking neural networks and neuromorphic technology. We demonstrated that our HFO detection pipeline can be applied to recordings from different modalities (intracranial electroencephalography, electrocorticography, and scalp electroencephalography) and validated its operation in a custom-designed neuromorphic processor. Our HFO detection approach resulted in high accuracy and specificity in the prediction of seizure outcome in patients implanted with intracranial electroencephalography and electrocorticography, and in the prediction of epilepsy severity in patients recorded with scalp electroencephalography. Our research provides a further step toward the real-time detection of HFO using compact and low-power neuromorphic devices. The real-time detection of HFO in the operation room may improve the seizure outcome of epilepsy surgery, while the use of our neuromorphic processor for non-invasive therapy monitoring might allow for more effective medication strategies to achieve seizure control. Therefore, this work has the potential to improve the quality of life in patients with epilepsy by improving epilepsy diagnostics and treatment.

Protocol for multicentre comparison of interictal high-frequency oscillations as a predictor of seizure freedom.

In drug-resistant focal epilepsy, interictal high-frequency oscillations (HFOs) recorded from intracranial EEG (iEEG) may provide clinical information for delineating epileptogenic brain tissue. The iEEG electrode contacts that contain HFO are hypothesized to delineate the epileptogenic zone; their resection should then lead to postsurgical seizure freedom. We test whether our prospective definition of clinically relevant HFO is in agreement with postsurgical seizure outcome. The algorithm is fully automated and is equally applied to all data sets. The aim is to assess the reliability of the proposed detector and analysis approach. We use an automated data-independent prospective definition of clinically relevant HFO that has been validated in data from two independent epilepsy centres. In this study, we combine retrospectively collected data sets from nine independent epilepsy centres. The analysis is blinded to clinical outcome. We use iEEG recordings during NREM sleep with a minimum of 12 epochs of 5 min of NREM sleep. We automatically detect HFO in the ripple (80-250 Hz) and in the fast ripple (250-500 Hz) band. There is no manual rejection of events in this fully automated algorithm. The type of HFO that we consider clinically relevant is defined as the simultaneous occurrence of a fast ripple and a ripple. We calculate the temporal consistency of each patient's HFO rates over several data epochs within and between nights. Patients with temporal consistency <50% are excluded from further analysis. We determine whether all electrode contacts with high HFO rate are included in the resection volume and whether seizure freedom (ILAE 1) was achieved at ≥2 years follow-up. Applying a previously validated algorithm to a large cohort from several independent epilepsy centres may advance the clinical relevance and the generalizability of HFO analysis as essential next step for use of HFO in clinical practice.

Scalp HFO rates are higher for larger lesions.

High-frequency oscillations (HFO) in scalp EEG are a new and promising noninvasive epilepsy biomarker, providing added prognostic value, particularly in pediatric lesional epilepsy. However, it is unclear if lesion characteristics, such as lesion volume, depth, type, and localization, impact scalp HFO rates. We analyzed scalp EEG from 13 children and adolescents with focal epilepsy associated with focal cortical dysplasia (FCD), low-grade tumors, or hippocampal sclerosis. We applied a validated automated detector to determine HFO rates in bipolar channels. We identified the lesion characteristics in MRI. Larger lesions defined by MRI volumetric analysis corresponded to higher cumulative scalp HFO rates (P = .01) that were detectable in a higher number of channels (P = .05). Both superficial and deep lesions generated HFO detectable in the scalp EEG. Lesion type (FCD vs tumor) and lobar localization (temporal vs extratemporal) did not affect scalp HFO rates in our study. Our observations support that all lesions may generate HFO detectable in scalp EEG, irrespective of their characteristics, whereas larger epileptogenic lesions generate higher scalp HFO rates over larger areas that are thus more accessible to detection. Our study provides crucial insight into scalp HFO detectability in pediatric lesional epilepsy, facilitating their implementation as an epilepsy biomarker in a clinical setting.

Scalp HFO rates decrease after successful epilepsy surgery and are not impacted by the skull defect resulting from craniotomy.

Epilepsy surgery can achieve seizure freedom in selected pediatric candidates, but reliable postsurgical predictors of seizure freedom are missing. High frequency oscillations (HFO) in scalp EEG are a new and promising biomarker of treatment response. However, it is unclear if the skull defect resulting from craniotomy interferes with HFO detection in postsurgical recordings. We considered 14 children with focal lesional epilepsy who underwent presurgical evaluation, epilepsy surgery, and postsurgical follow-up of ≥ 1 year. We identified the nearest EEG electrodes to the skull defect in the postsurgical MRI. We applied a previously validated automated HFO detector to determine HFO rates in presurgical and postsurgical EEG. Overall, HFO rates showed a positive correlation with seizure frequency (p < 0.001). HFO rates in channels over the HFO area decreased following successful epilepsy surgery, irrespective of their proximity to the skull defect (p = 0.005). HFO rates in channels outside the HFO area but near the skull defect showed no increase following surgery (p = 0.091) and did not differ from their contralateral channels (p = 0.726). Our observations show that the skull defect does not interfere with postsurgical HFO detection. This supports the notion that scalp HFO can predict postsurgical seizure freedom and thus guide therapy management in focal lesional epilepsy.

Blinded study: prospectively defined high-frequency oscillations predict seizure outcome in individual patients.

Interictal high-frequency oscillations are discussed as biomarkers for epileptogenic brain tissue that should be resected in epilepsy surgery to achieve seizure freedom. The prospective classification of tissue sampled by individual electrode contacts remains a challenge. We have developed an automated, prospective definition of clinically relevant high-frequency oscillations in intracranial EEG from Montreal and tested it in recordings from Zurich. We here validated the algorithm on intracranial EEG that was recorded in an independent epilepsy centre so that the analysis was blinded to seizure outcome. We selected consecutive patients who underwent resective epilepsy surgery in Geneva with post-surgical follow-up > 12 months. We analysed long-term recordings during sleep that we segmented into intervals of 5 min. High-frequency oscillations were defined in the ripple (80-250 Hz) and the fast ripple (250-500 Hz) frequency bands. Contacts with the highest rate of ripples co-occurring with fast ripples designated the relevant area. As a validity criterion, we calculated the test-retest reliability of the high-frequency oscillations area between the 5 min intervals (dwell time ≥50%). If the area was not fully resected and the patient suffered from recurrent seizures, this was classified as a true positive prediction. We included recordings from 16 patients (median age 32 years, range 18-53 years) with stereotactic depth electrodes and/or with subdural electrode grids (median follow-up 27 months, range 12-55 months). For each patient, we included several 5 min intervals (median 17 intervals). The relevant area had high test-retest reliability across intervals (median dwell time 95%). In two patients, the test-retest reliability was too low (dwell time < 50%) so that outcome prediction was not possible. The area was fully included in the resected volume in 2/4 patients who achieved post-operative seizure freedom (specificity 50%) and was not fully included in 9/10 patients with recurrent seizures (sensitivity 90%), leading to an accuracy of 79%. An additional exploratory analysis suggested that high-frequency oscillations were associated with interictal epileptic discharges only in channels within the relevant area and not associated in channels outside the area. We thereby validated the automated procedure to delineate the clinically relevant area in each individual patient of an independently recorded dataset and achieved the same good accuracy as in our previous studies. The reproducibility of our results across datasets is promising for a multicentre study to test the clinical application of high-frequency oscillations to guide epilepsy surgery.

Peroral Trigeminal Rhizotomy Using a Novel 3-Dimensional Printed Patient-Specific Guidance Tool.

BACKGROUND: Ganglion Gasseri rhizotomy is a viable therapeutic option for trigeminal pain (TP). For this neurosurgical procedure, different potential operative and technical nuances exist. OBJECTIVE: To evaluate a novel peroral trigeminal rhizotomy method and 3-dimensional printed patient-specific guidance tool (3D-PSGT) with respect to their applicability and safety. METHODS: Between March 2018 and February 2021, 20 peroral balloon compression rhizotomy procedures with a 3D-PSGT were performed in 18 consecutive TP patients (13 female, mean age 58 yr). We registered the procedure duration, side effects, complications, and trigeminal function. The therapeutic effect was gauged from reduction of TP and use of analgesics. RESULTS: All catheter insertions and rhizotomy procedures were successful at the first attempt. Apart from fluoroscopy, no auxiliary material was necessary. The average length of surgery was 19 min (range, 11-27 min). In total, 8 patients indicated complete analgesia and 6 patients pain relief; in 4 patients, persistence of TP was observed during follow-up examinations of up to 20 mo. In total, 6 patients reported of new mild to moderate facial hypesthesia affecting the trigeminal branches V2, V3, or V1-3. No masticatory musculature or corneal affections and device-related complications occurred. CONCLUSION: The peroral 3D-PSGT trigeminal rhizotomy is straightforward for the neurosurgeon. This operative approach allows for rapid, safe, and simple foramen ovale cannulation in TP patients and reduces the use of additional equipment, radiation exposure, and procedure time.

Preoperative risk factors associated with new focal neurological deficit and other major adverse events in first-time intracranial meningioma neurosurgery.

BACKGROUND: Neurosurgical resection is the mainstay of meningioma treatment. Adverse event (AE) rates of meningioma resections are significant, but preoperative risk factors for major AEs in patients undergoing first-time meningioma surgery are largely unknown. The aim of this study was to explore major AEs and identify preoperative risk factors in patients undergoing first-time meningioma surgery. METHODS: Data on all meningioma resections performed at the University Hospital Zurich from 1 January 2013 to 31 December 2018 were collected in a prospective registry. All AEs that occurred within 3 months of surgery were documented in detail and classified as "minor" or "major." Statistical analysis included initial individual bivariate analyses of all preoperative factors and the occurrence of major AEs. Statistically significant variables were then included in a logistic regression model to identify predictors. RESULTS: Three hundred forty-five patients were included in the study. Mean age was 58.1 years, and 77.1% of patients were female. The overall major AE rate was 20.6%; the most common of which was a new focal neurological deficit (12.8% of patients). Six preoperative factors showed a significant association with the occurrence of major AEs in bivariate analysis. All variables included in the logistic regression model showed increased odds of occurrence of major AE, but only tumor complexity as measured by the Milan Complexity Scale was a statistically significant predictor, with a score of 4 or more having twice the odds of major AEs (OR: 2.00, 95% CI: 1.15-3.48). CONCLUSION: High tumor complexity is an independent predictor of the occurrence of major AEs following meningioma resection. Preoperative assessment of tumor complexity using the Milan Complexity Scale is warranted and can aid communication with patients about AE rates and surgical decision-making.

Epileptic High-Frequency Oscillations in Intracranial EEG Are Not Confounded by Cognitive Tasks.

Rationale: High-frequency oscillations (HFOs) in intracranial EEG (iEEG) are used to delineate the epileptogenic zone during presurgical diagnostic assessment in patients with epilepsy. HFOs are historically divided into ripples (80-250 Hz), fast ripples (FR, >250 Hz), and their co-occurrence (FRandR). In a previous study, we had validated the rate of FRandRs during deep sleep to predict seizure outcome. Here, we ask whether epileptic FRandRs might be confounded by physiological FRandRs that are unrelated to epilepsy. Methods: We recorded iEEG in the medial temporal lobe MTL (hippocampus, entorhinal cortex, and amygdala) in 17 patients while they performed cognitive tasks. The three cognitive tasks addressed verbal working memory, visual working memory, and emotional processing. In our previous studies, these tasks activated the MTL. We re-analyzed the data of these studies with the automated detector that focuses on the co-occurrence of ripples and FRs (FRandR). Results: For each task, we identified those channels in which the HFO rate was modulated during the task condition compared to the control condition. However, the number of these channels did not exceed the chance level. Interestingly, even during wakefulness, the HFO rate was higher for channels within the seizure onset zone (SOZ) than for channels outside the SOZ. Conclusion: Our prospective definition of an epileptic HFO, the FRandR, is not confounded by physiological HFOs that might be elicited by our cognitive tasks. This is reassuring for the clinical use of FRandR as a biomarker of the EZ.

A spiking neural network (SNN) for detecting high frequency oscillations (HFOs) in the intraoperative ECoG.

To achieve seizure freedom, epilepsy surgery requires the complete resection of the epileptogenic brain tissue. In intraoperative electrocorticography (ECoG) recordings, high frequency oscillations (HFOs) generated by epileptogenic tissue can be used to tailor the resection margin. However, automatic detection of HFOs in real-time remains an open challenge. Here we present a spiking neural network (SNN) for automatic HFO detection that is optimally suited for neuromorphic hardware implementation. We trained the SNN to detect HFO signals measured from intraoperative ECoG on-line, using an independently labeled dataset (58 min, 16 recordings). We targeted the detection of HFOs in the fast ripple frequency range (250-500 Hz) and compared the network results with the labeled HFO data. We endowed the SNN with a novel artifact rejection mechanism to suppress sharp transients and demonstrate its effectiveness on the ECoG dataset. The HFO rates (median 6.6 HFO/min in pre-resection recordings) detected by this SNN are comparable to those published in the dataset (Spearman's [Formula: see text] = 0.81). The postsurgical seizure outcome was "predicted" with 100% (CI [63 100%]) accuracy for all 8 patients. These results provide a further step towards the construction of a real-time portable battery-operated HFO detection system that can be used during epilepsy surgery to guide the resection of the epileptogenic zone.

Intraoperative Neurophysiologic Assessment in Deep Brain Stimulation Surgery and its Impact on Lead Placement.

OBJECTIVES: While the efficacy of deep brain stimulation (DBS) to treat various neurological disorders is undisputed, the surgical methods differ widely and the importance of intraoperative microelectrode recording (MER) or macrostimulation (MS) remains controversially debated. The objective of this study is to evaluate the impact of MER and MS on intraoperative lead placement. PATIENTS AND METHODS: We included 101 patients who underwent awake bilateral implantation of electrodes in the subthalamic nucleus with MER and MS for Parkinson's disease from 2009 to 2017 in a retrospective observational study. We analyzed intraoperative motor outcomes between anatomically planned stimulation point (PSP) and definite stimulation point (DSP), lead adjustments and Unified Parkinson's Disease Rating Scale Item III (UPDRS-III), levodopa equivalent daily dose (LEDD), and adverse events (AE) after 6 months. RESULTS: We adjusted 65/202 leads in 47/101 patients. In adjusted leads, MS results improved significantly when comparing PSP and DSP (p < 0.001), resulting in a number needed to treat of 9.6. After DBS, UPDRS-III and LEDD improved significantly after 6 months in adjusted and nonadjusted patients (p < 0.001). In 87% of leads, the active contact at 6 months still covered the optimal stimulation point during surgery. In total, 15 AE occurred. CONCLUSION: MER and MS have a relevant impact on the intraoperative decision of final lead placement and prevent from a substantial rate of poor stimulation outcome. The optimal stimulation points during surgery and chronic stimulation strongly overlap. Follow-up UPDRS-III results, LEDD reductions, and DBS-related AE correspond well to previously published data.

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery.

OBJECTIVE: Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impairment. METHODS: The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS: In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS: Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.

High-frequency oscillations in scalp EEG mirror seizure frequency in pediatric focal epilepsy.

High-frequency oscillations (HFO) are promising EEG biomarkers of epileptogenicity. While the evidence supporting their significance derives mainly from invasive recordings, recent studies have extended these observations to HFO recorded in the widely accessible scalp EEG. Here, we investigated whether scalp HFO in drug-resistant focal epilepsy correspond to epilepsy severity and how they are affected by surgical therapy. In eleven children with drug-resistant focal epilepsy that underwent epilepsy surgery, we prospectively recorded pre- and postsurgical scalp EEG with a custom-made low-noise amplifier (LNA). In four of these children, we also recorded intraoperative electrocorticography (ECoG). To detect clinically relevant HFO, we applied a previously validated automated detector. Scalp HFO rates showed a significant positive correlation with seizure frequency (R2 = 0.80, p < 0.001). Overall, scalp HFO rates were higher in patients with active epilepsy (19 recordings, p = 0.0066, PPV = 86%, NPV = 80%, accuracy = 84% CI [62% 94%]) and decreased following successful epilepsy surgery. The location of the highest HFO rates in scalp EEG matched the location of the highest HFO rates in ECoG. This study is the first step towards using non-invasively recorded scalp HFO to monitor disease severity in patients affected by epilepsy.

High-density ECoG improves the detection of high frequency oscillations that predict seizure outcome.

OBJECTIVES: Residual fast ripples (FR) in the intraoperative ECoG are highly specific predictors of postsurgical seizure recurrence. However, a FR is generated by a small patch of cortical tissue. Spatial sampling with standard electrodes may thus miss clinically relevant information. METHODS: We analyzed FR rates in the intraoperative ECoG of 22 patients that underwent resective epilepsy surgery. We used standard electrodes with 10 mm inter-contact spacing (standard ECoG) in 14 surgeries and high-density grid electrodes with 5 mm spacing (hd-ECoG) in 8 surgeries. We detected FR using a previously validated automatic detector. RESULTS: Postoperative seizure freedom was achieved in 14/22 (64%) cases. Across all 42 ECoG recordings, FR rates were higher for hd-ECoG than for standard ECoG. In the 14 seizure free patients (ILAE 1), no residual FR were detected (specificity = 100%). In the 8 patients with seizure recurrence (ILAE > 1), residual FR were detected in 1/7 standard ECoG and 1/1 hd-ECoG (Accuracy ACCstandard ECoG = 57%, CI [29% 82%], ACChd-ECoG = 100%, CI [63% 100%]). CONCLUSION: Denser spatial sampling by hd-ECoG improved FR detection compared to standard ECoG. SIGNIFICANCE: Hd-ECoG may advance seizure freedom after epilepsy surgery.

Smoking status and perioperative adverse events in patients undergoing cranial tumor surgery.

INTRODUCTION: Smoking is agreed to be a major health risk factor, but it is debated whether it has an influence on perioperative adverse events (AEs) in elective cranial tumor surgery. METHODS: We analyzed the 2013-2016 data from our prospective institutional patient registry. Consecutive patients undergoing elective microsurgical tumor surgery of a glioma or a meningioma were included. Patients were categorized as active smokers, former smokers, and non-smokers. AE were graded by the therapy-oriented Clavien-Dindo scale. Possible predictors of postoperative AE were identified with the help of a binomial logistic regression model. RESULTS: We identified 798 patients, out of which 480 were non-smokers, 193 active smokers, and 125 former smokers. The rate of AEs for active smokers (30%, 95% CI [23-37%]) was indistinguishable from the AE rate of non-smokers (32%, 95% CI [28-37%]). No difference between smoking status was found looking at all AE individually, the odds ratio of suffering from local AE and systemic AE respectively were the same between all smoking groups. The modified Rankin scale at hospital admission was a strong and significant predictor of postoperative AE (P = 0.013). CONCLUSIONS: Active smoking was not associated with an increased risk for postoperative AE, neither looking at the total number of AE nor looking at individual AE. Smoking status should therefore not be a major factor in preoperative decision making. Although not based on data of this study, doctors should always encourage patients to stop smoking due to its well-known detrimental health effect.