Integrated clinical genomic analysis reveals xenobiotic metabolic genes are downregulated in meningiomas of current smokers.

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recently, various genetic classification systems for meningioma have been described. We sought to identify clinical drivers of different molecular changes in meningioma. As such, clinical and genomic consequences of smoking in patients with meningiomas remain unexplored. METHODS: 88 tumor samples were analyzed in this study. Whole exome sequencing (WES) was used to assess somatic mutation burden. RNA sequencing data was used to identify differentially expressed genes (DEG) and genes sets (GSEA). RESULTS: Fifty-seven patients had no history of smoking, twenty-two were past smokers, and nine were current smokers. The clinical data showed no major differences in natural history across smoking status. WES revealed absence of AKT1 mutation rate in current or past smokers compared to non-smokers (p = 0.046). Current smokers had increased mutation rate in NOTCH2 compared to past and never smokers (p < 0.05). Mutational signature from current and past smokers showed disrupted DNA mismatch repair (cosine-similarity = 0.759 and 0.783). DEG analysis revealed the xenobiotic metabolic genes UGT2A1 and UGT2A2 were both significantly downregulated in current smokers compared to past (Log2FC = - 3.97, padj = 0.0347 and Log2FC = - 4.18, padj = 0.0304) and never smokers (Log2FC = - 3.86, padj = 0.0235 and Log2FC = - 4.20, padj = 0.0149). GSEA analysis of current smokers showed downregulation of xenobiotic metabolism and enrichment for G2M checkpoint, E2F targets, and mitotic spindle compared to past and never smokers (FDR < 25% each). CONCLUSION: In this study, we conducted a comparative analysis of meningioma patients based on their smoking history, examining both their clinical trajectories and molecular changes. Meningiomas from current smokers were more likely to harbor NOTCH2 mutations, and AKT1 mutations were absent in current or past smokers. Moreover, both current and past smokers exhibited a mutational signature associated with DNA mismatch repair. Meningiomas from current smokers demonstrate downregulation of xenobiotic metabolic enzymes UGT2A1 and UGT2A2, which are downregulated in other smoking related cancers. Furthermore, current smokers exhibited downregulation xenobiotic metabolic gene sets, as well as enrichment in gene sets related to mitotic spindle, E2F targets, and G2M checkpoint, which are hallmark pathways involved in cell division and DNA replication control. In aggregate, our results demonstrate novel alterations in meningioma molecular biology in response to systemic carcinogens.

Efficacy of deep brain stimulation for treatment-resistant obsessive-compulsive disorder: systematic review and meta-analysis.

Deep brain stimulation (DBS) is an established and growing intervention for treatment-resistant obsessive-compulsive disorder (TROCD). We assessed current evidence on the efficacy of DBS in alleviating OCD and comorbid depressive symptoms including newly available evidence from recent trials and a deeper risk of bias analysis than previously available. PubMed and EMBASE databases were systematically queried using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies reporting primary data on multiple patients who received DBS therapy with outcomes reported through the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Primary effect measures included Y-BOCS mean difference and per cent reduction as well as responder rate (≥35% Y-BOCS reduction) at last follow-up. Secondary effect measures included standardised depression scale reduction. Risk of bias assessments were performed on randomised controlled (RCTs) and non-randomised trials. Thirty-four studies from 2005 to 2021, 9 RCTs (n=97) and 25 non-RCTs (n=255), were included in systematic review and meta-analysis based on available outcome data. A random-effects model indicated a meta-analytical average 14.3 point or 47% reduction (p<0.01) in Y-BOCS scores without significant difference between RCTs and non-RCTs. At last follow-up, 66% of patients were full responders to DBS therapy. Sensitivity analyses indicated a low likelihood of small study effect bias in reported outcomes. Secondary analysis revealed a 1 standardised effect size (Hedges' g) reduction in depressive scale symptoms. Both RCTs and non-RCTs were determined to have a predominantly low risk of bias. A strong evidence base supports DBS for TROCD in relieving both OCD and comorbid depression symptoms in appropriately selected patients.

Predicting surgical decision-making in vestibular schwannoma using tree-based machine learning.

OBJECTIVE: Vestibular schwannomas (VSs) are the most common neoplasm of the cerebellopontine angle in adults. Though these lesions are generally slow growing, their growth patterns and associated symptoms can be unpredictable, which may complicate the decision to pursue conservative management versus active intervention. Additionally, surgical decision-making can be controversial because of limited high-quality evidence and multiple quality-of-life considerations. Machine learning (ML) is a powerful tool that utilizes data sets to essentialize multidimensional clinical processes. In this study, the authors trained multiple tree-based ML algorithms to predict the decision for active treatment versus MRI surveillance of VS in a single institutional cohort. In doing so, they sought to assess which preoperative variables carried the most weight in driving the decision for intervention and could be used to guide future surgical decision-making through an evidence-based approach. METHODS: The authors reviewed the records of patients who had undergone evaluation by neurosurgery and otolaryngology with subsequent active treatment (resection or radiation) for unilateral VS in the period from 2009 to 2021, as well as those of patients who had been evaluated for VS and were managed conservatively throughout 2021. Clinical presentation, radiographic data, and management plans were abstracted from each patient record from the time of first evaluation until the last follow-up or surgery. Each encounter with the patient was treated as an instance involving a management decision that depended on demographics, symptoms, and tumor profile. Decision tree and random forest classifiers were trained and tested to predict the decision for treatment versus imaging surveillance on the basis of unseen data using an 80/20 pseudorandom split. Predictor variables were tuned to maximize performance based on lowest Gini impurity indices. Model performance was optimized using fivefold cross-validation. RESULTS: One hundred twenty-four patients with 198 rendered decisions concerning management were included in the study. In the decision tree analysis, only a maximum tumor dimension threshold of 1.6 cm and progressive symptoms were required to predict the decision for treatment with 85% accuracy. Optimizing maximum dimension thresholds and including age at presentation boosted accuracy to 88%. Random forest analysis (n = 500 trees) predicted the decision for treatment with 80% accuracy. Factors with the highest variable importance based on multiple measures of importance, including mean minimal conditional depth and largest Gini impurity reduction, were maximum tumor dimension, age at presentation, Koos grade, and progressive symptoms at presentation. CONCLUSIONS: Tree-based ML was used to predict which factors drive the decision for active treatment of VS with 80%-88% accuracy. The most important factors were maximum tumor dimension, age at presentation, Koos grade, and progressive symptoms. These results can assist in surgical decision-making and patient counseling. They also demonstrate the power of ML algorithms in extracting useful insights from limited data sets.

Identification of novel fusion transcripts in meningioma.

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recent next generation sequencing analyses have elaborated the molecular drivers of this disease. We aimed to identify and characterize novel fusion genes in meningiomas. METHODS: We performed a secondary analysis of our RNA sequencing data of 145 primary meningioma from 140 patients to detect fusion genes. Semi-quantitative rt-PCR was performed to confirm transcription of the fusion genes in the original tumors. Whole exome sequencing was performed to identify copy number variations within each tumor sample. Comparative RNA seq analysis was performed to assess the clonality of the fusion constructs within the tumor. RESULTS: We detected six fusion events (NOTCH3-SETBP1, NF2-SPATA13, SLC6A3-AGBL3, PHF19-FOXP2 in two patients, and ITPK1-FBP2) in five out of 145 tumor samples. All but one event (NF2-SPATA13) led to extremely short reading frames, making these events de facto null alleles. Three of the five patients had a history of childhood radiation. Four out of six fusion events were detected in expression type C tumors, which represent the most aggressive meningioma. We validated the presence of the RNA transcripts in the tumor tissue by semi-quantitative RT PCR. All but the two PHF19-FOXP2 fusions demonstrated high degrees of clonality. CONCLUSIONS: Fusion genes occur infrequently in meningiomas and are more likely to be found in tumors with greater degree of genomic instability (expression type C) or in patients with history of cranial irradiation.

Fractionated stereotactic radiotherapy for local control of resected brain metastases.

PURPOSE: Postoperative stereotactic radiosurgery (SRS) has been shown to establish local control in patients with resected brain metastases, yet its efficacy may be limited, particularly for resected lesions with large post-operative resection cavities. We describe the efficacy of postoperative fractionated stereotactic radiotherapy (FSRT) for local control in patients who have undergone resection for brain metastases. METHODS: In this retrospective cohort study, we analyzed patients who received FSRT for resected brain metastases in 3 or 5 fractions. Time to local recurrence was the primary endpoint in this study. RESULTS: Sixty-seven patients (n = 29 female, n = 38 male) met study criteria for review. The median age of the cohort was 62 years (range 18-79 years). Median preoperative tumor volume was 11.1 cm3 (range 0.4-77.0 cm3). The rate of local control was 91.0% at 6 months, 85.1% at 12 months, and 85.1% at 18 months. Estimates of freedom from local recurrence at 6 and 12 months were 90.9% and 84.3%, respectively. Higher biologically equivalent doses (BED10) were found to be predictive of longer freedom from local recurrence on univariate and multivariable analysis. Larger cavity volumes were found to correspond to longer time to local recurrence on univariate and multivariable analysis. CONCLUSION: Our results suggest that postoperative FSRT may be an effective method for providing local control to the surgical bed in patients with resected brain metastases, particularly for larger tumors not amenable to conventional, single-fraction SRS. Additional prospective studies are needed to confirm these findings.

Firearm-Related Traumatic Brain Injuries in Adults: A Scoping Review.

BACKGROUND AND OBJECTIVES: Firearm-related traumatic brain injury (TBI) has emerged as a significant public health issue in the United States, coinciding with a rapid increase in gun-related deaths. This scoping review aims to update our understanding of firearm-related TBI in adult populations. METHODS: A comprehensive search of 6 online databases yielded 22 studies that met the inclusion criteria. The reviewed studies predominantly focused on young adult men who were victims of assault, although other vulnerable populations were also affected. RESULTS: Key factors in evaluating patients with firearm-related TBI included low Glasgow Coma Scale scores, central nervous system involvement, hypotension, and coagulopathies at presentation. Poor outcomes in firearm-related TBIs were influenced by various factors, including the location and trajectory of the gunshot wound, hypercoagulability, hemodynamic instability, insurance status, and specific clinical findings at hospital admission. CONCLUSION: Proposed interventions aimed to reduce the incidence and mortality of penetrating TBIs, including medical interventions such as coagulopathy reversal and changes to prehospital stabilization procedures. However, further research is needed to demonstrate the effectiveness of these interventions. The findings of this scoping review hope to inform future policy research, advocacy efforts, and the training of neurosurgeons and other treating clinicians in the management of firearm-related TBI.

Neck Pain: Differential Diagnosis and Management.

Axial neck pain is a common and important problem in the outpatient setting. In isolation, neck pain tends to have a musculoskeletal etiology and responds best to medication and targeted physical therapy. Careful history and physical examination are required to ascertain if there is a neurologic component in addition to the patient's neck pain. For patients needing surgical intervention, there are a variety of approaches and operations that can decompress the appropriate nerve root or the spinal cord itself. These operations are generally well-tolerated and provide significant benefit for appropriately selected patients.

Neurosurgical Approaches for Treatment-Resistant Obsessive-Compulsive Disorder.

Treatment-resistant obsessive-compulsive disorder (trOCD) is a severely disabling, life-threatening psychiatric disorder affecting ∼0.5% of the US population. Following the failure of multiple medical and psychotherapeutic treatment lines, patients with trOCD, like others with functional disorders, may benefit from invasive neuromodulation. Cumulative evidence suggests that disrupting abnormal hyperdirect cortico-striato-thalamo-cortical (CSTC) pathway activity offers sustainable, robust symptomatic relief in most patients. Multiple surgical approaches allow for modulation of the CSTC pathway, including stereotactic lesions and electrical stimulation. This review aims to describe the modern neurosurgical approaches for trOCD, recent advances in our understanding of pathophysiology, and future therapeutic directions.

A computer vision approach to identifying the manufacturer of posterior thoracolumbar instrumentation systems.

OBJECTIVE: Knowledge of the manufacturer of the previously implanted pedicle screw systems prior to revision spinal surgery may facilitate faster and safer surgery. Often, this information is unavailable because patients are referred by other centers or because of missing information in the patients' records. Recently, machine learning and computer vision have gained wider use in clinical applications. The authors propose a computer vision approach to classify posterior thoracolumbar instrumentation systems. METHODS: Lateral and anteroposterior (AP) radiographs obtained in patients undergoing posterior thoracolumbar pedicle screw implantation for any indication at the authors' institution (2015-2021) were obtained. DICOM images were cropped to include both the pedicle screws and rods. Images were labeled with the manufacturer according to the operative record. Multiple feature detection methods were tested (SURF, MESR, and Minimum Eigenvalues); however, the bag-of-visual-words technique with KAZE feature detection was ultimately used to construct a computer vision support vector machine (SVM) classifier for lateral, AP, and fused lateral and AP images. Accuracy was tested using an 80%/20% training/testing pseudorandom split over 100 iterations. Using a reader study, the authors compared the model performance with the current practice of surgeons and manufacturer representatives identifying spinal hardware by visual inspection. RESULTS: Among the three image types, 355 lateral, 379 AP, and 338 fused radiographs were obtained. The five pedicle screw implants included in this study were the Globus Medical Creo, Medtronic Solera, NuVasive Reline, Stryker Xia, and DePuy Expedium. When the two most common manufacturers used at the authors' institution were binarily classified (Globus Medical and Medtronic), the accuracy rates for lateral, AP, and fused images were 93.15% ± 4.06%, 88.98% ± 4.08%, and 91.08% ± 5.30%, respectively. Classification accuracy decreased by approximately 10% with each additional manufacturer added. The multilevel five-way classification accuracy rates for lateral, AP, and fused images were 64.27% ± 5.13%, 60.95% ± 5.52%, and 65.90% ± 5.14%, respectively. In the reader study, the model performed five-way classification on 100 test images with 79% accuracy in 14 seconds, compared with an average of 44% accuracy in 20 minutes for two surgeons and three manufacturer representatives. CONCLUSIONS: The authors developed a KAZE feature detector with an SVM classifier that successfully identified posterior thoracolumbar hardware at five-level classification. The model performed more accurately and efficiently than the method currently used in clinical practice. The relative computational simplicity of this model, from input to output, may facilitate future prospective studies in the clinical setting.

Patient, Disease, and Treatment-Related Factors Affecting Progression-Free and Disease-Specific Survival in Recurrent Chondrosarcomas of the Skull Base.

BACKGROUND: Recurrent skull base chondrosarcomas (CSA) are difficult to treat, and limited data are available to help guide subsequent therapy. OBJECTIVE: To further characterize the natural history of CSA and identify treatment modalities that were most effective in prolonging progression-free (PFS) and disease-specific survival (DSS). METHODS: We conducted a single-institution retrospective review of patients with recurrent skull base CSA from 1993 to 2021. Kaplan-Meier survival analyses for PFS and DSS were completed. Univariable and multivariable Cox proportional hazards regression models were used to identify patient-related, treatment-related, and disease-related factors that predicted PFS and DSS. RESULTS: A total of 28 patients and 84 episodes of recurrence were included. One-year PFS was 70.6%, 5-year PFS was 28.9%, and 10-year DSS was 78.5%. The median time to first progression was 23.9 months (range, 2.8-282 months). In univariable Cox proportional hazards regression, male sex, higher grade histology, fourth or greater progression episode status, distal pattern of recurrence, and treatment of recurrence without surgery or with chemotherapy alone predicted worse PFS. Multivariable regression predicted shortened DSS in male patients (hazard ratio [HR] 0.16; P = .021) and higher-grade tumors (HR 0.22; P = .039). Treatment of recurrence with surgery was associated with, but did not significantly predict, improved DSS (HR 1.78; P = .11). CONCLUSION: Several patient and disease-specific factors were associated with shorter PFS and DSS in recurrent skull base chondrosarcoma. For recurrences amenable to resection, surgery is recommended for treatment of recurrent CSA. Local recurrence management without surgery results in shorter PFS and DSS.

Arachnoid Granulation Causing Unilateral Pulsatile Tinnitus Treated With Dural Venous Sinus Stenting.

BACKGROUND: Large arachnoid granulations that protrude into dural venous sinuses and partially obstruct outflow are an underappreciated etiology of pulsatile tinnitus (PT). Endovascular dural venous sinus stenting is thought to diminish turbulent venous outflow and may relieve obstruction caused by arachnoid granulations. METHODS: Four patients at two institutions were evaluated for unilateral PT. Magnetic resonance imaging and digital subtraction angiography revealed moderate-to-severe stenoses from large arachnoid granulations within the implicated transverse sinus. All patients underwent venous manometry and endovascular sinus stenting. RESULTS: All patients experienced immediate and complete remission of their PT. Stenoses were relieved by a mean of 93% by Warfarin-Aspirin Symptomatic Intracranial Disease criteria. There were no procedural or periprocedural complications. All patients continued to report complete symptom resolution at a mean of 8-month follow-up. CONCLUSIONS: PT from arachnoid granulations are an underappreciated pathomechanism. Endovascular dural venous sinus stenting is an effective intervention for treating unilateral PT secondary to large arachnoid granulation.

Comparative study of preoperative functional imaging combined with tractography for prediction of iatrogenic motor deficits.

OBJECTIVE: Robust preoperative imaging can improve the extent of resection in patients with brain tumors while minimizing postoperative neurological morbidity. Both structural and functional imaging techniques can provide helpful preoperative information. A recent study found that transcranial magnetic stimulation (TMS) tractography has significant predictive value for permanent deficits. The present study directly compares the predictive value of TMS tractography and task-based functional MRI (fMRI) tractography in the same cohort of glioma patients. METHODS: Clinical outcome data were collected from charts of patients with motor eloquent glioma and preoperative fMRI and TMS studies. The primary outcome was a new or worsened motor deficit present at the 3-month postoperative follow-up, which was termed a "permanent deficit." Postoperative MR images were overlaid onto preoperative plans to determine which imaging features were resected. Multiple fractional anisotropic thresholds (FATs) were screened for both TMS and fMRI tractography. The predictive value of the various thresholds was modeled using receiver operating characteristic curve analysis. RESULTS: Forty patients were included in this study. Six patients (15%) sustained permanent postoperative motor deficits. A significantly greater predictive value was found for TMS tractography than for fMRI tractography regardless of the FAT. Despite 35% of patients showing clinically relevant neuroplasticity captured by TMS, only 2.5% of patients showed a blood oxygen level-dependent signal displaced from the precentral gyrus. Comparing the best-performing FAT for both modalities, TMS seeded tractography showed superior predictive value across all metrics: sensitivity, specificity, positive predictive value, and negative predictive value. CONCLUSIONS: The results from this study indicate that the prediction of permanent deficits with TMS tractography is superior to that with fMRI tractography, possibly because TMS tractography captures clinically relevant neuroplasticity. However, future large-scale prospective studies are needed to fully illuminate the proper role of each modality in comprehensive presurgical workups for patients with motor-eloquent tumors.

Cost-effectiveness analysis of radiosurgical capsulotomy versus treatment as usual for treatment-resistant obsessive-compulsive disorder.

OBJECTIVE: Stereotactic radiosurgical capsulotomy (SRS-C) is an effective neurosurgical option for patients with treatment-resistant obsessive-compulsive disorder (TROCD). Unlike other procedures such as deep brain stimulation and radiofrequency ablation, the cost-effectiveness of SRS-C for TROCD has not been investigated. The authors herein report the first cost-effectiveness analysis of SRS-C for TROCD. METHODS: Using a decision analytic model, the authors compared the cost-effectiveness of SRS-C to treatment as usual (TAU) for TROCD. Treatment response and complication rates were derived from a review of relevant clinical trials. Published algorithms were used to convert Yale-Brown Obsessive Compulsive Scale scores into utility scores reflecting improvements in quality of life. Costs were approached from the healthcare sector perspective and were drawn from Medicare reimbursement rates and available healthcare economics data. A Monte Carlo simulation and probabilistic sensitivity analysis were performed to estimate the incremental cost-effectiveness ratio. RESULTS: One hundred fifty-eight TROCD patients across 9 studies who had undergone SRS-C and had at least 36 months of follow-up were included in the model. Compared to TAU, SRS-C was more cost-effective, with an estimated incremental cost-effectiveness ratio of $28,960 per quality-adjusted life year (QALY) gained. Within the 3-year time horizon, net QALYs gained were greater in the SRS-C group than the TAU group by 0.27 (95% CI 0.2698-0.2702, p < 0.0001). At willingness-to-pay thresholds of $50,000 and $100,000 per QALY, the Monte Carlo simulation revealed that SRS-C was more cost-effective than TAU in 83% and 100% of iterations, respectively. CONCLUSIONS: Compared to TAU, SRS-C for TROCD is more cost-effective under a range of possible cost and effectiveness values.

Association of clinical outcomes and connectivity in awake versus asleep deep brain stimulation for Parkinson disease.

OBJECTIVE: Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes. METHODS: Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who received implants of bilateral DBS leads. In subset analysis, implanted electrodes were reconstructed using the Lead-DBS toolbox. Volumes of tissue activated (VTAs) were used as seed points in group volumetric and connectivity analysis. RESULTS: The clinical courses of 122 patients (52 asleep, 70 awake) were reviewed. Operating room and procedure times were significantly shorter in asleep cases. LEDD reduction, MDS-UPDRS III score improvement, and TEED at the 6-month follow-up did not differ between groups. In subset analysis (n = 40), proximity of active contact, VTA overlap, and desired network fiber counts with motor STN correlated with lower DBS energy requirement and improved motor scores. Discriminative structural fiber tracts involving supplementary motor area, thalamus, and brainstem were associated with optimal clinical improvement. Areas of highest structural and functional connectivity with VTAs did not significantly differ between the two groups. CONCLUSIONS: Compared to awake STN DBS, asleep procedures can achieve similarly optimal targeting-based on clinical outcomes, electrode placement, and connectivity estimates-in more efficient procedures and shorter operating room times.

Tractography-Based Modeling Explains Treatment Outcomes in Patients Undergoing Deep Brain Stimulation for Obsessive-Compulsive Disorder.

BACKGROUND: Deep brain stimulation (DBS) is an established and expanding therapy for treatment-refractory obsessive-compulsive disorder. Previous work has suggested that a white matter circuit providing hyperdirect input from the dorsal cingulate and ventrolateral prefrontal regions to the subthalamic nucleus could be an effective neuromodulatory target. METHODS: We tested this concept by attempting to retrospectively explain through predictive modeling the ranks of clinical improvement as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in 10 patients with obsessive-compulsive disorder who underwent DBS to the ventral anterior limb of internal capsule with subsequent programming uninformed by the putative target tract. RESULTS: Rank predictions were carried out using the tract model by a team that was completely uninvolved in DBS planning and programming. Predicted Y-BOCS improvement ranks significantly correlated with actual Y-BOCS improvement ranks at the 6-month follow-up (r = 0.75, p = .013). Predicted score improvements correlated with actual Y-BOCS score improvements (r = 0.72, p = .018). CONCLUSIONS: Here, we provide data in a first-of-its-kind report suggesting that normative tractography-based modeling can blindly predict treatment response in DBS for obsessive-compulsive disorder.

Stereo-EEG-guided network modulation for psychiatric disorders: Surgical considerations.

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. RESULTS: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). CONCLUSION: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.

Firearm-Related Pediatric Head Trauma: A Scoping Review.

BACKGROUND: Firearm-related injury is a significant cause of morbidity and mortality in pediatric populations. Despite a disproportionate role in the most morbid outcomes in both traumatic brain injury and firearm-related injury populations, firearm-related traumatic brain injury (frTBI) is an understudied epidemiological entity. There is need to increase understanding and promote interventions that reduce this burden of disease. OBJECTIVE: To assess the evidence characterizing pediatric frTBI to highlight trends and gaps regarding burden of disease and interventions to reduce frTBI. METHODS: We conducted a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) guidelines on peer-reviewed studies across 5 databases (Medline OVID, EMBASE, Web of Science Legal Collection, PsychINFO, and Academic Search Complete). English studies examining pediatric frTBI epidemiology, prevention, and/or social or legal policy advocacy were included. Articles were excluded if they more generally discussed pediatric firearm-related injury without specific analysis of frTBI. RESULTS: Six studies satisfied inclusion criteria after screening and full-text assessment. Limited studies specifically addressed the burden of disease caused by frTBI. There was an increased risk for both injury and death from frTBI in men, preteenage and teenage youths, minorities, and individuals in firearm-owning households. Further study is required to ascertain if suggested methods of targeted patient screening, firearm-injury prevention counseling, and advocacy of safety-oriented policy tangibly affect rates or outcomes of pediatric frTBI. CONCLUSION: By understanding published epidemiological data and areas of intervention shown to reduce frTBIs, neurosurgeons can become further engaged in public health and prevention rather than strictly treatment after injury.

Established and Emerging Therapies in Acute Spinal Cord Injury.

Acute spinal cord injury (SCI) is devastating for patients and their caretakers and has an annual incidence of 20-50 per million people. Following initial assessment with appropriate physical examination and imaging, patients who are deemed surgical candidates should undergo decompression with stabilization. Earlier intervention can improve neurological recovery in the post-operative period while allowing earlier mobilization. Optimized medical management is paramount to improve outcomes. Emerging strategies for managing SCI in the acute period stem from an evolving understanding of the pathophysiology of the injury. General areas of focus include ischemia prevention, reduction of secondary injury due to inflammation, modulation of the cytotoxic and immune response, and promotion of cellular regeneration. In this article, we review established, emerging, and novel experimental therapies. Continued translational research on these methods will improve the feasibility of bench-to-bedside innovations in treating patients with acute SCI.

Thalamic stereoelectroencephalography in epilepsy surgery: a scoping literature review.

OBJECTIVE: Stereoelectroencephalography (sEEG) is a well-established surgical method for defining the epileptogenic network. Traditionally reserved for identifying discrete cortical regions for resection or ablation, sEEG in current practice is also used for identifying more broadly involved subcortical epileptic network components, driven by the availability of brain-based neuromodulation strategies. In particular, sEEG investigations including thalamic nuclei are becoming more frequent in parallel with the increase in therapeutic strategies involving thalamic targets such as deep brain stimulation (DBS) and responsive neurostimulation (RNS). The objective to this study was to evaluate existing evidence and trends regarding the purpose, techniques, and relevant electrographic findings of thalamic sEEG. METHODS: MEDLINE and Embase databases were systematically queried for eligible peer-reviewed studies involving sEEG electrode implantation into thalamic nuclei of patients with epilepsy. Available data were abstracted concerning preoperative workup and purpose for implanting the thalamus, thalamic targets and trajectories, and electrophysiological methodology and findings. RESULTS: sEEG investigations have included thalamic targets for both basic and clinical research purposes. Medial pulvinar, dorsomedial, anterior, and centromedian nuclei have been the most frequently studied. Few studies have reported any complications with thalamic sEEG implantation, and no studies have reported long-term complications. Various methods have been utilized to characterize thalamic activity in epileptic disorders including evoked potentials, power spectrograms, synchronization indices, and the epileptogenicity index. Thalamic intracranial recordings are beginning to be used to guide neuromodulation strategies including RNS and DBS, as well as to understand complex, network-dependent seizure disorders. CONCLUSIONS: Inclusion of thalamic coverage during sEEG evaluation in drug-resistant epilepsy is a growing practice and is amenable to various methods of electrographic data analysis. Further study is required to establish well-defined criteria for thalamic implantation during invasive investigations as well as safety and ethical considerations.

Repeat laser interstitial thermal therapy for recurrent primary and metastatic intracranial tumors.

Background: Repeat craniotomy in patients with primary and metastatic brain tumors carries significant morbidity and can delay adjuvant treatments. Repeat laser interstitial thermal therapy (LITT) for recurrent disease has been described and could benefit patients with limited cytoreductive options. We aim to describe the indications, safety, and efficacy of repeat LITT for recurrent primary and metastatic intracranial tumors. Methods: Patients undergoing repeat ablations for the same lesion were included in the study. We retrospectively analyzed 13 patients treated with 29 total LITT ablations. Results: Eleven patients were treated for glioblastoma (GBM), while two had brain metastases. Eleven patients had LITT performed only 2 times, while three patients underwent three total iterations of LITT for disease recurrence. Median length of stay after the 1st ablation was 2 days, while the median length of stay after the 2nd ablation was 1 day. The median time to resuming adjuvant treatments after the 1st LITT was 11 days. The median time to resuming adjuvant treatments after the 2nd LITT was 28 days. Four patients after the 1st and 2nd LITT sustained deficits persisting through 30-day follow-up. The median progression-free survival among the GBM patients from the first ablation was 6.0 months, 3.2 months from the 2nd ablation, and 2.1 months from the 3rd ablation. Conclusion: Recurrent tumors, especially GBM, can be safely treated using repeat LITT when surgery cannot be effectively performed. Our results indicate that patients tolerate the procedure well and have a meaningful survival given the salvage nature of the procedure.