Validation of a deep learning model for traumatic brain injury detection and NIRIS grading on non-contrast CT: a multi-reader study with promising results and opportunities for improvement.

PURPOSE: This study aimed to assess and externally validate the performance of a deep learning (DL) model for the interpretation of non-contrast computed tomography (NCCT) scans of patients with suspicion of traumatic brain injury (TBI). METHODS: This retrospective and multi-reader study included patients with TBI suspicion who were transported to the emergency department and underwent NCCT scans. Eight reviewers, with varying levels of training and experience (two neuroradiology attendings, two neuroradiology fellows, two neuroradiology residents, one neurosurgery attending, and one neurosurgery resident), independently evaluated NCCT head scans. The same scans were evaluated using the version 5.0 of the DL model icobrain tbi. The establishment of the ground truth involved a thorough assessment of all accessible clinical and laboratory data, as well as follow-up imaging studies, including NCCT and magnetic resonance imaging, as a consensus amongst the study reviewers. The outcomes of interest included neuroimaging radiological interpretation system (NIRIS) scores, the presence of midline shift, mass effect, hemorrhagic lesions, hydrocephalus, and severe hydrocephalus, as well as measurements of midline shift and volumes of hemorrhagic lesions. Comparisons using weighted Cohen's kappa coefficient were made. The McNemar test was used to compare the diagnostic performance. Bland-Altman plots were used to compare measurements. RESULTS: One hundred patients were included, with the DL model successfully categorizing 77 scans. The median age for the total group was 48, with the omitted group having a median age of 44.5 and the included group having a median age of 48. The DL model demonstrated moderate agreement with the ground truth, trainees, and attendings. With the DL model's assistance, trainees' agreement with the ground truth improved. The DL model showed high specificity (0.88) and positive predictive value (0.96) in classifying NIRIS scores as 0-2 or 3-4. Trainees and attendings had the highest accuracy (0.95). The DL model's performance in classifying various TBI CT imaging common data elements was comparable to that of trainees and attendings. The average difference for the DL model in quantifying the volume of hemorrhagic lesions was 6.0 mL with a wide 95% confidence interval (CI) of - 68.32 to 80.22, and for midline shift, the average difference was 1.4 mm with a 95% CI of - 3.4 to 6.2. CONCLUSION: While the DL model outperformed trainees in some aspects, attendings' assessments remained superior in most instances. Using the DL model as an assistive tool benefited trainees, improving their NIRIS score agreement with the ground truth. Although the DL model showed high potential in classifying some TBI CT imaging common data elements, further refinement and optimization are necessary to enhance its clinical utility.

Antiseizure medication use and medical resource utilization after resective epilepsy surgery in children in the United States: A contemporary nationwide cross-sectional cohort analysis.

OBJECTIVE: Antiseizure drug (ASD) therapy can significantly impact quality of life for pediatric patients whose epilepsy remains refractory to medications and who experience neuropsychological side effects manifested by impaired cognitive and social development. Contemporary patterns of ASD reduction after pediatric epilepsy surgery across practice settings in the United States are sparsely reported outside of small series. We assessed timing and durability of ASD reduction after pediatric epilepsy surgery and associated effects on health care utilization. METHODS: We performed a retrospective analysis of 376 pediatric patients who underwent resective epilepsy surgery between 2007 and 2016 in the United States using the Truven MarketScan database. Filled ASD prescriptions during the pre- and postoperative periods were compared. Univariate and multivariate analyses identified factors associated with achieving a stable discontinuation of or reduction in number of ASDs. Health care utilization and costs were systematically compared. RESULTS: One hundred seventy-one patients (45.5%) achieved a >90-day ASD-free period after surgery, and 84 (22.3%) additional patients achieved a stable reduction in number of ASDs. Achieving ASD freedom was more common in patients undergoing total hemispherectomy (n = 21, p = .002), and less common in patients with tuberous sclerosis (p = .003). A higher number of preoperative ASDs was associated with a greater likelihood of achieving ASD reduction postoperatively (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 1.50-2.28), but was not associated with a significant difference in the likelihood of achieving ASD freedom (0.83, 95% CI: 0.49-1.39). Achieving an ASD-free period was associated with fewer hospital readmissions within the first year after surgery. SIGNIFICANCE: Patterns of ASD use and discontinuation after pediatric epilepsy surgery provide an unbiased surgical outcome endpoint extractable from administrative databases, where changes in seizure frequency are not captured. This quantitative measure can augment traditional surgical outcome scales, incorporating a significant clinical parameter associated with improved quality of life.

An integrated risk model stratifying seizure risk following brain tumor resection among seizure-naive patients without antiepileptic prophylaxis.

OBJECTIVE: The natural history of seizure risk after brain tumor resection is not well understood. Identifying seizure-naive patients at highest risk for postoperative seizure events remains a clinical need. In this study, the authors sought to develop a predictive modeling strategy for anticipating postcraniotomy seizures after brain tumor resection. METHODS: The IBM Watson Health MarketScan Claims Database was canvassed for antiepileptic drug (AED)- and seizure-naive patients who underwent brain tumor resection (2007-2016). The primary event of interest was short-term seizure risk (within 90 days postdischarge). The secondary event of interest was long-term seizure risk during the follow-up period. To model early-onset and long-term postdischarge seizure risk, a penalized logistic regression classifier and multivariable Cox regression model, respectively, were built, which integrated patient-, tumor-, and hospitalization-specific features. To compare empirical seizure rates, equally sized cohort tertiles were created and labeled as low risk, medium risk, and high risk. RESULTS: Of 5470 patients, 983 (18.0%) had a postdischarge-coded seizure event. The integrated binary classification approach for predicting early-onset seizures outperformed models using feature subsets (area under the curve [AUC] = 0.751, hospitalization features only AUC = 0.667, patient features only AUC = 0.603, and tumor features only AUC = 0.694). Held-out validation patient cases that were predicted by the integrated model to have elevated short-term risk more frequently developed seizures within 90 days of discharge (24.1% high risk vs 3.8% low risk, p < 0.001). Compared with those in the low-risk tertile by the long-term seizure risk model, patients in the medium-risk and high-risk tertiles had 2.13 (95% CI 1.45-3.11) and 6.24 (95% CI 4.40-8.84) times higher long-term risk for postdischarge seizures. Only patients predicted as high risk developed status epilepticus within 90 days of discharge (1.7% high risk vs 0% low risk, p = 0.003). CONCLUSIONS: The authors have presented a risk-stratified model that accurately predicted short- and long-term seizure risk in patients who underwent brain tumor resection, which may be used to stratify future study of postoperative AED prophylaxis in highest-risk patient subpopulations.

Anticipatory human subthalamic area beta-band power responses to dissociable tastes correlate with weight gain.

The availability of enticing sweet, fatty tastes is prevalent in the modern diet and contribute to overeating and obesity. In animal models, the subthalamic area plays a role in mediating appetitive and consummatory feeding behaviors, however, its role in human feeding is unknown. We used intraoperative, subthalamic field potential recordings while participants (n = 5) engaged in a task designed to provoke responses of taste anticipation and receipt. Decreased subthalamic beta-band (15-30 Hz) power responses were observed for both sweet-fat and neutral tastes. Anticipatory responses to taste-neutral cues started with an immediate decrease in beta-band power from baseline followed by an early beta-band rebound above baseline. On the contrary, anticipatory responses to sweet-fat were characterized by a greater and sustained decrease in beta-band power. These activity patterns were topographically specific to the subthalamic nucleus and substantia nigra. Further, a neural network trained on this beta-band power signal accurately predicted (AUC ≥ 74%) single trials corresponding to either taste. Finally, the magnitude of the beta-band rebound for a neutral taste was associated with increased body mass index after starting deep brain stimulation therapy. We provide preliminary evidence of discriminatory taste encoding within the subthalamic area associated with control mechanisms that mediate appetitive and consummatory behaviors.

Contemporaneous evaluation of patient experience, surgical strategy, and seizure outcomes in patients undergoing stereoelectroencephalography or subdural electrode monitoring.

OBJECTIVE: Intracranial electrographic localization of the seizure onset zone (SOZ) can guide surgical approaches for medically refractory epilepsy patients, especially when the presurgical workup is discordant or functional cortical mapping is required. Minimally invasive stereotactic placement of depth electrodes, stereoelectroencephalography (SEEG), has garnered increasing use, but limited data exist to evaluate its postoperative outcomes in the context of the contemporaneous availability of both SEEG and subdural electrode (SDE) monitoring. We aimed to assess the patient experience, surgical intervention, and seizure outcomes associated with these two epileptic focus mapping techniques during a period of rapid adoption of neuromodulatory and ablative epilepsy treatments. METHODS: We retrospectively reviewed 66 consecutive adult intracranial electrode monitoring cases at our institution between 2014 and 2017. Monitoring was performed with either SEEG (n = 47) or SDEs (n = 19). RESULTS: Both groups had high rates of SOZ identification (SEEG 91.5%, SDE 88.2%, P = .69). The majority of patients achieved Engel class I (SEEG 29.3%, SDE 35.3%) or II outcomes (SEEG 31.7%, SDE 29.4%) after epilepsy surgery, with no significant difference between groups (P = .79). SEEG patients reported lower median pain scores (P = .03) and required less narcotic pain medication (median = 94.5 vs 594.6 milligram morphine equivalents, P = .0003). Both groups had low rates of symptomatic hemorrhage (SEEG 0%, SDE 5.3%, P = .11). On multivariate logistic regression, undergoing resection or ablation (vs responsive neurostimulation/vagus nerve stimulation) was the only significant independent predictor of a favorable outcome (adjusted odds ratio = 25.4, 95% confidence interval = 3.48-185.7, P = .001). SIGNIFICANCE: Although both SEEG and SDE monitoring result in favorable seizure control, SEEG has the advantage of superior pain control, decreased narcotic usage, and lack of routine need for intensive care unit stay. Despite a heterogenous collection of epileptic semiologies, seizure outcome was associated with the therapeutic surgical modality and not the intracranial monitoring technique. The potential for an improved postoperative experience makes SEEG a promising method for intracranial electrode monitoring.

Postoperative outcomes following pediatric intracranial electrode monitoring: A case for stereoelectroencephalography (SEEG).

BACKGROUND: For patients with medically refractory epilepsy, intracranial electrode monitoring can help identify epileptogenic foci. Despite the increasing utilization of stereoelectroencephalography (SEEG), the relative risks or benefits associated with the technique when compared with the traditional subdural electrode monitoring (SDE) remain unclear, especially in the pediatric population. Our aim was to compare the outcomes of pediatric patients who received intracranial monitoring with SEEG or SDE (grids and strips). METHODS: We retrospectively studied 38 consecutive pediatric intracranial electrode monitoring cases performed at our institution from 2014 to 2017. Medical/surgical history and operative/postoperative records were reviewed. We also compared direct inpatient hospital costs associated with the two procedures. RESULTS: Stereoelectroencephalography and SDE cohorts both showed high likelihood of identifying epileptogenic zones (SEEG: 90.9%, SDE: 87.5%). Compared with SDE, SEEG patients had a significantly shorter operative time (118.7 versus 233.4 min, P < .001) and length of stay (6.2 versus 12.3 days, P < .001), including days spent in the intensive care unit (ICU; 1.4 versus 5.4 days, P < .001). Stereoelectroencephalography patients tended to report lower pain scores and used significantly less narcotic pain medications (54.2 versus 197.3 mg morphine equivalents, P = .005). No complications were observed. Stereoelectroencephalography and SDE cohorts had comparable inpatient hospital costs (P = .47). CONCLUSION: In comparison with subdural electrode placement, SEEG results in a similarly favorable clinical outcome, but with reduced operative time, decreased narcotic usage, and superior pain control without requiring significantly higher costs. The potential for an improved postoperative intracranial electrode monitoring experience makes SEEG especially suitable for pediatric patients.

Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor.

BACKGROUND: Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options. METHODS: Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques. RESULTS: Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery. CONCLUSIONS: Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.

The role of regulatory T cells and microglia in glioblastoma-associated immunosuppression.

Cell-mediated suppression of anti-tumor immunity is multifactorial in patients with cancer, and recent studies have focused on several distinct cellular agents that are associated with this phenomenon. This review will focus on the potential role of regulatory T cells (Tregs) and microglia in the suppression of cellular immunity observed in patients with glioblastoma. We discuss the ontogeny, basic biology, evidence for activity, and potential clinical options for targeting Tregs and microglia as part of immunotherapy in affected patients.

Trends in the Utilization of Surgical Modalities for the Treatment of Drug-Resistant Epilepsy: A Comprehensive 10-Year Analysis Using the National Inpatient Sample.

BACKGROUND AND OBJECTIVES: Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide. Our study aims to analyze the national trends in different treatment modalities for individuals with drug-resistant epilepsy and investigate the outcomes associated with these procedural trends in the United States. METHODS: Using the National Inpatient Sample database from 2010 to 2020, patients with drug-resistant focal epilepsy who underwent laser interstitial thermal therapy (LITT), open surgical resection, vagus nerve stimulation (VNS), or responsive neurostimulation (RNS) were identified. Trend analysis was performed using piecewise joinpoint regression. Propensity score matching was used to compare outcomes between 10 years prepandemic before 2020 and the first peak of the COVID-19 pandemic. RESULTS: This study analyzed a total of 33 969 patients with a diagnosis of drug-resistant epilepsy, with 3343 patients receiving surgical resection (78%), VNS (8.21%), RNS (8%), and LITT (6%). Between 2010 and 2020, there was an increase in the use of invasive electroencephalography monitoring for seizure zone localization (P = .003). There was an increase in the use of LITT and RNS (P < .001), while the use of surgical resection and VNS decreased over time (P < .001). Most of these patients (89%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (11%) underwent treatment during the COVID pandemic (2020). After propensity score matching, the rate of pulmonary complications, postprocedural hematoma formation, and mortality were slightly higher during the pandemic compared with the prepandemic period (P = .045, P = .033, and P = .026, respectively). CONCLUSION: This study indicates a relative decrease in the use of surgical resections, as a treatment for drug-resistant focal epilepsy. By contrast, newer, minimally invasive surgical approaches including LITT and RNS showed gradual increases in usage.

Spectro-spatial features in distributed human intracranial activity proactively encode peripheral metabolic activity.

Mounting evidence demonstrates that the central nervous system (CNS) orchestrates glucose homeostasis by sensing glucose and modulating peripheral metabolism. Glucose responsive neuronal populations have been identified in the hypothalamus and several corticolimbic regions. However, how these CNS gluco-regulatory regions modulate peripheral glucose levels is not well understood. To better understand this process, we simultaneously measured interstitial glucose concentrations and local field potentials in 3 human subjects from cortical and subcortical regions, including the hypothalamus in one subject. Correlations between high frequency activity (HFA, 70-170 Hz) and peripheral glucose levels are found across multiple brain regions, notably in the hypothalamus, with correlation magnitude modulated by sleep-wake cycles, circadian coupling, and hypothalamic connectivity. Correlations are further present between non-circadian (ultradian) HFA and glucose levels which are higher during awake periods. Spectro-spatial features of neural activity enable decoding of peripheral glucose levels both in the present and up to hours in the future. Our findings demonstrate proactive encoding of homeostatic glucose dynamics by the CNS.

Laser Interstitial Thermal Therapy for Epilepsy.

Laser interstitial thermal therapy is an important new technique with a diverse use in epilepsy. This article gives an up-to-date evaluation of the current use of the technique within epilepsy, as well as provides some guidance to novice users appropriate clinical cases for its use.

Rapid intraoperative diagnosis of pediatric brain tumors using Raman spectroscopy: A machine learning approach.

Background: Surgical resection is a mainstay in the treatment of pediatric brain tumors to achieve tissue diagnosis and tumor debulking. While maximal safe resection of tumors is desired, it can be challenging to differentiate normal brain from neoplastic tissue using only microscopic visualization, intraoperative navigation, and tactile feedback. Here, we investigate the potential for Raman spectroscopy (RS) to accurately diagnose pediatric brain tumors intraoperatively. Methods: Using a rapid acquisition RS device, we intraoperatively imaged fresh ex vivo brain tissue samples from 29 pediatric patients at the Lucile Packard Children's Hospital between October 2018 and March 2020 in a prospective fashion. Small tissue samples measuring 2-4 mm per dimension were obtained with each individual tissue sample undergoing multiple unique Raman spectra acquisitions. All tissue samples from which Raman spectra were acquired underwent individual histopathology review. A labeled dataset of 678 unique Raman spectra gathered from 160 samples was then used to develop a machine learning model capable of (1) differentiating normal brain from tumor tissue and (2) normal brain from low-grade glioma (LGG) tissue. Results: Trained logistic regression model classifiers were developed using our labeled dataset. Model performance was evaluated using leave-one-patient-out cross-validation. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve for our tumor vs normal brain model was 0.94. The AUC of the ROC curve for LGG vs normal brain was 0.91. Conclusions: Our work suggests that RS can be used to develop a machine learning-based classifier to differentiate tumor vs non-tumor tissue during resection of pediatric brain tumors.

Development of an integrated risk scale for prediction of shunt placement after neonatal intraventricular hemorrhage.

OBJECTIVE: Neonatal intraventricular hemorrhage (IVH) is a major cause of mortality and morbidity, particularly following premature birth. Even after the acute phase, posthemorrhagic hydrocephalus is a long-term complication, frequently requiring permanent ventriculoperitoneal shunt (VPS) placement. Currently, there are no risk classification methods integrating the constellation of clinical data to predict short- and long-term prognosis in neonatal IVH. To address this need, the authors developed a two-part machine learning approach for predicting short- and long-term outcomes after diagnosis of neonatal IVH. Integrating both maternal and neonatal characteristics, they developed a binary classifier to predict short-term mortality risk and a clinical scale to predict the long-term risk of VPS placement. METHODS: Neonates with IVH were identified from the Optum Clinformatics Data Mart administrative claims database. Matched maternal and childbirth characteristics were obtained for all patients. The primary endpoints of interest were short-term (30 day) mortality and long-term VPS placement. Classification of short-term mortality risk was evaluated using 5 different machine learning approaches and the best-performing method was validated using a withheld validation subset. Prediction of long-term shunt risk was performed using a multivariable Cox regression model with stepwise variable selection, which was subsequently converted to an easily applied integer risk scale. RESULTS: A total of 5926 neonates with IVH were identified. Most patients were born before 32 weeks' gestation (67.2%) and with low birth weight (81.2%). Empirical 30-day mortality risk was 10.9% across all IVH grades and highest among grade IV IVH (34.3%). Among the neonates who survived > 30 days, actuarial 12-month postdiagnosis risk of shunt placement was 5.4% across all IVH grades and 31.3% for grade IV IVH. The optimal short-term risk classifier was a random forest model achieving an area under the receiver operating characteristic curve of 0.882 with important predictors ranging from gestational age to diverse comorbid medical conditions. Selected features for long-term shunt risk stratification were IVH grade, respiratory distress syndrome, disseminated intravascular coagulation, and maternal preeclampsia or eclampsia. An integer risk scale, termed the Shunt Prediction After IVH in Neonates (SPAIN) scale, was developed from these 4 features, which, evaluated on withheld cases, demonstrated improved risk stratification compared with IVH grade alone (Harrell's concordance index 0.869 vs 0.852). CONCLUSIONS: In a large cohort of neonates with IVH, the authors developed a two-pronged, integrated, risk classification approach to anticipate short-term mortality and long-term shunt risk. The application of such approaches may improve the prognostication of outcomes and identification of higher-risk individuals who warrant careful surveillance and early intervention.

Complex negative emotions induced by electrical stimulation of the human hypothalamus.

BACKGROUND: Stimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated. OBJECTIVE: To examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions. METHODS: We examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus. We combined direct electrical stimulation with tractography, cortico-cortical evoked potentials (CCEP), and functional connectivity using resting state intracranial electroencephalography (EEG). RESULTS: Recordings in the hypothalamus did not reveal any epileptic abnormalities. Electrical stimulations near the ventromedial hypothalamus induced profound shame, sadness, and fear but not rage or anger. When repeated single-pulse stimulations were delivered to the hypothalamus, significant responses were evoked in the amygdala, hippocampus, ventromedial-prefrontal and orbitofrontal cortices, anterior cingulate, as well as ventral-anterior and dorsal-posterior insula. The time to first peak of these evoked responses varied and earliest propagations correlated best with the measures of resting-state EEG connectivity and structural connectivity. CONCLUSION: This patient's case offers details about the affective state induced by the stimulation of the human hypothalamus and provides causal evidence relevant to current theories of emotion. The complexity of affective state induced by the stimulation of the hypothalamus and the profile of hypothalamic electrophysiological connectivity suggest that the hypothalamus and its connected structures ought to be seen as causally important for human affective experience.

Pilot study of responsive nucleus accumbens deep brain stimulation for loss-of-control eating.

Cravings that precede loss of control (LOC) over food consumption present an opportunity for intervention in patients with the binge eating disorder (BED). In this pilot study, we used responsive deep brain stimulation (DBS) to record nucleus accumbens (NAc) electrophysiology during food cravings preceding LOC eating in two patients with BED and severe obesity (trial registration no. NCT03868670). Increased NAc low-frequency oscillations, prominent during food cravings, were used to guide DBS delivery. Over 6 months, we observed improved self-control of food intake and weight loss. These findings provide early support for restoring inhibitory control with electrophysiologically-guided NAc DBS. Further work with increased sample sizes is required to determine the scalability of this approach.

Hybrid Fluoroscopic and Neurophysiological Targeting of Responsive Neurostimulation of the Rolandic Cortex.

BACKGROUND: Precise targeting of cortical surface electrodes to epileptogenic regions defined by anatomic and electrophysiological guideposts remains a surgical challenge during implantation of responsive neurostimulation (RNS) devices. OBJECTIVE: To describe a hybrid fluoroscopic and neurophysiological technique for targeting of subdural cortical surface electrodes to anatomic regions with limited direct visualization, such as the interhemispheric fissure. METHODS: Intraoperative two-dimensional (2D) fluoroscopy was used to colocalize and align an electrode for permanent device implantation with a temporary in Situ electrode placed for extraoperative seizure mapping. Intraoperative phase reversal mapping technique was performed to distinguish primary somatosensory and motor cortex. RESULTS: We applied these techniques to optimize placement of an interhemispheric strip electrode connected to a responsive neurostimulator system for detection and treatment of seizures arising from a large perirolandic cortical malformation. Intraoperative neuromonitoring (IONM) phase reversal technique facilitated neuroanatomic mapping and electrode placement. CONCLUSION: In challenging-to-access anatomic regions, fluoroscopy and intraoperative neurophysiology can be employed to augment targeting of neuromodulation electrodes to the site of seizure onset zone or specific neurophysiological biomarkers of clinical interest while minimizing brain retraction.

Adverse Events and Bundled Costs after Cranial Neurosurgical Procedures: Validation of the LACE Index Across 40,431 Admissions and Development of the LACE-Cranial Index.

OBJECTIVE: Anticipating postdischarge complications after neurosurgery remains difficult. The LACE index, based on 4 hospitalization descriptors, stratifies patients by risk of 30-day postdischarge adverse events but has not been validated in a procedure-specific manner in neurosurgery. Our study sought to explore the usefulness of the LACE index in a population undergoing cranial neurosurgery and to develop an enhanced model, LACE-Cranial. METHODS: The OptumClinformatics Database was used to identify cranial neurosurgery admissions (2004-2017). Procedures were grouped as trauma/hematoma/intracranial pressure, open vascular, functional/pain, skull base, tumor, or endovascular. Adverse events were defined as postdischarge death/readmission. LACE-Cranial was developed using a logistic regression framework incorporating an expanded feature set in addition to the original LACE components. RESULTS: A total of 40,431 admissions were included. Predictions of 30-day readmissions was best for skull base (area under the curve [AUC], 0.636) and tumor (AUC, 0.63) admissions but was generally poor. Predictive ability of 30-day mortality was best for functional/pain admissions (AUC, 0.957) and poorest for trauma/hematoma/intracranial pressure admissions (AUC, 0.613). Across procedure types except for functional/pain, a high-risk LACE score was associated with higher postdischarge bundled payment costs. Incorporating features identified to contribute independent predictive value, the LACE-Cranial model achieved procedure-specific 30-day mortality AUCs ranging from 0.904 to 0.98. Prediction of 30-day and 90-day readmissions was also improved, with tumor and skull base cases achieving 90-day readmission AUCs of 0.718 and 0.717, respectively. CONCLUSIONS: Although the unmodified LACE index shows inconsistent classification performance, the enhanced LACE-Cranial model offers excellent prediction of short-term postdischarge mortality across procedure groups and significantly improved anticipation of short-term postdischarge readmissions.

Status epilepticus after intracranial neurosurgery: incidence and risk stratification by perioperative clinical features.

OBJECTIVE: Status epilepticus (SE) is associated with significant mortality, cost, and risk of future seizures. In one of the first studies of SE after neurosurgery, the authors assess the incidence, risk factors, and outcome of postneurosurgical SE (PNSE). METHODS: Neurosurgical admissions from the MarketScan Claims and Encounters database (2007 through 2015) were assessed in a longitudinal cross-sectional sample of privately insured patients who underwent qualifying cranial procedures in the US and were older than 18 years of age. The incidence of early (in-hospital) and late (postdischarge readmission) SE and associated mortality was assessed. Procedural, pathological, demographic, and anatomical covariates parameterized multivariable logistic regression and Cox models. Multivariable logistic regression and Cox proportional hazards models were used to study the incidence of early and late PNSE. A risk-stratification simulation was performed, combining individual predictors into singular risk estimates. RESULTS: A total of 197,218 admissions (218,217 procedures) were identified. Early PNSE occurred during 637 (0.32%) of 197,218 admissions for cranial neurosurgical procedures. A total of 1045 (0.56%) cases of late PNSE were identified after 187,771 procedure admissions with nonhospice postdischarge follow-up. After correction for comorbidities, craniotomy for trauma, hematoma, or elevated intracranial pressure was associated with increased risk of early PNSE (adjusted OR [aOR] 1.538, 95% CI 1.183-1.999). Craniotomy for meningioma resection was associated with an increased risk of early PNSE compared with resection of metastases and parenchymal primary brain tumors (aOR 2.701, 95% CI 1.388-5.255). Craniotomies for infection or abscess (aHR 1.447, 95% CI 1.016-2.061) and CSF diversion (aHR 1.307, 95% CI 1.076-1.587) were associated with highest risk of late PNSE. Use of continuous electroencephalography in patients with early (p < 0.005) and late (p < 0.001) PNSE rose significantly over the study time period. The simulation regression model predicted that patients at high risk for early PNSE experienced a 1.10% event rate compared with those at low risk (0.07%). Similarly, patients predicted to be at highest risk for late PNSE were significantly more likely to eventually develop late PNSE than those at lowest risk (HR 54.16, 95% CI 24.99-104.80). CONCLUSIONS: Occurrence of early and late PNSE was associated with discrete neurosurgical pathologies and increased mortality. These data provide a framework for prospective validation of clinical and perioperative risk factors and indicate patients for heightened diagnostic suspicion of PNSE.

The insulo-opercular cortex encodes food-specific content under controlled and naturalistic conditions.

The insulo-opercular network functions critically not only in encoding taste, but also in guiding behavior based on anticipated food availability. However, there remains no direct measurement of insulo-opercular activity when humans anticipate taste. Here, we collect direct, intracranial recordings during a food task that elicits anticipatory and consummatory taste responses, and during ad libitum consumption of meals. While cue-specific high-frequency broadband (70-170 Hz) activity predominant in the left posterior insula is selective for taste-neutral cues, sparse cue-specific regions in the anterior insula are selective for palatable cues. Latency analysis reveals this insular activity is preceded by non-discriminatory activity in the frontal operculum. During ad libitum meal consumption, time-locked high-frequency broadband activity at the time of food intake discriminates food types and is associated with cue-specific activity during the task. These findings reveal spatiotemporally-specific activity in the human insulo-opercular cortex that underlies anticipatory evaluation of food across both controlled and naturalistic settings.

Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study.

BACKGROUND: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited. OBJECTIVE: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients. METHODS: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (<18 yr) and young adults (>18 yr) and compared with prior literature pertaining to adult patients. RESULTS: Of 35 patients identified, 17 were <18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had <50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in our cohort or between our cohort and the adult literature. CONCLUSION: These preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age. Data regarding long-term efficacy and safety in children will be critical to optimize patient selection.